Improve Blood Flow By Hanging Upside Down?

It might sound a bit odd, but apparently it’s possible to improve metabolic measures related to blood flow simply by hanging upside down. However, get it wrong and you might end up killing yourself.

It’s well-known that regular aerobic exercise is good for the heart. But various yoga positions also appear to do a similar trick without the need for so much sweating.

One particular yoga pose of specific interest is the upside down position. Of course, as you can see below, there are plenty of different ways of achieving this.

What are the upside down benefits?

A 2011 review 1  into the benefits of yoga in general considered that upside down (or inverted) yoga poses were of benefit to the cardiovascular system:

Inverted poses encourage venous blood flow from the legs and pelvis back to the heart and then pumped through the lungs where it becomes freshly oxygenated. Many studies 2 3 4 show yoga lowers the resting heart rate, increases endurance, and can improve the maximum uptake and utilisation of oxygen during exercise.

There are plenty of yoga websites 5 6 7 8 that give advice on the best way to achieve this inverted pose – variously called supported headstand, sirsasana, inversions, and so forth.

Any yoga’s good yoga

Naturally, this is not the only yoga pose that studies have shown has health benefits. Studies suggest a wide range of benefits, such as:

  • neurological disorders 9 , including:
    • multiple sclerosis 10
    • stroke 11
    • epilepsy 12
    • Parkinson’s disease 13
    • dementia 14
    • Alzheimer’s 15
  • hypertension 16
  • obesity 17
  • diabetes 18
  • depression 19

The list goes on and on…

Dying to be upside down

However, you should be warned that this is not one of those things where a little is good and a lot is even better. Too much inversion can kill 20 .

In 2009, a guy called John Jones, who lived in Utah, died after spending 28 hours stuck upside down in a cave 21 , most likely from asphyxiation.

Upside down lungs

It transpires that our lungs evolved to sit on top of all the other organs for a very good reason. They are such delicate organs that it doesn’t take them long to get squashed by the larger and heavier organs such as the liver and intestines that usually sit below them. 22

This isn’t a problem for sloths, since they have their lungs “taped” to their ribs 23 .

But for us mere humans, having our heads directly underneath our feet for extended periods of time means that the lungs simply can’t absorb enough oxygen given the restricted space they have to work within.

Upside down brain

And it’s not just our lungs that have difficulty. Our bodies are set up to move blood around when we’re upright. Our blood vessels are customised to make sure blood doesn’t pool in our feet. This system is a “one-way street”, since our bodies didn’t evolve to prevent blood from pooling in the brain. This is patently not the case with bats. They have one-way valves in their arteries that prevent blood from flowing backwards. This is why they are able to hang upside down without the blood rushing to their heads 24 .

However, unlike bats, Batman would get into all sorts of vascular trouble (with or without the help of Robin) – ruptured blood vessels and potential brain haemorrhage included.

Upside down heart

And the heart is no lover of too much life down under 25 . It’s thought that heart failure accounts for most upside down fatalities. Just as with the brain, when the heart is above the head, it pumps more slowly and starts to receive more blood than it has the capacity to deal with at any one time. The result is that it begins to have a hard time maintaining blood pressure. Eventually, it will lose its ability to move sufficient blood around to maintain all the body’s essential functions.

Hanging around for too long will eventually kill you – a risk which increases as we age or if we are sick.

Inversion can be torture

It should be remembered that inversion was used as a torture method is ye olde days. It combined pain with a smattering of humiliation. Often the torture of choice for those sinners with unorthodox beliefs, it was used by the Romans with Christians and the Spanish with Jews and Muslims 26 27  . The Japanese even have a word for it – Tsurushi or “reverse hanging” 28 .

Nice to see how relaxed that monk-like executioner appears!

Another thing they used to do was to keep the victim inverted for some time and then make them stand upright again. Apparently, this is very painful as the blood pools to the feet again. Of course, they’re then hung upside down again. This process usually kills them within 8 to 10 hours.

Oh how inventive we humans are…

Final thoughts

It’s probably the case that any exercise is good exercise – whether it’s resistance training with weights, aerobic, or yoga. The important thing is to ensure you get plenty of regular daily exercise – either 90 mins low-moderate intensity (e.g. walking) or 45 mins of high-intensity exercise (e.g cycling, running, or rowing). It’s generally suggested 29 that you can work out your maximum heart rate by simply subtracting your age from 220. Then you can think of low-moderate intensity as being 50 – 70% of the resulting figure, whilst high-intensity would be 70-85%.

Spending a little time upside down appears to be something worth considering – however, some methods of achieving this are better than others…


  1. Int J Yoga. 2011 Jul-Dec; 4(2): 49–54. Exploring the therapeutic effects of yoga and its ability to increase quality of life. Catherine Woodyard. []
  2. Effect of yoga on cardiovascular system in subjects above 40 years. Bharshankar JR, Bharshankar RN, Deshpande VN, Kaore SB, Gosavi GB. Indian J Physiol Pharmacol. 2003 Apr; 47(2):202-6. []
  3. Hatha yoga: improved vital capacity of college students. Birkel DA, Edgren L Altern Ther Health Med. 2000 Nov; 6(6):55-63. []
  4. Effects of Hatha yoga and Omkar meditation on cardiorespiratory performance, psychologic profile, and melatonin secretion. Harinath K, Malhotra AS, Pal K, Prasad R, Kumar R, Kain TC, Rai L, Sawhney RC J Altern Complement Med. 2004 Apr; 10(2):261-8. []
  5. Yoga Journal: Supported Headstand []
  6. Yoga Journal: Everybody Upside-Down []
  7. YouTube video: How to Do a Headstand (Sirsasana) Yoga []
  8. DoYouYoga: 10 Most Popular Yoga Inversions []
  9. J Clin Neurosci. 2017 Sep;43:61-67. doi: 10.1016/j.jocn.2017.05.012. Epub 2017 Jun 7. Evidence based effects of yoga in neurological disorders. Mooventhan A, Nivethitha L. []
  10. PLoS One. 2014 Nov 12;9(11):e112414. doi: 10.1371/journal.pone.0112414. eCollection 2014. Yoga for multiple sclerosis: a systematic review and meta-analysis. Cramer H, Lauche R, Azizi H, Dobos G, Langhorst J. []
  11. Cochrane Database Syst Rev. 2017 Dec 8;12:CD011483. doi: 10.1002/14651858.CD011483.pub2. Yoga for stroke rehabilitation. Lawrence M, Celestino Junior FT, Matozinho HH, Govan L, Booth J, Beecher J. []
  12. Cochrane Database Syst Rev. 2017 Oct 5;10:CD001524. doi: 10.1002/14651858.CD001524.pub3. Yoga for epilepsy. Panebianco M, Sridharan K, Ramaratnam S. []
  13. Trials. 2017 Nov 2;18(1):509. doi: 10.1186/s13063-017-2223-x. The effects of yoga versus stretching and resistance training exercises on psychological distress for people with mild-to-moderate Parkinson’s disease: study prxotocol for a  randomized controlled trial. Kwok JYY, Kwan JCY, Auyeung M, Mok VCT, Chan HYL. []
  14. Int J Geriatr Psychiatry. 2017 Jan;32(1):118. doi: 10.1002/gps.4538. The therapeutic effects of yoga in people with dementia: a systematic review. Du Q, Wei Z. []
  15. Res Gerontol Nurs. 2014 Jul-Aug;7(4):171-7. doi: 10.3928/19404921-20140218-01. Epub 2014 Feb 26. The effect of chair yoga in older adults with moderate and severe Alzheimer’s disease. McCaffrey R, Park J, Newman D, Hagen D. []
  16. Exp Clin Endocrinol Diabetes. 2016 Feb;124(2):65-70. doi: 10.1055/s-0035-1565062. Epub 2015 Nov 17. The Efficacy and Safety of Yoga in Managing Hypertension. Cramer H. []
  17. Prev Med. 2016 Jun;87:213-232. doi: 10.1016/j.ypmed.2016.03.013. Epub 2016 Apr 4. A systematic review and meta-analysis on the effects of yoga on weight-related outcomes. Lauche R, Langhorst J, Lee MS, Dobos G, Cramer H. []
  18. Prev Med. 2017 Dec;105:116-126. doi: 10.1016/j.ypmed.2017.08.017. Epub 2017 Sep 4. The effects of yoga among adults with type 2 diabetes: A systematic review and meta-analysis. Thind H et al. []
  19. Depress Anxiety. 2013 Nov;30(11):1068-83. doi: 10.1002/da.22166. Epub 2013 Aug 6. Yoga for depression: a systematic review and meta-analysis. Cramer H, Lauche R, Langhorst J, Dobos G. []
  20. Quora: How long could a human being survive hanging upside down if they’re being fed, hydrated, etc. Would spending one’s life hanging upside down shorten one’s lifespan? Amandi Dilshara. Oct 24 2019. []
  21. ABC News: Man in Utah Cave Faced Tough Odds, Doctors Say John Jones’ upside down position in the cave left rescue workers little time. By LAUREN COX. Nov. 26, 2009. []
  22. HowStuffWorks: How Your Lungs Work. BY CRAIG FREUDENRICH, PH.D. []
  23. National Geographic: SCIENCE & INNOVATION. To Breathe Upside-Down, Sloths Tape Organs To Their Ribs. BY ED YONG. PUBLISHED APRIL 23, 2014. []
  24. Bat Worlds: Bat Anatomy. Nov 5, 2013. []
  25. How StuffWorks: How Your Heart Works. CARL BIANCO. []
  26. The Marseille Tarot Revealed: A Complete Guide to Symbolism, Meanings & Methods. By Yoav Ben-Dov. []
  27. Bustle: 7 Incredibly Disturbing Execution Methods From The Middle Ages (You Really Should Not Read This) By LARA RUTHERFORD-MORRISON. May 14 2015. []
  28. Wikipedia: Tsurushi. []
  29. Mayo Clinic: Exercise intensity: How to measure it. []

Lose weight Without Exercising or Making Any Dietary Change?

Tackling obesity without exercise or dietary changes? Everyone’s heard of fat tissue (also called adipose tissue), but what about brown adipose tissue (BAT) and “beige” adipose tissue – ever heard of them? Although sounding pretty unappetising,  these adipocytes1 share the unique ability of being able to convert chemical energy into heat and, thereby, play a critical role in promoting something called non-shivering thermogenesis – a little-known process that is central to the human species’ ability to spread across the globe and, as an interesting sideline, can potentially help in weight-loss without even having to lift a single barbell or place a tentative trainer on that running machine gathering dust in your garage. Or is it just too good to be true?

BAT & beige adipocytes

Until relatively recently, the physiological role of BAT and beige adipocyte depots were thought to be limited to small mammals and only relevant to humans when they were neonates (newborn infants). Puppy fat or baby fat was thought to all-but disappear with the passing years into adulthood. However, the discovery that there’s more BAT in adult humans than previously thought, has led to studies which show enthusiasm for BAT’s potential role in treating obesity and other disorders caused by sustained positive energy balance (more calories in than out). Adult humans having more BAT than previously thought was revealed 2 3 during routine scans  (FDG-PET scans4 to detect metastatic cancers. 5  Autopsies were also able to reveal these fat concentrations. 6

Brown & white fat

BAT (often abbreviated to “brown fat”) is found in virtually all mammals, but notably in newborn humans and mammals that hibernate 7 . Of course, the usual white adipose tissue (“white fat”) that we think of when we talk about fat is found in far higher quantities. 8 . The following provides an overview of the differences between the brown and white fat tissue:

The main differences between brown and white fat can be summarised as:

  • white contains a single lipid droplet while brown contains numerous smaller droplets
  • brown contains a much much higher number of (iron-containing) mitochondria – hence the brown (rusty) colour of the tissue 9
  • brown contains more blood capillaries than white – hence a better oxygen supply, more nutrient-provision and the ability to distribute the produced heat throughout the body

Two types of BAT

BAT itself can also broken down into two types which have similar functions but are located in different cell populations within the body: 10

  • brown adipocytes found in comparatively larger separate deposits within the body, and
  • “beige” or “brite” (“brown in white”) adipocytes found interspersed within white adipose tissue and which develop out of white adipocytes under the stimulation of the sympathetic nervous system (SNS) 11
Brown adipose tissue in a woman shown in a PET/CT scan exam.

BAT in infants & adults

BAT in infants eventually “turns into” white fat in adulthood. In infancy, however, it tends to be located in the following “depots” within the body:

  • interscapular 12
  • supraclavicular 13
  • suprarenal 14
  • pericardial 15
  • paraaortic 16
  • around the pancreas, kidney and trachea 17

BAT in adults tend to be located in the following depots:

  • supraclavicular
  • suprarenal
  • paravertebral 18
  • mediastinal 19
  • paraaortic 20

It’s still not absolutely clear whether these adult BAT depots are the “classical” brown or the beige/brite fat. 21 . However, BAT is metabolically active in adult humans 22  and decreases in quantity as we age 23 . Another characteristic of BAT is that it becomes more visible (that is, becomes more metabolically active) with cold exposure – as can be seen by analysing it with PET scans.

BAT & thermoregulation

The primary function of BAT is thermoregulation. That is, ensuring the body remains sufficiently warm in cold environments. It achieves this autonomic heating of the body in two ways: firstly, through shivering thermogenesis (causing muscles to shiver) and, secondly, through non-shivering thermogenesis (as the name suggests – heating the body without shivering) – an adaptive thermogenesis response. The first option, shivering thermogenesis, will certainly warm up the body, but at the expense of using up relatively more precious energy.

However, the unique ability of BAT to convert energy stores (brown fat) into heat (without needing to use energy-sapping shivering) is achieved through a process within BAT mitochondria (the energy-producing cellular power plants). Instead of the usual process, where ATP (the energy molecule) is produced during oxidative phosphorylation, a protein called thermogenin or UCP1 (Uncoupling Protein 1) promotes a proton leak in the inner membrane of the mitochondria, dissociating the oxidative phosphorylation of substrate from the generation of ATP. In essence, this results in an increase in non-shivering thermogenesis, where the metabolic rate increases, and chemical energy is shunted into heat energy that can then spread around the body via the bloodstream.

This means the endothermic organisms (you and me) stand a better chance of survival against unfavourable environmental conditions with the least possible consumption of energy stores 24 . This can be seen in a little more clearly in the following diagram:

Just to be clear, all cells of endotherms are able to give off heat to some degree, particularly when body temperature is below a regulatory threshold; but BAT is highly specialised for this non-shivering thermogenesis. This is largely because of two of the features mentioned above: firstly, each BAT cell has a higher number of mitochondria compared to typical cells and, secondly, these mitochondria have a higher-than-normal concentration of thermogenin (UCP1) in the inner membrane.

Why do newborns have so much BAT?

In newborn infants, BAT comprises around 5% of body mass (located on the upper half of the spine and toward the shoulders). At this age, infants are at a much higher risk of hypothermia than adults. This is largely because of the following:

Infants have:

  • underdeveloped nervous systems that don’t respond quickly and/or appropriately to cold via vasoconstriction (the contraction of blood vessels in and just below the skin)
  • inability to move away from cold materials or air currents or towards warmer materials/environments
  • low amount of musculature and an inability to shiver (shivering thermogenesis)
  • lack of thermal insulation such as subcutaneous fat and fine body hair
  • higher ratio of body surface area (proportional to heat loss) to body volume (proportional to heat production)
  • higher proportional surface area of the head
  • the obvious inability to use adult ways of keeping warm – putting clothes on, exercising, drying their skin, etc

Thus, heat production in BAT provides infants with an alternative means of heat regulation.

Evolutionary advantage of BAT

Mammals (and birds, to some extent) have the unique ability to maintain their core temperature independently of the external environmental temperature. This homeothermic 25 ability has allowed great evolutionary success compared to poikilotherms2627

The main components of this response to temperature are:

  • thermal insulation
  • non-shivering thermogenesis, and
  • shivering thermogenesis 28

From an evolutionary point of view, excess energy expenditure aimed at maintaining core temperature represents a trade-off between survival and the maintenance of energy stores, since energy availability will usually represent a major limiting factor to growth and reproduction. Thus, moving from an insulative response (energy neutral), to a non-shivering and eventually shivering thermogenesis will require a progressively greater dissipation of energy stores, as can be seen in the following chart.

Model of adaptive thermogenesis. As the environmental temperature decreases from thermoneutrality, the adaptive thermogenesis response moves from insulative to non-shivering and eventually shivering thermogenesis. This progression is mirrored by an increase in the energy expenditure required to maintain the core temperature. Green, energy expenditure due to basal metabolic rate; red, expenditure due to adaptive thermogenesis.

Over recent evolutionary development, humans gained the ability to “control” their environment by using clothes and controlling the temperature in their buildings. As a result, cold exposure is a relatively rare condition and, unless acclimatised, individuals would tend to respond by shivering thermogenesis – where heat is a side product of uncontrolled shivering – also known as muscle fasciculation 29

Losing weight & improving health with BAT

Recent discoveries regarding BAT may, it’s claimed, lead to new methods of weight loss, since brown fat (when exposed to cold temperatures) takes calories from normal fat and burns it. As well as this, adaptive (non-shivering) thermogenesis also appears to promote glucose disposal. To test this weight-loss ability of BAT, it would involve exposing subjects to cold temperatures and monitoring whether they do, in fact, lose weight without having to exercise or change dietary patterns. The following is a selection of some BAT studies that throw some light on this subject.

A 1961 study 30 when individuals had prolonged exposure to cold, showed that they became resilient and stopped displaying shivering thermogenesis, indicating that other mechanisms were being recruited.

In 2009, four separate studies 31 32 33 34 indicated clearly that BAT was present in a significant number of adults and that there was a correlation between its presence and activity related to indices of healthy metabolism.

In 2010, a study 35 showed that there was an inverse correlation between BAT activity and between obesity, diabetes and ageing – that is, the more active BAT was, the less obesity, diabetes and ageing was seen.

Naturally, up to this point, the relationship was one of correlation and no causal mechanism had been established. However, researchers were very interested in finding out more about the capacity and activity of human BAT as a therapeutic means of treating the various metabolic consequences of obesity. The majority of the consequent studies focused on this BAT adaptive thermogenesis response by exposing volunteers to cold.

A 2011 study 36 exposed individuals to short but intense cold (e.g. immersing a limb in ice-cold water). Whilst they showed that this does indeed increase energy expenditure, it’s a method that fails completely to correspond with day-to-day experience and is impossible to sustain over time.

Additional research demonstrated that such extreme cold exposure was not necessary to stimulate sustained physiologic adaptive thermogenesis. It could be stimulated by even mild cold exposure as that controlled within normal (and bearable) climate-controlled buildings. This was shown in a 2010 crossover study 37 which looked at the effects of the adaptive thermogenesis response to minimal changes in environmental temperature. Healthy volunteers underwent two 12-hour periods in a whole room calorimeter (Metabolic Chamber) at 19 and 24 °c to monitor energy expenditure (EE). Results indicated that such minimal modulation of environmental temperature was sufficient to increase EE by around 6%. Might not seem much but, if projected over a 24 hour period, it would represent a drop of 100 kcal in an individual of between 70-80 kg.

Hormonal axes and organ-system response to mild cold exposure.

In addition to burning extra calories, exposure to mild cold (with the resulting increase in non-shivering thermogenesis) was shown to be sufficient to drive an adrenergic response 38 , which promotes lipolysis39 (with fatty acids being the preferred substrate in BAT depots) and increased postprandial glucose disposal. Additionally, the intervention generated an increase in cortisol 40  and a state of relative insulin resistance during fasting, which indicate an activation of the stress response. These, and other responses are shown in the adjacent table.

The researchers point out that, although the magnitude of this change may appear insignificant – only one fifth of the negative energy balance recommended to achieve sustained weight loss – it is relevant to note that, over a 1-year period (all things being equal), these differences would be equivalent to a 20-day fast and to a daily 30-min walk at a moderate pace.

A subsequent 2013 study 41 confirmed BAT contributes to energy expenditure (EE) in response to mild cold exposure – namely, 12-hour metabolic chamber exposure to either 19 or 24 ° C.

Two other 2013 studies showed, in the first case 42 , that a short-term, moderate (10 days acclimatisation with exposure at 17 ° C daily for 2 hours) cold exposure was sufficient to increase the quantity of BAT, and, in the second case 43 , that a longer period of time (6 weeks acclimatisation with exposure at 17 ° C daily for 2 hours) resulted in “significant fat mass reduction“- as shown in the following photos and chart:

BAT activation was shown to improve glucose homeostasis 44 and insulin sensitivity 45 in humans. Additional studies 46 47 looked at BAT and the hormone FGF-21 (fibroblast growth factor 21 production). FGF-21 is a critical metabolic regulator that governs glucose and lipid (fat) metabolism and plays an important role in the treatment of metabolic diseases, such as T2D (type 2 diabetes) and obesity. In T1D (type 1 diabetes), FGF-21 also reduces blood glucose levels and prevents diabetic complications.  It was demonstrated that BAT activation through cold exposure can up-regulate circulating FGF-21 in humans by 37%. FGF21 improves insulin sensitivity and glucose metabolism which may partially explain its longevity promoting benefits.

This offers hope for those with impaired insulin function who might benefit from BAT activation. And it’s not just those with clinically impaired insulin function, such as type 2 diabetics, who could benefit from this. Over time, even mildly elevated blood glucose levels in otherwise healthy non-diabetic humans are associated with other physiological damage. This has been shown to result in higher levels of the damaging AGE’s (advanced glycation end products – found in animal products, processed and fried/barbecued/roasted fatty foods), as well as damage to the brain, eyes, tendons, endothelial cells and the cardiovascular system 48 49 50 .

In a longer 2014 study 51 over four consecutive months, environmental temperature was modulated overnight – 24 ° C (run-in period), (cold acclimatisation), 24 ° C (wash-out period), and 30 ° C (heat acclimatisation). After a month of exposure to mild cold (19 ° C ), BAT volume and activity almost doubled, but after a month of exposure to warm temperature (30 ° C), BAT activity was negligible. The researchers commented that: “Remarkably, the increase in BAT activity following the cold acclimatisation was accompanied by a significant increase in postprandial glucose disposal, but only during mild cold exposure.

One study 52 looked at levels of irisin (a relatively newly discovered hormone) as a result of both intense exercise and cold exposure. Irisin is nicknamed the “exercise hormone” since  it’s released during moderate aerobic endurance activity and is known to be an anti-obesity and anti-diabetes hormone that regulates fat tissue and blood sugar, improving insulin sensitivity, bone quality/quantity 53 54 , and building lean muscle mass. In essence, irisin is thought to help reduce obesity by converting white fat to brown fat 55 . Being that irisin is released by muscles during physical exercise 56 , if cold-exposure also releases irisin, then perhaps the metabolic benefits of such exposure would be similar to those when irisin is released through exercise. And, indeed, this study demonstrated that this appears to be the case.

