Debate about whether veganism is a healthy diet for humans or a fast track to deficiency has been raging since time immemorial (or at the very least, since the advent of Facebook comment sections).
The controversy is fueled by ardent claims from both sides of the fence: long-term vegans reporting good health (and insisting anyone who struggles must be “doing it wrong”), and ex-vegs recounting their gradual or rapid decline (in some cases, convinced the day will come when “successful” vegans confess it was all a ruse).
Luckily, science is nudging us closer to an understanding of why people respond differently to low- or no-animal-food diets — with a great deal of the answer rooted in genetics and gut health. No matter how nutritionally adequate a vegan diet looks on paper, metabolic variation can determine whether someone thrives or flounders when going meat-free and beyond.
1. Vitamin A Conversion
Vitamin A is a true rock star in the nutrient world. It helps maintain vision, supports the immune system, promotes healthy skin, assists in normal growth and development, and is vital for reproductive function — just to name a few of its many jobs (1).
Contrary to popular belief, plant foods don’t contain true vitamin A (known as retinol); instead, they contain vitamin A precursors, the most famous being beta-carotene. In the intestine and liver, beta-carotene is converted to vitamin A by the enzyme beta-carotene-15,15′-monoxygenase (BCMO1) — a process that, when running smoothly, lets us make retinol from plant foods like carrots and sweet potatoes.
(Animal foods, by contrast, supply vitamin A in the form of retinoids, which don’t require BCMO1 conversion.)
Here’s the bad news. Several gene mutations can slash BCMO1 activity and thwart carotenoid conversion, rendering plant foods inadequate as vitamin A sources. For example, two frequent polymorphisms in the BCMO1 gene (R267S and A379V) can collectively reduce beta-carotene conversion by 69% (2). A less common mutation (T170M) can reduce conversion by about 90% in people who carry two copies (3).
In all, about 45% of the population carry polymorphisms that make them “low responders” to beta-carotene (4).
Worse, a host of non-genetic factors can lower carotenoid conversion and absorption as well — including low thyroid function, compromised gut health, alcoholism, liver disease and zinc deficiency (5, 6, 7). If any of these get thrown into the poor-genetic-converter mix, the ability to produce retinol from plant foods can dwindle even further.
So, why isn’t such a widespread issue causing mass epidemics of vitamin A deficiency? Simple: in the Western world, carotenoids provide less than 30% of people’s vitamin A intake, whereas animal foods provide over 70% (8). An omnivorous BCMO1 mutant can generally skate by on vitamin A from animal sources, blissfully unaware of the carotenoid battle waging within.
But for those who eschew animal products, the effects of a dysfunctional BCMO1 gene will be obvious — and eventually detrimental. When poor converters go vegan, they can eat carrots until they’re orange in the face (literally!) without actually obtaining enough vitamin A for optimal health. Carotenoid levels simply rise (hypercarotenemia), while vitamin A status nosedives (hypovitaminosis A), leading to deficiency amidst seemingly adequate intake (3).
Even for low-converting vegetarians, the vitamin A content of dairy and eggs (which don’t hold a candle to meat products like liver — the vitamin A King of Kings) might not be enough to stave off deficiency, especially if absorption issues are also at play.
Not surprisingly, the consequences of inadequate vitamin A mirror the problems reported by some vegans and vegetarians. Thyroid dysfunction, night blindness and other vision issues, impaired immunity (more colds and infections) and problems with tooth enamel can all result from poor vitamin A status (9, 10, 11, 12).
Meanwhile, vegans with normal BCMO1 function — and who dine on plenty of carotenoid-rich fare — can generally produce enough vitamin A from plant foods to stay healthy.
Bottom Line: People who are efficient carotenoid converters can generally get enough vitamin A on vegan diets, but poor converters can become deficient even when their intake meets recommended levels.
2. Gut Microbiome and Vitamin K2
Our gut microbiome — the collection of organisms residing in the colon — performs a dizzying number of duties, ranging from nutrient synthesis to fiber fermentation to toxin neutralization (13).
There’s ample evidence that our gut microbiome is flexible, with bacterial populations shifting in response to diet, age and environment (13, 14). But a great deal of our resident microbes are also inherited or otherwise established from a young age.
