The Vegan Guide to Dietary Supplements: B12, Iron and More

Attracted to its low environmental impact and potential health benefits, more and more people are beginning to follow a vegan diet and lifestyle. Just a few months ago, John experimented with a vegan diet for a week and wrote a blog detailing favorable results. Many people will find benefit from going vegan for the short term, however, over the course of many months and years, nutrient deficiencies are a concern. As much as the Vegan community likes to claim otherwise, animal foods are the best source of many key nutrients. To be fair, going Vegan isn’t the only way to miss out on key nutrients, this is also an issue for many following an omnivorous diet. There are myriad resources out there helping to ensure Vegans follow a healthy diet, either through food choice or direct supplementation. Since this is Gene Food, my purpose today is to walk you through genetic differences that could make it harder, or easier, for some to go Vegan than for others. I’m going to have a look at key nutrients associated with a vegan diet, and see if there are any particular genetic “mutations” that might be of interest as well.

Potential dietary deficiencies

When I was writing this post I was of two minds about how best to split the SNPs of interest. I had thought to split by pathway, but the groupings were quite diverse and there was a lot of overlap. So instead I decided to focus on nutrient type. So the SNPs listed in the various sections below are related in deficiency, but may have widely different functions. Check out the specific gene pages for more info about each SNP.

Vitamins

Vitamins are fundamental to the proper functioning of the body, and vitamin deficiency is widespread throughout the population. While a lot of vitamin rich food sources may be off the table to vegans it is entirely possible to maintain a proper intake with correct diet choice and proper supplementation. But are there any specific genotypes that might prove harmful to those with a reduced vitamin intake?

Gene	SNP ID	Risk Allele	Science Score	Potential Deficiency
BCO1	rs12934922	T	5	Vitamin A
	rs7501331	T	5	Vitamin A
PEMT	rs7946	A	8	Choline
MTRR	rs1801394	G	6	Vitamin B12
MTHFR	rs1801133	T	10	Vitamin B2
CYP2R1	rs10741657	G	8	Vitamin D
	rs10500804	G	5	Vitamin D
	rs2060793	G	4	Vitamin D
GC	rs2282679	C	8	Vitamin D
GPX4	rs713041	T	6	Selenium
GPX1	rs1050450	T	9	Selenium
SOD3	rs1799895	G	8	Zinc
SOD2	rs4880	T	10	Iron
NOS3	rs1800779	G	6	Iron
	rs1799983	T	6	Iron
	rs1800783	A	5	Iron

As you can see in the table above we’ve got three groups of SNPs associated with a lack of vitamin A, B2 and B12 and D.

Vitamin D

Let’s start with vitamin D, CYP2R1, or cytochrome P450 2R1 to give it its even less catchy full name, is an enzyme which catalyzes the conversion of vitamin D, either from the diet or generated in the skin, into calcifediol which then circulates in the blood. Calcifediol can be converted to calcitriol in the kidneys, the bioactive form of vitamin D. The three SNPs in the table above are associated with a reduction in detected levels of calcifediol, with those carrying two copies of the risk ‘G’ allele of rs10741657 being at particular risk of developing vitamin D deficiency. Similarly, the risk ‘C’ allele of rs2282679 in the GC gene is also associated with a reduction in detected vitamin D levels. GC encodes for vitamin D binding protein which is responsible for shuttling active vitamin D around the circulatory system. Those carrying a single ‘C’ allele are reported to have a 10% reduction in the amount of circulating vitamin D, whereas those with two copies can see a 20% reduction. In both instances correction by supplementation is entirely possible, a normal intake of 10 micrograms of vitamin D per day is recommended to ensure good health, especially over winter when the short days can really impact on vitamin D production in the skin. Achieving this level of intake is difficult for anyone, but vegans may find it more difficult to source appropriate supplements. While vitamin D2 is always suitable for vegans, vitamin D3 is often derived from animal sources such as sheep’s wool, although vegan friendly lichen derivatives are available.

Vitamin A

Vitamin A is vital for a wide variety of functions including tissue development and repair, and as a fully formed vitamin it can only be sourced from animal products. John wrote a good post in the subject, which can be viewed here. However, many plants (carrots, squash and dark green vegetables) are rich in the vitamin A precursor beta-carotene which can be converted into vitamin A in the body. A key enzyme in this conversion is beta-carotene oxygenase 1, encoded for by the BCO1 gene, which catalyzes the oxidative cleavage of beta-carotene into two retinal molecules, the key first step in the conversion. Put simply, certain BCO1 genotypes will have a harder time getting sufficient levels of Vitamin D from plant sources alone. In the table above, two SNPs are listed which show reduced BCO1 function, although in the associated paper the researchers did not describe any association with any particular poor health outcomes. However, vegans who are likely have reduced vitamin A intake compared to omnivores, may be at increased risk of developing a deficiency. While it is entirely possible to tailor dietary intake to ensure a sufficient level of vitamin A, supplementation is to be encouraged if levels are low.

