The Vitamins

TL;DR. Thirteen compounds your body cannot make in adequate amounts and must obtain from food. Four are fat-soluble and can accumulate to toxic levels; nine are water-soluble and mostly cannot. The deficiencies that shaped history (scurvy, beriberi, pellagra, rickets) are largely solved by food supply and fortification, and the ones people genuinely run short of today are a much shorter list: vitamin D in high-latitude winters, B12 in vegans and older adults, folate before conception, and iron, which is a mineral but belongs in the same conversation. For everyone else, supplementation has repeatedly failed to show benefit in trials, and in a few notable cases has caused harm.

Key takeaways

• Fat-soluble (A, D, E, K) accumulate; water-soluble (C and the B group) are mostly excreted, with B6 the important exception, which causes nerve damage in excess.
• Vitamin D is the one supplement with a broad case in high-latitude populations, and even then the trial evidence for outcomes beyond bone health is weaker than the enthusiasm.
• B12 comes only from animal foods or fortification, is absorbed via a two-step mechanism that fails with age, and its deficiency causes irreversible nerve damage if missed.
• Folate before and during early pregnancy prevents neural tube defects. This is one of the strongest findings in nutrition and the basis of mandatory fortification in over 80 countries.
• Beta-carotene supplements increased lung cancer in smokers in two large trials. More is not safer.

The thirteen, at a glance

RDA values vary between countries; these are broadly the US/EU adult figures. "RAE" is retinol activity equivalents, "NE" niacin equivalents, "DFE" dietary folate equivalents: each accounts for different forms having different potency.

Fat-soluble: A, D, E, K

In short: Absorbed with dietary fat, stored in liver and fat tissue, and capable of accumulating to toxic levels.

Because these are stored, deficiency takes longer to develop and excess is a genuine risk. They also all require fat in the meal to be absorbed, which is why bile duct disease, pancreatic insufficiency, cystic fibrosis, and fat malabsorption produce combined deficiencies of all four.

Vitamin A

Comes in two forms that behave differently. Preformed vitamin A (retinol, retinyl esters) from animal foods is directly usable and is the form that causes toxicity. Provitamin A carotenoids (beta-carotene, alpha-carotene, beta-cryptoxanthin) from plants must be converted, and conversion is regulated and inefficient, which is why you cannot poison yourself with carrots. You can, however, turn orange: carotenoderma is a harmless yellow-orange discolouration of the palms and soles from very high carotene intake.

What it does: Retinal is the light-sensitive molecule in your retina; without it, night vision fails first. Retinoic acid regulates gene expression in epithelial tissue and immune cells.

Deficiency is the leading preventable cause of childhood blindness worldwide, and it also raises mortality from infection substantially. Vitamin A supplementation programmes in deficient populations are among the highest-return public health interventions available. Sequence: night blindness → dry eye (xerophthalmia) → Bitot's spots → corneal ulceration → irreversible blindness.

Toxicity is real and specific to the preformed form. Acute: headache, nausea, raised intracranial pressure. Chronic: liver damage, bone loss, hair loss, and, importantly, birth defects. This is why isotretinoin (a vitamin A derivative used for acne) requires strict pregnancy prevention, and why pregnant women are advised to avoid liver and liver products, which can contain enormous amounts.

Vitamin D

The one with the strongest general case for supplementation and the most oversold outcome claims.

It is not really a vitamin. It is a hormone precursor you make in your skin: UVB radiation converts 7-dehydrocholesterol to previtamin D3, which is hydroxylated in the liver to 25(OH)D (the form measured in blood tests) and then in the kidney to the active 1,25(OH)₂D.

What it does: raises calcium and phosphate absorption from the gut, which is essential for bone mineralisation. It also has receptors in most tissues including immune cells, which is the basis for the wider claims.

Why deficiency is so common:

• Latitude. Above roughly 37 degrees north or south, UVB is insufficient for synthesis for several winter months. In the UK, essentially no vitamin D is made from October to March.
• Skin pigmentation. Melanin absorbs UVB, so people with darker skin need substantially longer sun exposure for the same synthesis, which is why deficiency rates are much higher in dark-skinned populations at high latitudes.
• Indoor life, clothing, and sunscreen. SPF 30 correctly applied blocks most vitamin D synthesis, though in practice people apply too little for that to fully hold.
• Age. Skin synthesis declines substantially in older adults.
• Few food sources. Oily fish, egg yolks, liver, and fortified foods. It is genuinely hard to get enough from an unfortified diet.

What the evidence supports:

• Established: prevention and treatment of rickets and osteomalacia. This is not in doubt.
• Reasonable: fracture prevention in older adults, but mainly in combination with calcium and mainly in institutionalised or deficient populations. Trials in vitamin-D-replete community-dwelling adults have been largely negative.
• Weak or negative: the very large VITAL trial (over 25,000 participants, 2,000 IU/day) found no reduction in cancer incidence or cardiovascular events. Similar large trials have been negative for diabetes prevention, depression, and cognitive decline. Observational associations with almost every disease are abundant and are heavily confounded, because ill and inactive people go outside less.
• Respiratory infections: meta-analyses suggest a small protective effect, largest in people who were deficient and given daily rather than bolus dosing. Modest.

