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

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. nutritionfacts.org. 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. nutritionfacts.org. 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. nutritionfacts.org. 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.


References

  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. nutritionfacts.org. 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. nutritionfacts.org. 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. https://ntp.niehs.nih.gov/ntp/roc/content/profiles/butylatedhydroxyanisole.pdf. []
  17. https://www.fda.gov/downloads/Food/GuidanceRegulation/FSMA/UCM517402.pdf. []
  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. nutritionfacts.org. 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…


References

  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

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  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 []
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  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. []
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  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. []
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  37. GOAT is essential for ghrelin-mediated elevation of GH, necessary to prevent death from severe calorie restriction through preservation of blood glucose levels. []
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  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 []
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  42. Intestinal mobility is the movements of the digestive system, and the transit of the contents within it. []
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  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. []
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  102. Morphology is a branch of biology dealing with the study of the form and structure of organisms and their specific structural features. []
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  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. Nutritionfacts.org: 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.)

1.

Where is leptin produced in the body? 

2.

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

3.

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?

References

  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.)

1.

Where is leptin produced in the body? 

2.

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

3.

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?

References

  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. []

All Ultra-Processed Foods Linked to Increased Cancer Links

A major 2018 prospective study 1 , involving 104,980 French participants, shows a shocking link between ultra-processed foods and cancer. And don’t think that this term ‘ultra-processed’ refers to foods that most of us are unlikely to eat – unless you eat an exclusively non-SOS WFPB diet, most people in our societies are most likely to be eating these foods on a regular basis.

At the risk of repeating  myself…

Whilst the press is treating this research as having just been released2 , a previous blog3 looked at this research when it was first published in February 2018 (maybe it takes this length of time for the mainstream media to catch up with such research findings). In any case, because the information is so important, it seems worthwhile reiterating some points, as well as processing some food definitions .

The Study

The BMJ study, entitled “Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort study“, looked for associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer. To do this, they followed a large number of individuals for over 8 years, getting a wide range of data from them and analysing the results to see if there was a convincing link between consumption of so-called ‘ultra-processed foods’ and various forms of cancer.

Study Results

And, yes, they did. They concluded:

In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer.

Pretty clear confirmation of a relationship although, of course, in any observational study, no matter how long and far-reaching, there’s always a question of whether a causal relationship exists between the two variables.

Irrespective of Dietary Habits

The relationship between 10% increase in ultra-processed food consumption and over 10% increased risk of developing various forms of cancer did not vary with diet. This means that, regardless of whether you’re a vegan, vegetarian, omnivore, or have a higher or lower ratio of particular macronutrients (carbs, fat or protein) in your diet, the risk remained statistically the same: anyone, no matter how healthy your diet, eating these ultra-processed foods appears to have their risk of cancer increased by the same percentage.

 The 4 Definitions of Processed

In the study, they define 4 groups of foods, as outlined by the NOVA Group 4 .

  1. a. Unprocessed or b. minimally-processed foods
  2. Processed culinary ingredients
  3. Processed foods
  4. Ultra-processed food and drink products

I’m going to explain the above 4 classifications in a fair bit of detail. I think this important since most of us are going to get confused by what differences exist between these groups. Indeed, most of only use two terms, “unprocessed” and “processed”, and even this is mostly done without being absolutely certain what we’re really talking about.

Group 1. Unprocessed or minimally processed foods

a. Unprocessed (or natural) foods are edible parts of plants (seeds, fruits, leaves, stems, roots) or of animals (muscle, offal, eggs, milk), and also fungi, algae and water, after separation from nature.

b. Minimally processed foods are natural foods altered by processes such as:

  • removal of inedible or unwanted parts
  • drying
  • crushing
  • grinding
  • fractioning 5
  • filtering
  • roasting
  • boiling
  • pasteurisation
  • refrigeration
  • freezing
  • placing in containers
  • vacuum-packaging
  • nonalcoholic fermentation

None of these processes adds substances such as salt, sugar, oils or fats to the original food.

The main purpose of the processes used in the production of group 1a. foods is to extend the life of unprocessed foods, allowing their storage for longer use, such as chilling, freezing, drying, and pasteurising.

Other purposes include facilitating or diversifying food preparation, such as:

  • removal of inedible parts
  • fractioning vegetables
  • crushing or grinding seeds
  • roasting coffee beans or tea leaves
  • fermentation of milk to make yoghurt

Foods included in Group 1:

  • fresh, squeezed, chilled, frozen, or dried fruits and leafy and root vegetables
  • grains such as brown, parboiled or white rice, corn cob or kernel, wheat berry or grain
  • legumes such as beans of all types, lentils, chickpeas
  • starchy roots and tubers such as potatoes and cassava, in bulk or packaged
  • fungi such as fresh or dried mushrooms
  • meat, poultry, fish and seafood, whole or in the form of steaks, fillets and other cuts, or chilled or frozen
  • eggs
  • milk, pasteurised or powdered
  • fresh or pasteurised fruit or vegetable juices without added sugar, sweeteners or flavours
  • grits, flakes or flour made from corn, wheat, oats, or cassava
  • pasta, couscous and polenta made with flours, flakes or grits and water
  • tree and ground nuts and other oil seeds without added salt or sugar
  • spices such as pepper, cloves and cinnamon
  • herbs such as thyme and mint, fresh or dried
  • plain yoghurt with no added sugar or artificial sweeteners added
  • tea, coffee, drinking water

Group 1 also includes foods made up from two or more items in this group:

  • dried mixed fruits
  • granola made from cereals, nuts and dried fruits with no added sugar, honey or oil
  • foods with vitamins and minerals added generally to replace nutrients lost during processing, such as wheat or corn flour fortified with iron or folic acid

Group 1 items may infrequently contain additives used to preserve the properties of the original food:

  • vacuum-packed vegetables with added anti-oxidants
  • ultra-pasteurised milk with added stabilisers.

Group 2 – Processed culinary ingredients

These are substances obtained directly from group 1 foods or from nature by processes such as:

  • pressing
  • refining
  • grinding
  • milling
  • spray drying

Purpose of processing –  to produce products that can be used in both home and restaurant kitchens to prepare, season and cook group 1 foods and to make with them varied and enjoyable hand-made dishes, soups and broths, breads, preserves, salads, drinks, desserts and other culinary preparations.

