You may have come across warnings about consuming foods high in nitrates and/or nitrites, with respect to both animal- and plant-based foods. But what does the science say? Whilst previous blogs have touched on this subject – specifically in relation to chewing vs juicing 1 and whether athletic performance is affected by nitrate consumption 2 – here, the subject of dietary nitrates and nitrites is covered in more depth, to provide some clarity on which foods are to be avoided and which are to be embraced.
Nitric Oxide – The Good Stuff
Really, this is all about a vital molecule called nitric oxide (with the chemical formula NO). In any list of the most important compounds within the human body, NO is right up there.
It’s so important because it gets involved in pretty much every single organ system within the body and has a central role as a major and powerful vasodilator. This means that it makes blood vessels wider – of immense importance in allowing the blood to flow without the heart having to strain.
There are a wide range of common diseases associated with insufficient NO, including:
- diabetes 3
- atherosclerosis 4
- cardiovascular disease 5
- stroke 6
- peripheral artery disease 7
- hyperlipidemia/hypercholesterolemia 8
- hypertension 9
- Alzheimer’s 10
- dementia 11
- depression 12
- psoriasis 13
- gout 14
- erectile dysfunction 15
- obstructive sleep apnea 16 17
The list goes on and on…really, it’s hard to over-estimate the importance of NO for human health.
But what have nitrates and nitrites got to do with nitric oxide?
Nitrates, Nitrites & Nitric Oxide
The above diagram 18 basically indicates that the body converts dietary nitrates to nitrites and then to NO (as well as to ammonia) 19 . During this process, an enzyme connected to the non-essential amino acid L-arginine (also just known as arginine) is required in order to produce NO from the nitrites. L-arginine is called ‘non-essential’ (or, more specifically, a ‘conditionally indispensable amino acid’) because, although it can be derived from foods, the body can also produce a certain amount of it. 20
L-arginine is found in many protein-containing foods, both animal- and plant-based 21 .
- Some animal foods high in L-arginine:
- turkey breast
- pork loin
- Some plant foods high in L-arginine:
- leafy green vegetables 22
- nuts & seeds (pumpkin seeds, sesame seeds, walnuts, almonds, pine nuts)
- legumes (soybeans, chickpeas, peanuts)
A problem with L-Arginine
Increasing age, smoking, high cholesterol, inflammation, dietary deficiencies and other factors can negatively affect the functioning of the enzyme required for this conversion of L-arginine to NO. And the problem of insufficient L-arginine is not solved by taking L-arginine supplements – indeed, L-arginine supplements have been shown, not only to be ineffective and even cause less NO to be produced 23 , but such supplements have led to increased mortality when given to patients who have had heart attacks :
“L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-arginine should not be recommended following acute myocardial infarction.” 24 .
So what do we need to do to ensure that we have optimal NO levels?
First – A Bit of NO History
In 1987, Bob Furchgott 25 was the first to propose that NO was the EDRF (endothelium-derived relaxing factor) – i.e. that NO was the stuff responsible for the observed dilation of blood vessels, as well as a range of other vital physiological processes. Thus, NO is a relative newcomer to pharmacology. However, its impact was so significant that Bob Furchgott and his two collaborators, Louis J Ignarro and Ferid Murad, received the Nobel Prize in Physiology for its discovery.
Since then, hundreds of thousands of papers have been published with reference to NO – both in respect of NO as the endothelium-derived relaxing factor, as well as the role of L-arginine in NO synthesis.
During the time since 1987, the significance of the L-arginine:NO pathway has increased considerably – in relation to both the importance and the range of physiological roles this pathway plays. Roles which include:
- maintenance of vascular tone
- neurotransmitter function regulation in both the central and peripheral nervous systems
- mediation of cellular defence
- interaction within mitochondrial systems to:
- regulate cell respiration, and
- augment generation of reactive oxygen species, thereby
- triggering mechanisms of cell survival or death 26
Nitrates, Nitrites & Cancer
During this time, and until fairly recently, there was a particular concern about a potential increase in cancer risk from dietary nitrates and nitrites. This concern was accompanied by (and perhaps, to some extent, based on) the mistaken belief that the enzyme responsible for synthesising L-arginine within the body was the only pathway to produce NO in humans.
However, it’s been shown that when we ingest dietary nitrate, bacteria in the oral saliva convert it to nitrite. This nitrite is then swallowed and gets further converted into NO within the stomach, blood vessels and tissues 27 28 .
Mouthwashes, Antibiotics, Spitting & NO
We’ve looked previously 29 at the important role played by the bacteria in our mouths (the oral microbiome), and how it differs between meat- and plant-eaters. It’s important to stress that these oral bacteria are absolutely essential for the production of NO from our foods. Indeed, they are vital for this process, since humans can’t convert dietary nitrate to nitrite – it’s the bacteria living in our mouths that do the conversion.