And irisin has other interesting effects. A study 57 on the reasons why healthy centenarians are healthy noted that they tend to have increased serum irisin levels, whilst irisin levels were significantly lower in younger patients with myocardial infarction 58 . So, although somewhat an aside to the main thrust of this blog, such findings are likely to prompt further research into the role of irisin in vascular disorders and life span extension.

Another hormone, adiponectin 59 , has associations with both BAT activation and centenarians. It’s been shown 60 that when BAT is activated through cold exposure, adiponectin levels increase within just two hours, resulting in a 70% increase in circulating adiponectin in adult men. Interestingly, both male and female centenarians (as well as their offspring) have been found 61  both to have genetics which boost adiponectin and to have generally higher circulating levels of adiponectin. This suggests a further link between BAT activation and longevity – this time because of the increased production of adiponectin. Furthermore, these high concentrations of plasma adiponectin in centenarians were associated 62 with other favourable metabolic factors as well as with lower levels of C-reactive protein 63  and E-selectin64 . It was mentioned earlier that BAT activation results in the production of FGF-21 – a hormone that improves insulin sensitivity and glucose metabolism. The latter benefits may explain why this hormone has been shown 46  to play a role in promoting longevity in humans.

In relation to fat and irisin, it was shown 65 that applying irisin to human preadipocytes (cells that can be transformed into different fat cells through the process of adipogenesis) , ordinary white adipocytes could be changed into beige adipocytes. This helps confirm the role of irisin as a myokine66 that can expand beige adipocyte mass, increasing the non-shivering thermogenesis capacity and, thereby, promoting a shift from inefficient and non-sustainable shivering thermogenesis to more efficient and sustainable non-shivering thermogenesis. In the following diagram, FGF-21 (fibroblast growth factor 21) promotes BAT’s activity of cold-induced non-shivering thermogenesis in humans.

Model of interplay between shivering and non-shivering thermogenesis. Exposure to cold promotes shivering in non-acclimated individuals, with the release of irisin. This response is unsustainable and costly from an energy-conservation perspective. Irisin promotes the expansion and differentiation of beige adipocytes, which increase resilience to cold enhancing non-shivering thermogenesis and delays the onset of shivering.

All the above studies indicate both that human BAT is extremely plastic, and that activation via cold exposure is necessary to generate a significant metabolic response.

Final thoughts

So, merely reducing the environmental temperature in your home could help to lose some body weight (represented by an additional energy expenditure of around 100 kcal) without actually undergoing exercise or changing one’s dietary habits. However, the amount of body fat you could lose through undergoing even colder and, consequently, more uncomfortable temperatures is something that I can’t imagine many people wanting to opt for as a weight-loss method.

Of course, integrating a bit of low temperature “therapy” might reduce one’s heating bills. And, of course, there is another weight-loss method associated with temperature modulation – namely, sweating your socks off in a sauna, albeit really just water that you’ll lose, and you’ll put the weight back on pretty soon afterwards when you rehydrate.

However, there is another simple non-exercise/non-dieting weight-loss method which is similar in effect to turning down the thermostat – namely, something called a standing desk. A standing desk is simply a matter of raising the height of one’s table (and hence the computer , book or paperwork thereon) and standing instead of sitting. Interestingly, this method has been shown 67 to increase calories burnt (in this case in young schoolchildren):

Another study 68 found that standing burned an extra 0.15 calories per minute, on average, compared with sitting. Men burned an extra 0.2 calories per minute while standing, which was twice as much as women, who burned an extra 0.1 calories. This was because men they typically have more muscle mass than women. This would mean that a person weighing around 63 kg (140 pounds/10 stones), replacing sitting with standing for six hours a day would burn an extra 54 calories per day.

Naturally, pharmaceutical companies may well try to come up with a “magic pill” that will stimulate BAT activity without the need for subjecting oneself to cold temperatures – maybe an injection or pill to stimulate BAT activity without having to ensure cold temperatures; but experience teaches us that most of these pharmaceutical wonder cures have unpleasant side effects and rarely prove as effective as their manufacturers initially claim.

So, whether of itself, or even when combined with another simple non-exercise/non-dietary change weight-loss method, it would seem that the benefits are interesting, though not comparable with the weight-loss benefits of a combination of exercise and eating a low-fat plant-based diet.

References & Notes

  1. Adipocytes are cells specialised in fat storage and are found in connective tissue. []
  2. Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, von Schulthess GK (2002) Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med Mol Imaging 29: 1393– 1398. []
  3. Agrawal A, Nair N, Baghel NS (2009) A novel approach for reduction of brown fat uptake on FDG PET. Br J Radiol 82: 626– 631. []
  4. PET stands for positron-emission tomography (PET) and is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the body as an aid to the diagnosis of disease. FDG stands for fludeoxyglucose, an analogue of glucose – the biologically active tracer molecule chosen for this type of scan. []
  5. Yeung HW, Grewal RK, Gonen M, Schöder H, Larson SM (2003). “Patterns of (18)F-FDG uptake in adipose tissue and muscle: a potential source of false-positives for PET”. J Nucl Med. 44 (11): 1789–96. []
  6. Huttunen P, Hirvonen J, Kinnula V (1981) The occurrence of brown adipose tissue in outdoor workers. Eur J Appl Physiol Occup Physiol 46: 339– 345. []
  7. Gesta S, Tseng YH, Kahn CR (October 2007). “Developmental origin of fat: tracking obesity to its source”. Cell. 131 (2): 242–56. []
  8. Cinti S (2005). “The adipose organ”. Prostaglandins Leukot Essent Fatty Acids. 73 (1): 9–15. []
  9. Enerbäck S (2009). “The origins of brown adipose tissue”. New England Journal of Medicine. 360 (19): 2021–2023. []
  10. Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerbäck S, Schrauwen P, Spiegelman BM (2012). “Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human”. Cell. 150 (2): 366–76. []
  11. In response to a stressor, the sympathetic nervous system orchestrates what you familiarly call the fight-or-flight response. It increases muscle blood flow and tension, dilates pupils, accelerates heart rate and respiration, and increases perspiration and arterial blood pressure. []
  12. Interscapular – of, relating to, situated in, or occurring in the region between the scapulae, shoulder blades []
  13. Supraclavicular – of, relating to, situated in, or occurring in the region above the scapulae, shoulder blades []
  14. Suprarenal – of, relating to, situated in, or occurring in the region above or anterior to the kidneys []
  15. Pericardial – of, relating to, situated in, or occurring in the pericardium, two thin layers of a sac-like tissue that surround the heart, which hold it in place and help it work []
  16. Paraaortic – of, relating to, situated in, or occurring in the region of the front of the lumbar vertebrae near the aorta []
  17. Heaton JM (1972). “The distribution of brown adipose tissue in the human”. J Anat. 112 (Pt 1): 35–9. []
  18. Paravertebral – of, relating to, situated in, or occurring in the region on each side of the vertebrae []
  19. Mediastinal – of, relating to, situated in, or occurring in the region in the middle of the chest that lies between the sternum (breastbone) and spinal column. The area contains vital organs including the heart, oesophagus, and trachea. []
  20. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009). “Cold-activated brown adipose tissue in healthy men”. N Engl J Med. 360 (15): 1500–8. []
  21. Lidell ME, Betz MJ, Enerbäck S (2014). “Two types of brown adipose tissue in humans”. Adipocyte. 3 (1): 63–6. []
  22. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009). “High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity”. Diabetes. 58 (7): 1526–31. []
  23. Graja A, Schulz TJ (2015). “Mechanisms of aging-related impairment of brown adipocyte development and function”. Gerontology. 61 (3): 211–7. []
  24. Brown adipose tissue— when it pays to be inefficient. N Engl J Med 2009. 360: 1553– 1556. []
  25. Homeotherms maintain thermal homeostasis []
  26. A poikilotherm is an animal whose internal temperature varies considerably and depends on the external environment. Reptiles and fish are poikilotherms. []
  27. Vianna CR, Hagen T, Zhang CY, Bachman E, Boss O, Gereben B, Moriscot AS, Lowell BB, Bicudo JE, Bianco AC (2001) Cloning and functional characterization of an uncoupling protein homolog in hummingbirds. Physiol Genomics 5: 137– 145. []
  28. Celi FS, Le TN, Ni B (2015) Physiology and relevance of human adaptive thermogenesis response. Trends Endocrinol Metab 26: 238– 247. []
  29. Fasciculation is a brief spontaneous contraction affecting a small number of muscle fibres, often causing a flicker of movement under the skin. []
  30. Davis TR (1961) Chamber cold acclimatization in man. J Appl Physiol 16: 1011– 1015. []
  31. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360: 1509– 1517. []
  32. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360: 1518– 1525. []
  33. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360: 1500– 1508. []
  34. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58: 1526– 1531. []
  35. Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, Reimold M, Haring HU, Claussen CD, Stefan N (2010) Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 59: 1789– 1793. []
  36. Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, Saito M (2011) Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 19: 13– 16. []
  37. Celi FS, Brychta RJ, Linderman JD, Butler PW, Alberobello AT, Smith S, Courville AB, Lai EW, Costello R, Skarulis MC, Csako G, Remaley A, Pacak K, Chen KY (2010) Minimal changes in environmental temperature result in a significant increase in energy expenditure and changes in the hormonal homeostasis in healthy adults. Eur J Endocrinol 163: 863– 872. []
  38. Andrenergic relates to nerve cells in which adrenaline, noradrenaline, or a similar substance acts as a neurotransmitter. The result of this is that there is a stimulation of the sympathetic nervous system (SNS), which is responsible for the fight-or-flight response, which is triggered for example by exercise or fear causing situations. This response dilates pupils, increases heart rate, mobilises energy, and diverts blood flow from non-essential organs to skeletal muscle. These effects together tend to increase physical performance/energy usage momentarily. []
  39. Lipolysis is the breakdown of fats and other lipids by hydrolysis to release fatty acids. []
  40. Cortisol helps to control blood sugar levels, regulate metabolism, help reduce inflammation, and assist with memory formulation. It has a controlling effect on salt and water balance and helps control blood pressure. []
  41. Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, Herscovitch P, Millo CM, Remaley A, Lee P, Celi FS (2013) Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab 98: E1218– E1223. []
  42. van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, Jorgensen JA, Wu J, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2013) Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 123: 3395– 3403. []
  43. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M (2013) Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 123: 3404– 3408. []
  44. Stanford, Kristin I.; Middelbeek, Roeland J.W.; Townsend, Kristy L.; An, Ding; Nygaard, Eva B.; Hitchcox, Kristen M.; Markan, Kathleen R.; Nakano, Kazuhiro; Hirshman, Michael F. (2013-01-02). “Brown adipose tissue regulates glucose homeostasis and insulin sensitivity”. The Journal of Clinical Investigation. 123 (1): 215–223. []
  45. Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M. (2014-07-23). “Brown Adipose Tissue Improves Whole Body Glucose Homeostasis and Insulin Sensitivity in Humans”. Diabetes. 63 (12): 4089–99. []
  46. Camporez, João Paulo G.; Jornayvaz, François R.; Petersen, Max C.; Pesta, Dominik; Guigni, Blas A.; Serr, Julie; Zhang, Dongyan; Kahn, Mario; Samuel, Varman T. (2013-09-01). “Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice”. Endocrinology. 154 (9): 3099–3109. [] []
  47. Lee, Paul; Linderman, Joyce D.; Smith, Sheila; Brychta, Robert J.; Wang, Juan; Idelson, Christopher; Perron, Rachel M.; Werner, Charlotte D.; Phan, Giao Q. (2014-02-04). “Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans”. Cell Metabolism. 19 (2): 302–309. []
  48. Bjørnholt, J. V.; Erikssen, G.; Aaser, E.; Sandvik, L.; Nitter-Hauge, S.; Jervell, J.; Erikssen, J.; Thaulow, E. (1999-01-01). “Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men”. Diabetes Care. 22 (1): 45–49. []
  49. Snedeker, Jess G. (2016-01-01). How High Glucose Levels Affect Tendon Homeostasis. Advances in Experimental Medicine and Biology. 920. pp. 191–198. []
  50. Cherbuin, Nicolas; Sachdev, Perminder; Anstey, Kaarin J. (2012-09-04). “Higher normal fasting plasma glucose is associated with hippocampal atrophy The PATH Study”. Neurology. 79 (10): 1019–1026. []
  51. Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY, Celi FS (2014b) Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes 63: 3686– 3698. []
  52. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, Kebebew E, Pacak K, Chen KY, Celi FS (2014c) Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 19: 302– 309. []
  53. Devlin, Maureen J. (2015-02-01). “The “Skinny” on brown fat, obesity, and bone”. American Journal of Physical Anthropology. 156: 98–115. []
  54. Lee, P.; Brychta, R.J.; Collins, M.T.; Linderman, J.; Smith, S.; Herscovitch, P.; Millo, C.; Chen, K.Y.; Celi, F.S. (2013-04-01). “Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women”. Osteoporosis International. 24 (4): 1513–1518. []
  55. Colaianni, Graziana; Cuscito, Concetta; Mongelli, Teresa; Pignataro, Paolo; Buccoliero, Cinzia; Liu, Peng; Lu, Ping; Sartini, Loris; Di Comite, Mariasevera (2015-09-29). “The myokine irisin increases cortical bone mass”. Proceedings of the National Academy of Sciences of the United States of America. 112 (39): 12157–12162. []
  56. Harmon, Katherine. “Newly Discovered Hormone Boosts Effects of Exercise, Could Help Fend Off Diabetes”. []
  57. Emanuele, Enzo; Minoretti, Piercarlo; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Garatachea, Nuria; Lucia, Alejandro (2014-09-01). “Serum irisin levels, precocious myocardial infarction, and healthy exceptional longevity”. The American Journal of Medicine. 127 (9): 888–890. []
  58. Myocardial infarction is commonly known as a heart attack, and occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. []
  59. Adiponectin is a protein hormone that is produced by fat cells. Its physiological effects include the reduction of inflammation and atherogenesis (the formation of fatty deposits in the arteries) and enhancement of the response of cells to insulin. []
  60. Imbeault, Pascal; Dépault, Isabelle; Haman, François (2009-04-01). “Cold exposure increases adiponectin levels in men”. Metabolism: Clinical and Experimental. 58 (4): 552–559. []
  61. Atzmon, Gil; Pollin, Toni I.; Crandall, Jill; Tanner, Keith; Schechter, Clyde B.; Scherer, Philipp E.; Rincon, Marielisa; Siegel, Glenn; Katz, Micol (2008-05-01). “Adiponectin levels and genotype: a potential regulator of life span in humans”. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 63 (5): 447–453. []
  62. Arai, Yasumichi; Nakazawa, Susumu; Kojima, Toshio; Takayama, Michiyo; Ebihara, Yoshinori; Shimizu, Ken-ichirou; Yamamura, Ken; Homma, Satoki; Osono, Yasunori (2006-02-27). “High adiponectin concentration and its role for longevity in female centenarians”. Geriatrics and Gerontology International. 6 (1): 32–39. []
  63. High C-reactive protein (CRP) levels in your blood indicate inflammation in your body, possibly indicating an infection or other condition. []
  64. E-selectin is also associated with inflammation, mediating leukocyte rolling (adhesion) on activated endothelial cells at inflammatory sites. It may also support tumour cell adhesion during hematogenous metastasis (cancer spread) and may play roles in angiogenesis (cancer development) and haematopoiesis (production of blood cells). []
  65. Lee P, Werner CD, Kebebew E, Celi FS (2014a) Functional thermogenic beige adipogenesis is inducible in human neck fat. Int J Obes (Lond) 38: 170– 176. []
  66. A myokine is one of several hundred cytokines or other small proteins and proteoglycan peptides that are produced and released by muscle cells in response to muscular contractions. []
  67. Am J Public Health. 2011 August; 101(8): 1433–1436. The Impact of Stand-Biased Desks in Classrooms on Calorie Expenditure in Children. Mark E. Benden et al. []
  68. Eur J Prev Cardiol. 2018 Mar;25(5):522-538. Differences of energy expenditure while sitting versus standing: A systematic review and meta-analysis. Saeidifard F et al. []

Vegan Pie Comes Top in British Pie Awards 2019

Oh the scandal! The outrage! Grass-eaters winning a competition that should be dominated by pies filled with traditional steak and kidney, bacon and egg, pork and venison? And, to top it all, taking place in the hallowed heart of pork pie heaven, Melton Mowbray – the home of the classic pork pie.

For the sensitive souls (and taste buds) of the noble omnivore, this egregious affront to human taste and dignity comes far too soon on the back of Greggs’ launch of their ridiculously successful vegan sausage roll 1 . So successful, indeed, that it’s been credited as the cause of the 7% rise in the company’s share value 2 .

The vegan “pie” was produced by a company called Jon Thorner’s of Somerset 3 . As if it wouldn’t be so bad winning just one prize, they ended up winning a total of three awards at the recent 2019 British Pie Awards 4  for their Curried Sweet Potato & Butternut Squash, namely: “Best in Class”, “Best Producer” and “Supreme Pie Champion 2019”, beating 886 other competitors 5 at the contest in Melton Mowbray, Leicestershire 6 .

The leading chef, Richard Corrigan 7 , has blasted this butternut squash thing “a disgrace”. And, surely, the opinion of this Michelin-starred chef should be honoured and respected when he calls it a “pie in the sky”. All sane gastronomes will be relieved when he promises to make his “pig’s feet and black pudding and Swede pie” the next prize winner. 8

That’ll show those lily-livered lentil lovers!

While being interviewed by the Telegraph 9 , this bastion of butchery, who has proved his credentials as an arbiter of taste by having cooked for the Queen not once, but twice – showed how deeply affected he was by this culinary onslaught by uttering: “Please, please I’m going to cry.”

And, in support of the moderate and fair majority of people, he reminded us all of what proper food should be: “Pies are supposed to be filled with the most delicious morsels of steak and liver and kidney, with the jelly and little pieces of fat in the middle delicately dripping onto your tongue.

As though we’ve not had enough of populist nonsense – what with Brexiteers bandying around such outdated words like “democracy” and “national pride”. But to now have this travesty inflicted upon our already bowed and bruised heads by…one can hardly bear to say the word…v e g a n s.

As Chef Corrigan explains: “The oldest culinary art form left in the world and the vegans have taken it away. It’s a disgrace…The millennials have taken over…We should all just retire now.”

Matthew O’Callaghan, chairman of the 2019 British Pie Awards, appears to have slipped from the comforting embrace of omnivore common sense when he claims: “This year’s Supreme Champion was outstanding and well deserving of the accolade. From its very appearance on the judging tray you knew it was going to do well and it didn’t disappoint when it was opened and tasted. This pie isn’t just for vegans, it’s a pie for everybody. With this award we can truly say that veganism is now entering the mainstream of British food.” 5

The scale of the challenge ahead from marauding lettuce-lovers should not daunt the still-virtuous veganphobic nation of true meat-eaters.

Even as the faceless hordes of herbivores lay siege to the once great nation and its noble gastronomic traditions, I am reminded of John of Gaunt’s spirit-raising words of encouragement, as he lay on his death bed in Act One of Shakespeare’s Richard II:

“This royal throne of kings, this scepter’d isle,
This earth of majesty, this seat of Mars,
This other Eden, demi-paradise,
This fortress built by Nature for herself
Against infection and the hand of war,
This happy breed of men, this little world,
This precious stone set in the silver sea,
Which serves it in the office of a wall,
Or as a moat defensive to a house,
Against the envy of less happier lands,
This blessed plot, this earth, this realm, this England,
This nurse, this teeming womb of royal kings,
Fear’d by their breed and famous by their birth,
Renowned for their deeds as far from home,
For Christian service and true chivalry,
As is the sepulchre in stubborn Jewry,
Of the world’s ransom, blessed Mary’s Son,
This land of such dear souls, this dear dear land,
Dear for her reputation through the world,
Is now leased out, I die pronouncing it,
Like to a tenement or pelting farm:
England, bound in with the triumphant sea
Whose rocky shore beats back the envious siege
Of watery Neptune, is now bound in with shame,
With inky blots and rotten parchment bonds:
That England, that was wont to conquer others,
Hath made a shameful conquest of itself.
Ah, would the scandal vanish with my life,
How happy then were my ensuing death!”

He may as well have been making this speech now, just as the lights are being extinguished in the finest meat and two veg eateries across our nation…

Final thought

Now, I’m not claiming that the likes of Thorner’s vegan pie or Greggs’ vegan sausage roll are either ideal foods for optimal human health or what I would recommend as part of a WFPB diet – except maybe the very occasional “treat” to remind ourselves of what too much added salt and oil taste like. I mean, the name of my Greggs’ blog (“Greggs’ Vegan Sausage Rolls – Why Veganism Can Fail“) was not chosen for no reason!

However, the amount of venom spewed out by newspaper readers is somewhat over-the-top by anyone’s standards.

Such as some of those following the Telegraph article  9 :

  • What’s the problem? They are made out of Vegans, aren’t they?”
  • “I can’t eat grass; animals can. I can eat animals.”
  • “Sorry, vegans. I only eat fatty pork pies, or pies with succulent chunks of cow floating in ale and gravy.”
  • You can keep your veggie rubbish.”
  • “I’m with Mr Corrigan: if it’s “vegan” you can’t call it a pie. That would be an insult to the centuries of gloriously rich, meaty, aromatic, mouth-watering pies that have gone before. A non-meat snack for trendy neurotics, perhaps?”
  • Meat is good and the majority of people will not succumb to this utter BS.”
  • Also why salad lovers liberally apply dressing: because chomping on grass is not for humans it’s for ruminants. Cows eat the grass, we eat the cows, that’s the way the food chain works.”
  • You do know you’re made of meat right? And when your vegan body starts to starve you start to digest it to survive. That will be the least of your problems.”

And if you think that trying to educate people about veganism is a bit of a challenge, try espousing the virtues of a non-SOS WFPB diet. You’d lose count of the toys thrown out of prams.