Group 2 items are rarely consumed in the absence of group 1 foods, for instance:

  • salt mined or from seawater
  • sugar and molasses obtained from cane or beet
  • honey extracted from combs
  • syrup from maple trees
  • vegetable oils crushed from olives or seeds
  • butter and lard obtained from milk and pork
  • starches extracted from corn and other plants

Products consisting of two group 2 items remain in this group, such as:

  • salted butter
  • group 2 items with added vitamins or minerals (e.g. iodised salt)
  • vinegar made by acetic fermentation of wine
  • some alcoholic drinks (see group 4)

Group 2 items may contain additives used to preserve the product’s original properties, such as:

  • vegetable oils with added anti-oxidants
  • cooking salt with added anti-humectants 6
  • vinegar with added preservatives that prevent microorganism proliferation

Group 3. – Processed foods

These are relatively simple products made by adding sugar, oil, salt or other group 2 substances to group 1 foods. Most processed foods have two or three ingredients.

Processes include various preservation or cooking methods, and, in the case of breads and cheese, non-alcoholic fermentation.

Main purpose of processed food manufacture is to increase durability of group 1 foods, or to modify or enhance their sensory qualities.

Typical examples of group 3 processed foods include:

  • canned or bottled vegetables
  • canned or bottled fruits and legumes
  • salted or sugared nuts and seeds
  • salted, cured, or smoked meats [including fish]
  • canned fish
  • fruits in syrup
  • cheeses
  • unpackaged freshly-made breads

Processed foods may contain additives used to preserve their original properties or to resist microbial contamination. For instance:

  • fruits in syrup with added anti-oxidants
  • dried salted meats with added preservatives
  • alcoholic drinks produced by fermentation of group 1 foods (such as beer, cider and wine)

Group 4. – Ultra-processed food and drink products

These are industrial formulations typically with five or more and usually many ingredients, including those also used in group 3 processed foods, such as:

  • sugar
  • oils
  • fats
  • salt
  • anti-oxidants
  • stabilisers
  • preservatives

Ingredients only found in group 4 ultra-processed products include:

  • substances not commonly used in culinary preparations
  • additives whose purpose is to imitate sensory qualities of group 1 foods
  • additives whose purpose is to imitate culinary preparations of group 1 foods
  • additives used to disguise undesirable sensory qualities of the final product

Group 1 foods are a small proportion of or are even absent from group 4 ultra-processed products.

Substances only found in ultra-processed products include:

  • some directly extracted from foods, for instance:
    • casein
    • lactose
    • whey
    • gluten
  • some derived from further processing of food constituents, for instance:
    • hydrogenated oils 7
    • hydrolysed proteins 8
    • soy protein isolate 9
    • maltodextrin 10
    • invert sugar 11
    • high fructose corn syrup 12

Classes of additive only found in ultra-processed products include:

  • dyes and other colours
  • colour stabilisers
  • flavours
  • flavour enhancers
  • non-sugar sweeteners
  • processing aids, such as:
    • carbonating agents
    • firming agents
    • bulking agents
    • anti-bulking agents
    • defoaming agents
    • anti-caking agents
    • glazing agents
    • emulsifiers 13
    • sequestrants 14
    • humectants

Several industrial processes with no domestic equivalents are used in the manufacture of group 4 ultra-processed products, such as  extrusion 15moulding and pre-processing for frying.

The main purpose of industrial ultra-processing is to create products that are ready to eat, to drink or to heat. Unfortunately, these will probably replace both unprocessed or minimally processed foods in the diet – the latter being naturally ready to consume, such as fruits and nuts, milk and water, and freshly prepared drinks, dishes, desserts and meals.

Common attributes of group 4 ultra-processed products are:

  • hyper-palatability
  • sophisticated and attractive packaging
  • multi-media and other aggressive marketing to children and adolescents
  • health claims
  • high profitability
  • branding/ownership by transnational corporations

Examples of typical group 4 ultra-processed products include:

  • carbonated drinks
  • sweet or savoury packaged snacks [including crisps – potato chips in the US]
  • ice-cream
  • chocolate
  • candies (confectionery)
  • mass-produced packaged breads and buns
  • margarines and spreads
  • cookies (biscuits)
  • pastries
  • cakes and cake mixes
  • breakfast ‘cereals’
  • ‘cereal’ and ‘energy’ bars
  • ‘energy’ drinks
  • milk drinks
  • ‘fruit’ yogurts
  • ‘fruit’ drinks
  • cocoa drinks
  • meat and chicken extracts
  • ‘instant’ sauces
  • infant formulas
  • follow-on milks
  • other baby products
  • ‘health’ and ‘slimming’ products, such as:
    • powdered meal substitutes
    • ‘fortified’ meal substitutes
  • many ready to heat products, including:
  • pre-prepared pies
  • pasta dishes
  • pizza dishes
  • poultry ‘nuggets’
  • fish ‘nuggets’ or ‘sticks’
  • sausages
  • burgers
  • hot dogs
  • other reconstituted meat products
  • powdered and packaged ‘instant’ soups
  • ‘instant’ noodles
  • powdered and ‘instant’ desserts

Group 4 foods also include any products made solely of group 1 or group 3 foods which also contain cosmetic or sensory intensifying additives, such as:

  • plain yoghurt with added artificial sweeteners
  • breads with added emulsifiers

Group 4 also includes any alcoholic drinks which are identified as foods which are produced by fermentation of group 1 foods followed by distillation of the resulting alcohol, such as:

  • whisky
  • gin
  • rum
  • vodka

Everything but group 4’s okay, then?

Short answer? No.

Adding single additives like salt 16 , sugar 17 , and oils 18 have detrimental effects on health. All animal foods are associated with serious health issues 19 , compared with plant foods 20 . Cured/smoked fish, in particular, though it’s in group 3, has been shown to be carcinogenic 21 .

It’s also worth noting that this is a survey from the country historically known to be the centre of culinary excellence – noted for its supposedly health Mediterranean diet 18 . It would be no surprise, then, that populations in other Western countries – particularly the UK and USA 22 – have considerably more consumption of ultra-processed foods.

All clear now?

If you’ve got all the food types, food combinations and preparation methods nice and sorted in your head, then you’re cleverer than most of us. Whilst some elements have been made clear by this research, there remains some lack of clarity about which items out of groups 1 to 3 might still cause adverse effects.

Perhaps, the only sure way to know that the foods you are eating offer optimal protection against developing cancer is to eat a non-SOS WFPB diet.  Foods on the plate that look remarkably similar to how they looked when they were first harvested.