Vitamin B2 and B12

So onto the B vitamins, or as this category actually ends up being, the methylation group. We’ve covered MTHFR and MTRR extensively, with a major focus on the roles that the relevant B vitamins play in their activity. Luckily, due to the major role of these B vitamins in our body it is common to find fortified foods (many of which are vegan friendly) with which it is possible to achieve the required supplement intake. Importantly vitamin B12 intake should be spread throughout the day as smaller doses are more readily absorbed than a single large dose supplement. For example, for intakes under 1 microgram approximately 50% will be absorbed (0.5 microgram), but for large doses of over 1,000 micrograms only ~0.5% is absorbed (5 micrograms), in other words a lot of wasted intake.

Metals

Next onto metals, many of these will be well known to our vegan readers with iron and calcium deficiency well known as a potential issue.

Iron

Iron deficiency is thought to be the most common nutrient deficiency in the world, and although some animal products are perhaps the richest source, there are numerous iron rich vegan options available including lentils, chickpeas and other beans as well as tofu and many nuts and seeds. But what about at the genetic level, are there any genes which may be of specific interest in relation to iron? The three Nitric oxide synthase 3 (NOS3) SNPs listed are associated with an increased cardiovascular risk due to reduced enzyme activity. Nitric oxide (NO) can act as a vasodilator which when secreted diffuses across the surface of a blood vessel into the surrounding smooth muscle tissue causing it to relax. Furthermore, NO also inhibits the formation of clots within blood vessels by preventing platelets, the small cells found in blood which form clots, from binding and also prevents immune cells from sticking to the walls of blood vessels. So, it is great at reducing blood pressure and also the risk of clot formation. Iron is a key co-factor for NOS3 and is required for it to function, so ensuring a good iron intake is vital to maximize potential enzyme activity. This is especially true for the SNP rs1799983 which has a strong association with cardiovascular risk in women, given that women are often at greater risk of being iron deficient, carriers of the risk allele ‘T’ should take special care to ensure correct supplementation. John has covered SOD2 in a previous post, and shown how its antioxidant capacity is key in protecting against numerous diseases. As with NOS3 above, iron is a key co-factor for SOD2 required in order to function correctly. Interestingly NOS3 and SOD2 have been shown to be linked, with increased levels of NO correlating with increased expression of SOD2, so in this instance iron supplementation will likely be highly beneficial.

Selenium

Selenium is a key co-factor for many enzymes in our body, but here I’m interested in GPX1 and GPX4 in particular, while not especially limited in vegan diets it is commonly provided in all-in-one supplements.  These glutathione peroxidase enzymes play a major antioxidant role in our body protecting against oxidative damage, with selenium playing a key role. Interestingly for both the risk ‘T’ allele was actually associated with increased DNA damage following selenium supplementation. The science behind this unclear, but for those carrying the risk allele in either SNP care should be taken when sourcing supplements.

Zinc

As above zinc is a co-factor for many enzymes but is also thought to play a role in fighting infection which John covers in his previous post (also contains a warning about overdoing it). SOD3 follows on from SOD2 and GPX1 and 4 in being an antioxidant enzyme, and in this case,  it requires zinc to function correctly. Unlike SOD2 and GPX1 and 4 SOD3 is thought to act as an early defense mechanism preventing antioxidants from reaching delicate cells and tissues by being secreted into the blood. I’ve listed it here because it is undoubtedly relevant (vegans having the potential to be zinc deficient), but it got me thinking about the overall antioxidant capacity of vegans compared to omnivores. The last widespread study I could find was from 2000, and the authors summaries the findings rather nicely (R):

Compared with omnivores, vegetarians have significantly higher levels of antioxidant vitamins (vitamin C, vitamin E, and β-carotene) in the plasma or serum, but comparable or in some cases lower levels of antioxidant minerals (zinc, copper, and selenium).

They then go on to state that further research is required as the studies they assess are rather small. More recent studies focused on particular aspects however are more promising, with this 2017 paper describing a large benefit for those with rheumatic disorders, who began following a vegan diet, an affect which is attributed to the increased antioxidant capacity of the diet (R). So it seems that the potential scarcity of metals in the diet is offset by the increased vitamin intake, suggesting that proper metal supplementation could further improve antioxidant capacity.

Other Nutrients

The other nutrients section could in fact be renamed choline. Choline is a vital nutrient required throughout the body although it is particularly important in maintaining brain and liver health. Phosphatidylethanolamine N-Methyltransferase or PEMT is an enzyme which converts phosphatidylethanolamine (PE) into phosphatidylcholine (PC) in the liver. The eagle eyed amongst you will have spotted the highlighted choline, and indeed breakdown of PC is a major source of choline in tissues. The risk ‘A’ allele of rs7946 has been shown to be associated with a 30% reduction in PEMT activity and so a reduction in PC production. This reduction in activity has also been linked with an accumulation of dietary fat in the liver, although this aspect may of less concern for those following a vegan diet. Regardless, if PC levels are reduced then supplementation with choline should defiantly be considered to ensure a proper supply to the tissues. Again, beans to the rescue as these contain relatively high levels of choline and are vegan friendly.

Take home message

This post isn’t intended to debate the pros and cons of a vegan diet, rather it is supposed to serve to highlight genes and SNPs which may be of particular interest to vegans. Understanding you genetics, in conjunction with your actual metabolism, can be really powerful and allow you to target your dietary and supplementation choices correctly. Importantly, while the vegan diet may have the potential to be poorer than a balanced diet containing animal products, it is perfectly possible to correct this with diet choice and supplementation. Moreover, how many people who eat animal products can say that their diet is truly balanced?