For instance, higher levels of Bifidobacteria are associated with the gene for lactase persistence (indicating a genetic component to the microbiome), and babies born vaginally scoop up their first bundle of microbes in the birth canal — leading to bacterial compositions that differ over the long-term from C-section babies (15, 16).
In addition, trauma to the microbiome — such as a bacterial wipeout from antibiotics, chemotherapy or certain illnesses — can cause permanent changes to a once-healthy community of gut critters. There’s some evidence that certain bacterial populations never return to their former glory after antibiotic exposure, stabilizing instead at less abundant levels (17, 18, 19, 20, 21).
In other words, despite an overall adaptability of the gut microbiome, we might be “stuck” with certain features due to circumstances beyond our control.
So, why does this matter for vegans?
Our gut microbiome plays a huge role in how we respond to different foods and synthesize specific nutrients, and some microbial communities may be more veg-friendly than others.
For example, certain gut bacteria are needed for synthesizing vitamin K2 (menaquinone), a nutrient with unique benefits for skeletal health (including teeth), insulin sensitivity and cardiovascular health, as well as prostate and liver cancer prevention (22, 23, 24, 25, 26, 27, 28, 29, 30). The main K2-producers include certain Bacteroides species, Prevotella species, Escheria coli and Klebsiella pneumoniae, as well as some gram-positive, anaerobic, non-sporing microbes (31).
Unlike vitamin K1, which is abundant in leafy greens, vitamin K2 is found almost exclusively in animal foods — the main exception being a fermented soybean product called natto, which has a taste that can be euphemistically described as “acquired” (32).
Studies have demonstrated that full-spectrum antibiotic usage dramatically lowers levels of vitamin K2 in the body by obliterating the bacteria responsible for K2 synthesis (33). And one intervention trial found that when participants were put on a high-plant, low-meat (less than two ounces daily) diet, the main determinant of their fecal K2 levels was the proportion of Prevotella, Bacteroides and Escheria/Shigella species in their gut (34).
So, if someone’s microbiome is short on vitamin-K2-producing bacteria — whether from genetic factors, environment or antibiotic usage — and animal foods are removed from the equation, then vitamin K2 levels can sink to tragic levels. Although research on the topic is scant, this could feasibly rob vegans (and some vegetarians) of the many gifts K2 bestows — potentially contributing to dental problems, a greater risk of bone fractures and reduced protection against diabetes, cardiovascular disease and certain cancers.
Conversely, people with a robust, K2-synthesizing microbiome (or who otherwise identify as natto gourmands) might be able to obtain enough of this vitamin on a vegan diet.
Bottom Line: Vegans without enough bacteria for synthesizing vitamin K2 can face problems related to inadequate intake, including a higher risk of dental issues and chronic disease.
3. Amylase and Starch Tolerance
Although there are certainly exceptions, meat-free diets tend to be higher in carbohydrates than fully omnivorous ones (35, 36, 37). In fact, some of the most famous plant-based diets hover around the 80% carb mark (coming mostly from starchy grains, legumes and tubers), including the Pritikin Program, the Dean Ornish Program, the McDougall Program and Caldwell Esselstyn’s diet for heart disease reversal (38, 39, 40, 41).
While these diets have an impressive track record on the whole — Esselstyn’s program, for instance, effectively slashed cardiac events in those who diligently adhered — some people report less savory results after switching to high-starch vegan diets (42). Why the dramatic difference in response?
The answer may, again, be lurking in our genes — and also in our spit.
Human saliva contains alpha-amylase, an enzyme that lops starch molecules into simple sugars via hydrolysis. Depending on how many copies of the amylase-coding gene (AMY1) we carry, along with lifestyle factors like stress and circadian rhythms, amylase levels can range from “barely detectable” to 50% of the total protein in our saliva (43).
In general, people from starch-centric cultures (like the Japanese) tend to carry more AMY1 copies (and have higher levels of salivary amylase) than people from populations that historically relied more on fat and protein, pointing to a role of selective pressure (44). In other words, AMY1 patterns appear linked to the traditional diets of our ancestors.
Here’s why this matters: amylase production strongly influences how we metabolize starchy foods — and whether those foods send our blood sugar on a gravity-defying rollercoaster or on a more leisurely undulation. When people with low amylase consume starch (especially refined forms), they experience steeper, longer-lasting blood sugar spikes compared to folks with naturally high amylase levels (45).