  1. Greggs’ Vegan Sausage Rolls – Why Veganism Can Fail []
  2. The Guardian: Success of vegan sausage roll gives Greggs surge in sales []
  3. Jon Thorner’s of Somerset []
  4. British Pie Awards – 2019 []
  5. LeicestershireLive: Vegan pie named ‘supreme champion’ at British Pie Awards – for the first time ever [] []
  6. Location of Melton Mowbray, Leicestershire. []
  7. Wikipedia: Richard Corrigan. []
  8. Richard Corrigan: Facebook. []
  9. Telegraph. 8 March 2019: British Pie Awards 2019: Vegan pie is crowned Supreme Champion . [] []

Vitamin B12 Status in Spanish Veggies & Vegans

A previous blog 1 looked at a pre-published study on vitamin B12 status in Spanish vegetarians and vegans. Because there are very few reports on plant-based dietary patterns in Spain, this blog will look at the same study 2 in more detail, now that it has been published in its final form. While looking at B12 status amongst lacto-ovo vegetarians (LOV) and vegans (VN), it became clear that establishing true levels of this vitamin is a much more complex matter than most people realise. And, since side-effects of B12 deficiency are so nasty, this might be a blog worth reading – especially if you’re a plant-eater.

Thus, before looking at this study, it’s worth going into a bit more detail about vitamin B12.

Why is B12 status so important?

In normal healthy bodies, vitamin B12 (cobalamin) is readily absorbed in the distal ileum (the last part of the small intestine). However, in order for it to be absorbed, it must combine with a vital substance called intrinsic factor, which is a glycoprotein secreted by parietal cells of the gastric mucosa within the stomach. Without intrinsic factor, vitamin B12 will simply pass through the body and get excreted in stools.

Both vitamin B12 and vitamin B9 (folate) are necessary for the formation and maturation of red blood cells (erythrocytes) and the synthesis of DNA – the genetic material of cells. Vitamin B12 is also necessary for normal nerve function.

Since B12 is so essential for the formation of mature blood cells, any deficiency of this vitamin can result in anaemia, causing the body’s cells to receive insufficient oxygen from the haemoglobin within the red blood cells.

There are actually two forms of anaemia related to B12 deficiency and both are referred to as macrocytic anaemias 3 which can be either megaloblastic or pernicious anaemia:

Megaloblastic anaemia

This is characterised by abnormally large red blood cells (macrocytes) and abnormal white blood cells. It may not develop until 3-5 years after the deficiency starts. This is because around 3-5 years worth of B12 can be stored in the liver – so long as you’re an adult who has already been able to store sufficient quantities. No other B vitamin (or vitamin C) can be stored in the body like this, since they are all water-soluble (including B12) and are generally flushed out of the body if there is excess within the diet. On the other hand, the fat-based vitamins (A, E, D and K) can be stored in fat tissues as well as the liver. This means that daily intakes of the water-based vitamins (vitamins C, B1, B2, B3, B5, B6, B7, B9 and B12) is really important for maintenance of optimal health.

Megaloblastic anaemia is where insufficient B12 (or folate) is available to allow the normal DNA synthesis of red blood cells. It can be due to a number of causes, including:

  • insufficient B12 in the diet
  • overgrowth of bacteria in part of the small intestine
  • impaired absorption (malabsorption disorders such as coeliac disease or certain pancreatic disorders)
  • inflammatory bowel disease (IBD)
  • fish tapeworm infection
  • AIDS
  • surgery that removes the part of the small intestine where vitamin B12 is absorbed
  • drugs such as antacids and metformin (used to treat diabetes)
  • repeated exposure to nitrous oxide (laughing gas)
  • lack of intrinsic factor (see pernicious anaemia below)
  • decreased stomach acidity (common among older people)

As we age, our ability to absorb B12 decreases. This happens irrespective of dietary habits, but obviously there’s a bigger threat of deficiency (in all ages) for those who don’t eat animal products- the major source of B12. Bacteria in the soil and elsewhere produce B12. Animals don’t actually produce it themselves. If we still drank from pure streams and ate food we picked up from untreated soils, we’d get sufficient B12. However, with chlorinated water, pesticide-treated soils, and shrink-wrapped food, we either have to eat animal products or take supplements to ensure we get enough B12. There are plants that contain some of the vitamin (see below), but they are generally considered insufficient on their own to maintain healthy B12 levels.

Pernicious anaemia

Pernicious anaemia is a form of megaloblastic anemia where intrinsic factor is lacking. There may well be plenty of B12 in the diet, but if intrinsic factor is not present or, for some other reason, is not able to play its role in the the absorption of vitamin B12 from the small intestine into the bloodstream, then the B12 passes through and out of the body. This may be due to a number of reasons. For instance, abnormal antibodies, produced by an overactive immune system, may attack and destroy the parietal cells in the stomach that produce intrinsic factor, resulting in an autoimmune reaction called autoimmune metaplastic atrophic gastritis. Alternatively, intrinsic factor may be lacking because the part of the stomach where intrinsic factor is produced has been surgically removed.

Symptoms of B12 deficiency

Anaemia caused by vitamin B12 deficiency develops gradually. This allows the body to adapt to some extent, but this can mean that symptoms are mild while the anaemia is actually very severe.

Mild anemia symptoms can include:

  • paleness
  • weakness
  • fatigue

More serious anaemia symptoms can include:

  • shortness of breath
  • dizziness
  • rapid heart rate
  • spleen and liver enlargement

Pernicious anaemia in younger adults (due to lack of intrinsic factor) is more likely to result in the development of stomach and other gastrointestinal cancers.

B12 deficiency and nerve damage

Because B12 plays a significant role in the synthesis and maintenance of myelin4 , prolonged deficiency can result in damage to the central (CNS) and peripheral (PNS) nervous systems. In relation to CNS damage, white matter of the spinal cord and brain can suffer, resulting in such conditions as subacute combined degeneration (SCD) 5 and optic nerve atrophy. PNS issues are commonly manifested as nerve damage to the legs and arms, with the legs usually being affected earlier and more often than the arms. Symptoms include:

  • tingling in the feet and hands
  • loss of sensation in the legs, feet, and hands
  • weakness in arms and legs
  • loss of position sense – that is, people can’t tell so well where their arms and legs are and fail to feel vibrations
  • mild to moderate muscle weakness
  • loss of normal reflexes
  • difficulty in walking

In addition to the above neurological effects, some people can also become confused, irritable, and mildly depressed.

Advanced vitamin B12 deficiency may lead to delirium, paranoia and impaired mental function, including dementia.

Diagnosis of B12 deficiency

Diagnosis is via:

  • blood tests
  • the Schilling test (often in younger patients)
  • endoscopy
Blood tests

Routine serum blood tests can often show a suspected B12 deficiency if large red blood cells are detected. Since folate (vitamin B9) is also responsible for red blood cell synthesis, a possible B9 deficiency would normally also be investigated.

B12 deficiency can also be suspected if people complain of the typical symptoms associated with nerve damage, such as tingling or loss of sensation. If the deficiency is suspected, the level of vitamin B12 in the blood is measured.

Additionally, serum gastrin 6  levels or autoantibodies 7  to intrinsic factor may be measured.

Schilling test

The Schilling test involves the patient being given two doses of B12. The first is ‘labelled’ with a small amount of a radioactive substance and is then taken by mouth. The second is an injection of a larger amount of B12 that is not radioactively labelled.

After the injection is given, the amount of labelled B12 (that which had been taken orally) is measured by testing the urine to determine whether the body absorbed a normal amount of the vitamin.

If this normal amount has not been absorbed (revealed by a high amount being found in the urine), then the deficiency is confirmed. The same test is then repeated to check for the cause. This time, people are given intrinsic factor with the B12 taken by mouth. If intrinsic factor enables the body to absorb more of the vitamin, then it’s confirmed that the deficiency is caused by a lack of intrinsic factor, and the diagnosis of pernicious anemia can be made.


Endoscopy is the use of a flexible viewing tube to directly examine internal structures. It may be done to check for destruction of the parietal stomach cells that produce intrinsic factor.

If vitamin B12 deficiency is confirmed in an older person, it’s unlikely that either Schilling or endoscopy will be used. This is because the cause is likely to be the usual age-related reduction in stomach acidity, and is usually not serious. However, in a younger person, other tests, including other blood tests, Schilling test and endoscopy are likely to be used in order to establish intrinsic factor status.

Folate, B12 deficiency & plant-based diets

It’s important to note that high folate (vitamin B9) levels can give a false negative for B12 deficiency. That is, high levels of folate in the blood sample can make it look like there’s no B12 deficiency. This is because the constant supply of folate allows the red blood cells to appear normal in size, while the other serious neurological damage of B12 deficiency can go unnoticed, in spite of the person having regular blood tests for B12 deficiency.

Of course, those people most likely to have a B12 deficiency while having high dietary folate intake are those eating a plant-based diet – given that there’s so much folate in plant foods. This is why B12 supplementation is so important.

Treatments for B12 deficiency

For less advanced deficiency, B12 supplements generally do the trick; however, if people already have nerve damage, or they have pernicious anaemia (for instance, caused by having had the part of the stomach removed which produced intrinsic factor), then the B12 is normally given by injections into a muscle for defined periods so long as the disorder is uncorrected.

Since the B12 in supplements is easier to absorb than that in meat, older people with deficiency can benefit from taking B12 supplements.

In most people with mild to moderate anaemia, there is a normalisation in around 6 weeks of treatment with high doses of B12 supplements. However, in severe cases due to nerve damage or loss of ability to produce intrinsic factor, the treatment by B12 injection could last for the rest of their lives.

Unfortunately, in those with dementia resulting from B12 deficiency (mostly older people), mental function would not be expected to improve after treatment.

How much B12 should I supplement?

I covered this subject in some detail in a previous blog 8 , which I suggest you take a look at if you are unsure about how often and how much B12 you should be supplementing.

Non-animal foods containing vitamin B12

Several mushroom species contain some B12, including:

  • shiitake (Lentinula edodes)
  • black trumpet (Craterellus cornucopioides), and
  • golden chanterelle (Cantharellus cibarius)

Certain algae and cyanobacteria 9 such as:

  • chlorella 10 , and
  • spirulina (Arthrospira platensis11

The above are some of the foods normally used to produce B12 supplements for veggies and vegans.

Animal foods containing B12

Animal sources highest in vitamin B12 include meats (especially beef, pork, liver, and other organ meats), eggs, fortified cereals, milk, clams, oysters, salmon, and tuna.

It’s been reported that B12 deficiency exists much more widely in omnivore populations than one might imagine, since modern animal rearing practices are causing a reduction in the levels of B12 in meat. This can be seen particularly clearly, for instance, in the need to given cobalt supplements to cattle and sheep because of the reduced levels of cobalt in modern cultivated soils (B12 is called cobalamin because it contains a cobalt atom) 12 .

The Spanish study 2

The 49 lacto-ovo vegetarians and 54 vegans in the study filled out a Food Frequency Questionnaire (FFQ), and were tested to establish the following classical and functional markers (explanation of all terms in green can be seen by holding the cursor over the adjacent footnote number):

  • serum B12 13
  • erythrocyte folate (vitamin B9) 14
  • homocysteine (Hcy) 15 / hyperhomocysteinaemia (HHcy) 16  
  • methylmalonic acid (MMA) 17
  • mean corpuscular haemoglobin (MCH) 18
  • mean corpuscular erythrocyte volume (MCV) 19

In broad terms, two parts of this study are of particular interest: firstly, the difficulties involved in accurately diagnosing B12 deficiency (and the suggested additional tests by which this can be more accurately diagnosed) and, secondly, to see if there was any pattern of B12 deficiency between the two groups – lacto-ovo-vegetarian (LOV) and vegan (VN).

1. Difficulties in diagnosing B12 deficiency

In order to understand the potential difficulties involved in diagnosing B12 deficiency, it’s useful to understand the vital processes B12 undergoes within the body, and this will involve knowing about two biological cycles: the methionine cycle and the folate cycle, both of which are essential for DNA and RNA synthesis, the production of red blood cells (erythropoiesis) and the production of neurotransmitters. 20 21

Vitamin B12 acts as a cofactor 22 of the enzymes methionine synthase 23 , which acts in the conversion of homocysteine (Hcy) to methionine, and methylmalonyl-CoA mutase 24 , that produces succinyl-CoA from methylmalonyl-CoA, the active form of methylmalonic acid (MMA)17 .

The above reactions are involved in the methionine cycle 25 and the folate cycle 26 , both essential for DNA and RNA synthesis, erythropoiesis and the production of neurotransmitters.

The folate cycle is so important to the methionine cycle (also called the methylation cycle) that it’s often included in descriptions and diagrams of the methionine cycle. The following diagram should give you an idea of how interlinked and complex these cycles are.

Problems with Serum B12 tests

As mentioned above, testing levels of serum B12 is probably the most widely used means of assessing deficiency. However, a major problem is that it can appear perfectly normal whilst, at the same time. functional deficiency still lurks unseen beneath the surface. The long latency period of B12 deficiency showing up in the blood serum can regularly produce both false positives and false negatives – that is, appearing to have a deficiency but not having one, or not appearing to have a deficiency but actually having one. 27

Folate (vitamin B9) & B12

Since it’s known both that high levels of folate can mask B12 deficiency and that low levels of folate can account for hyperhomocysteinaemia (HHcy)16 , it follows that testing for folate levels would be rather useful. By establishing that folate levels are high (as they are likely to be in most plant-eaters – unless, of course, they’re living on a diet of doughnuts and chips!) , it would be possible to quickly discard folate deficiency as being responsible for HHcy or the presence of megaloblastic anaemia. 28

Homocysteine & B12

Testing for homocysteine (Hcy) levels – a more specific marker of functional vitamin B12 deficiency – would be a useful additional test. This is because Hcy levels rise in the presence of cellular B12 deficiency. So, is that sorted, then? Well, not quite. Another problem arises – namely, that Hcy levels can also be raised with deficiencies of vitamins B9 (folate) or B6 (pyridoxine) as well as by diets rich in methionine 29 . So back to the drawing board.

Methylmalonic acid (MMA) & B12

So, what about testing for MMA levels? This represents probably the most specific marker for vitamin B12 deficiency, since it’s independent of folate and vitamin B6 status. MMA levels increase when there’s a B12 deficiency, and this happens even before there are any obvious clinical symptoms of the deficiency.

The more the merrier

So, the researchers in this study suggest that when testing for B12 deficiency, relying on just one single standard marker of deficiency is to be avoided. Instead, several markers should be used – levels of serum B12/B9, Hcy and MMA 30 .

2. B12 status of Spanish lacto-ovo-vegetarians & vegans

Finally, we come to the findings of this study:

  • the overall prevalence of clinical vitamin B12 deficiency was very low in the individuals tested
  • when serum B12 levels alone were tested, there was no indication of B12 deficiency in either diet group

Various B12 markers

However, when MMA was measured, some subclinical deficiencies were detected, particularly in the non-users of vitamin B12 supplements, with no significant differences between VN and LOV. With elevated MMA being detected in more than 10 % of the study subjects, it’s clear that using this marker to detect subclinical deficiencies is a pretty good idea.

  • although macrocytosis (enlarged red blood cells) was observed in several participants, no clear relationship to any biomarkers of vitamin B12 deficiency could be found
  • HHcy was found in more than 30 % of the subjects

They recommend that both MMA and Hcy (together with serum B12) should be used since each of these biomarkers gives information about the actions of B12 in different metabolic pathways. For instance, the metabolic reactions leading to the production of MMA and Hcy require different cobalamin forms:

  • methylcobalamin acts in the Hcy pathway
  • adenosylcobalamin acts in the formation of succinyl-CoA

The latter occur in different cell compartments:

  • the methionine and folate cycles occur in the cell’s cytoplasm 31
  • the synthesis of succinyl-CoA (SCS) 32  occurs in the mitochondria33

When B12 status was assessed with serum vitamin B12, MMA and Hcy simultaneously, the proportion of subjects with values out of range of at least one of the biomarkers was remarkably higher than the proportion detected by using only serum B12.

Most of the hyperhomocysteinaemic individuals presented mild HHcy (16–30 µmol/l) while only three volunteers had moderate HHcy (31–100 µmol/l).

Hcy variation in veggies from different European countries

Interestingly, this study comments on the fact that there’s great variability in the B12 values obtained in vegetarians from different European countries:

  • German vegetarians had lower Hcy levels 34
  • Slovak and Austrian vegetarians had higher Hcy levels 35

In the current study, Hcy was higher in LOV than in VN, which contrasted with other studies 36 .

High folate levels

Erythrocyte folate levels were high in all participants, with more than 50 % surpassing the suggested 37 cut-off for high erythrocyte folate (1360 nmol/l). This is in line with other research 38 that found higher folate intakes in plant-eaters than in omnivores.

Methionine & Hcy/HHcy

With folate repletion and under similar B12 levels, it was observed that LOV had higher levels of both Hcy and HHcy than VN. The researchers said this might be due to the fact that LOV consume more protein and, thus, more methionine, being that both dairy and egg are higher in methionine than plant foods. By increasing blood levels of Hcy, high methionine levels are linked to increased risk of heart disease, tumour growth, brain damage and even death.

The importance of supplementation

Various studies 36 have reported lower B12 levels in vegans, but this was not observed in the present study. The reason for this is thought to be that the members of both Spanish groups had a high and extended use of cobalamin (B12) supplements, with B12 supplement users exhibiting higher serum B12 and erythrocyte folate levels (as well as lower MMA and Hcy) than non-users. This underlines the importance of supplementation for vegans and lacto-ovo vegetarians.

These results are, of course, consistent with previous studies that recommend intake of B12 in supplement form. The reason generally given – which seems perfectly fair – is that it’s difficult for plant-eaters to achieve consistent and sufficient B12 levels without taking B12 supplements. The intake of fortified food items is not enough, of itself, to provide the required doses of the vitamin.39 40

Supplementation, diet or socioeconomic variation?

In recent studies on vegetarian Indians 41 42 , a prevalence of B12 deficiency was found in around 70 % of those tested, with more than 50 % of the subjects also presenting HHcy.

An explanation for this variation between results from Spain and India may be explained by differences in both diet composition and socioeconomic status. 43 

However, even in studies of B12 status in European countries (where one would expect vegetarians to have similar socioeconomic status and diet composition as found in Spain), similar differences (that is, less B12 deficiency in Spanish vegetarians) was seen in Germany, the Netherlands and the UK. 44

Thus, the researchers maintain that the sufficient B12 status observed in both Spanish groups (LOV and VN) can be mainly accounted for by the extended use of cobalamin supplements in the Spanish participants compared with the lower amount of such supplementation reported in other European studies.

Spanish plant milks are not fortified

Having spent a significant time at our mountain retreat in Spain, it has always interested me that the Spanish do not fortify their plant milks – unlike the UK and elsewhere in Europe. This is a very good reason why any veggie living (or spending extended periods) in Spain should not rely on plant milks for their B12. Indeed, the current study emphasises that such milks had no influence on the analysed biomarkers in this research, being that these milks are not B12-fortified.

Final thoughts

Two limitations of this study were, firstly, that they didn’t add an additional omnivore group for comparison, since this would have shown whether and by how much these groups (LOV and VN) differed from the general meat-eating Spanish population and, secondly, this was a small sample (103 individuals) from which to generalise to the whole Spanish LOV and VN population – of which veggies are thought 45 to comprise around 1.5%.

What would have been interesting, in addition, would have been to include a WFPB dietary group. Naturally, this is something that would prove very difficult in almost any country (perhaps excluding certain ‘enlightened’ populations within the US), since the number of people eating a WFPB diet is still very low.

The report did not consider the influence of any potential genetic polymorphisms 46 that might be involved in the B12 and folate routes. Perhaps future B12 studies could look at this, as well as include a larger number of subjects and include both omnivores and those eating a WFPB diet.

In any case, the take-home message is that anyone eating a plant-based diet needs to take B12 supplementation. It’s a cheap and highly effective way of avoiding health conditions that would undo some of the wonderful work achieved by eating this way.

