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
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
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
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
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
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
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
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”
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
The answer may, again, be lurking in our genes — and also in
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
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
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
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
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
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
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
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.