Podcast by the authors

You may be interested in listing to a short podcast 23 , where two of the authors of the above study are interviewed by a representative from the BMJ (British Medical Journal):

Final thoughts

It would surprise me greatly if many people reading this could say with hand on heart that they never eat any of the above group 4 foods. They have become such a mainstay of our modern Western diets that they go largely unnoticed and accepted without question.

Are the scientists helping?

Have you ever heard anyone talking about ‘ultra-processed’ foods before? Of course not – we conventionally refer to group 4 foods as simply ‘processed foods’.

Whether the likes of McDonald’s Egg McMuffin or Walker’s Prawn-Flavoured Crisps will ever be referred to as ‘ultra-processed’ foods by the general population is, I think, unlikely. So, once again, there’ll be an unfortunate disconnect between the technical terms used in scientific reports and the terminology used ‘on the street’.

However, the study makes one thing certain: If you want to maintain optimal health and longevity, you’re not going to get it by eating the processed foods that most people eat, most days.

With a greater than 10% increase of an early (probably painful and humiliating) death from every 10% increase in the percentage of processed (group 4) foods we can’t resist stuffing into our mouths – what’s the difference between eating this junk or smoking a few cigarettes a day?

Finally, you may like to have a go at the quiz below.


Ultra-Processed Foods

(All answers are contained in the article.)

1.

Where is leptin produced in the body? 

2.

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

3.

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?

References

  1. BMJ. 2018 Feb 14;360:k322. doi: 10.1136/bmj.k322. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. Fiolet T, Srour B, Sellem L, Kesse-Guyot E, Allès B, Méjean C, Deschasaux M, Fassier P, Latino-Martel P, Beslay M, Hercberg S, Lavalette C, Monteiro CA, Julia C, Touvier M. []
  2. Daily Telegraph 13th February 2019: How to identify ‘ultra-processed’ foods – the grub that’s linked to death []
  3. Ultra-Processed Food & Cancer []
  4. NOVA Group: Food classification. Public health
    NOVA. The star shines bright. []
  5. “Fractioning” foods or, simply, “fractionation” is a separation process in which a certain quantity of a mixture (gas, solid, liquid, enzymes, suspension, or isotope) is divided during a phase transition, into a number of smaller quantities in which the composition varies according to a gradient. []
  6. An anti-humectant (or anti-humidity) product is a moisture blocker which aims to resist potential moisture intrusion. []
  7. Hydrogenated oils are oils treated with hydrogen. It is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic compounds.
  8. interesterified oils  ((Interesterified oils or fat is a type of oil where the fatty acids have been moved from one triglyceride molecule to another. This is generally done to modify the melting point, slow rancidification and create an oil more suitable for deep frying or making margarine with good taste and low saturated fat content. []
  9. Hydrolysed protein is a protein that has been at least partially hydrolysed or broken down into its component amino acids. While many means of achieving this exist, two of the most common methods are prolonged boiling in a strong acid or strong base (alkaline), or using an enzyme such as pancreatic protease to simulate the naturally occurring hydrolytic process, where hydrogen and oxygen molecules in water are separated using electricity. []
  10. Soy protein isolate is produced through a process called hexane extraction. The fats are separated from the soybean in a hexane bath. Hexane is a gasoline byproduct  and the USDA classifies it as a neurotoxin which they do not allow to be used in food defined as organic. Once the fats are removed from the soybean, it’s then soaked in an ethanol or an acidic bath to remove carbohydrates and any lingering flavour. []
  11. Maltodextrin is a polysaccharide that is used as a food additive. It is produced from starch by partial hydrolysis and is usually found as a white hygroscopic spray-dried powder. Maltodextrin is easily digestible, being absorbed as rapidly as glucose and might be either moderately sweet or almost flavourless. []
  12. Inverted sugar (also called inverted sugar syrup) is a mixture of two simple sugars – glucose and fructose. It’s made by heating sucrose with water. Sweeter than table sugar, the foods containing it can retain moisture and, thus, crystallise less easily. Bakers, who call it ‘invert syrup’, may use it more than other sweeteners. []
  13. Dangerous stuff: 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, Perez-Pozo SE, Lillo JL, Grases F, Schold JD, Kuwabara M, Sato Y, Hernando AA, Garcia G, Jensen T8, Rivard C, Sanchez-Lozada LG, Roncal C, Lanaspa MA. []
  14. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Benoit Chassaing, Omry Koren, Julia K. Goodrich, Angela C. Poole, Shanthi Srinivasan, Ruth E. Ley & Andrew T. Gewirtz. Nature volume 519, pages 92–96 05 March 2015. []
  15. A sequestrant is a food additive which improves the quality and stability of foods. A sequestrant forms chelate complexes with polyvalent metal ions, especially copper, iron and nickel, which can prevent the oxidation of the fats in the food. Sequestrants are a type of preservative. []
  16. Extrusion is is a process by which a set of mixed ingredients are forced through an opening in a perforated plate or die with a design specific to the food, and is then cut to a specified size by blades. []
  17. Don’t Be Fooled – Salt Can Kill You []
  18. Three Reasons Why Sugar May Make Us Ill []
  19. Olive Oil Injures Endothelial Cells [] []
  20. Animal Foods Are The Smoking Gun []
  21. Nutrients in Plant and Animal Foods []
  22. Food Processing & Preserving Causes Cancer []
  23. UK eats almost four times more packaged food than fresh. The Guardian. []
  24. BMJ talk medicine: “We don’t really know the impact of these products on our health”: Ultraprocessed food & cancer risk []

Seven Dates a Day Keeps Colon Cancer Away?

Surely dates taste far too nice to be good for us! Isn’t there a catch? Well, it appears research is pretty clear about whether or not eating seven dates a day is a healthy option. We’ll look specifically at whether such a sweet addition to the daily diet helps to protect against colon cancer. In addition, some other surprising potential benefits will also come under scrutiny.

Antioxidant content of sweeteners

Compared with other sweeteners, date sugar (a powder made simply from powdered dried dates) has the most antioxidants, as shown in the following chart 1 :

Other health claims for dates

One study 2 makes pretty wide claims about the benefits of dates for a whole range of diseases – although the research was based largely on experiments with rats:

Although there needs to be more research regarding several of the above claims before drawing final conclusions, there are at least two of the benefits mentioned for which there’s support from some compelling studies – namely, aiding relaxation during labour and delivery 3 4 5 6 7 and possessing an anti-tumour effect . Dr Greger has a couple of videos on the former (i.e. dates and pregnancy) 8 9 , if you’re interested. However, our main focus here is on the anti-tumour (anti-cancer) effects, particularly with regard to the colon.