So, predictably enough, it’s been shown 30 31 that, if you kill these oral bacteria by using an antibacterial mouthwash or taking antibiotics, the production of NO from dietary nitrate can stop completely. Additionally, if you spit a lot, you can deplete the bacterial concentration in your mouth, and this has a significant effect on nitrate conversion 28 .
Antacids & NO
Stomach acid also provides another important step in the production of NO from dietary nitrate 32 . Therefore, reducing the concentration of stomach acid by taking certain medication, including antacids and acid-reducing medications (such as Losec 33 ) can also decrease NO production and, thus, diminish its protective benefits 27 .
Today, dietary nitrate is understood as a highly significant precursor to NO in a dose-dependent manner 34 . So, the more nitrate consumed, the more NO becomes available in the body. There are, of course, upper limits, but these are only when nitrates are consumed in very large quantities, and this is unlikely (if even possible) from eating a WFPB diet – unless you’re unwise enough to take supplements.
Plant Nitrates vs Animal Nitrites
Plants are the primary source of dietary nitrates, while processed/cured meats are the primary sources of dietary nitrites (used as preservatives). It will comes as no surprise that the latter have a different impact on human health than the former.
Ingesting nitrates in plants increases NO and provides protective and healing benefits for a wide range of diseases characterised by insufficient NO (see the above list).
Ingesting nitrites in processed and cured meats (bacon, frankfurters, etc) can cause the nitrites to react with the amino acids, fat and haem iron already present within the meat, resulting in the formation of harmful substances before the meat is even cooked or eaten 35 36 .
A previous blog 37 went into more detail on how meat preservation methods have led to such foods being classified as Group 1 carcinogens, along with tobacco and asbestos.
When nitrites are consumed in animal foods, they can form nitrosamines 38 39 – one of the carcinogenic agents also present in cigarette smoke. Nitrosamines in processed meats (smoked, canned and preserved), as well as in grilled meats, are formed from nitrites in the absence of phytonutrients and antioxidants found in plant foods. “Just a few hot dogs may contain the carcinogenic nitrosamine load of a pack of cigarettes. In fact, just the smell of frying bacon even contains nitrosamines.” 40 Indeed, whenever you consume a diet high in animal foods (whether it’s processed meats or organically-produced eggs or dairy), you’re consuming nitrites in the absence of the phytochemicals and antioxidants that only plants contain.
Athletic Performance, NO & ATP
A previous blog, which looked at the effects of NO on athletes 2 , emphasised how important NO is for optimal athletic performance and recovery. Basically, dietary nitrate in plant foods increases the diameter of blood vessels, thereby increasing the volume of blood moved around the body with each heartbeat. This increases oxygen production to the muscles and thus increases muscle strength.
Another aspect of the relationship of NO to physical activity is ATP (adenosine triphosphate) . ATP is produced when the food we’ve eaten is metabolised in the presence of oxygen 41 . ATP is within every cell of our bodies and produces the energy we need to survive and function. The more oxygen within our red blood cells, the more ATP can be produced and, thereby, the more energy we can have available to us. However, it’s not just a matter of being an athlete with bigger lungs that facilitates this; recent research has shown 42 that dietary nitrate can actually decrease the amount of oxygen you need in order to produce sufficient ATP – that is, more work can be performed using the same amount of oxygen inhaled. Dietary intake of nitrates appears to be particularly effective for short-term, high-intensity rather than long-term, less intensive exercise.
Dietary Nitrate & Mitochondria
Furthermore, it appears 43 that dietary nitrate also improves the efficiency of our mitochondria (the energy-producing powerhouses within every human cell). Thus, increased nitrate consumption can have significance for athletes, people who live at high altitudes (where oxygen levels are lower in the air), and people with certain oxygen-limited diseases (e.g. lung disease or sleep disorders) .
Research has shown 44 particular benefits of nitrate consumption for those individuals who have lower fitness levels and/or impairments related to their muscles, heart and/or lungs, for instance in cases of non-ischaemic, dilated cardiomyopathy 45 , COPD 46 , heart failure 47 , and peripheral artery disease 48 .
Blood Pressure & NO
There are few conditions that cause more chronic illness and early deaths than hypertension. And the increase in the number of people affected is clearly associated with the increase in prevalence of the Western diet – richer in animal foods and processed junk than any time in human history.
And it’s all connected to the function of NO. Since two of NO’s major functions are to maintain the health of the single layer of delicate endothelial cells lining our blood vessels, and to ensure that our blood vessels dilate effectively, any reduction in production of NO is bound to result in damage to the integrity and flexibility of the vessels.