References & Notes

  1. B12 Supplements Are Efficient But Caution With Folic Acid []
  2. J Nutr Sci. 2019 Feb 26;8:e7. doi: 10.1017/jns.2019.2. eCollection 2019. Vitamin B12 and folate status in Spanish lacto-ovo vegetarians and vegans. Gallego-Narbón A, Zapatera B, Barrios L, Vaquero MP. [] []
  3. The term macrocytic is from Greek words meaning “large cell”. A macrocytic class of anaemia is an anaemia (defined as blood with an insufficient concentration of haemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume. []
  4. Myelin is an insulating layer, or sheath that forms around nerves, including those in the brain and spinal cord. It is made up of protein and fatty substances. This myelin sheath allows electrical impulses to transmit quickly and efficiently along the nerve cells. []
  5. Subacute combined degeneration (SCD) is characterised by symmetric dysesthesia, disturbance of position sense and spastic paraparesis or tetraparesis. []
  6. Gastrin is a hormone which stimulates secretion of gastric juice and is secreted into the bloodstream by the stomach wall in response to the presence of food. []
  7. An autoantibody is antibody produced by in response to a constituent of its own tissues. []
  8. Vegan Society Veg-1: Does It Contain Enough B12? []
  9. Cyanobacteria are a division of microorganisms related to bacteria but which are capable of photosynthesis. They are prokaryotic and represent the earliest known form of life on the earth. []
  10. a genus of single-celled green algae belonging to the division Chlorophyta. []
  11. Spirulina is a biomass of cyanobacteria (blue-green algae) from the two species Arthrospira platensis and A. maxima. It can be consumed by humans and other animals. Arthrospira is cultivated worldwide and is used as a dietary supplement or whole food, being also used as a feed supplement in the aquaculture, aquarium, and poultry industries. []
  12. J Dairy Sci. 1979 Aug;62(8):1195-206. Trace element deficiencies and fertility in ruminants: a review. Hidiroglou M. []
  13. In blood, serum is the liquid part but without the clotting factors (mainly fibrinogens). The liquid part with the clotting factors is the plasma. Serum still includes all the other proteins not used in blood clotting, along with all the electrolytes, antibodies, antigens, hormones, and any exogenous substances. []
  14. Red blood cell (erythrocyte) folate concentrations respond slowly to changes in dietary folate intake since the erythrocytes, which have a 120-day lifespan, accumulate folate only during the production of new red blood cells (erythropoiesis). Red blood cell folate concentrations are useful as indicators of long-term folate status. []
  15. Homocysteine (an intermediate in the metabolism of the amino acids methionine and cysteine) is a common amino acid in your blood. You get it mostly from eating meat. High levels of it are linked to early development of heart disease. and is associated with low levels of vitamins B6, B12, and folate, as well as with renal disease. []
  16. Hyperhomocysteinaemia is a medical condition characterised by an abnormally high level of homocysteine in the blood, conventionally described as being above 15 µmol/L. Hyperhomocysteinaemia is typically managed with vitamin B6, vitamin B9 and vitamin B12 supplementation.  Hyperhomocysteinaemia promotes the formation of active oxygen species and the release of inflammatory mediators, and therefore it is considered a risk factor for cardiovascular disease (CVD). [] []
  17. Methylmalonic acid (MMA) is a substance produced in very small amounts and is necessary for human metabolism and energy production. The measurement of elevated amounts of methylmalonic acid in the blood or urine serves as a sensitive and early indicator of vitamin B12 deficiency. [] []
  18. Mean corpuscular haemoglobin is the average mass of haemoglobin per red blood cell in a sample of blood. High MCH levels are commonly a sign of the macrocytic anaemia seen in B12 or folate deficiency. []
  19. Mean corpuscular volume is a measure of the average volume of a red blood corpuscle. The measure is attained by multiplying a volume of blood by the proportion of blood that is cellular, and dividing that product by the number of erythrocytes in that volume. High MCV implies the red blood cells are larger than normal (i.e. macrocytic) and is a test of B12 and folate deficiency. []
  20. Krishnaswamy K & Madhavan Nair K (2001) Importance of folate in human nutrition. Br J Nutr 85, Suppl. 2, S115–S124. []
  21. Kapoor A, Baig M, Tunio SA, et al. (2017) Neuropsychiatric and neurological problems among vitamin B12 deficient young vegetarians. Neurosciences (Riyadh) 22, 228–232. []
  22. A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme’s activity. Cofactors can be considered “helper molecules” that assist in biochemical transformations. []
  23. Methionine is an essential amino acid that has to be derived from our diet. Methionine synthase is responsible for the regeneration of methionine from homocysteine. []
  24. Methylmalonyl-CoA mutase (MCM) is a protein that in humans is encoded by the MUT gene. This vitamin B12-dependent enzyme catalyses the isomerisation of methylmalonyl-CoA to succinyl-CoA in humans. []
  25. In the methionine cycle, methionine (a sulphur-containing amino acid which enters the body through dietary proteins) is used in forming proteins in the body. In the methionine cycle, methionine acts as the precursor of the sulphur-containing amino acids homocysteine, cysteine, and taurine. Taurine is one of the few amino acids not used in protein synthesis, and is thus usually referred to as a “nonessential” amino acid, or more generously as a “conditionally essential” amino acid. []
  26. Within the folate cycle, folate coenzymes are responsible for the one-carbon unit transfer in intermediary metabolism and are required for several reactions in key metabolic processes, for example of purine, pyrimidine and methionine synthesis, and glycine and serine metabolism. []
  27. Klee GG (2000) Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B12 and folate. Clin Chem 46, 1277–1283. []
  28. Krajcovicova-Kudlackova M, Blazicek P, Kopcova J, et al. (2000) Homocysteine levels in vegetarians versus omnivores. Ann Nutr Metab 44, 135–138. []
  29. Kumar A, Palfrey HA, Pathak R, et al. (2017) The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond) 14, 78. []
  30. Yetley EA, Pfeiffer CM, Phinney KW, et al. (2011) Biomarkers of vitamin B12 status in NHANES: a roundtable summary. Am J Clin Nutr 94, 313S–321S. []
  31. Cytoplasm is a thick solution that fills each cell and is enclosed by the cell membrane. It’s mainly composed of water, salts, and proteins. All the organelles, such as the nucleus, endoplasmic reticulum, and mitochondria, are located in the cytoplasm within eukaryotic cells. Organelles are the organised or specialised structures within a living cell. Eukaryotic cells are cells that contain a nucleus and organelles, enclosed by a plasma membrane. Humans are composed of eukaryotic cells and are thus grouped into the biological domain Eukaryota. Eukaryotic cells are larger and more complex than prokaryotic cells, which are found in Archaea and Bacteria, the other two domains of life. []
  32. Succinyl-CoA or SCS facilitates the flux of molecules into other metabolic pathways by controlling the interconversion between succinyl CoA and succinate. This is important because succinyl CoA is an intermediate necessary for porphyrin, haem, and ketone body biosynthesis. It’s a necessary part of the energy-producing Krebs or citric acid cycle. []
  33. The mitochondria is an organelle found in large numbers in most cells, in which the biochemical processes of respiration and energy production occur – the “powerhouses” of energy production. []
  34. Waldmann A, Koschizke JW, Leitzmann C, et al. (2004) Homocysteine and cobalamin status in German vegans. Public Health Nutr 7, 467–472. []
  35. Majchrzak D, Singer I, Manner M, et al. (2006) B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans. Ann Nutr Metab 50, 485–491. []
  36. Elmadfa I & Singer I (2009) Vitamin B12 and homocysteine status among vegetarians: a global perspective. Am J Clin Nutr 89, 1693S–1698S. [] []
  37. Colapinto CK, O’Connor DL & Tremblay MS (2011) Folate status of the population in the Canadian Health Measures Survey. CMAJ 183, E100–E106. []
  38. Schüpbach R, Wegmüller R, Berguerand C, et al. (2017) Micronutrient status and intake in omnivores, vegetarians and vegans in Switzerland. Eur J Nutr 56, 283–293. []
  39. Gilsing AM, Crowe FL, Lloyd-Wright Z, et al. (2010) Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Eur J Clin Nutr 64, 933–939. []
  40. Pawlak R, Lester SE & Babatunde T (2014) The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. Eur J Clin Nutr 68, 541–548. []
  41. Naik S, Mahalle N & Bhide V (2018) Identification of vitamin B12 deficiency in vegetarian Indians. Br J Nutr 119, 629–635. []
  42. Yajnik CS, Deshpande SS, Lubree HG, et al. (2006) Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians. J Assoc Physicians India 54, 775–782. []
  43. Menal-Puey S & Marques-Lopes I (2017) Development of a food guide for the vegetarians of Spain. J Acad Nutr Diet 117, 1509–1516. []
  44. Herrmann W, Schorr H, Obeid R, et al. (2003) Vitamin B12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr 78, 131–136. []
  45. AECOSAN (2011) National Survey of Dietary Intake (2009–2010). Results on Consumption Data. Madrid: Spanish Agency for Consumer Affairs, Food Safety and Nutrition Government of Spain. []
  46. Polymorphisms are the occurrence of different forms among the members of a population or colony, or in the life cycle of an individual organism. []

Flaxseeds / Linseeds – Lignan Heaven

There are a wide number of reasons why it’s a pretty good idea to add flaxseeds to your food shopping list, whether or not you’re eating a plant-based diet. These little seeds are a powerhouse of goodness. If, as a result of reading this blog, you’re encouraged to include them in your daily diet, then I’ll be pretty confident that, in a small way, I’ve helped you towards a longer and healthier life.

Is flaxseed the same as linseed?

If you enter either word in Wikipedia, you get exactly the same page. I guess this indicates that they are, to all intents and purposes, the same thing – members of the plant family Linaceae and the genus Linum. Whilst there are variations within the genus, the only major difference you’ll notice is that the seeds can be either brown or golden (yellow) in colour.

Although fibrous parts of the flax plant are used for various purposes (including making clothing), and you’ll know about the uses of linseed oil (including protecting cricket bats), we’ll just concentrate on the linseed/flaxseeds themselves, which will be herein referred to as flaxseeds for the sake of brevity. By the way, my advice is to avoid consuming any the the oil prepared from flaxseeds, for the same reason as all oils are to be avoided 1 . Instead, just stick to the seeds.

Why do flaxseeds need to be ground?

Unlike most seeds, the outer protective shell of each tiny flaxseed is so tough that eating them whole will mean they ‘cut out the middle man’ and end up, intact, in the toilet bowl. By grinding them, all the wonderful goodness is released. I go into this in a bit more detail later.

What’s the nutritional value of flaxseeds?

Most flaxseeds have an almost identical nutritional profile, with the same number of omega-3 fatty acids. This makes them a really important part of any plant-based diet. There is, however, one variant of yellow flax (solin, usually under the trade name “Linola”) which is very low in omega-3 fatty acids. Fibre, protein, and fat profiles are excellent.

You’ll see from the nutritional value chart 2 that there are also plenty of vitamins and minerals in flaxseeds. But the good news doesn’t end there. Of all the individual so-called ‘super foods’ that you could think of, flaxseeds will be right up there at the top. The lignan content is just one weapon in their disease-fighting armoury. Essential fatty acids (ALA and AA) and fibre content are also remarkably high. To give you an idea of just how amazing the bundle of compounds in flaxseeds really are, the following is a list of some of the health benefits that these amazing little fellas may offer:

  • lowering blood pressure 3 , hence:
    • helping to prevent heart attacks 4
    • helping to prevent strokes 5
  • fighting cancer
    • prostate cancer 6 7
    • breast cancer 8 9
  • lowering blood cholesterol levels 10
  • reducing blood triglyceride levels 11
  • reducing blood sugar levels/insulin resistance/diabetes risk 12 13 14
  • reducing inflammation 15 16
  • preventing/treating constipation 17
  • reducing body weight/BMI 18
  • preventing osteoporosis/bone loss 19 20
  • preventing arthritis 21
  • improving skin health/healing 22
  • reducing number of menstrual periods 23

Omega-3 & flaxseeds

As I’ve pointed out in previous blogs, flaxseeds 24 25  and chia seeds 26 (along with walnuts) are probably the best non-fish sources of omega-3’s for those eating a plant-based diet. The long-chain polyunsaturated fatty acid (LC-PUFA) ALA (alpha-linolenic acid) is an essential fatty acid which we need to get from our diet since the human body can’t synthesise it on its own. When sufficient ALA is provided in the diet, the body can use it to make the longer-chain PUFA’s, DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), both of which are essential for our health. 27

The following diagrams illustrate the high levels of omega-3 oils in flaxseeds:

What are lignans?

From the Latin for “wood”  (lign-) plus the chemical suffix”-an”, lignans found in plants are a form of micronutrient called polyphenols 28 . In order for the plant lignans29 to be used by the human body, they have to be metabolised by our gut bacteria into the mammalian lignans called enterodiol and enterolactone (known as enterolignans – from the Greek énteron meaning intestine). So, plant lignans can be described as “lignan precursors” for our human versions.

Lignans are one of the major classes of phytoestrogens30 – oestrogen-like chemicals (found in foods like beans, seeds and grains) that also act as antioxidants. You’ll hear some comments on the internet that phytoestrogens are dangerous because they bind to and block important oestrogen receptors; however, this does not appear to be the case, since there are two different forms of oestrogen receptor, and phytoestrogens do not block those to which oestrogen normally attaches. Additionally, evidence exists 31 that they can help prevent cardiovascular diseases, diabetes and cancer of the breast, brain, colon, liver, ovaries and skin. They also appear to reduce LDL (“bad”) cholesterol and aid weight loss. While phytoestrogens found in plants do not decrease male fertility, the xenoestrogens 32, which, in terms of diet, are found mainly in fish, have been shown to drastically lower sperm count and cause early puberty.

Whilst the above long list 33 of health benefits offered by flaxseeds is, of course, also partly attributable to the other essential fatty acids, minerals, vitamins and phytochemicals they contain, the lignan content is especially powerful. Trying to decide exactly what each individual compound does is a really tough task, and perhaps not always necessary. After all, the compounds do not exist in isolation within plants and neither do they work in isolation within our bodies. Trying to pinpoint active compounds is something that pharmaceutical companies love to do, since they can then bottle them and sell them at high price, even though they often don’t work as they did when the compound was in its natural position within the complex of the original plant.

We’ve looked at the issue of wholism vs reductionism in a previous blog 34 . So, whether the cardiovascular protection afforded by flaxseeds is x% due to the omega-3, y% due to the fibre, and z% due to the lignans is, as far as I’m concerned, a secondary matter to what the whole seed is capable of doing with all three elements, plus the others we know about and the many we still haven’t even identified. And this doesn’t even touch on the vast array of interactions between these elements and the likelihood that there will be some variation between the physiology of individual humans – particularly in relation to the microbiome (gut, urinary, oral, etc) that our diets and lifestyles have provided us with.

In terms of lignans, why are flaxseeds so remarkable?

The type of lignans found in flaxseeds are not the only dietary lignans – others include sesamin 35 , matairesinol 36 , pinoresinol 37 and lariciresinol 38 . The main lignan in flaxseeds (as well as in sunflower, sesame, and pumpkin seeds) has the unpronounceable name “secoisolariciresinol diglucoside” or SDG for short. Regardless of the source of SDG, once it’s ingested, it’s “…converted in the colon into active mammalian lignans, enterodiol, and enterolactone, which have shown promise in reducing growth of cancerous tumors, especially hormone‐sensitive ones such as those of the breast, endometrium, and prostate. Known for their hydrogen‐donating antioxidant activity as well as their ability to complex divalent transition metal cations, lignans are propitious to human health.” 39 .  All well and good, but the remarkable thing about flaxseeds isn’t that the lignans they contain are not found in other seeds, rather it’s because of the incredibly high lignan content these little seeds have. Indeed, you’ll see from the following chart 40 that they contain around 100 times more lignans than almost every other food, with sesame seeds being the closest with 7 times less.

Add to this the fact that Dr Greger claims 41 there are no bad side effects to normal flaxseed consumption 42 – unless, of course, you’re one of the very few who has a flaxseed allergy 43 – and you have as near to a super food as you’re likely to get.

One study compared the results of flaxseeds and flaxseed oil: “SDG [the major type of lignan in flaxseeds] is a potent angiogenic and antiapoptotic agent that may have a role in cardio protection in ischemic heart disease. In conclusion, flaxseed, FLC, and SDG, but not flaxseed oil, suppress atherosclerosis, and FLC [flax lignan complex] and SDG slow progression of atherosclerosis but have no effect on regression. Flaxseed oil suppresses oxygen radical production by white blood cells, prolongs bleeding time, and in higher doses suppresses serum levels of inflammatory mediators and does not lower serum lipids.” 44

No lignans in flaxseed oil

It’s important to note that when you extract pure oil from flaxseeds, the important phytoestrogen lignans are removed 45 . This is another reason why it’s important to consume the whole seed and to generally keep away from extracted flaxseed oil – unless, of course, you want to grease your cricket bat! This rule applies to all extracted oils, of course, as mentioned above.

Flaxseed proteins

The following is a sample of research reviewed within one study 46  showing some of the varied health benefits from the proteins within flaxseeds:

Fatty acids in flaxseeds

The following chart (from the same study as above) indicates the levels of the major fatty acids within flaxseeds:

Historical & recent medicinal uses of flaxseeds

The following charts (from the same source as above) indicate some of the distant historical and more recent uses of flaxseeds (in the latter case, from flaxseed oil):

Microbiome & lignans

The nature of your gut bacteria (the intestinal microbiome) will affect how much of the lignan goodness is absorbed and utilised by your body. As one authority states: “It is likely that individual differences in the metabolism of lignans, possibly due to gut microbes, influence the biological activities and health effects of these compounds.” 47 As is the case with so much nutrient metabolism and absorption, having a healthy got microbiome is so important, and, as was shown in an earlier blog 48 a varied plant-based diet (as opposed to a meat- or processed food-based diet) provides by far the healthiest environment for intestinal bacteria.

How much ground flaxseed should we have each day?

Dr Greger can answer this for us. In response to one of the above-mentioned studies, entitled “Flaxseed: A Miraculous Defence Against Some Critical Maladies,” 3 , he states:

Miraculous”? Well, certainly super healthy, which is why a tablespoon of ground flaxseeds every day gets its own spot on the Daily Dozen checklist 49  I created to help inspire you to incorporate some of the healthiest foods into your daily routine.” 50

You can get your daily tablespoon of ground flaxseeds in so many ways: from mixing it in with your morning muesli to using it as a thickener in soups, stews, etc.

Dr Greger, flaxseeds & lignans

Talking about Dr G, you’d be able to get an idea of just how important a subject is by counting the number of videos he does on that subject. The following are just his most popular of videos which discuss the evidence for the lasting force of lignans and flaxseeds:

    • Which Are Better: Chia Seeds or Flax Seeds? 51
    • Flaxseeds for Hypertension 52
    • Can Flaxseeds Help Prevent Breast Cancer? 53
    • Flaxseeds for Breast Pain 54
    • Flaxseeds & Breast Cancer Survival: Clinical Evidence 55
    • Flaxseeds & Breast Cancer Survival: Epidemiological Evidence 56
    • Flaxseeds & Breast Cancer Prevention 57
    • Just the Flax, Ma’am? 58
    • Flaxseeds vs. Prostate Cancer 59
    • Flaxseeds vs. Diabetes 60
    • Was It the Flaxseeds, Fat Restriction, or Both? 61
    • Flaxseeds for Sensitive Skin 62
    • Flaxseeds vs. Chia Seeds 63
    • Which Are Better: Chia Seeds or Flaxseeds? 64

Final thoughts

It’s hard to believe that such a humble little seed can do so much good, but the evidence is there to support the claims – and the studies I’ve listed are but a small drop in the ocean of the research showing the multifarious benefits. The fact is, that it’s simply hard to over-egg (vegan alternative, of course!) the case for including flaxseed within one’s diet – especially if you’re completely plant-based and just want to ensure you get additional omega-3, along with walnuts.

So, why not make it a regular habit to include at least a tablespoon of flaxseeds in your daily diet?

Perhaps the best way to go about this is to have a supply always at the ready. Buy them whole in bulk. Buying pre-ground flaxseeds is much more expensive and it’s probably best to consume them within not too long a period of time after grinding – and you never know how long the ground version has been sitting on the shop shelf. So, possibly best to grind them yourself in a small coffee grinder and then store a kg of the ground up flaxseeds in a sealed container. So easy to dip into when you want. I also tend to make a weekly supply of muesli in a large container, into which I add ground flaxseeds from my 1kg flaxseed container. Since a tablespoon of flaxseeds weighs around 7 grams, I usually add around 100 grams for the week. Give it a good shake and you’re pretty confident about getting your weekly supply just from the muesli alone.

If it’s any help (although I’m not promoting either company), I buy flaxseeds in bulk (20 x 500 gram bags) from a company called Grapetree 65 . They appear to be one of the cheapest sources.

Additionally, I use a basic (but very effective) coffee grinder called the Duronic CG300 Electric Coffee Grinder Mill 66 , available from Amazon for £29.99. Of course, any coffee grinder will do the job. Just make sure you don’t grind the seeds too much (or you’ll get flaxseed butter) or too little (or you’ll leave intact and indigestible seeds). I tend to grind until the sound of the seeds hitting the top of the grinder stops, then scoop out the ground seeds.