Dates & the colon

Although this sounds like some 70’s Punk Band, dates seem to be seriously beneficial for the colon.

In several earlier blogs 10 11 12 13 , we looked at health issues related to the bacteria in our guts (variously referred to as ‘gut flora‘, ‘gut microbiome‘ or ‘gut microbiota‘ – technically, ‘microbiota’ refers to the microbes found in a specific environment, while ‘microbiome’ is the whole collection of microbial genomes in that environment.  In any case, the billions of bacteria living inside us seem to have astonishingly diverse and far-reaching influences on every aspect of human health – from psoriasis and MS to depression and fibromyalgia.

Central to the ability of the microbiota to do their best work for us, is the type of foods we consume – with prebiotics, such as fibre and polyphenols (a type of antioxidant phytonutrient), being really important to get the best out of these little chaps (and chapesses?). And, weirdly inappropriate gender allusion aside, it just so happens that dates contain lots of these prebiotics.

Dates in vitro 

Research 14 has shown the ability of dates (at least, in these in vitro tests), not only to increase the amount of ‘good’ bacteria, but also to kill off colon cancer cells. The researchers concluded: “…consumption of date fruits may enhance colon health by increasing beneficial bacterial growth and inhibiting the proliferation of colon cancer cells. This is an early suggestion that date intake by humans may aid in the maintenance of bowel health and even the reduction of colorectal cancer development.”

Dates in vivo

Of course, the latter were in vitro and not in vivo tests – that is, in a petri dish rather than in a dishy Peter (or Polly, for that matter). However, a subsequent randomised, controlled, cross-over, intervention study 15 , which looked for similar effects in actual human beings, found that consumption of seven dates for three weeks:

1. Significantly increases bowel movements and stool frequency

The additional fibre will play a big part here. Having regular (and easy!) bowel movements is, of course, a strong sign of good bowel health – helping to prevent constipation, diverticulosis (which can develop into diverticulitis), hiatal hernias, heartburn, GERD, etc. When eating a high fibre diet, two or three healthy bowel movements each day are quite normal. With enough fibre in the stool, you should be able to sit in any position and have a comfortable bowel movement 16 .

In terms of long-term ‘uncomfortable’ or infrequent bowel movements and the development of colon cancer, one study concludes: “Constipation was associated with a moderately increased risk of colorectal cancer.” 17 , while another study concludes: “Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation‐free patients. These risks increase with the severity of chronic constipation.” 18 .

Now, there is some debate about whether there’s a causal link between chronic constipation and colon cancer (also referred to as colorectal cancer or CRC, which covers the rectum as well as the colon).  But why take the chance?

2. Significantly reduces stool ammonia concentration

So what? Isn’t ammonia an alkaline? And previous blogs 19 20 have encouraged us to eat a more alkaline diet, even suggesting we use a litmus paper test to ensure we produce alkaline urine. So why wouldn’t it be a good thing to have alkaline poo?

Well, in overly simplistic terms, alkaline urine is good and alkaline poo is bad.

Back in 1981, a study 21 stated: “Considerable evidence suggests that the carcinogens or co-carcinogens responsible for the development of colorectal cancer are either bacterially degraded bile acids or cholesterol. It is proposed that a high colonic pH promotes co-carcinogen formation from these substances…

This potentially carcinogenic process is inhibited once the pH of stools drops below a pH of 6.5 – around the alkalinity of milk. The same study largely blames alkaline poo on a lack of vegetables in the diet, and recommends dietary changes that increase fibre content (i.e. eat more veggies), which gut bacteria will then break down to short-chain fatty acids (SCFA’s) and thereby help to neutralise the problem.

Following this, a 1982 population study 22 confirmed the above hypothesis, showing that those with a faecal pH of 8 or above (around the pH of eggs, by the way) were at particular risk of developing colon cancer.

A 2013 study 23 found that African Americans were 50-times more at risk of colon cancer then Native Africans, concluding: “Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids.

The importance of dietary fibre for the production of butyrate (and other SCFA’s such as propionate and acetate) was shown in previous blogs 24 25 , as was the importance of the metabolism of bile acids 26 in relation to alcohol-consumption.

The researchers continued: “In summary, our study supports the hypothesis that colon cancer risk is determined by the interaction between diet and gut microbiota 27 28 and that the higher risk in African Americans could be attributed to their chronically lower consumption of [soluble] fiber and resistant starch [insoluble fibre] and their higher consumption of dietary fat.” Furthermore, “The higher consumption of animal protein is one possible explanation for higher stool pH values in subjects on an omnivorous diet, as proteolytic putrefaction bacteria are able to increase stool pH by producing alkaline metabolites [such as ammonia].” 29

In one of his videos, “Testing Your Diet with Pee & Purple Cabbage” 30 , Dr Greger provides a clear explanation of why it is that we should be looking for purple poo and blue pee, when using his ‘red cabbage water down the loo’ technique!

3. Significant reduction in faecal genotoxicity

What this means is that eating those seven dates for just three weeks resulted in significantly less DNA-damage. This is really important, being that the inside protective walls of the colon are made up of DNA.

A 2015 study 31 looked in more detail at the the relationship between date-consumption and cancers. They did in vitro testing of whether or not dates (and they used a rather wide-range of different varieties) were able to kill off various cancer cells from common cancers, including:

  • stomach cancer
  • prostate cancers
  • colon cancer
  • breast cancer, and
  • lung cancer

They concluded: “…extracts from all 29 varieties of date fruits showed that it contained components than can act as reducing agents and free radical scavengers in cellular reactions in vivo…” It’s a well-accepted fact that free radicals are known to cause DNA-damage 32 , and that DNA-damage, in turn, is the major cause of cancer 33 .

“…Similarly, the inhibition of COX enzymes [enzymes responsible for prostanoid-formation] indicated that the extracts contain compounds that can inhibit the production of inflammation causing hormones such as prostaglandins and thromboxanes by preventing the formation of prostaglandin endoperoxide which then leads to the production of inflammatory intermediates…” We’ve seen before 34 how inflammation is responsible for considerable damage within the body – often leading to cancer-formation, and how plant-based diets are anti-inflammatory, while animal-based diets are pro-inflammatory.