It’s a matter of simple equations:
- increased plant foods + (decreased animal/processed foods) = increased dietary nitrates
- increased dietary nitrates = increased nitrite production in the body
- increased nitrite production in the body = increased NO
- increased NO = decreased blood pressure
- decreased NO = increased blood pressure
Even in early studies with young, healthy individuals, it’s been shown 49 50 that dietary nitrate-consumption decreases their blood pressure. More recent research also demonstrates 51 52 53 how it can also decrease blood pressure in those more at-risk populations who already have high blood pressure. One study 54 concluded: “an additional strategy, based on intake of nitrate-rich vegetables, may prove to be both cost-effective, affordable and favourable for a public health approach to hypertension.” Another study 55 showed how chronic OSA (obstructive sleep apnea) could be effectively treated by reducing blood pressure as a result of simply eating more dietary nitrates in plant-based foods. And research is starting to suggest 56 that brain disorders such as dementia, Alzheimer’s disease, etc may be helped by dietary nitrates helping to increase blood flow to the brain.
It took some time for scientists to be convinced that eating your veggies could really increase NO when other conventional therapies had continually failed to do so. But now, the sheer weight of research data supports this view – as one editor of an eminent journal stated 57 back in 2008: “Mother was right: eat your vegetables and do not spit!”
Long-Term vs Short-Term
As with most aspects of nutrition, doing the right thing for longer is more effective than doing it for shorter periods of time. This is no different with vegetable-consumption and NO production. It appears that the longer you eat a plant-based diet, the more beneficial the effects on your health. It makes sense, therefore, that transitioning to a life-long WFPB diet, rather than merely opting for a short period of relief from animal proteins (for instance, during Veganuary) and processed junk, is the way to enjoy maximum life-long benefits.
How Safe Is Dietary Nitrate?
Ingesting nitrates when they are inside vegetables is extremely safe, being that they are combined with fibre, antioxidants and phytochemicals. Having said this, infants under the age of three months should not be given dietary nitrates – that is, not fed vegetables 58 . This shouldn’t even be an issue since, as we saw in a highly-detailed previous blog on Vegan Pregnancy & Parenting 59 , all babies of this age should only be receiving breast milk or, if that is not available, appropriate formula milk.
Also, for those taking particular medications (including blood-thinning drugs like Warfarin), the high levels of vitamin K (phylloquinone) in green vegetables can be a potential issue, since vitamin K’s blood-clotting action can reduce the required actions of the prescribed drug. As Dr Greger says 60 : “In fact dark green leafies are so packed with vitamin K that if you’re on the drug coumadin (warfarin), a drug that works by poisoning vitamin K metabolism, you have to closely work with your physician to titrate the dose to your greens intake so as to not undermine the drug’s effectiveness!”
How To Increase Nitrate Intake
Although there is some variation in levels (depending on plant type and the quality of the soil used for growing), it’s important to understand that all whole plant foods contain nitrates. Whilst around 85% of nitrates will come from the plants you eat, around 15% is actually contained in the water you drink 61 .
Green, Leafy Veg
- rocket (arugula in the US)
- beetroot and rhubarb have moderate amounts
- carrots and other veg contain lesser amounts
USA & European Nitrate Consumption
Surveys of dietary habits in the US and Europe show 64 51 low levels of daily nitrate intake (~0.5-3 mmol/day), which is consistent with the low levels of vegetable consumption. All diets which tend to contain more vegetables (such as Japanese diets, the DASH diet, vegetarian and vegan diets), all show 65 a higher amount of nitrate intake (~20 mmol/day) than standard Western diets.
Regular & Sufficient Nitrates
The positive effects of dietary nitrate don’t last for ever. The peak effectiveness appears to be 28 at around three hours after consumption. There’s still some benefit after this point, but after 24 hours the effect of the nitrate is virtually nil. Thus, the ideal diet would consist of nitrate-rich foods being consumed at least a couple of times each day.
In terms of nitrate quantity, one study suggests 66 that 8.4-16.8 mmol/day produces the greatest improvement in NO utilisation (and, hence, in exercise performance), while 4.2 mmol/day produces little or no effect and anything above 16.8 mmol/day appears to achieve no additional benefits. The suggestion is that maximum benefit is achieved with ~10 mmol/day – quite manageable by eating a moderate amount of varied plant foods (green leafy veg, beetroot, rhubarb, etc). Exercise is also reported to increase NO production.
Whatever you may have heard to the contrary, the consistent scientific consensus is that green, leafy veg are one of the healthiest foods on the planet for humans, and many authorities maintain 67 68 28 that the NO-producing nitrates in those veg accounts for a lot of these health benefits. 69
Finally, how better to finish than a short video by Dr Michael Greger?
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- Special thanks to Conor Kerley PhD, writing on behalf of CNS, for his article “Nitric Oxide & Dietary Nitrate: Another Reason to Eat Your Vegetables”, December 13, 2017.