References & Notes

  1. Olive Oil Injures Endothelial Cells []
  2. United States Department of Agriculture. Agricultural Research Service. USDA Food Composition Databases: Flaxseeds. []
  3. Pak J Pharm Sci. 2013 Jan;26(1):199-208. Flaxseed – a miraculous defense against some critical maladies. Akhtar S, Ismail T, Riaz M. [] []
  4. Can J Cardiol. 2010 Nov; 26(9): 489–496.The cardiovascular effects of flaxseed and its omega-3 fatty acid, alpha-linolenic acid. Delfin Rodriguez-Leyva, MD, PhD, Chantal MC Bassett, PhD, Richelle McCullough, BSc, and Grant N Pierce, PhD. []
  5. Contemp Clin Trials. 2011 May 17. The effect of dietary flaxseed on improving symptoms of cardiovascular disease in patients with peripheral artery disease: rationale and design of the FLAX-PAD randomized controlled trial. Leyva DR, Zahradka P, Ramjiawan B, Guzman R, Aliani M, Pierce GN. []
  6. Cancer Epidemiol Biomarkers Prev. 2008 Dec; 17(12): 3577–3587. Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery. Wendy Demark-Wahnefried, et al. []
  7. J Med Food. 2013 Apr; 16(4): 357–360. Flaxseed-Derived Enterolactone Is Inversely Associated with Tumor Cell Proliferation in Men with Localized Prostate Cancer. Maria Azrad, et al. []
  8. L. U. Thompson, J. M. Chen, T. Li, K. Strasser-Weippl, P. E. Goss. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin. Cancer Res. 2005 11(10):3828 – 3835 []
  9. Front Nutr. 2018; 5: 4. The Effect of Flaxseed in Breast Cancer: A Literature Review. Ana Calado, Pedro Miguel Neves, Teresa Santos, Paula Ravasco. []
  10. Nutr Metab (Lond). 2012; 9: 8. Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type. Mette Kristensen, et al. []
  11. Rev Recent Clin Trials. 2015;10(1):61-7. Effect of flaxseed on blood lipid level in hyperlipidemic patients. Torkan M, Entezari MH, Siavash M. []
  12. J Res Med Sci. 2016; 21: 70. Published online 2016 Sep 1. The effect of flaxseed powder on insulin resistance indices and blood pressure in prediabetic individuals: A randomized controlled clinical trial Afrooz Javidi, et al. []
  13. Curr Pharm Des. 2016;22(2):141-4. Flaxseed and Diabetes. Prasad K, Dhar A. []
  14. Nutr Rev. 2018 Feb 1;76(2):125-139. Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials. Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom Z. []
  15. J Am Coll Nutr. 2017 Nov-Dec;36(8):646-653. Influence of Flaxseed Lignan Supplementation to Older Adults on Biochemical and Functional Outcome Measures of Inflammation. Di Y, et al. []
  16. ISRN Inflamm. 2013; 2013: 735158. Effect of L. usitatissimum (Flaxseed/Linseed) Fixed Oil against Distinct Phases of Inflammation. Gaurav Kaithwas, Dipak K. Majumdar. []
  17. Nutr Metab (Lond). 2018; 15: 36. A randomized trial of the effects of flaxseed to manage constipation, weight, glycemia, and lipids in constipated patients with type 2 diabetes. Noureddin Soltanian, Mohsen Janghorbani. []
  18. Obes Rev. 2017 Sep;18(9):1096-1107. The effect of flaxseed supplementation on body weight and body composition: a systematic review and meta-analysis of 45 randomized placebo-controlled trials. Mohammadi-Sartang M, et al. []
  19. Bioorg Med Chem Lett. 2016 Apr 1;26(7):1760-1. Cyclolinopeptides, cyclic peptides from flaxseed with osteoclast differentiation inhibitory activity. Kaneda T, Yoshida H, Nakajima Y, Toishi M, Nugroho AE, Morita H. []
  20. Pak J Biol Sci. 2008 Jul 1;11(13):1696-701. Preventive effects of flaxseed and sesame oil on bone loss in ovariectomized rats. Boulbaroud S, Mesfioui A, Arfaoui A, Ouichou A, el-Hessni A. []
  21. Nutrients. 2016 Mar; 8(3): 136. Effect of Flaxseed Intervention on Inflammatory Marker C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Guan-Yu Ren, et al. []
  22. Int J Biol Macromol. 2015 Jan;72:614-23. Flaxseed lignan wound healing formulation: characterization and in vivo therapeutic evaluation. Draganescu D, et al. []
  23. J Clin Endocrinol Metab. 1993 Nov;77(5):1215-9. Effect of flax seed ingestion on the menstrual cycle. Phipps WR, Martini MC, Lampe JW, Slavin JL, Kurzer MS. []
  24. Non-Fish Sources of Omega-3 []
  25. Omega 3 Supplements = Snake Oil []
  26. Chia Seeds To The Rescue Of Type 2 Diabetics []
  27. Reprod. Nutr. Dev. 45 (2005) 581–597 581 Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Graham C. Burdge, Philip C. Calder. Institute of Human Nutrition, University of Southampton, Southampton, UK. []
  28. Polyphenols are collections of many (hence “poly-“) phenol structural units. Phenols are organic chemical compounds that have a pair of molecular groups stuck together – namely, a phenyl group with the molecular formula −C6H (six carbon atoms and one hydrogen atom) and a hydroxy group with the formula −OH (one oxygen atom and one hydrogen atom). When these bond together it forms a phenol with the formula C6H5OH. []
  29. Plant lignans include pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, hydroxymatairesinol, syringaresinol and sesamin. []
  30. The other classes of phytoestrogens are isoflavones and coumestans. []
  31. Topic: Phytoestrogens. []
  32. Xenoestrogens are byproducts of the plastic and pesticide industries. Besides being a component of plastic, they are also found in conventional makeup/cosmetic products, household cleaners, laundry detergents, and some birth control medications. They are also found in sunscreens, chlorine and processed food. Naturally, with all this junk ending up in the oceans and rivers, fish become contaminated and people who eat fish thereby share in that contamination. []
  33. What’s the nutritional value of flaxseeds? []
  34. Wholism vs Reductionism – Not Just a War of Words []
  35. Sesamin is a lignan extracted from sesame seeds and a compound of sesame seed oil. A small amount is in flaxseeds. []
  36. Matairesinol is a plant lignan. It occurs with secoisolariciresinol in numerous foods such as oil seeds (including flaxseeds), whole grains, vegetables and fruits. []
  37. Pinoresinol is a lignan found in Styrax sp. and in Forsythia suspensa, as well as in the caterpillar of the cabbage butterfly, Pieris rapae where it serves as a defence against ants. It’s found in foods such as sesame seeds, Brassica vegetables, olive oil, and small amounts in flaxseeds. []
  38. Lariciresinol is a lignan, a type of phenylpropanoids. In food, it is found in sesame seeds and in Brassica vegetables. It is also found in the bark and wood of white fir. []
  39. Flaxseed Lignans: Biosynthesis, Metabolism, Antioxidant Activity, Bio‐Active Components, and Health Benefits. Alhassane Touré Xu Xueming. 29 April 2010. []
  40. Milder IE, Arts IC, van de Putte B, Venema DP, Hollman PC. Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br J Nutr. 2005;93(3):393-402. []
  41. Topic: Flax seeds. []
  42. There are websites that disagree with this, although there are few published studies showing negative effects, and those that do appear to relate more to consuming flax oil – usually called linseed oil. []
  43. Allergy Asthma Clin Immunol. 2010; 6(Suppl 2): P6. Flax seed allergy in children: an emerging allergen? Andrew O’Keefe, Sandeep Kapur, Gregory Rex, and Wade Watson. []
  44. J Cardiovasc Pharmacol. 2009 Nov;54(5):369-77. Flaxseed and cardiovascular health. Prasad K. []
  45. MayoClinic: Flaxseed and flaxseed oil. []
  46. J Food Sci Technol. 2014 Sep; 51(9): 1633–1653. Flax and flaxseed oil: an ancient medicine & modern functional food. Ankit Goyal, Vivek Sharma, Neelam Upadhyay, Sandeep Gill, Manvesh Sihag. []
  47. Oregon State University Linus Pauling Institute. Micronutrient Information Center: Lignans. []
  48. Two Types of Gut Bacteria: Plant Eaters’ & Meat Eaters’ []
  49. Dr. Greger’s Daily Dozen Checklist. Michael Greger M.D. FACLM March 30th, 2018 Volume 39 []
  50. Topics: Flax seeds. []
  51. Which Are Better: Chia Seeds or Flax Seeds? Michael Greger M.D. FACLM April 7th, 2017 Volume 35 []
  52. Flax Seeds for Hypertension. []
  53. Can Flax Seeds Help Prevent Breast Cancer? []
  54. Flax Seeds for Breast Pain. []
  55. Flax Seeds & Breast Cancer Survival: Clinical Evidence. []
  56. Flax Seeds & Breast Cancer Survival: Epidemiological Evidence. []
  57. Flaxseeds & Breast Cancer Prevention. []
  58. Just the Flax, Ma’am. Michael Greger M.D. FACLM August 22nd, 2007 Volume 1. []
  59. Flaxseeds vs. Prostate Cancer. []
  60. Flax Seeds vs. Diabetes. []
  61. Was It the Flaxseeds, Fat Restriction, or Both? []
  62. Flaxseeds for Sensitive Skin. []
  63. Flax Seeds vs. Chia Seeds. []
  64. Which Are Better: Chia Seeds or Flax Seeds? []
  65. Grapetree. Suppliers of flaxseeds. []
  66. Amazon: Duronic CG300 Electric Coffee Grinder Mill []

Why Whole Grains Are Better Than Flour

Okay, if you made bread from whole grains rather than floured grains, it would be a bit of a mess! However, there are compelling reasons why eating whole grains (wheat, barley, buckwheat, etc) provides far more health benefits than eating even the healthiest goods made with flour. And we’re not talking here about wholegrain1 as opposed to processed or refined grains – we’re talking about the whole grain – the complete edible part of the grain which has not been milled or ground down to millions of small particles, as happens when making any flour – be it wholegrain/wholemeal or highly refined (white flour).

The central message of this article concerns the different effects that grains and flours have inside your guts. First, though, a bit of background.

Anatomy of a grain

The above diagram shows the three parts of a grain:

  1. bran – the outer shell which protects the grain, containing most of the fibre
  2. endosperm – the major internal part providing food (energy) to the germ
  3. germ – the smaller internal part which provides the seed for future generations

What happens during flour milling?

When whole grains are milled to make refined flour, the bran and germ are removed, leaving only the endosperm. When whole grains are milled to make wholegrain flour, all three parts are ground down and made into a flour. Most people would have become aware that refined (white) flour is not as good for you as wholegrain flour, since the latter still provides some of the benefits of fibre, including:

  • helping to control blood glucose levels – thereby reducing sugar/insulin spikes
  • helping to maintain/ improve insulin resistance – a central feature of type 2 diabetes
  • increasing stool bulk – easing passage through the intestines and helping to prevent constipation
  • keeping you feeling full for longer
  • reducing blood cholesterol

Which grain has most fibre?

Just out of interest, the following is a list 2  of various grains, showing the average fibre content:

Take it out to put it back in

Vitamin E (a powerful antioxidant) 3 , B vitamins (essential for energy production, amongst other things) and trace minerals (including magnesium, selenium and zinc) 4  are partly destroyed by the time the final flour-based products have been baked. This is especially the case with ‘white’ flour (white because the darker-coloured fibre has been removed).

As an example, during milling, wheat loses 50% of its original phosphorus and calcium, 66% of iron, 50-70% of thiamine (vitamin B1)), 80% of niacin (vitamin B3), and 33% of tocopherol (vitamin E) 5 .

These and other nutrients – usually synthetic versions 6  – can then be added back into the final flour, thereby ‘enriching’ or ‘fortifying’ it. All well and good, but there’s plenty of strong evidence 7  suggesting, not only that the original nutrients combined within the actual plant (in this case, grains) are more effective than separately added vitamins and minerals, but studies 8  also show that some added ‘nutrients’ can be seriously harmful to health.

What else does commercially prepared flour contain?

I’m not even bothering to consider other flour products apart from bread (such as pies, pasties, cakes etc). The latter are generally so full of junk (whether animal- or plant-based) that, even if the pastry were of the highest possible quality, the product usually contains other ingredients than few WFPB nutritionists would recommend. However, if you’re determined to eat bread, the range of commercially produced offerings range from the reasonably okay to the downright awful.

Things to look out for, and, preferably, avoid:

  • salt 9
    • Dozens of similar studies demonstrate that if you reduce your salt intake, you may reduce your blood pressure. And the greater the reduction, the greater the benefit may be. But if you don’t cut down, chronic high salt intake can lead to a gradual increase in blood pressure throughout life.
  • sugar
    • some of my recipes contain a small amount, but commercial breads usually contain far too much
  • vegetable oils 10 11
    • Research confirms that ingestion of oil, no matter which type of oil or whether it was fresh or deep fried, showed a significant and constant decrease in arterial function.” 12
  • trans fats 13 14
    • trans fats (“partially hydrogenated” oils) are linked to serious health risks
  • potassium bromate (oxidising agent)
  • azodicarbonamide (dough conditioner/bleacher)
  • monoglycerides & diglycerides (emulsifiers E471)
  • butylated hydrocyanisole (BHA)
    • BHA is a preservative linked to cancer 15 16
  • caramel colouring
    • again, linked to increased cancer risk 17 18
  • high fructose corn syrup (HFCS)
    • HFCS is linked to kidney stones, metabolic syndrome, heart disease and diabetes 19 20 21 22
  • undeclared GMO soy oil 23
    • The bottom line is that there is no direct human data suggesting harm from eating GMOs, though in fairness such studies haven’t been done, which is exactly the point, critics counter. That’s why we need mandatory labelling on GMO products so that public health researchers can track whether GMOs are having any adverse effects.

And this isn’t a definitive list..

There have to be some benefits of refined flour…

Whilst there are no obvious health benefits to stripping whole grains of bran and germ, it does provide a longer shelf life. It also means the products ‘hit the sweet spot’ more quickly and can be a lot more addictive. The producers and retailers benefit when the consumer can’t resist another slice (or two) of the easily chewed and digested pap. So what if the blood glucose hits the roof? It’s well-known that when blood sugar levels rise quickly, they’ll drop just as quickly and result in rebound hunger. Your hunger won’t leave you alone.

Whole grains and the microbiome

This is the take-home bit of the blog. When you eat a milled grain, which consists of millions of tiny particles, most of it gets absorbed and digested well before it reaches your large intestine (the colon). However, when you eat a whole grain, chewing and digestion in the stomach and small intestine tend to leave much larger ‘chunks’ of grain that reach the colon.

So what?

In the colon, trillions of gut bacteria (the microbiota or gut flora) are waiting for these chunks of grain (prebiotics) so that they can further digest them and, thereby, release bi-products back into our bloodstream – bi-products which are of significant importance to our overall health – from reinforcing our immune system, protecting the endothelial cells of our blood vessels, to protecting us from mental depression.

The fascinating subject of gut bacteria has been covered in great detail in several previous blogs 24 25 26 27 . The chunks of whole grain act as prebiotics for our gut bacteria.

Final thoughts

So, if you want to provide valuable fuel for those little guys down there in your colon, stick to whole grains (boiled first, of course), and leave the bread, pasties, cakes, biscuits and other flour products on the shelf for the most part.

If you can’t live without bread, try to make it yourself. I’ve provided some really simple recipes 28 29 30 for a variety of bread types, each of which avoids the use of salt and oil. And if you can’t live without a bit of salt in your bread, then still best to make it yourself rather than buy commercially prepared bread.


  1. Wholegrain, wholewheat and wholemeal are all terms which tend to be used interchangeably to refer to the same thing. []
  2. Oldways Whole Grains Council: FIBER IN WHOLE GRAINS []
  3. The cereal grains: focus on vitamin E [2001]. Zielinski, H. Ciska, E. Kozlowska, H. []
  4. J Am Diet Assoc. 2001 Jul;101(7):780-5. The role of whole grains in disease prevention. Slavin JL, Jacobs D, Marquart L, Wiemer K. []
  5. White Enriched Bread vs. Whole Wheat Bread – Purdue e-Pubs. []
  6. Med Hypotheses. 2000 Dec;55(6):461-9. Natural vitamins may be superior to synthetic ones. Thiel RJ. []
  7. Vitamin C Supplements vs An Apple []
  8. How To Analyse the Health Claims Made for Dietary Supplements []
  9. Topics: salt. []
  10. CNS. Plant Oils Are Not a Healthy Alternative to Saturated Fat by T. Colin Campbell, PhD. July 21, 2016. []
  11. McDougall Newsletter August 2007. When Friends Ask: Why Do You Avoid Adding Vegetable Oils? []
  12. Topics: vegetable oil. []
  13. Vandana Dhaka, Neelam Gulia, Kulveer Singh Ahlawat, and Bhupender Singh Khatkarcorresponding. J Food Sci Technol. 2011 Oct; 48(5): 534–541. Published online 2011 Jan 28. doi: 10.1007/s13197-010-0225-8. Trans fats—sources, health risks and alternative approach – A review. []
  14. Trattner S, Becker W, Wretling S, Öhrvik V, Mattisson I. Food Chem. 2015 May 15;175:423-30. doi: 10.1016/j.foodchem.2014.11.145. Epub 2014 Dec 3. Fatty acid composition of Swedish bakery products, with emphasis on trans-fatty acids. []
  15. Otterweck AA, Verhagen H, Goldbohm RA, Kleinjans J, van den Brandt PA. Food Chem Toxicol. 2000 Jul;38(7):599-605. Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study. []
  16. []
  17. []
  18. Food caramels: a review – NCBI – NIH. []
  19. BMC Nephrol. 2018 Nov 8;19(1):315. doi: 10.1186/s12882-018-1105-0. Fructose increases risk for kidney stones: potential role in metabolic syndrome and heat stress. Johnson RJ et al. []
  20. Topics: High Fructose Corn Syrup. []
  21. Nutrients. 2017 Jan; 9(1): 11. High Dietary Fructose Intake on Cardiovascular Disease Related Parameters in Growing Rats. SooYeon Yoo, er al. []
  22. Glob Public Health. 2013;8(1):55-64. High fructose corn syrup and diabetes prevalence: a global perspective. Goran MI, Ulijaszek SJ, Ventura EE. []
  23. GMO Soy & Breast Cancer. Michael Greger M.D. FACLM November 17th, 2014 Volume 21. []
  24. Fibromyalgia, Probiotics & Gut Microbiota []
  25. Two Types of Gut Bacteria: Plant Eaters’ & Meat Eaters’ []
  26. Obstructive Sleep Apnea (OSA) & Gut Microbiota []
  27. Gut Microbiota & Depression []
  28. You Will Not Find A Simpler Bread Recipe []
  29. Yuri’s Wholesome Bread Recipe []
  30. Breads & Baking []

When the FUN is No Fun

It could be argued that the major nutritional problem experienced by those of us in ‘developed’ countries is an excess of macronutrients (particularly animal protein, saturated fat and sugar) plus salt. When this is combined, as it usually is, with a corresponding insufficient intake of micronutrients (minerals, vitamins, fibre and phytonutrients from fruit, veg, grains, legumes, nuts and seeds), then one descends the slippery slope towards truly unpleasant diseases and a likely early death.

Fatty under-nutrition

Whilst the term ‘over-nutrition’ is often used to define this modern dietary dilemma, it should really be thought of as ‘under-nutrition’, being that it’s too low in nutrients and too high in calories – a sort of nutrient starvation as the body expands. This is an utterly new paradox, probably never seen on this planet prior to the last few human generations.

When FUN is no fun

For the sake of clarity, I’m going to term this condition ‘Fatty Under-Nutrition’, or FUN for short.

The FUN starts young

The FUN starts early in life – even before birth. When women become pregnant, they’re usually urged to eat more because they’re “eating for two”, even though expectant and lactating mothers only require an additional 300 or so calories each day 1 . What all pregnant women really should watch is that they eat a healthy and varied diet, sufficient in macronutrients, but which includes all the micronutrients they and their baby need – notably, omega-3 fatty acids (DHA, in particular), iron, calcium, choline, iodine, vitamins C, D, B9 and, especially in the case of pregnant women eating a WFPB/vegan diet, plus sufficient vitamin B12 2 . Of course, any supplementation should always be in consultation with the medical professional (OB or GP) who is overseeing the pregnancy.

Excessive FUN, that is, a diet low in micronutrients but high in macronutrients (especially animal protein, saturated fat and sugar) during pregnancy can have a range of effects on the health of the mother and baby. The most obvious is excessively rapid weight gain in the mother. However, this factor alone has been shown 3 4 to:

  • increase the risk of labour induction
  • increase the risk of caesarean section
  • result in a higher birth weight
  • cause other complications during pregnancy and delivery

And it’s not just the mother

When infants and children are overfed, they can develop unhealthy dietary habits which may last a lifetime – being apparent in both their waistline and in the number of visits they need to make to their doctor and to the hospital later in life. Both quantity and type of food eaten in childhood can lead to metabolic implications with lifelong consequences.

Since mothers and expectant mothers want to do the very best for their children, they can be susceptible to over-feeding themselves and their babies in spite of their most loving and caring intentions. As one study stated: “In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations” 5 . Of course, in order to achieve this, the quality of the advice needs to be of the highest order.

In 2004, the American Dietetic Association pointed out that: “…the number of children who are overweight has more than doubled among 2- to 5-year-old children and more than tripled among 6- to 11-year-old children, which has major health consequences. This increase in childhood overweight has broadened the focus of dietary guidance to address children’s over consumption of energy-dense, nutrient-poor foods and beverages and physical activity patterns. Health promotion will help reduce diet-related risks of chronic degenerative diseases, such as cardiovascular disease, type 2 diabetes, cancer, obesity, and osteoporosis.” 6

A 2000 study stated that: “During early life and development the embryo, fetus and infant are relatively plastic in terms of metabolic function. The effect of any adverse environmental exposure is likely to be more marked than at later ages and the influence is more likely to exert a fundamental effect on the development of metabolic capacity” 7 . Whilst any baby, infant or young child faces health problems if they are significantly underweight, it’s increasingly understood that being overweight can be equally problematic – if not more so in some respects. 8 9 10

A 2005 review 11 concluded that: “Infants who are at the highest end of the distribution for weight or body mass index or who grow rapidly during infancy are at increased risk of subsequent obesity.

A 2006 study 12 showed that when a 4-month infant is fed more calories than recommended, it is a strong predictor of both increased weight gain before 2 years and increased risk of becoming obese in childhood and adulthood.

The take-home message of this is that parents and care-givers should choose foods that promote a healthy body weight and resist the temptation to ‘spoil’ with food or aim to promote the rapid growth of their child through overfeeding.

Teen FUN

An increasing percentage of adolescents are now over-weight. As of 2018, around a third of UK children between 2 and 15 are clinically obese13 , and US childhood obesity has more than doubled in the past 25 years 14 . Increases in pre-diabetes and full-blown type 2 diabetes (T2D) in childhood is just one disease correlated with childhood obesity 15 . Unless dietary changes are made, T2D symptoms are likely to remain and increase as these young people pass into adulthood. This is made more probable by the fact that the medical professions are slow to change from viewing T2D as a life-long, irreversible condition – thereby their efforts are aimed at merely ‘managing’ the disease, rather than viewing it as a completely reversible condition if appropriate dietary and lifestyle changes are made and adhered to. 16

Type 2 diabetes is rising rapidly in children and adolescents worldwide. Changing a child’s living environment to include physical activity, and a well balanced, low fat, high fiber diet, are important for the maintenance of a desirable body weight and improving insulin sensitivity…and decrease the risk of diabetes and cardiovascular disease.” 17

Fastest way to FUN

Just two words can sum up the major cause of FUN: ‘fast’ and ‘food’. Whether from take-aways, restaurants or supermarket shelves, fast food provides that perfect storm of high calories/low nutrients for children and adults alike.

One of the key findings of a 2018 study into fast food purchases for children by their parents in the US was:

Parents’ purchases of fast food for their children have increased in recent years:

  • In 2016, 91% parents reported purchasing lunch or dinner for their child in the past week at one of the four largest fast-food restaurants, on average twice per week. 
  • In contrast, 79% reported purchasing fast food for their child in the past week in 2010.” 18

As far back as 2003, a US report 19 indicated that fast-food use was reported by 42% of children, resulting in:

  • high intake of energy, fat, saturated fat, sodium, carbonated soft drinks, but
  • low intake of vitamins A and C, fruits and vegetables

FUN leads to yo-yo dieting

This problem becomes compounded when the adolescents try to lose weight by attempting various restrictive dieting regimes – most of which fail and many of which exacerbate existing and/or create new health problems.

Cross-sectional and prospective surveys have shown that a large percentage of adolescents, particularly females and even those of normal weight, diet at some time. While moderate changes in diet and exercise have been shown to be safe, significant psychologic and physiologic consequences may occur with extreme or unhealthy dieting practices. Moderate dieting has been shown to be associated with negative self-esteem in some adolescents. The very act of starting any diet increases the risk of eating disorders in adolescent girls. Extreme methods of weight loss can have adverse physiologic effects if not closely monitored. Electrolyte disturbances, cardiac dysrhythmias, and even sudden cardiac death can result from unhealthy or extreme dieting practices. Such practices are associated with other problem behavior in adolescents.” 20 .

A 2016 study 21 reported that, at any given time, more than 25% of male and around 60% of female adolescents are dieting in order to lose weight. In addition, up to 9% reported that they use maladaptive dieting habits, such as purging 22 .

Developing FUN in adulthood

It’s in so-called ‘developed’ countries that both children and adults are at particular risk from FUN.

Whilst a significant proportion (around 50%) of North Americans have inadequate intake of essential micronutrients and fibre, their energy balance is usually far in excess of physiological needs.  And it’s been known for some time that adults shouldn’t only be worried about this FUN leading to obesity and T2D:

Diet is estimated to contribute to about one-third of preventable cancers — about the same amount as smoking. Inadequate intake of essential vitamins and minerals might explain the epidemiological findings that people who eat only small amounts of fruits and vegetables have an increased risk of developing cancer. Recent experimental evidence indicates that vitamin and mineral deficiencies can lead to DNA damage.” 23

Energy density, portion size & availability

Standard foods, such as dairy, meat, sugar and vegetable oils tend to be more energy-dense in modern Western diets (often referred to as the SAD – Standard American Diet) when compared with the more traditional Asian and African diets, in which grains, legumes, and starchy vegetables play a much larger part.