…These results further support the health-benefits of date fruits over and above its nutritional value. The bioassay results also suggest that most varieties of date fruits studied provide similar levels of health benefits.

This may once again suggests just how interlinked everything is within our bodies, and provides additional support for a wholistic (that deals with the whole body) rather than a reductionist (one that deals with each cell, tissue, organ, or disease as relatively separate and unrelated entities) approach to human nutrition and general health. 35 We’re still relatively ignorant, not only about the true complexity and inter-relatedness of the nutrients we consume, but even about the sum total of nutrients that have not even been identified or named yet.

Naturally, the latter is an in vitro study, and more in vivo research is needed to establish any causal relationship between date-consumption and cancer-prevention/treatment. What was especially interesting in the latter results was that the positive effects were not just on the cancer cells normally coming into direct physical contact with the contents of our gastrointestinal tracts (that is, stomach and colon), but that cancer cells from other organs (prostate, breast and lung) were also killed by the date extract.

Final thoughts

In terms of constipation-avoidance, dates will, of course, only play a small part in alleviating or preventing this unpleasant and potentially dangerous condition. Eating a WFPB diet – including the seven daily dates – will ensure that you’re doing the best for the smooth-running within the plumbing “down there”, as my mother used to say…

Avoiding high levels of saturated fat and animal protein, while filling up on the fibre-rich plant foods, appears to be the way to ensure that what comes out of our bottoms falls on the right side of the pH scale. This is borne out by research 36 37  on plant-based diets and how their gut microbiome was populated by more health-beneficial bacteria species, such as Bifidobacterium and Lactobacillus, when compared with the typical omnivore Western diets. And such ‘good’ bacteria are responsible for releasing organic products such as lactic acid and acetic acid, which decrease pH value. So, once again, it’s the plant foods, including dates, of course, that keep it all above board down below.

If just seven dates a day for three weeks can reduce both free radicals and inflammation, what’s to be lost in making them a daily staple? I simply chop up seven dates and add them to my daily fruity-muesli breakfast – making sure there are no stones accidentally left lurking within, of course.

Finally, you may be interested in having a go at the little quiz below, covering aspects of this blog.


Seven Dates a Day

(All answers are contained in the article.)

1.

Where is leptin produced in the body? 

2.

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

3.

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?

References

  1. Manickavasagan A. “Dates as Potential Substitute for Added Sugar in Food.” Dates: Production, Processing, Food, and Medicinal Values. CRC Press, Boca Raton, FL. 2012;317-321. []
  2. Rahmani AH, Aly SM, Ali H, Babiker AY, Srikar S, Khan AA. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity. Int J Clin Exp Med. 2014;7(3):483-91. []
  3. Al-Kuran O, Al-Mehaisen L, Bawadi H, Beitawi S, Amarin Z. The effect of late pregnancy consumption of date fruit on labour and delivery. J Obstet Gynaecol. 2011;31(1):29-31. []
  4. Kordi M, Meybodi FA, Tara F, Nemati M, Shakeri MT. The Effect of Late Pregnancy Consumption of Date Fruit on Cervical Ripening in Nulliparous Women. JMRH. 2014;2:150-156. []
  5. Khadem N, Sharaphy A, Latifnejad R, Hammod N, Ibrahimzadeh S. Comparing the Efficacy of Dates and Oxytocin in the Management of Postpartum Hemorrhage. Shiraz E Med J. 2007;8(2):64-71. []
  6. Razali N, Mohd Nahwari SH, Sulaiman S, Hassan J. Date fruit consumption at term: Effect on length of gestation, labour and delivery. J Obstet Gynaecol. 2017;37(5):595-600. []
  7. Kordi M, Salek Nasiri N, Safarian M, Esmaili H, Shadjuo K. The Effect of Oral Honey- Date Syrup Intake during Labor on Labor Progress of Nulliparous Women. Iranian J Obstetr, Gynecol Infert. 2010;13(2):23-30. []
  8. Best Food for Late Pregnancy. NutritionFacts.org. Published on Oct 15, 2018 []
  9. Best Food for Labor & Delivery. Michael Greger M.D. FACLM October 17th, 2018 Volume 44 []
  10. Fibromyalgia, Probiotics & Gut Microbiota []
  11. Two Types of Gut Bacteria: Plant Eaters’ & Meat Eaters’ []
  12. Obstructive Sleep Apnea (OSA) & Gut Microbiota []
  13. Gut Microbiota & Depression []
  14. Eid N, Enani S, Walton G, et al. The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation. J Nutr Sci. 2014;3:e46. []
  15. Eid N, Osmanova H, Natchez C, et al. Impact of palm date consumption on microbiota growth and large intestinal health: a randomised, controlled, cross-over, human intervention study. Br J Nutr. 2015;114(8):1226-36. []
  16. Bowel Movements. Nutritionfacts topic summary contributed by Charlie. []
  17. Asian Pac J Cancer Prev. 2011;12(8):2025-30. Constipation and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Tashiro N1, Budhathoki S, Ohnaka K, Toyomura K, Kono S, Ueki T, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Maekawa T, Yasunami Y, Takenaka K, Ichimiya H, Terasaka R. []
  18. Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation. A. Guérin R. Mody B. Fok K. L. Lasch Z. Zhou E. Q. Wu W. Zhou N. J. Talley. First published: 15 May 2014. []
  19. Alkaline Diet – So What?! []
  20. Psoriasis & Eczema Cured by Alkaline Diet? Caution: Some Graphic Images []
  21. J R Thornton. High colonic pH promotes colorectal cancer. Lancet. 1981 May 16;1(8229):1081-3. []
  22. S L Malhotra. Faecal urobilinogen levels and pH of stools in population groups with different incidence of cancer of the colon, and their possible role in its aetiology. J R Soc Med. 1982 Sep;75(9):709-14. []
  23. J Ou, F Carbonero, E G Zoetendal, J P Delany, M Wang, K Newton, H R Gaskins, S J O’Keefe. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013 Jul;98(1):111-20. []
  24. Butyrate – Why Dietary Fibre is So Important []
  25. Oat Bran & UC []
  26. All alcohol in your drinks is ethanol []
  27. Dethlefsen L, Eckburg PB, Bik EM, Relman DA. Assembly of the human intestinal microbiota. Trends Ecol Evol 2006;21:517–23. []
  28. O’Keefe SJD. Nutrition and colonic health: the critical role of the microbiota. Curr Opin Gastroenterol 2008;24:51–8. []
  29. Stool pH & Colon Cancer. Michael Greger M.D. FACLM February 23rd, 2015 Volume 23. []
  30. Testing Your Diet with Pee & Purple Cabbage []
  31. Zhang CR, Aldosari SA, Vidyasagar PSPV, Shukla P, Nair MG. Health-benefits of date fruits produced in Saudi Arabia based on in vitro antioxidant, anti-inflammatory and human tumor cell proliferation inhibitory assays. Journal of the Saudi Society of Agricultural Sciences. 2017;16(3):287-293. []
  32. Free Radic Biol Med. 2002 Jun 1;32(11):1102-15. Free radical-induced damage to DNA: mechanisms and measurement. Dizdaroglu M1, Jaruga P, Birincioglu M, Rodriguez H. []
  33. ICR: DNA damage and cancer. []
  34. Where’s the beef? Look for the inflammation. []
  35. Wholism vs Reductionism – Not Just a War of Words []
  36. J Zimmer, B Lange, JS Frick, H Sauer, K Zimmermann, et al. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr. 2012 Jan;66(1):53-60. []
  37. J Maukonen, M Saarela. Human gut microbiota: does diet matter? Proc Nutr Soc. 2015 Feb;74(1):23-36. []