Not surprisingly, low amylase producers have a heightened risk of metabolic syndrome and obesity when eating standard high-starch diets (46).
What does this mean for vegetarians and vegans?
Although the amylase issue is relevant to anyone with a mouth, plant-based diets centered on grains, legumes and tubers (like the aforementioned Pritikin, Ornish, McDougall and Esselstyn programs) are likely to bring any latent carb intolerance to the fore.
For low amylase producers, radically upping starch intake could have devastating consequences — potentially leading to poor blood sugar regulation, low satiation and weight gain. But for someone with the metabolic machinery to crank out plenty of amylase, handling a high-carb, plant-based diet might be a piece of cake.
Bottom Line: Salivary amylase levels influence how well (or how poorly) different people do on starchy vegan or vegetarian diets.
4. PEMT Activity and Choline
Although it hasn’t received as much media airtime as some other nutrients-du-jour (like omega-3 fatty acids and vitamin D), it’s no less important — choline deficiency is a major player in fatty liver disease, a skyrocketing problem in Westernized nations (48). Choline deficiency can also increase the risk of neurological conditions, heart disease and developmental problems in children (49).
In general, the most choline-abundant foods are animal products — with egg yolks and liver dominating the charts, and other meats and seafood also containing decent amounts. A wide variety of plant foods contain much more modest levels of choline (50).
Our bodies can also produce choline internally with the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which methylates a molecule of phosphatidylethanolamine (PE) into a molecule of phosphatidylcholine (PC) (51).
In many cases, the small amounts of choline offered by plant foods, combined with the choline synthesized through the PEMT pathway, can be enough to collectively meet our choline needs — no eggs or meat required.
But for vegans, it’s not always smooth sailing on the choline front.
First, despite efforts to establish adequate intake (AI) levels for choline, people’s individual requirements can vary tremendously — and what looks like enough choline on paper can still lead to deficiency. One trial found that 23% of male participants developed symptoms of choline deficiency when consuming the “adequate intake” of 550 mg per day (52).
Second, not everyone’s bodies are equally productive choline factories. Due to estrogen’s role in boosting PEMT activity, postmenopausal women (who have lower estrogen levels and stymied choline-synthesizing abilities) need to eat more choline than women who are still in their reproductive years (52).
And even more significantly, common mutations in folate pathways or in the PEMT gene can make low-choline diets downright hazardous (56). One study found that women carrying a MTHFD1 G1958A polymorphism (related to folate) were 15 times more susceptible to developing organ dysfunction on a low-choline diet (57).
Additional research shows that the rs12325817 polymorphism in the PEMT gene — found in about 75% of the population — significantly raises choline requirements, and people with the rs7946 polymorphism might need more choline in order to prevent fatty liver disease (58).
Although further research is needed, there’s also some evidence that the rs12676 polymorphism in the choline dehydrogenase (CHDH) gene makes people more susceptible to choline deficiency — meaning they need a higher dietary intake to stay healthy (59).
So, what does this mean for people who drop high-choline animal foods from their diet?
If someone has normal choline requirements and a fortunate assortment of genes, it’s possible to stay choline-replete on a vegan diet (and certainly as a vegetarian who eats eggs).
But for new or soon-to-be mothers, men or postmenopausal women with lower estrogen levels, as well as people with one of the many gene mutations that inflate choline requirements, plants alone might not supply enough of this critical nutrient. In those cases, going vegan could be the harbinger of muscle damage, cognitive problems, heart disease and increased buildup of fat in the liver.
Bottom Line: Variations in PEMT activity and individual choline requirements can determine whether someone can (or can’t) get enough choline on a vegan diet.
Take Home Message
So, what can we conclude from all this? When the right genetic (and microbial) elements are in place, vegan diets — supplemented with the requisite vitamin B12 —have a greater chance of meeting a person’s nutritional needs. But when issues with vitamin A conversion, gut microbiome makeup, amylase levels or choline requirements enter the picture, the odds of thriving as a vegan start to plummet.
This isn’t to say there aren’t vegans who really did “do it wrong” (case in point, a diet of potato chips and Pepsi qualifies as vegan), who used their diet to mask an eating disorder or who faced other circumstances that doomed their success from the start.
But science is increasingly supporting the idea that individual variation drives the human response to different diets. Some people are simply better equipped to glean what they need from plant foods — or produce what they need with the fabulous mechanics of the human body.