Add to this the fact that, in Western societies, food portion sizes are larger and calorie dense/nutrient poor foods are much more easily available, and you have an adult population experiencing epidemic obesity-related diseases: coronary heart disease, hypertension, diabetes, and cancer. 24

FUN into old age – if you last that long…

As our populations reach advanced age, metabolic syndrome 25 is becoming the norm rather than the exception, with more than 40% of people in their 60’s and 70’s being affected 26 and, thereby, running a greater risk of dying prematurely 27 .

And dying isn’t even the worst of it. These chronic illnesses, during later years of one’s life, require regular hospitalisation, invasive, painful, and often humiliating medical procedures, restrictions of one’s privacy and independence, and severe limitations on the quality and enjoyment of one’s wise elderly years – years that should be active, happy and golden.

When the FUN stops

When you choose to eat a balanced WFPB diet, the FUN stops and the fun begins. Nutrient-rich foods become the norm and both micronutrients and macronutrients take care of themselves, with the ideal ratio of protein, fat and carbohydrate already wrapped up by nature with all the vitamins, minerals, phytochemicals and fibre that your body needs.

And no longer will you have to restrict how much you eat, nor worry about your weight, another paradox – albeit a very welcome one! – since, with such naturally healthy eating, you can’t help but get back to your ideal weight, thereby obviating the risk of falling into the cycle of yo-yo dieting.

Naturally, you’ll still be strongly advised to take B12 supplements and ensure you get enough sunlight, or else take vitamin D supplements; but apart from this, you can just concentrate on enjoying the rest of your life while your body and mind are naturally fuelled for optimal performance.

And all this by simply eating unadulterated plant foods…


  1. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) . Washington, DC: National Academies Press; 2005. []
  2. Piccoli, G., Clari, R., Vigotti, F., Leone, F., Attini, R., Cabiddu, G., … Avagnina, P. (2015). Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review. BJOG: An International Journal of Obstetrics & Gynaecology, 122(5), 623–633. doi:10.1111/1471-0528.13280 []
  3. Maier JT et al: Antenatal body mass index (BMI) and weight gain in pregnancy – its association with pregnancy and birthing complications. J Perinat Med 44:397, 2016. []
  4. Kabiru W, Raynor BD: Obstetric outcomes associated with increase in BMI category during pregnancy. Am J Obstet Gynecol 191:928, 2004. []
  5. Roseboom TJ et al: Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 185:93, 2001 []
  6. Nicklas T, Johnson R, American Dietetic Association: Position of the American Dietetic Association: Dietary guidance for healthy children ages 2 to 11 years. J Am Diet Assoc 104:660, 2004 []
  7. Jackson AA: Nutrients, growth, and the development of programmed metabolic function. Adv Exp Med Biol 478:41, 2000. []
  8. N. Kapral, S. E. Miller, R. J. Scharf, M. J. Gurka, M. D. DeBoer. Associations between birthweight and overweight and obesity in school-age children. Pediatric Obesity, 2017 []
  9. Pediatr Obes. 2014 Apr;9(2):135-46. doi: 10.1111/j.2047-6310.2013.00155.x. Epub 2013 Apr 2. Socioeconomic status, infant feeding practices and early childhood obesity. Gibbs BG, Forste R. []
  10. Matern Child Nutr. 2013 Jan;9 Suppl 1:105-19. doi: 10.1111/mcn.12010. Nutrition in pregnancy and early childhood and associations with obesity in developing countries. Yang Z, Huffman SL. []
  11. Baird J et al: Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 331:, 2005 []
  12. Ong KK et al: Dietary energy intake at the age of 4 months predicts postnatal weight gain and childhood body mass index. Pediatrics 117:e503, 2006. []
  13. House of Commons Health Committee. Childhood obesity: Time for action. Eighth Report of Session 2017–19. Report, together with formal minutes relating to the report. Ordered by the House of Commons. 23 May 2018. []
  14. Baird J et al: Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 331:, 2005. []
  15. Whitlock EP et al: Screening and interventions for childhood overweight: a summary of evidence for the US Preventive Services Task Force. Pediatrics 116:e125, 2005 []
  16. Diet Reverses Type 2 Diabetes – How Long Have We Known This? []
  17. Vivian EM: Type 2 diabetes in children and adolescents–the next epidemic? Curr Med Res Opin 22:297, 2006 []
  18. UConn Rudd Center for Food Policy and Obesity. Parents’ report of fast-food purchases for their children: Have they improved? September 2018. []
  19. Paeratakul S et al: Fast-food consumption among US adults and children: dietary and nutrient intake profile. J Am Diet Assoc 103:1332, 2003 []
  20. Starling P et al: Fish intake during pregnancy and foetal neurodevelopment–a systematic review of the evidence. Nutrients 7:2001, 2015 []
  21. Zullig KJ, Matthews-Ewald MR, Valois RF: Weight perceptions, disordered eating behaviors, and emotional self-efficacy among high school adolescents. Eat Behav 21:1, 2016 []
  22. Purging – a practice known as bulimia – oscillates with bingeing and can result in a wide range of health issues, including rupture of the oesophagus or stomach, dental and oral damage due to stomach acid exposing during vomiting. []
  23. Ames BN, Wakimoto P: Are vitamin and mineral deficiencies a major cancer risk? Nat Rev Cancer 2:694, 2002 []
  24. Isganaitis E, Lustig RH: Fast food, central nervous system insulin resistance, and obesity. Arterioscler Thromb Vasc Biol 25:2451, 2005 []
  25. Metabolic syndrome is a combination of central obesity, dysglycaemia, dyslipidemia and arterial hypertension. Most of the disorders associated with metabolic syndrome have no visible symptoms except for a large waist circumference. Additional symptoms include increased thirst and urination, fatigue, and blurred vision. []
  26. Arq Bras Cardiol. 2014 Mar; 102(3): 263–269. Prevalence of Metabolic Syndrome in Elderly and Agreement among Four Diagnostic Criteria. Maria Auxiliadora Nogueira Saad et al. []
  27. Firdaus M: Prevention and treatment of the metabolic syndrome in the elderly. J Okla State Med Assoc 98:63, 2005 []

Ghrelin & Obesity – A Tentative Step Through the Minefield

Increased appetite is a driving force for weight gain, and unchecked weight gain does, of course, lead to obesity. There’s a growing body of literature suggesting that ghrelin, the so-called hunger hormone” or “starvation hormone”, plays an important role in appetite fluctuations. Whilst we looked at leptin, the “satiety hormone” in the previous blog 1 , this one is an analysis of some research on ghrelin and obesity 2 .

Because this is a rather complex blog, technical terms are in green – either click associated number to go to References/Notes section (blue arrow returns to same place in the text), or hold cursor over relevant number to reveal contents.

What is ghrelin?

The complexity of this topic starts as soon as one looks for the derivation of the word “ghrelin”, with some authorities 3 stating that it’s derived from “ghre” (grow) and “relin” (release), while another authorities4 appear to relate its etymological roots to the use of letters from its understanding as a “Growth Hormone RELease INducing” hormone. In any case, it is agreed that it was first isolated and identified by Kojima and Kangawa et al in 1999 5 . Three years later, its specific brain receptor, GHS-R 1a, was also identified 6 .

Whilst leptin is mainly secreted by fat cells 7 and insulin is secreted by beta cells in the islets of Langerhans within the pancreas, ghrelin is primarily secreted from cells in the stomach (see below for more detail on this).

Ghrelin vs leptin

Having already looked at leptin in the previous blog, it’s worth starting by drawing comparisons between it and ghrelin, since they are regarded as working together (although in opposite directions) to help regulate appetite and metabolism.

Ghrelin and leptin are the two hormones 8 that are most responsible for regulating appetite – to ensure you don’t eat too few calories and starve to death while also ensuring you don’t eat too many calories and become obese. Well, that’s the hope anyway!

As an appetite stimulant, ghrelin is called an orexigenic hormone9 that stimulates food intake and thereby helps regulate body weight, while the appetite-inhibiting hormone leptin is known as an anorexigenic hormone 10

They are both homeostatic 11  hormones which means they are going to act on the hypothalamus 12 , the part of the brain that maintains the body’s internal balance (homeostasis).

The hypothalamus acts as the link between the endocrine 13 and nervous 14 systems. The hypothalamus produces releasing and inhibiting hormones, which stop and start the production of other hormones throughout the body.

Ghrelin and leptin act on different parts (receptors) within the hypothalamus.

Ghrelin acts on the lateral 15  hypothalamic brain cells16 , while leptin acts on the ventromedial 17 hypothalamic brain cells.

Ghrelin makes you Grow” – makes you eat, while “Leptin makes you Lean” – makes you stop eating. These are two mnemonics that might help to remember which is which.

Ghrelin is the only peripheral 18 orexigenic hormone that activates receptors found in the appetite centre – viz. the hypothalamus and pituitary gland.

Ghrelin is produced by endocrine cells 19 of the oxyntic glands20 within the gastric fundus21 . It’s also secreted, to a lesser extent, by the body of the stomach, the mucosa of the duodenum and jejunum 22 , the lungs, the urogenital organs, and the pituitary gland.

Stomach distension reducing ghrelin-production and inhibiting appetite.

Once produced in the stomach, ghrelin is released into the bloodstream, passes through the blood-brain-barrier 23 to the lateral hypothalamus, and causes a hunger response.

Ghrelin will also have an effect on the stomach itself, causing an increase in gastric acid production and gastric motility 24 . This prepares the stomach for the food that’s been anticipated by the brain. Daily habits (breakfast, lunch and dinner) become ingrained so that our ghrelin production starts to increase before we’re even consciously aware that we’re hungry.

Ghrelin stimulants (or inducers) include hypoglycaemia (low blood glucose), an empty stomach, and low body weight (low body fat content).

Ghrelin suppressants (or inhibitors) include activation of the stomach’s stretch receptors as the stomach becomes full of food (stomach distension).

Leptin, on the other hand, is primarily produced by white adipose tissue.

As the fat cells increase in size, they produce more leptin. A negative feedback signal 25 is caused when leptin travels from the fat cells, through the bloodstream and blood-brain-barrier to the ventromedial hypothalamic cells in the hypothalamus – reducing appetite and food intake. Ideally, this means that fat controls its own levels within the body. 26

Inducers for leptin include insulin and emotional stress. Below, we consider how modern dietary changes may have messed with the normally healthy relationship between stress and hunger hormones.

Leptin and insulin share common effects in controlling food intake and energy metabolism, with each playing an important role in blood glucose homeostasis. They directly regulate each other: leptin inhibits insulin and insulin stimulates leptin synthesis and secretion.

Note: ANS = Autonomic Nervous System.

Leptin increases insulin sensitivity 27 , in part, by decreasing adiposity and lipotoxicity 28 . Leptin decreases hepatic (liver) production of glucose – glycogenolysis 29 – contributing to its glucose-lowering effects. 30

Studies have revealed that leptin has the effect of normalising hyperglycaemia 31 and hyperinsulinaemia  ((Hyperinsulinaemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions.)). It’s also clear 32 that levels of both need to drop for fat burning – i.e. gluconeogenesis 33 – to commence.

Whilst it would seem intuitively obvious in evolutionary terms that when the body is under stress (fight or flight), appetite for food would be switched off – perhaps causing the production of leptin to achieve this, studies 34 have pointed out a complication in the modern world with psychological stress: namely, that it often results in “comfort eating” (usually fatty, sweet, high calories foods). The latter modern habit can confuse the picture.

The previous blog pointed 1 out the paradox that obese humans tend to have higher levels of leptin – the hunger-inhibiting hormone – suggesting they have developed leptin resistance. This results in a toxic cycle of increased leptin insensitivity leading to increased leptin levels (irrespective of insulin and ghrelin levels) leading to increased amounts of fat being stored in the body, leading to the fat cells producing even more leptin.

To test the latter, researchers intravenously increased leptin levels during times of emotional stress in order to see whether this would lower the compensatory intake of such comfort food. They concluded that “…initial findings suggest that acute changes in leptin [i.e. increasing it in the short term] may be one of the factors modulating down [reducing] the consumption of comfort food following stress.” 35

A major inhibitor of leptin is short term fasting. When you haven’t eaten for several hours, leptin levels should drop and ghrelin levels should rise. A theory which appears to work okay in healthy, non-obese individuals.

Active & inactive ghrelin

The acylation of inactive (non-acyl) to active (acyl) ghrelin.

There are several different forms of ghrelin, but the main two are called the “inactive” (des-acyl ghrelin) and “active” (acyl ghrelin – a peptide of 28 amino acids) forms. The inactive form accounts for more than 90% circulating within the bloodstream 36 . However, the inactive form has to be converted into the active form in order to do its work as an appetite stimulant. It does this via an enzyme called ghrelin O-acyltransferase or GOAT 37 38  . This process is critical both for the orexigenic and the gastric-emptying actions of ghrelin.

How ghrelin exerts its effect on the body

There are various possible actions by which ghrelin exerts its effect within the body, including:

  • overproduction/underproduction of ghrelin before and/or after meals
  • increased/decreased receptor sensitivity to ghrelin action

Ghrelin & positive feedback

The appetite-generating effect of ghrelin can be described as a direct positive feedback loop39  which maintains increased activity of AgRP neurons 40 so as to drive feeding behaviour until satiety is reached 41 , when leptin kicks in to do its job of suppressing appetite.

Other physiological functions of ghrelin

The discovery of the GOAT enzyme revealed that ghrelin is involved in many additional physiological functions, ranging from regulation of the immune and cardiovascular systems, up-regulation of insulin-like growth factor (IGF-1), to a dominant role in the gastrointestinal system and involvement in gastric emptying and intestinal motility 42 .

Although it has a role as a growth factor secretagogue 43 , stomach-derived ghrelin doesn’t appear to be necessary for growth and appetite stimulation, since ghrelin-deficient animals still appear to grow and eat quite normally 44 .

There must, therefore, be some form of redundancy within the body – that is, other physiological processes that promote growth and appetite which are able to compensate for the absence of ghrelin.

Actions and therapeutic pathways of ghrelin for gastrointestinal disorders

As can be seen in the diagram, ghrelin affects multiple systems. Whilst being secreted mainly by the stomach, it has effects in multiple areas, including the CNS (central nervous system), the immune system, the adrenal gland and the cardiovascular system. It can also affect the proliferation of osteoblasts 45  and neoplastic cells 46 .

Ghrelin, obesity & appetite

The precise role of ghrelin in the pathophysiology of obesity is still under investigation. It’s considered by some that if we’re able to get a firm grip on how ghrelin initiates appetite, then increasing its level could be a revolutionary new method of obesity management and treatment.

The role of ghrelin in the development of obesity.

Reduced postprandial suppression of ghrelin in obese individuals

In a number of studies of obese adults and obese children 47 48 , it’s been reported that postprandial suppression of ghrelin is lower in such obese groups compared to controls with normal body mass index (BMI).

This makes it a reasonable assumption that higher consumption of food by obese individuals is linked to a continuing feeling of hunger, even after consuming a meal with sufficient caloric content to satisfy their physiological needs. These findings have supported the ‘disease pattern’ of obesity which has underlying mechanisms and causes like other common disorders.

What’s the problem with ghrelin in relation to obesity?

So, is the obesity-ghrelin problem (and, by inference, the insulin-ghrelin problem) a matter of an overproduction of ghrelin or is it similar to what we’ve seen with leptin and insulin – i.e. insensitivity leading to resistance?

Since studies (mentioned above) 44 have shown that animals completely deficient in ghrelin can still grow normally without becoming obese, it would seem that the likeliest problem is the overproduction of ghrelin (regardless of the how much food is consumed) rather than a ghrelin insensitivity or oversensitivity.  Various studies support this hypothesis 49 50 51 , although uncertainty still remains regarding the precise mechanism/s involved, which range from a possible dysfunction in the gene for ghrelin to the production of antibodies to the peptide receptors which antagonise 52 ghrelin’s effects which, in turn, might lead to disturbances in the production and actions of ghrelin. Additionally, interactions with other hormones (insulin, growth hormone (GH), etc)  are likely to account for at least some of the ghrelin-obesity anomalies.

We still don’t fully understand the relationship between ghrelin and insulin – a relationship which appears to be based on an overproduction of ghrelin leading to a similar overproduction and eventual insensitivity/resistance to insulin 53 .

The view that the obesity-ghrelin problem is not due to an overproduction of ghrelin in obese individuals is supported by many studies. showing that the mean serum ghrelin level is generally lower in obese patients compared to lean individuals 54 55 , although the number of ghrelin-producing cells was found to be more abundant in the fundus of morbidly obese patients.

You’d be excused for expecting obese individuals to have lots more of this appetite-promoting hormone floating around their bloodstream than would non-obese individuals, given that the former continue eating beyond their physiological needs. And you wouldn’t be alone. The following graph 56  reveals that, though ghrelin levels rise in expectation of a meal and fall after that meal in both obese and non-obese individuals, the levels of ghrelin are consistently higher in non-obese than in obese individuals.

A further study concluded: “Contrary to our hypothesis, however, obese subjects have lower plasma concentrations of the adipogenic 57 hormone ghrelin than age-matched lean control subjects.” 58

The same study made some suggestion about what’s actually happening with ghrelin in obese individuals, suggesting that it may be a downregulation 59 of ghrelin as a consequence of elevated insulin or leptin, because fasting plasma ghrelin levels are negatively correlated with fasting plasma levels of insulin and leptin.

They also speculated that decreased secretion of ghrelin could be responsible for decreased levels of circulating growth hormone (GH) 60 in obese individuals 61  .

Ghrelin, growth hormone (GH), diabetes & obesity

Ghrelin, as stated above, causes the release of growth hormone (hence the proposed origin of its name – Growth Hormone Release Inducing hormone). The relationships between obesity, adipose tissue, GH and ghrelin make an already complex situation even more complex.

Obesity induces hyperinsulinaemia, hypoadiponectinaemia 62 , hyperleptinaemia 63 , reduced serum ghrelin, and increased free fatty acid levels. The effect of this is that GH secretion from the pituitary gland is suppressed 64 .

But what’s the relationship between low levels of GH and ghrelin in obese/diabetic individuals?

Insulin resistance is highly associated with visceral obesity, non-alcoholic liver disease, and type 2 diabetes. In turn, all these conditions are associated with low GH secretion. Since high levels of GH are likely to contribute to the development of insulin resistance when, that is, caloric intake is greater than physiological demand (when you eat more calories than you burn), the body’s reduction in GH secretion in obesity may be an adaptive phenomenon which is aimed at preventing insulin resistance occurring.

However, a problem occurs with this situation: namely, when GH secretion is reduced, it’s likely to lead to further increases in fat accumulation by reducing the process of lipolysis 65 . It’s clear to see how this increased retention of fat can exacerbate obesity and establish a dangerous vicious circle. Indeed, truncal adiposity 66  is one of the most important clinical findings of a condition known as adult GH deficiency syndrome (GHD) 67 .

So, when levels of circulating GH are reduced, as they are in cases of obesity, it’s proposed 58 that decreased plasma ghrelin concentrations – which are seen in obesity – represent a physiological adaptation to the positive energy balance 68 associated with this disease.

GH (like insulin) is essential in adapting the utilisation of calories to the amount of ingested food, promoting anabolism 69 in the case of positive energy balance, with catabolism 70 occurring in the case of negative energy balance 71 . While insulin is the main metabolic hormone in the fed state (positive energy balance), GH assumes a key role as stimulator of lipolysis during prolonged fasting (negative energy balance), when it causes preferential oxidation of lipids and protein synthesis 72 .

The increase in GH secretion that occurs with fasting may have represented an evolutionary advantage in times of food scarcity. However, GH and IGF-I have opposite effects on glucose homeostasis, with the former reducing insulin sensitivity (mainly acting in the liver) and the latter increasing it in the muscle.” 73

Plenty more detail on the relationship of ghrelin and GH is available in a number of excellent studies 74 .

Ghrelin and diets

As you’d expect, levels of ghrelin increase during dieting. This could explain why it’s very difficult to achieve long-term success from dieting. 75 76

Two way to manage obesity

There are two main approaches in managing obesity:

  • conservative – e.g. diet, exercise and lifestyle changes
  • surgical – through various weight-loss surgical procedures, widely known as bariatric surgery

The conservative ways of preventing and treating diabetes, primarily through dietary changes, have been covered in such detail in previous blogs 77 78 79 80 that we hardly need to repeat them here.

Ghrelin & bariatric surgery

It’s clear that bariatric surgery is going to cause some purely mechanical effects (less room for food) that would be responsible for subsequent increased food restriction, as well as often leading to malabsorption 81 . After all, the person concerned has had bits of their guts removed and/or joined together. However, during the past couple of decades, the identification of significant humoural 82 changes (that lead to less hunger or earlier satiety postprandially) has complicated the picture of why appetite changes occur after such surgical procedures 83 47 .

Ghrelin & two types of bariatric surgery

Researchers have recently tried to explain the impressive results of bariatric surgery in terms of weight loss by evaluating the changes in ghrelin concentration following roux-en-y gastric bypass (RYGB) 84 and especially sleeve gastrectomy (SG) 85 . In the latter procedure, the gastric fundus, where most ghrelin is produced, is totally removed. A recent meta-analysis 50 showed that the ghrelin level does fall significantly following SG. In patients who undergo RYGB, the results of various studies are contradictory 86 .

Does bariatric surgery work?

Both these techniques lead to exceptionally good results in weight loss. Based on the fact that, anatomically, SG is purely restrictive compared to RYGB, which additionally creates malabsorption by the rapid shunt of undigested food to the distal small intestine 87 , the role of ghrelin is now being investigated more than ever. Whether or not bariatric surgery works, we know that even morbidly obese individuals can return to a normal healthy weight without the need for such extreme dietary measures 88 . Additionally, once the body is back to a healthy homeostatic state, one would assume that ghrelin levels would also normalise.

Ghrelin & age-related obesity

The adjacent graph 89 shows that ghrelin levels decrease with age, backed up by other studies 90 . This would be in line with the fact that ageing is accompanied by a decrease in both energy expenditure and locomotor activity – with decreases in muscle strength and endurance leading to functional decline. The latter factors, taken in isolation, would imply that there would be a corresponding increase in body weight, particularly in the form of fat.