What Happens When You Eat a Bowl of Kellogg’s Frosties?

Further to recent blogs on breakfasts 1 and the ‘bliss point’ in processed foods 2 , I thought it would be interesting to take a more detailed look inside the body, just to see what actually happens when a highly processed sugary product, specifically Kellogg’s Frosties, meets the inside of a human body – touching on associated issues, ranging from insulin resistance and cellular respiration to diabesity and non-alcoholic fatty liver disease.

Grrreat for whom?

It’s quite true that such breakfast cereals are great for the manufacturer’s profit and loss account, but what’s their true cost in terms of human health?

In order to understand what happens to those sweet, crunchy morsels once they get into our bodies, we’ll need to delve into a bit of nutritional science. So here goes…

Frosties – ingredients & nutritional information

As you will see from the footnote below 3 , a 100 g of Frosties contains 87 g processed carbohydrates, 37 g of which is pure sugar (specifically, sucrose – a disaccharide consisting of one glucose and one fructose molecule). The carbohydrates are processed to remove nearly three quarters of the fibre contained in the original whole corn (also called maize) – 2 g/100 from 7-8 g/100 g in whole corn. This gives Frosties a glycaemic index (GI) of 51 compared to 100 for pure glucose 4 . To its credit, Frosties is at least fortified with several vitamins and doesn’t contain any palm oil.

From mouth to bloodstream

As soon as Frosties enter the mouth, the carbohydrate-digesting enzyme amylase produced in saliva starts to break down the sucrose into its two monosaccharides, glucose and fructose, and the lump of food in the mouth is then referred to as a ‘bolus’.

From the mouth, the bolus passes to the stomach, during which time it magically changes its name to ‘chyme’ – a pulpy acidic fluid consisting of gastric juices and partly-digested food.

From the stomach, the chyme passes into the first part of the small intestine, the duodenum.

A signal then passes to the pancreas for it to release pancreatic amylase along a duct and into the duodenum.

At this point, a number of enzymes have pretty much completed the digestion of the sugars and any starches, producing the end product of the monosaccharide, glucose.

The resulting glucose within the mixed contents of the intestine (the ‘lumen’) then passes through the wonderfully complex epithelial membrane and into the bloodstream through an absorption process called ‘active transport’.

Here comes the insulin – hopefully…

Once the glucose levels rise in the bloodstream, the beta cells of the islets of Langerhans within the pancreas detect this increase and release the hormone, insulin – in healthy individuals, that is.

The situation is different for those with type 1 diabetes (T1D), where the pancreas does not produce insulin (or only very small quantities).

For those with type 2 diabetes (T2D), the situation is not the same, since plenty of insulin may be released from the pancreas but, for reasons covered below, fails to do its job properly.

If blood glucose levels are too low, another hormone called glucagon is released into the bloodstream, this time from the alpha cells in the islets of Langerhans within the pancreas.

Glucagon’s function is to instruct the release of some glucose which has been stored as glycogen in the liver and muscle cells (a process called glycogenolysis).

This is just one of the wonderful examples of homeostasis – a continual balancing act occurring within our bodies every second of every day. Put simply:

  • when blood glucose levels rise above a certain level, the pancreas produces more insulin
  • when blood glucose levels fall below a certain level, insulin production stops and glucagon production starts

From blood to cell

In our scenario, the sugar in the Frosties has been converted into glucose and has ended up in the bloodstream. Insulin’s main job now is to get that glucose into the body’s cells. If it does so successfully – and this is the big IF when it comes to those with T2D – the glucose is oxidised in the cells (that is, the glucose combines chemically with oxygen) and becomes a source of energy. This intracellular energy-production process is known as ‘cellular respiration’.

Cellular respiration (also known as internal respiration) is a complex process, involving three metabolic pathways: glycolysis, the citric acid (Krebs) cycle, and oxidative phosphorylation; but the important result is that the glucose from our Frosties is converted into energy. This energy is in the form of ATP (adenosine triphosphate), known as the “molecular (or energy) currency” of intracellular energy transfer. This only takes place within cells,  mostly within the mitochondria (the ‘energy factories’) but also, to a lesser degree, within the cytoplasm of the cell. The product is the energy our bodies require for every function.

If there’s any excess glucose which is not required immediately, it will get stored as glycogen in the liver or skeletal muscles for future use (a process rather confusingly called glycogenesis – the reverse process to glycogenolysis).

If you’re interested in a little more detail on the process of carbohydrate metabolism not covered above, see the note 5 below.

Now comes the spike

If glycogen reserves in the liver are saturated, the excess glucose gets converted into fat for long-term storage in the adipose (fat) tissues – beneath the skin (subcutaneous fat), around internal organs (visceral fat) and in bone marrow (yellow bone marrow).

Because Frosties contain highly refined carbs, rather than the complex starchy carbs found in whole plants, the glucose is released very rapidly. Basically, the more processed the carbs, the quicker they end up as glucose in the bloodstream. Thus, the Frosties are likely to cause what is called an initial ‘insulin spike‘.

In the long term:

  • insulin spikes can cause serious and irreversible damage to organs, nerves, and blood vessels
  • there’s likely to be an excess of glucose produced as a result of eating such foods as Frosties – unless you’re running fast on a treadmill when you’re eating! This means that regular consumption may lead to increased body fat and all the health problems associated with that

In the short term:

  • the sudden hit of these simple carbs (the ‘sugar rush‘) is likely to upset the delicate balance in the blood sugar level and is known to cause some fluctuations in energy levels and mood over the following hours – which could leave the person irritable and tired as the ‘sugar crash‘ arrives and glucose levels settle back to normal
  • it’s also likely that the person will feel hungry again very soon, since they didn’t get enough of the other nutrients to sustain energy, like protein and fibre
  • while eating the Frosties, the person’s brain would have responded to the sugar by creating a surge of the “feel-good” brain chemicals dopamine and serotonin. This also happens with certain drugs, such as cocaine. In a similar way to a drug, the body craves more after the initial high. This is one of the reasons that it is very much easier to overeat simple carbs, while complex starchy carbs don’t have the same effect

When the spikes have burst the insulin bubble

Prediabetes 6 – arguably a disease in itself – usually takes a number of years to develop into full-blown T2D, where muscle and other cells stop responding to insulin. Known as insulin resistance, this condition causes blood sugar and insulin levels to stay high long after eating. The excessive demands made on the insulin-making cells can eventually wear them out so much that insulin production can eventually cease. 7

Insulin resistance & diabetes

Before pinning down what insulin resistance is, we probably need to be clear on just what diabetes is.

As far back as a 1927 study 8 , a clear link between diabetes and fat consumption was demonstrated. In this study, young, healthy people were split into two groups: half were put on a fat-rich diet, and the other half were put on a carb-rich diet. Within just two days, glucose intolerance rose alarmingly in the fat-rich group, with twice as much blood sugar as the carb-rich group. The same principle revealed in this study has been duplicated and confirmed ever since, namely:

  • as fat in the diet rises, blood sugar spikes rise

Why is this? As it happens, it took around seven decades before the answer could be provided and, thus, form the basis of the current understanding of the cause of T2D. In basic terms, fat in the cells blocks insulin from being able to usher glucose into the cells to be used as energy. As a result of this, the sugar stays in the bloodstream, eventually filling available organs and muscle cells with fat, and reaping havoc on the body as a whole.

Every vampire needs an invitation

“Prepare ye the way for the Lord”!

I think it was Dr Greger who drew the comparison between blood sugar (glucose) and vampires. Just as a vampire requires an invitation before entering private homes, glucose needs an invitation before it can enter our cells. Within our bodies, that invitation comes in the form of insulin.

When a cell requires additional energy, it binds to one of the insulin molecules passing by in the bloodstream and that molecule binds to a specific insulin receptor on the surface of the cell membrane. Once there, the insulin acts like a key, opening up a ‘gap’ in the cell membrane – through the release of a number of enzymes – so that glucose, also circulating in the bloodstream, can enter the cell. It’s important to understand that there’s no other way that glucose can enter the cell than through this insulin receptor.

Glucose (C6H12O6) is a large molecule with 6 carbon atoms. As such. it’s too big to get into the cell through simple diffusion. This is why it needs its own John the Baptist (insulin) to ‘prepare the way for the load‘. The term used for this is ‘facilitated diffusion‘ (also known as ‘facilitated transport’) and it happens down a concentration gradient – that is, it will only happen when there’s more glucose outside the particular cell than there is inside it. If the cell has sufficient glucose inside already, it will close up the insulin receptor and no more glucose will get inside, until more is required.

This form of glucose transport within our muscles is responsible for clearing around 85% of the glucose from our blood.

By the way, all of this is something a simplification of the whole process, of course. In actual fact, even the insulin receptor (one of many different types of cell receptors) has multiple additional roles in physiological processes within us.

The diagram below 9  gives a brief overview of this complexity (sometimes referred to as pleiotropy – where one gene affects other seemingly unrelated traits).

Insulin through its receptor affects multiple physiological processes in the organism (left) by increasing (green arrows) or decreasing (red arrows) various intracellular metabolic pathways (right).

Time to call the locksmith

All well and good, but if the pancreas doesn’t produce insulin (as in T1D) then our muscle cells don’t get any energy, no matter how much glucose is floating around in the bloodstream, because there’s no key (insulin) to open the lock (insulin receptor in the cell membrane). This is why sufferers of T1D have to have insulin injections (the locksmith), otherwise blood sugar levels would simply rise and rise and eventually result in death. A person with T1D will have to monitor their blood sugar levels very carefully if they’re in the habit of eating bowls of Frosties – a habit which would not be recommended by any medical expert.

When the fat hits the fan

But what about T2D, where there’s still plenty of insulin being released into the bloodstream from the pancreas – at least, until later stages of untreated/unreversed 10 diabetes? If our muscle cells are so full of intramyocellular lipids (fat stored as a result of less-than-ideal dietary habits, where sugary foods like Frosties and high-saturated fat products have been eaten over extended periods of time), the key won’t be able to open the lock – again, no matter how much insulin and glucose might be available. The result is similar to T1D: blood sugar levels can rise and rise11

Dr Greger explains this process in more detail in his video, “What Causes Insulin Resistance?” 12 .

Diabesity

The link between obesity and diabetes (so strong now that the term ‘diabesity’ 13 has been coined) can be explained by realising that the fat spilling into the bloodstream from fat cells in obese individuals can get lodged in the very muscle cells we’ve been talking about. This then leads to insulin resistance and the onset of T2D.

So, although Frosties contain very little fat (only 0.6%), if the person eating them is already obese, the blood glucose quickly resulting from their consumption will end up in the bloodstream and find that the muscle cells are already fully or partially blocked by the intracellular fat 14 . Some of the glucose will be stored as further fat deposits, while some will continue to circulate in the bloodstream.

Non-alcoholic fatty liver disease

In T2D, the pancreas has been pumping out more and more insulin in an effort to overcome the fat induced insulin resistance in muscle cells. Over time, these high blood insulin levels can lead to accumulation of fat in the liver – non-alcoholic fatty liver disease (NAPFD).

Before the final diagnosis of T2D, the liver will certainly be protesting, without its owner ever hearing its silent screams. But eventually, this fat build up in the liver will make it, too, resistant to insulin in the same way as it does with the muscles.