This has an effect on food intake as well as energy expenditure, thereby potentially preventing the development of age-related obesity. 91

Ghrelin and anorexia

Due to the proven relationship of ghrelin with appetite, researchers are also investigating the potential connection of ghrelin to anorexia. Insight into the modification of the endogenous ghrelin system seems to be promising not only for the control of obesity, but also for the management of clinically significant anorexia and pathological weight reduction.

Does anorexia produce ghrelin insensitivity?

Accumulating evidence has shown that in patients with anorexia nervosa, there’s a paradoxical increase in plasma ghrelin level even when compared with matched controls or obese patients 92 , suggesting that the situation may be one of ghrelin-insensitivity 93 .

Ghrelin – homeostatic and non-homeostatic feeding

Anorexia nervosa, bulimia nervosa 94 and other eating disorders appear to have pathophysiologies 95 linked to dysfunctions of reward mechanisms. 96 Additional research 97  supports the hypothesis that ghrelin doesn’t just increase appetite by homeostatic need – that is, feeding driven by a metabolic need where hormones “speak to one another” in order to create homeostatic balance, but also by non-homeostatic feeding  – that is, feeding driven by non-metabolic factors, such as reward (“hedonic feeding” 98 ) and memory. The latter factors have less to do with the body trying to reach homeostatic balance than with emotional, psychological and social factors.

Tail wagging the dog

The huge increase in the consumption of ultra-processed foods (high in sugar/fat/calories and low in nutrients) could be regarded as a causal factor in the dysregulation of homeostatic hormonal systems (ghrelin, leptin, insulin, etc), resulting in the tail (learned emotional need) wagging the dog (actual physiological need).  This results in our medical professions struggling to cope with the ever-increasing effects of diet-related diseases, and in millions of suffering people who end up with diseased bodies and shortened lives.

Cancer and ghrelin administration

Ghrelin and cancer.

In vitro studies 99  have documented that both intra-peritoneal 100 and systemic 101 administration of ghrelin have the potential of improving appetite and nutritional status, and at the same time reducing the metabolic rate in patients with end-stage cancer.

This research suggests a likelihood that additional gastric disorders (e.g. gastritis, GI tract carcinoma, and other functional GI disorders) disrupt the morphological structure 102 of the stomach, and thus alter ghrelin production – being that the stomach is its major source. “These alterations may induce various GI disorders including functional GI disorders, eating disorders, abnormal energy homeostasis and growth. By understanding ghrelin secretion in the regulation of GI disorders, ghrelin levels may serve as a good diagnostic biomarker for early detection of GI disorders.” 99

The roles that ghrelin may play in relation to cancer is still relatively unclear. One study concludes: “It is currently unclear whether the ghrelin axis has tumor-promoting effects, or indeed whether it may inhibit tumorigenesis in vivo, and further studies are therefore required to elucidate its role in cancer.” 103

Limitations of Studies Investigating Ghrelin

There are several limitations in investigating ghrelin:

  • very small number of studies and RCTs (randomised controlled trials)
  • there are two forms of circulating ghrelin, inactive ghrelin (90%), and active acylated ghrelin (10%) 49 and published studies tending to measure total rather than active ghrelin levels
  • the active form of ghrelin has been reported to be unstable at room temperature
  • there’s a current lack of standardisation in ghrelin measurement in terms of timing of sample collection, collection method, follow-up period, sample storage, and the radioimmunoassays 104 being used

The latter issues make precise measurement a challenge and this may be an issue in the reproducibility of results in the future.

Prader-Willi syndrome (PWS)

PWS, a congenital form of obesity, is caused by a mutation on chromosome 15. One of the effects of this is that ghrelin levels are hugely increased and the individual is forever hungry. If untreated, eating far, far too much – resulting in morbid obesity. It’s thought 105 that elevated ghrelin levels in PWS children precede the onset of obesity.

Prader-Willi syndrome.

Prader-Willi syndrome vs non-congenital obesity

When ghrelin levels were compared between children with PWS and children with non-congenital obesity (i.e. nothing wrong with their chromosome 15), it was found 106 that, even immediately after eating meals, ghrelin levels remained comparatively much more elevated in the PWS children.

The reason for this is speculated 107  to be that hyperghrelinaemia 108 in early infancy might be a response to the failure to thrive, and that chronic or persistent hyperghrelinaemia eventually promotes hyperphagia (overeating) in early childhood. 109

Once again, it would appear that more complexity has befallen us, since the obesity in PWS individuals is accompanied by elevated levels of ghrelin in the blood, while in non-congenitally obese individuals, ghrelin levels appear to be reduced even compared with non-obese individuals.

Further research on ghrelin

Whilst ghrelin research is ongoing, and all will hopefully be made clearer in the near future, a two-part YouTube video 110 111 presents a very detailed analysis of the discovery of ghrelin and its receptor, along with its relationship to GH and its role in starvation-prevention.

Final thoughts

The above is by no means a comprehensive analysis either of the specific role/s of ghrelin in the development of obesity nor of its other varied physiological roles. Indeed, I haven’t even touched on another important appetite-suppressing hormone, namely PYY 112 . Its relationship with ghrelin and other hormones is sufficiently complex to warrant a separate analysis, although there are plenty of studies for the interested reader. 113 114 115

What is clear, though, is that ghrelin appears to be attracting attention with regard to the treatment of obesity.

However, it does continue to be a source of irritation that, within the realm of medical research, so much emphasis is directed towards treatment (usually through searches for pharmaceutical and/or gene-based solutions) rather than prevention. And, as strong evidence suggests, obesity is best treated through dietary change; with the most effective and long-lasting dietary change being one that increases the ratio of whole plant foods to processed and/or animal foods 116 117 118 .

My expectation is that most research dollars will be spent on developing highly-profitable pharmaceutical solutions for perceived problems that relate to ghrelin and associated hormones. The elephant in the room is dietary change, of course. When we looked at toxic hunger vs real hunger 119 , we merely touched on the issue of ghrelin. However, it would seem relevant to this discussion to consider that eating a WFPB diet – which has significant impact on both homeostatic (the physiological effects of hormones, etc) and non-homeostatic feeding (‘comfort eating’ and ‘addictive’ dietary habits) – would also have direct and/or indirect effects on the effectiveness of the ghrelin-leptin-insulin-GH axis. Once again, more research is needed in this area, although where the research dollars come for this type of research is likely to be an ongoing problem.

References & Notes

  1. Leptin – The “Fat” Hormone? [] []
  2. In Vivo. 2017 Nov-Dec;31(6):1047-1050. Ghrelin and Obesity: Identifying Gaps and Dispelling Myths. A Reappraisal. Makris MC, Alexandrou A, Papatsoutsos EG, Malietzis G, Tsilimigras DI, Guerron AD, Moris D. []
  3. Walker A K, Gong Z, Park W M, Zigman J M, Sakata I. Expression of Serum Retinol Binding Protein and Transthyretin within Mouse Gastric Ghrelin Cells. PLoS One. 2013;8:e64882. []
  4. Open University: The Science of Nutrition& Healthy Eating. []
  5. Methods Enzymol. 2012;514:3-32. doi: 10.1016/B978-0-12-381272-8.00001-5. History to the discovery of ghrelin. Bowers CY. []
  6. Hormones (Athens). 2016. Effects of ghrelin in energy balance and body weight homeostasis. Mihalache L, Gherasim A, Niţă O, Ungureanu MC, Pădureanu SS, Gavril RS, Arhire LI. []
  7. Leptin is mainly secreted by adipocytes (fat cells) of white adipose tissue. It’s also produced in brown adipose tissue, placenta syncytiotrophoblasts, ovaries, skeletal muscle, the lower part of the fundic glands within the stomach, mammary epithelial cells, bone marrow, gastric chief cells and P/D1 cells. []
  8. A hormone is any member of a class of signalling molecules produced by glands in multicellular organisms that are transported by the circulatory system to target distant organs to regulate physiology and behaviour. []
  9. Orexigenic – An orexigenic, or appetite stimulant, is a drug, hormone, or compound that increases appetite and may induce hyperphagia – overeating. This can be a naturally occurring neuropeptide hormone such as ghrelin, orexin or neuropeptide Y, or a medication which increases hunger and therefore enhances food consumption. []
  10. Anorexigenic – an anorexigenic hormone reduces or inhibits appetite. []
  11. Homeostasis is the state of steady internal conditions maintained by living things. This dynamic state of equilibrium is the condition of optimal functioning for the organism and includes many variables, such as body temperature, fluid balance, blood sugar levels, and body weight being kept within certain pre-set limits. []
  12. The hypothalamus is an endocrine gland. Endocrine glands within the endocrine system secrete their products, hormones, directly into the blood rather than through a duct. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, adrenal glands and, of course, the hypothalamus. []
  13. The endocrine system is a chemical messenger system consisting of hormones, the group of glands of an organism that secrete those hormones directly into the circulatory system to regulate the function of distant target organs, and the feedback loops which modulate hormone release so that homeostasis is maintained. []
  14. The nervous system is the part of an animal that coordinates its actions by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that impact the body, then works in tandem with the endocrine system to respond to such events. []
  15. Lateral means of, at, towards, or from the side or sides. The green cells on the diagram. []
  16. specifically, on the cell receptor known as the ghrelin/growth hormone secretagogue receptor or GHS-R. Secretagogue receptors are those that promote secretion. []
  17. Ventral means on or relating to the underside of an animal, plant or object – in this case the brain; while ventromedial indicates that it’s situated towards the middle of the ventral part. The red cells on the diagram. []
  18. Peripheral – that is, produced or taking place outside of the central nervous system , CNS – i.e. outside the brain and spinal cord []
  19. International Journal of Peptides. Volume 2010, Article ID 945056, 7 pages. Ghrelin Cells in the Gastrointestinal Tract. Ichiro Sakata, Takafumi Sakai. []
  20. Oxyntic glands – these are made up of secretory cells which produce hydrochloric acid in the main part of the stomach, or the glands which they compose []
  21. the upper part of the stomach, which forms a bulge above the level of the opening of the oesophagus, furthest from the pylorus []
  22. Duodenum and jejunum are the first and second parts of small intestine, with the ileum being the final part before entering the large intestine, the colon. []
  23. The blood-brain barrier is a semipermeable membrane separating the blood from the cerebrospinal fluid, and constituting a barrier to the passage of cells, particles, and large molecules. Only specific substances, including ghrelin, are able to pass through this barrier. []
  24. Gastric or gastrointestinal motility is defined by the movements of the digestive system, and the transit of the contents within it. []
  25. A negative feedback (or balancing feedback) signal occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. []
  26. (Morton G. J., Schwartz M. W. (2011). Leptin and the central nervous system control of glucose metabolism. Physiol. Rev. 91, 389–411. []
  27. Kamohara S., Burcelin R., Halaas J. L., Friedman J. M., Charron M. J. (1997). Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377 10.1038/38717 []
  28. Lipotoxicity is a metabolic syndrome that results from the accumulation of lipid intermediates in non-adipose tissue, leading to cellular dysfunction and death. The tissues normally affected include the kidneys, liver, heart and skeletal muscle. []
  29. Glycogenolysis is the breakdown of the molecule glycogen into glucose, a simple sugar that the body uses to produce energy. The opposite of glycogenolysis is glycogenesis, which is the formation of glycogen from molecules of glucose. []
  30. Indian J Endocrinol Metab. 2012 Dec; 16(Suppl 3): S549–S555. Leptin therapy, insulin sensitivity, and glucose homeostasis. Gilberto Paz-Filho, Claudio Mastronardi, Ma-Li Wong, and Julio Licinio. []
  31. Hyperglycaemia is an excess of glucose in the bloodstream, often associated with type 2 diabetes, also known as diabetes mellitus. []
  32. Cell. Volume 172, issue 1, P234-248.E17, January 11, 2018. Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation. Rachel J. Perry et al. []
  33. Gluconeogenesis is is a metabolic pathway that results in the generation of glucose, to be burned as energy, from certain non-carbohydrate carbon substrates, including fat and protein. []
  34. Physiol Behav. 2012 Aug 20; 107(1): 34–39. Leptin concentrations in response to acute stress predict subsequent intake of comfort foods. A. Janet Tomiyama et al. []
  35. Physiol Behav. 2012 Aug 20;107(1):34-9. Leptin concentrations in response to acute stress predict subsequent intake of comfort foods. Tomiyama AJ et al. []
  36. Total and active ghrelin levels in women with polycystic ovary syndrome. S. Ferrero P. Anserini V. Remorgida G. Bentivoglio N. Ragni. Human Reproduction, Volume 21, Issue 2, 1 February 2006, Pages 565. []
  37. GOAT is essential for ghrelin-mediated elevation of GH, necessary to prevent death from severe calorie restriction through preservation of blood glucose levels. []
  38. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Goldstein JL, Brown MS. Proc Natl Acad Sci U S A. 2010 Apr 20; 107(16):7467-72. []
  39. Positive Feedback – a physiological cyclic process or action that can continue to amplify the body’s response to a stimulus until a negative feedback response, its opposite, takes over. []
  40. AgRP neurons – brain neurons that make agouti-related peptides – hence AgRP – that potently stimulate food intake []
  41. Hunger Circuit. Science Signalling. by W Wong – ‎2011. []
  42. Intestinal mobility is the movements of the digestive system, and the transit of the contents within it. []
  43. A secretagogue is a substance that stimulates secretion of another substance – in this case, ghrelin stimulates the release of growth factor (GH) from the pituitary gland. []
  44. Rev Endocr Metab Disord. 2006 Dec;7(4):237-49. Role of endogenous ghrelin in growth hormone secretion, appetite regulation and metabolism. Dimaraki EV, Jaffe CA. [] []
  45. Osteoblasts are the cells required for bone synthesis and mineralisation, both during the initial formation of bone and during bone remodelling. []
  46. A neoplasm is an abnormal new growth of cells. The cells in a neoplasm usually grow more rapidly than normal cells and will continue to grow if not treated. []
  47. Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study. Ann Surg. 2013;257(4):647–654. [] []
  48. Wiley Online Library: Obese children aged 4–6 displayed decreased fasting and postprandial ghrelin levels in response to a test meal. Jenny Önnerfält, Charlotte Erlanson‐Albertsson, Caroline Montelius, Kristina Thorngren‐Jerneck. 24 November 2017. []
  49. Camilleri M, Papathanasopoulos A, Odunsi ST. Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol. 2009;6(6):343–352. [] []
  50. Anderson B, Switzer NJ, Almamar A, Shi X, Birch DW, Karmali S. The impact of laparoscopic sleeve gastrectomy on plasma ghrelin levels: a systematic review. Obes Surg. 2013;23(9):1476–1480. [] []
  51. Groschl M, Uhr M, Kraus T. Evaluation of the comparability of commercial ghrelin assays. Clin Chem. 2004;50(2):457–458. []
  52. An antagonist is a substance which interferes with or inhibits the physiological action of another. []
  53. Molecular and Cellular Endocrinology
    Volume 340, Issue 1, 20 June 2011, Pages 26-28. Molecular and Cellular Endocrinology. Review. Ghrelin in Type 2 diabetes mellitus and metabolic syndrome. []
  54. Abdemur A, Slone J, Berho M, Gianos M, Szomstein S, Rosenthal RJ. Morphology, localization, and patterns of ghrelin-producing cells in stomachs of a morbidly obese population. Surg Laparosc Endosc Percutan Tech. 2014;24(2):122–126. []
  55. Vincent RP, le Roux CW. Changes in gut hormones after bariatric surgery. Clin Endocrinol (Oxf) 2008;69(2):173–179. []
  56. ResearchGate. The role of gastrointestinal hormones in the pathogenesis of obesity and Type 2 diabetes. May 2014. []
  57. Adipogenesis is the formation of adipocytes (fat cells) from undifferentiated fibroblasts (preadipocytes). Fibroblasts are cells that are responsible for producing connective tissues in the body. []
  58. Circulating Ghrelin Levels Are Decreased in Human Obesity. Matthias Tschöp, Christian Weyer, P. Antonio Tataranni, Viswanath Devanarayan, Eric Ravussin, Mark L. Heiman. Diabetes 2001 Apr; 50(4): 707-709. [] []
  59. Downregulation is the process of reducing or suppressing a response to a stimulus. In this case, it’s a reduction in a cellular responses to ghrelin molecules due to changes in the number of activity of receptors. []
  60. Growth hormone is released from the pituitary gland to cause growth in children and affects bone density, lipid metabolism, and muscle in children and adults, stimulating amino acid uptake and protein synthesis in muscle and other tissues. Because a major role of growth hormone is to to stimulate the liver and other tissues to secrete IGF-1, this can be a problem if too much IGF-1 is produced in adults. Due to its insulin-like properties, IGF-1 can have serious and potentially fatal health effects including: diabetic (hypoglycaemic) coma, heart palpitations (tachycardia), facial nerve pain or paralysis (Bells Palsy), swelling of the hands, and so forth. []
  61. Maccario M, Grottoli S, Procopio M, Oleandri SE, Rossetto R, Gauna C, Arvat E, Ghigo E: The GH/IGF-I axis in obesity: influence of neuroendocrine and metabolic factors. Int J Obes Relat Metab Disord (Suppl. 2):96–99, 2000 []
  62. Hypoadiponectinaemia is characterised by low plasma adiponectin levels – a protein hormone that is produced by fat cells. Its physiological effects include the reduction of inflammation and atherogenesis (the formation of fatty deposits in the arteries) and enhancement of the response of cells to insulin. []
  63. Hyperleptinaemia is the presence of a higher than normal amount of leptin in the bloodstream. []
  64. S. Savastano, C. Di Somma, L. Barrea, A. Colao, The complex relationship between obesity and the somatropic axis: the long and winding road. Growth Horm. IGF Res. 24, 221–226. 2014. []
  65. Lipolysis is the breakdown of lipids and involves hydrolysis of triglycerides into glycerol and free fatty acids. It mainly occurs in adipose tissue, and is used to mobilise stored energy during fasting or exercise. []
  66. Truncal adiposity refers to obesity – fat retention – around the trunk of the body. []
  67. M.E. Molitch, D.R. Clemmons, S. Malozowski, G.R. Merriam, M.L. Vance, Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1587–1609. 2011. []
  68. Positive energy balance occurs when the intake of food is greater than the output of work (as in muscular or secretory activity). The result is that the body stores extra food as fats. Negative energy balance occurs when the body draws on stored fat to provide energy for work. []
  69. Anabolism is a process a process that involves the synthesis of complex molecules from simpler molecules. These processes produce growth and differentiation of cells and increases in body size. Examples of anabolic processes include the growth and mineralisation of bone and increases in muscle mass. []
  70. Catabolism is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidised to release energy or used in other anabolic reactions. []
  71. Negative energy balance is when energy demands exceed caloric supply – the opposite of positive energy balance. []
  72. A.A. Sakharova, J.F. Horowitz, S. Surya, N. Goldenberg, M.P. Harber, K. Symons, A. Barkan, Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting. J. Clin. Endocrinol. Metab. 93, 2755–2759. 2008. []
  73. Endocrine. June 2015, Volume 49, Issue 2, pp 304–306. Growth hormone deficiency in patients with obesity. Roberto Salvatori. []
  74. Ghrelin and growth hormone: Story in reverse. Ralf M. Nass, Bruce D. Gaylinn, Alan D. Rogol, and Michael O. Thorner. PNAS May 11, 2010 107 (19) 8501-8502. []
  75. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346(21):1623–1630. []
  76. Geloneze B, Tambascia MA, Pilla VF, Geloneze SR, Repetto EM, Pareja JC. Ghrelin: a gut-brain hormone: effect of gastric bypass surgery. Obes Surg. 2003;13(1):17–22. []
  77. Can The UK Government Really Combat Child Obesity? []
  78. England’s Obesity Hotspots []
  79. Vegan Pregnancy & Parenting []
  80. Bliss Points, Pleasure Traps & Wholefood Plant-Based Diets []
  81. Malabsorption occurs when the small intestine can’t absorb enough of certain nutrients and fluids – including macronutrients – proteins, carbohydrates, and fats – and micronutrients – vitamins and minerals – or both []
  82. relating to the body fluids, especially with regard to immune responses involving antibodies in body fluids as distinct from cells []
  83. National Task Force on the Prevention Treatment of Obesity Overweight, obesity, and health risk. Arch Intern Med. 2000;160(7):898–904. []
  84. Roux-en-y gastric bypass (RYGB) – from César Roux, the surgeon who first described it – a form of anastomosis – an anastomosis is a connection or opening between two things that are normally diverging or branching, such as between blood vessels, leaf veins, or streams – involving a division of the small intestine, resulting in a Y-shaped configuration []
  85. Sleeve Gastrectomy (SG) – a surgical weight-loss procedure in which the stomach is reduced to about 15% of its original size, by surgical removal of a large portion of the stomach along the greater curvature. []
  86. Liou JM, Lin JT, Lee WJ, Wang HP, Lee YC, Chiu HM, Wu MS. The serial changes of ghrelin and leptin levels and their relations to weight loss after laparoscopic minigastric bypass surgery. Obes Surg. 2008;18(1):84–89. []
  87. The distal small intestine is the part furthest from the stomach – the ileum. []
  88. Morbid Obesity Solution: A Long-Term Plant-Based Case Study. 24 Jan 2017. []
  89. ResearchGate. Serum ghrelin level is associated with cardiovascular risk score. Romanian journal of internal medicine. 53(2):140-5 · September 2015. []
  90. Aging Cell. 2017 Aug;16(4):859-869. doi: 10.1111/acel.12618. Epub 2017 Jun 6. Deletion of ghrelin prevents aging-associated obesity and muscle dysfunction without affecting longevity. Guillory B1, Chen JA, Patel S, Luo J, Splenser A, Mody A, Ding M, Baghaie S, Anderson B, Iankova B, Halder T, Hernandez Y, Garcia JM. []
  91. Aging Cell. 2017 Aug; 16(4): 859–869. Deletion of ghrelin prevents aging‐associated obesity and muscle dysfunction without affecting longevity. Bobby Guillory et al. []
  92. Korek E, Krauss H, Gibas-Dorna M, Kupsz J, Piatek M, Piatek J. Fasting and postprandial levels of ghrelin, leptin and insulin in lean, obese and anorexic subjects. Prz Gastroenterol. 2013;8(6):383–389. []
  93. Mequinion M, Langlet F, Zgheib S, Dickson S, Dehouck B, Chauveau C, Viltart O. Ghrelin: central and peripheral implications in anorexia nervosa. Front Endocrinol (Lausanne) 2013;4:15. []
  94. Bulimia nervosa is an emotional disorder characterised by a distorted body image and an obsessive desire to lose weight, in which bouts of extreme overeating are followed by fasting or self-induced vomiting or purging. []
  95. Pathophysiology or physiopathology is the disordered physiological processes associated with disease or injury. []
  96. ResearchGate. Getting to the bottom of feeding behaviour: Who’s on top? Applied Physiology Nutrition and Metabolism 32(2):177-89 · May 2007. []
  97. Psychoneuroendocrinology. 2013 Mar. Dysfunctions of leptin, ghrelin, BDNF and endocannabinoids in eating disorders: beyond the homeostatic control of food intake. Monteleone P, Maj M. []
  98. Cell Metabolism. Volume 27, issue 1, P42-56, January 09, 2018. Overlapping Brain Circuits for Homeostatic and Hedonic Feeding. Mark A. Rossi, Garret D. Stuber. []
  99. Cheung CK, Wu JC. Role of ghrelin in the pathophysiology of gastrointestinal disease. Gut Liver. 2013;7(5):505–512. [] []
  100. Intra-peritoneal means within or administered through the peritoneum – the thin, transparent membrane that lines the walls of the abdominal (peritoneal) cavity and contains/encloses the abdominal organs such as the stomach and intestines []
  101. systemic administration is a route of administration of medication, nutrition or other substance into the circulatory system so that the entire body is affected. Administration can take place via either, 1. enteral, that is, via the gastrointestinal tract by oral, sublingual, oesophagus, stomach, small/large intestine and rectum, or by 2. parenteral administration, that is via means that bypass the gastrointestinal tract, mainly by intramuscular, subcutaneous, or intravenous injections that bypass skin and mucous membranes []
  102. Morphology is a branch of biology dealing with the study of the form and structure of organisms and their specific structural features. []
  103. The Ghrelin Axis—Does It Have an Appetite for Cancer Progression? Lisa K. Chopin Inge Seim Carina M. Walpole Adrian C. Herington. Endocrine Reviews, Volume 33, Issue 6, 1 December 2012, Pages 849–891. []
  104. radioimmunoassay is a technique for determining antibody levels by introducing an antigen (a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies) labelled with a radioisotope and measuring the subsequent radioactivity of the antibody component []
  105. Feigerlová E, Diene G, Conte-Auriol F, et al. Hyperghrelinemia precedes obesity in Prader-Willi syndrome. J Clin Endocrinol Metab 2008;93:2800-5. 10.1210/jc.2007-2138 []
  106. Gumus Balikcioglu P, Balikcioglu M, Muehlbauer MJ, et al. Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome. J Clin Endocrinol Metab 2015;100:3822-31. 10.1210/jc.2015-2503 []
  107. Am J Med Genet A. 2015 Jan;167A(1):69-79. doi: 10.1002/ajmg.a.36810. Epub 2014 Oct 29. Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia. Kweh FA, Miller JL, Sulsona CR, Wasserfall C, Atkinson M, Shuster JJ, Goldstone AP, Driscoll DJ. []
  108. Hyperghrelinaemia is, as the name suggests, an abnormally high level of ghrelin. []
  109. Transl Pediatr. 2017 Oct; 6(4): 274–285. Review of Prader-Willi syndrome: the endocrine approach. Ryan Heksch, Manmohan Kamboj, Kathryn Anglin,Kathryn Obrynba. []
  110. Surviving Starvation: The Ghrelin-Growth Hormone Axis. Part 1. []
  111. Surviving Starvation: The Ghrelin-Growth Hormone Axis. Part 2. []
  112. PYY (Peptide YY or peptide tyrosine tyrosine)  – a peptide that in humans is encoded by the PYY gene. Peptide YY is a short peptide released from cells in the ileum and colon. Soon after eating, and before food reaches the lower small intestine (ileum), PYY is secreted into the blood by cells lining the ileum and colon. []
  113. Nature. 2002 Aug 8;418(6898):650-4. Gut hormone PYY(3-36) physiologically inhibits food intake. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. []
  114. Braz J Med Biol Res. 2012 Jul; 45(7): 656–664. Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants. XiaFang Chen et al. []
  115. J Physiol. 2009 Jan 1; 587(Pt 1): 19–25. The role of peptide YY in appetite regulation and obesity. Efthimia Karra, Keval Chandarana, Rachel L Batterham. []
  116. J Geriatr Cardiol. 2017 May; 14(5): 369–374. A plant-based diet for overweight and obesity prevention and treatment. Gabrielle Turner-McGrievy, Trisha Mandes, and Anthony Crimarco. []
  117. CNS. Morbid Obesity Solution: A Long-Term Plant-Based Case Study. By Roberta Russell. January 24, 2017. []
  118. Obesity. []
  119. Toxic Hunger vs Real Hunger []

Leptin – The “Fat” Hormone?

If you’re not familiar with leptin, it’s certainly familiar with you. Known by various nicknames, such as the ‘satiety hormone’ or ‘fat hormone’, leptin plays a leading role in daily dietary dramas. But, is it more responsible for over-eating (hyperphagia) and obesity than mere lack of will-power?

What is leptin?

In healthy, non-obese individuals, the hormone leptin controls appetite. After you’ve eaten a meal, this anorexigenic (appetite-suppressing) hormone gets released by adipose tissue (fat cells) and acts on the hypothalamus in the brain to produce a feeling of satiety (fullness) which then suppresses the appetite and (hopefully) stops you from over-eating. It also speeds up your resting metabolism, thereby increasing energy expenditure. 1

This is a pretty sensible mechanism, from an evolutionary point of view, since it would help stop members of our species from getting too fat to be able to run away from sabre-toothed tigers. 2

On the other hand, there were perfectly good reasons why we might have needed to store up as much fat as possible –  to get through periods of famine, for instance. 3 This is why there are mechanisms, including the orexigenic (appetite-stimulating) hormone ghrelin (the “hunger hormone“) 4 , which act in the opposite direction from leptin, actively stimulating us to feel hungry5

However, evolution wasn’t so good at predicting the appearance of McDonald’s Whoppers or Chocolate Hobnobs. And this is where the problem starts with leptin. If we continue to eat the ‘wrong’ foods, the brain doesn’t realise we’ve actually had enough to eat.

Before looking into a bit more detail about why leptin might not be doing its job properly – evident by the widespread increase in obesity – it’s worth mentioning that other mechanism supposed to help us moderate food intake – namely, stretch receptors in the stomach 6 . If these are supposed to activate as the stomach expands in size, you can see from the above graphic that high-calorie/low-bulk foods will not stretch the stomach as much as low-calorie/high-bulk foods – that is, plant foods which are high in fibre content.

Such foods (mostly processed with high levels of sugar, saturated fat and salt) tend to be high in calories but low in nutrients (such as fibre, vitamins, minerals and phytonutrients). 7 . This is where we come across the differences between toxic hunger and real hunger, as discussed in a previous blog 8 . It’s called “toxic” because it can end up causing us to chronically over-eat and become obese, resulting in all the nasty associated problems like type 2 diabetes, heart disease and various cancers.

Leptin – Animal-Eaters vs Plant-Eaters

So, turning back to leptin, a recent study 9 took a small number of healthy women from three different dietary groups: omnivores, lacto-ovo-vegetarians, and vegans to see if there were any difference in leptin levels between them. What they found was in line with previous studies 10 11 12 , namely: “…people who adopted a vegetarian dietary pattern had lower plasma levels of leptin when compared to the meat consumers.” The mean plasma leptin levels were:

  • omnivores – 7.45 ng/ml
  • lacto-ovo-vegetarians – 3.87 ng/ml
  • vegans – 2.89 ng/ml

Leptin & Obesity

It’s well-established that meat-eaters are more likely than plant-eaters to become obese 13 14 . So, does this mean that meat-eaters don’t have enough leptin to inform their brains that they have eaten enough, and that plant-eaters have too much leptin? Oddly enough, quite the reverse.

Leptin Insensitivity/Resistance

What’s actually happening is that the abundance of swollen fat cells produce so much leptin that the hypothalamus starts to become insensitive and eventually resistant to leptin’s action. Thus, the brain keeps telling the obese individual “You’re still hungry!“. Eating plant-based diets – ideally WFPB diets, since vegan diets can still lead to obesity if they contain loads of junk food 15 – does not result in such fat storage in the body and, hence, leptin continues to do its job without the body getting “fed up of it”…

You’ve probably already drawn a parallel here with leptin resistance/insensitivity – namely, to type 2 diabetes. By definition, T2D is a condition which transitions through a stage where the pancreas still pumps plenty of insulin into the bloodstream, but cells become resistant/insensitive to it 16 .

It’s similar to how taste buds become insensitive to salt and sugar, how one can develop tolerance for cigarettes or alcohol, even though the body is silently screaming.

Do I Need To Increase Leptin levels?

Perhaps the more appropriate question should be “How do I make my body more sensitive to the already high levels of leptin in my body?”

The simplest and healthiest way is likely to be through changing to a plant-based diet. Not only is this likely to clear up any existing problem with leptin resistance, it will also help to reverse a huge range of diseases – including obesity 17 , type 2 diabetes 18 , cardiovascular disease 19 , and even many cancers 20 .

Final thoughts

The above brief analysis has suggested that, A. leptin works best within non-obese bodies and, B. that non-obese bodies are more likely to be inhabited by plant-eaters than by meat-eaters.

We also know that plant-eaters are less likely than omnivores to suffer from metabolic syndrome –  a complex of conditions in which triglycerides, total cholesterol, low-density lipoprotein (LDL), blood glucose, blood pressure, waist circumference, and body mass index (BMI) are all increased to seriously unhealthy levels21 .

It’s The Fat!

And much of the problem is simply to do with the amount of fat within the body – not that we grow more fat cells, since we actually retain a reasonably constant number of fat cells throughout adult life 22 , rather the fat cells we have can grow and grow until they’re so stuffed full that they leach fat back into the bloodstream without us even needing to consume any dietary fat –  a process known as “reintoxication” 23 Yuk!

So What About Will-Power?

It’s so easy to think that overweight/obese individuals lack sufficient will-power. However, it may be more likely that they are simply acting in accordance with what their brain is telling them or, rather, what their brain is failing to tell them.

How Do I Know If I’m Leptin Resistant?

It may sound too simple, but – just look in the mirror or see if you can grab a handful of fat around the middle of your body. Basically, there’s a really strong chance that leptin is not doing its job inside you if you are overweight.

How Do I Reverse Leptin Resistance?

I keep hammering away at this…but, all the evidence strongly suggests that the healthiest, most natural and sustainable diet for weight loss, general disease-resistance and healthy longevity is a wholefood plant-based diet24 25 . It’s also probably the healthiest for the rest of life on Earth, too 26 .

How about having a go at the short quiz below?

Leptin & Diet

(All answers are contained in the article.)


Where is leptin produced in the body? 


Ghrelin ........... appetite.


Leptin resistance cannot happen if there is plenty of leptin in the bloodstream. True/False?

4. What's perhaps the best way of increasing the effectiveness of leptin?
5. What conditions are known to be involved in metabolic syndrome?


  1. Waugh, Anne; Grant, Allison. Ross & Wilson Anatomy and Physiology in Health and Illness E-Book (p. 284). Elsevier Health Sciences. Kindle Edition. []
  2. The evolution of body fatness: trading off disease and predation risk. John R. Speakman. []
  3. A Nonadaptive Scenario Explaining the Genetic Predisposition to Obesity: The “Predation Release” Hypothesis. Literature Review. Cell Metabolism 6(1):5-12 · August 2007. []
  4. Ghrelin is the primary hunger hormone. It’s released from your stomach (with smaller amounts being released by the small intestine, pancreas and brain) into the blood and to the brain to stimulate hunger to alert you that you’re hungry. It has many functions throughout your body besides hunger. It also functions within the pleasure/reward centre of the brain, and plays a role in memory formation, immune function, and even sleep. []
  5. Curr Opin Clin Nutr Metab Care. 2013 Nov; 16(6): 619–624. Ghrelin: much more than a hunger hormone. Geetali Pradhan, Susan L. Samson, and Yuxiang Sun. []
  6. Paintal, A. S. (1954). A study of gastric stretch receptors. Their role in the peripheral mechanism of satiation of hunger and thirst. The Journal of Physiology, 126(2), 255–270. []
  7. Health = Nutrient Intake ÷ Calories []
  8. Toxic Hunger vs Real Hunger []
  9. Association between different types of plant-based diets and leptin levels in healthy volunteers. Gogga P, Śliwińska A, Aleksandrowicz-Wrona E, Małgorzewicz S. Acta Biochim Pol. 2019 Feb 15. doi: 10.18388/abp.2018_2725. []
  10. AmbroszkiewiczJ,Laskowska-Klita T,Klemarczyk W (2004) Low se-rum leptin concentration in vegetarian prepubertal children. Rocz Akad Med Bialymst 49: 103–105. []
  11. AmbroszkiewiczJ,Klemarczyk W,Gajewska J,Chełchowska M,Ro-wicka G, Ołtarzewski M, Laskowska-Klita T (2011) Serum concen-tration of adipocytokines in prepubertal vegetarian and omnivorous children. Med Wieku Rozwoj 15: 326–334 []
  12. Kim MH, Bae YJ (2015) Comparative study of serum leptin and insu-lin resistance levels betweenKorean postmenopausalvegetarianandnon-vegetarian women. Clin Nutr Res 4: 175–181. []
  13. Int J Obes (Lond). 2009 Jun; 33(6): 621–628. Meat consumption is associated with obesity and central obesity among US adults. Y Wang and MA Beydoun. []
  14. Vegetarian diets and childhood obesity prevention. Joan Sabaté Michelle Wien. The American Journal of Clinical Nutrition, Volume 91, Issue 5, 1 May 2010, Pages 1525S–1529S. []
  15. Greggs’ Vegan Sausage Rolls – Why Veganism Can Fail []
  16. Every vampire needs an invitation []
  17. CNS: Morbid Obesity Solution: A Long-Term Plant-Based Case Study. Roberta Russell. January 24, 2017. []
  18. J Geriatr Cardiol. 2017 May; 14(5): 342–354. A plant-based diet for the prevention and treatment of type 2 diabetes. Michelle McMacken and Sapana Shah. []
  19. J Geriatr Cardiol. 2017 May; 14(5): 317–320. A plant-based diet and coronary artery disease: a mandate for effective therapy. Caldwell B Esselstyn. []
  20. Surely Foods Can’t Fight Cancer []
  21. RizzoNS,Sabaté J,Jaceldo-Siegl K,Fraser GE (2011) Vegetariandietary patterns are associated with a lower risk of metabolic syn-drome: the adventist health study 2. Diabetes Care 34: 1225–1227. []
  22. NIH RESEARCH MATTERS. May 12, 2008. Fat Cell Numbers in Teen Years Linger for a Lifetime. []
  23. Br J Pharmacol. 2009 Nov; 158(5): 1330–1337. Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure. N Gunasekaran et al. []
  24. Which Diets Work for Weight-Loss? []
  25. Vegetarian Diets and the Risk of Diabetes []
  26. A Sustainable Diet for Our Planet []

Vegan Burgers – Healthy & Yum Yum? Forget it!

If you count yourself among the one in three vegans choosing a plant-based diet for health reasons 1 , then think again before following the thronging crowds to pig out (if that’s not speciesist) on the growing range of vegan fast foods – particularly yummy burgers that try so hard to imitate those traditionally made from meat.

The article

A reader sent me an article, entitled “Vegan burgers can contain more saturated fat than TWO McDonald’s Big Macs” 2 , which basically expanded on what’s clear from the article’s title.

Saturated fat – what’s the problem?

Consuming even moderate quantities of saturated fat has been proven 3 4 5  to be a really dumb option – if, that is, you want to be healthy. Naturally, if you don’t care about your health and the length of your useful life, then eating foods with saturated fat – especially if they’re also accompanied by lots of sugar, oil, salt and cholesterol – will certainly titillate your taste buds, while, of course,  simultaneously totalling your ticker.

And it’s not just your heart that cringes when it sees those burgers or fatty patties approaching the hallowed doors of your intestinal tract. The following are just some of the conditions with strong links to saturated fat consumption 6 :

Oh, and I nearly forgot, also MS (Multiple Sclerosis), covered in detail in a previous blog 7 .

Surely vegan burgers can’t be that bad…they’re vegan!

This is the list of burgers mentioned in the article:

You’ll notice Marstons’ Moving Mountain’s B12 and Aldi’s  The Meat Free Butcher: Juicy Quarter Pounder vegan burgers each contain more saturated fat than a McDonald’s Big Mac, and the vegan All Bar One Beyond Burger has more than a standard McDonald’s hamburger. Only Iceland’s vegan No Bull Burger drops below the saturated fat content of McDonald’s meaty offerings.

What’s the recommended daily allowance of saturated fat?

The answer to this depends on whether you want to eat the recommended amount for normal people who end up having all the normal diseases. If so, then the UK government health recommendations 8 are that the average man aged 19-64 years should eat no more than 30 g of saturated fat a day, while the average woman aged 19-64 years should eat no more than 20 g of saturated fat a day. Less for people younger or older than this. Meanwhile, the US FDA recommendations9 are that less than 20 g per day should be eaten, based on a 2,000 calorie diet – higher or lower depending on calorie requirements.

However, if you want the hard truth about tolerable limits of saturated fat (or trans fats or cholesterol) the answer is that anything above zero is not tolerable. “The Institute of Medicine did not set upper limits for trans fat, saturated fat, and cholesterol because any intake level above zero increased bad cholesterol (LDL cholesterol).” 5 10

What’s the saturated fat in vegan burgers?

Usually it’s coconut oil – one of the few plant-derived foods that is not recommended at all as part of a WFPB diet. A previous blog 11 , entitled “Coconut Oil is ‘Pure Poison’ says Harvard Professor” dealt with this Frankenfood 12 in more detail.

Pause for a giggle

At the start of this Mirror online article about the dangers of processed vegan foods, it was rather ironic that the video-advert included was for another super-unhealthy ultra-processed food:

They just can’t stop themselves, can they?

Final thoughts

It’s no surprise that these ultra-processed 13 14 vegan burgers, and similar vegan fast foods, are modified in order to appeal to our vulnerable taste buds, in just the way that similar meat-based products are; but the fleeting buzz from all that fatty nonsense is always closely followed by a nasty sting. And whether you consciously feel it or not, the cells, tissues and organs within your body certainly do. You just have to look at some of the mass of research on dietary saturated fats, using brachial artery flow‐mediated dilation tests 15 16 17 18 19 20 21 22 , to see how much immediate damage is caused by consuming these foods.

Since coconut oil is 100% fat with 87% being saturated fat, my best advice to you is, if you come across a product that contains it, avoid it like the plague.

It gets repeated time and time again on this website, but the only way you can be absolutely certain you’re avoiding all these dietary pitfalls and food industry tricks is to eat the optimal diet for human health and longevity: a non-SOS WFPB diet.

Fancy a quick quiz?

Vegan Burgers

(All answers are contained in the article.)


Where is leptin produced in the body? 


Ghrelin ........... appetite.


Leptin resistance cannot happen if there is plenty of leptin in the bloodstream. True/False?

4. What's perhaps the best way of increasing the effectiveness of leptin?
5. What conditions are known to be involved in metabolic syndrome?


  1. Vegan Society: Why Go Vegan? []
  2. The Mirror: “Vegan burgers can contain more saturated fat than TWO McDonald’s Big Macs.”  13th February 2019. []
  3. Ann Nutr Metab. 2017 Apr; 70(1): 26–33. Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update. Joyce A. Nettleton, Ingeborg A. Brouwer, Johanna M. Geleijnse, and Gerard Hornstrad. []
  4. PLoS One. 2017; 12(11): e0186672. Health effects of saturated and trans-fatty acid intake in children and adolescents: Systematic review and meta-analysis. Lisa Te Morenga, Jason M. Montez, C. Mary Schooling, []
  5. Trumbo PR, Shimakawa T. Tolerable upper intake levels for trans fat, saturated fat, and cholesterol. Nutr Rev. 2011 May;69(5):270-8. doi: 10.1111/j.1753-4887.2011.00389.x. [] []
  6. Nutritionfacts: Saturated Fat. []
  7. Multiple Sclerosis & Saturated Fat []
  8. NHS Eat Well: How to eat less saturated fat. []
  9. US FDA: Saturated Fat. []
  10. Trans Fat, Saturated Fat, & Cholesterol: Tolerable Upper Intake of Zero. Michael Greger M.D. FACLM December 23rd, 2011 Volume 6. []
  11. Coconut Oil is ‘Pure Poison’ says Harvard Professor []
  12. Dr Fuhrman: Frankenfoods []
  13. Ultra-Processed Food & Cancer []
  14. All Ultra-Processed Foods Linked to Increased Cancer Links []
  15. Blood viscosity/tissue oxygenation & plant-based diets []
  16. Plotnick G. D., Corretti M. C., and Vogel R. A.. 1997. Effect of antioxidant vitamins on the transient impairment of endothelium—dependent brachial artery vasoactivity following a single high‐fat meal. JAMA 278:1682–1686. []
  17. Vogel R. A., Corretti M. C., and Plotnick G. D.. 1997. Effect of a single high‐fat meal on endothelial function in healthy subjects. Am. J. Cardiol. 79:350–354. []
  18. Bae J.‐H., Bassenge E., Kim K.‐B., Kim Y.‐N., Kim K.‐S., Lee H.‐J., et al. 2001. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis 155:517–523. []
  19. Tsai W.‐C., Li Y.‐H., Lin C.‐C., Chao T.‐H., and Chen J.‐H.. 2004. Effects of oxidative stress on endothelial function after a high‐fat meal. Clin. Sci. 106:315–319. []
  20. Padilla J., Harris R. A., Fly A. D., Rink L. D., and Wallace J. P.. 2006. The effect of acute exercise on endothelial function following a high‐fat meal. Eur. J. Appl. Physiol. 98:256–262. []
  21. Tucker W. J., Sawyer B. J., Jarrett C. L., Bhammar D. M., Ryder J. R., Angadi S. S., et al. 2018. High‐intensity interval exercise attenuates, but does not eliminate, endothelial dysfunction after a fast‐food meal. Am. J. Physiol. Heart Circ. Physiol. 314:H188–H194. []
  22. Physiol Rep. 2018 Sep; 6(18): e13867. Fast‐food meal reduces peripheral artery endothelial function but not cerebral vascular hypercapnic reactivity in healthy young men. Jordan C. Patik, Wesley J. Tucker, Bryon M. Curtis, Michael D. Nelson, Aida Nasirian, Suwon Park, Robert M. Brothers. []