Breakfast & the liver

Between meals, a normal liver will constantly be turning its stores of glycogen into glucose, which it then pumps into the blood to keep the brain alive; and when we do eat breakfast, after a night without dietary intake, the insulin released from the meal should turn off liver glucose production. However, if there’s too much fat in the liver, it fails to respond to that breakfast signal.

The twin vicious cycles of diabetes 15

Cycle #1

The fatty liver continues pumping out glucose all day long, on top of whatever we’re eating. The pancreas responds to the high level of blood sugar by releasing more insulin, causing the liver to get fatter and fatter. Meanwhile, fatty muscles (i.e. muscle cells that have been stuffed with surplus fat), within the context of eating too many calories, leads to the fatty liver getting even fattier.

And this all starts before diabetes is even diagnosed. This is why it’s a mistake to under-estimate the danger of being prediabetic.

Cycle #2

Fatty liver can be fatal and, because our bodies do all they possibly can to keep us alive (in spite of the relentless pressure we may impose on them), the liver tries to offload the fat by dumping it back into the bloodstream in the form of VLDL (very low density lipoprotein). This then finds its way into the beta (or so-called eyelet) cells of the pancreas, making it into a fatty pancreas – thereby destroying the ability of the pancreas to produce insulin. Blood sugar levels go up and up, leading to hyperglycemia – damaging the vessels supplying blood to vital organs, increasing the risk of heart disease, stroke, kidney disease, vision loss and irreversible nerve damage, gangrene, amputations and, of course, death.

Thus, by looking at these two cycles, it’s possible to see how T2D diabetes develops and to understand how it is a condition of excess fat inside our organs.

Final thoughts

Just eating the odd bowl of Frosties isn’t, of course, going to lead to diabesity; but if we tell ourselves that eating such foods “isn’t really all that bad” (they are, after all, fortified with added vitamins and minerals!), then we’re also likely to justify eating a whole load of other processed foods. And it’s the combination of these fatty, sugary, salty, processed foods being eaten over extended periods of time that ends up causing serious diet-related diseases.

Another important aspect is that every time we choose such unhealthy foods, we establish habits and addictions that can keep us locked in to vicious cycles – starting with those silent screams within, but ending up with very apparent indications of harm that’s already been done.

I think I’ll give Mr Kellogg’s offerings a miss.

You may want to have a go at the brief quiz below…


Quick Quiz - Diabetes

(All answers are contained in the article.)

1.

Where is leptin produced in the body? 

2.

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

3.

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?

References

  1. Breakfast Confusion []
  2. Bliss Points, Pleasure Traps & Wholefood Plant-Based Diets []
  3.  Source: Waitrose. []
  4. GI of Frosties. []
  5. A little more information on carbohydrate metabolism: Not all cells in the body are the same in relation to their requirements for glucose and only glucose. Erythrocytes (red blood cells) and neurones (brain cells) can use only glucose for fuel. This means that the maintenance of blood glucose levels is vital to ensure the provision of a constant energy source to these cells.

    Most other cells can also use other sources of fuel (amino acids, fatty acids, glycerol and occasionally nucleic acid) in a process called gluconeogenesis.

    So, while some glucose is transported to the liver (to satisfy its own significant energy requirements), and some will be oxidised in other cells around the body, a certain level of glucose has to remain in the circulating blood to maintain the normal blood glucose of about 3.5– 8 mmol/ L (63– 144 mg/ 100 ml). If there is excess glucose above blood level requirements, insulin will convert it to the insoluble polysaccharide, glycogen, in the liver and in skeletal muscles.

    Glycogen is the main storage form of glucose in animal cells. In humans, most glycogen is found in the liver (10% of the liver mass), with muscles only containing a relatively low amount (1% of the muscle mass), and small amounts of glycogen also being stored in some glial cells in the brain.

    Inside cells, glycogen-formation is a means of storing carbohydrate without upsetting osmotic equilibrium. However, before it can be used to maintain blood levels or provide ATP, it has to be broken down again into its constituent glucose units.

    Liver glycogen stores constitute a store of glucose used for liver activity and to maintain the blood glucose level.

    Muscle glycogen stores provide glucose requirements of muscle activity.

    Glucagon isn’t the only hormone associated with the breakdown of glycogen to glucose, adrenaline (epinephrine) and thyroxine are are also involved. Naturally, if there is an excess of carbohydrate, above that required to maintain blood glucose level and glycogen stores in the tissues, it will be converted to fat and stored in the fat depots around the body.

    This is just a glimpse at the complex world of carb metabolism, and doesn’t even touch on the metabolism of the other two macronutrients, protein and fat. If you want to delve deeper into this subject, I can recommend the following introductory book: Ross & Wilson Anatomy and Physiology in Health and Illness. 2018 edn. Anne Waugh BSc(Hons) MSc CertEd SRN RNT PFHEA (Author), Allison Grant BSc PhD FHEA. []

  6. Dr Michael Greger Podcast – start at 6:30 mins – The Latest on Children’s Health. []
  7. Hocking S, Samocha-Bonet D, Milner K-L, Greenfield JR, Chisholm DJ. Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots. Endocr Rev. 2013 August; 34(4): 463-500. []
  8. J Shirley Sweeney. DIETARY FACTORS THAT INFLUENCE THE DEXTROSE TOLERANCE TEST A PRELIMINARY STUDY. JAMA Int Med, Dec, 1927, Vol 40, No. 6. []
  9. Endotext: The Insulin Receptor and Its Signal Transduction Network
    Pierre De Meyts, MD, PhD, F.A.C.E. []
  10. Diet Reverses Type 2 Diabetes – How Long Have We Known This? []
  11. Roden M. How free fatty acids inhibit glucose utilization in human skeletal muscle. News Physiol Sci. 2004; 19: 92-96. []
  12. What Causes Insulin Resistance by Michael Greger M.D. FACLM January 6th, 2017 Volume 33. []
  13. Diabesity Hardcover – 1 Oct 2004 by Francine R., MD Kaufman []
  14. Estadella D, da Penha Oller do Nasciment CM, Oyama LM, Ribeiro EB, et al. Lipotoxicity: effects of dietary saturated and transfatty acids. Mediators Inflamm. 2013: 137579. doi: 10.1155/2013/137579. Epub 2013 Jan 31. []
  15. Diabetes as a Disease of Fat Toxicity. Michael Greger M.D. FACLM April 8th, 2015 Volume 24 []