Practical position: in a high-latitude country, a daily supplement of 10 µg (400 IU) in winter, as the UK NHS advises for everyone, or 20 µg (800 IU) for older adults and those with darker skin or little sun exposure, is cheap, safe, and sensible. Doses above 100 µg (4,000 IU) daily long term are not advisable, and very high doses cause hypercalcaemia, kidney stones, and, paradoxically, in some trials, more falls and fractures. More is not better here.

Vitamin E

A group of eight compounds, of which alpha-tocopherol is the one humans retain. It is a lipid-soluble antioxidant protecting membrane fats from oxidation.

Deficiency is rare outside fat malabsorption conditions. And this is the vitamin with the clearest cautionary supplement history: high-dose vitamin E supplements have been associated with increased all-cause mortality in meta-analyses, and the SELECT trial found a statistically significant increase in prostate cancer in men taking 400 IU daily. Do not take high-dose vitamin E.

Vitamin K

K1 (phylloquinone) from green leafy vegetables is the main dietary form. K2 (menaquinones) comes from fermented foods (natto is by far the richest) and some animal products, and from gut bacteria.

Its job is to activate specific proteins by carboxylating them: clotting factors II, VII, IX, and X, and also osteocalcin in bone and matrix Gla protein in blood vessels.

Two practical points. Newborns are given vitamin K at birth because they are born with low stores and no gut flora, and haemorrhagic disease of the newborn, including intracranial bleeding, is devastating and entirely preventable. The evidence here is overwhelming and declining this injection is a genuinely bad decision.

And warfarin works by blocking vitamin K recycling, which is why people on warfarin are told to keep their green vegetable intake consistent rather than low. Sudden changes in intake destabilise the INR in either direction (Chapter 75).

Water-soluble: the B group and C

In short: Not stored to any great extent, so intake needs to be regular, and excess is mostly excreted, with a few exceptions.

Vitamin C

Humans, other primates, guinea pigs, and bats lost the enzyme to make it. Most other animals make their own.

What it does: it is an essential cofactor for the enzymes that hydroxylate proline and lysine in collagen, which is why deficiency causes connective tissue to fail. It is also a water-phase antioxidant and it dramatically enhances absorption of non-haem (plant) iron.

Scurvy is worth describing because it is the archetypal deficiency disease and the history is instructive. Collagen synthesis fails, so existing collagen is not replaced: bleeding gums, loose teeth, poor wound healing (old scars reopen), perifollicular haemorrhages, joint pain, and eventually death. It killed more sailors than combat during the age of sail. James Lind's 1747 shipboard experiment comparing six treatments in twelve sailors is a founding example of the controlled clinical trial, and the Royal Navy still took over forty years to adopt citrus routinely. Roughly 10 mg a day prevents it, which is about a sixth of an orange.

Does it prevent colds? This is the most-tested question in supplement history. The Cochrane review of over 29 trials is clear: routine supplementation does not reduce the incidence of colds in the general population. It does shorten duration slightly, by around 8 percent in adults and 14 percent in children, roughly half a day. The exception is people under extreme physical stress (marathon runners, soldiers in subarctic training), where supplementation roughly halved incidence. Linus Pauling, whose advocacy created the entire belief, was a brilliant chemist who was wrong about this.

Upper limit is 2,000 mg, above which osmotic diarrhoea and increased oxalate excretion (hence kidney stone risk in susceptible people) become issues.

Vitamin B12

The one that matters most for anyone eating a plant-based diet.

Only bacteria and archaea make B12. Animals get it by eating bacteria or bacteria-fed food, or from their own gut bacteria in ruminants. Plants contain essentially none. Fortified foods and supplements are made by bacterial fermentation.

Absorption is a two-stage relay and unusually fragile:

1. Stomach acid and pepsin release B12 from food protein.
2. It binds to haptocorrin from saliva.
3. Pancreatic enzymes release it in the duodenum.
4. It binds intrinsic factor, made by stomach parietal cells.
5. The complex is absorbed by a specific receptor in the terminal ileum.

Break any step and absorption fails. Hence deficiency in: pernicious anaemia (autoimmune destruction of parietal cells), gastric surgery, ileal disease or resection (Crohn's), and crucially atrophic gastritis, which affects a substantial proportion of adults over 60 and impairs the release of B12 from food while leaving supplement absorption intact. That last point is why B12 supplementation is often recommended for older adults regardless of diet.

Metformin reduces B12 absorption measurably, and long-term users should have levels checked. Proton pump inhibitors do the same, by removing the acid needed for the first step.

Deficiency produces megaloblastic anaemia and, separately, neurological damage: peripheral neuropathy, subacute combined degeneration of the spinal cord, cognitive impairment. The neurological damage can become irreversible if untreated, which is what makes this the most important vitamin deficiency to catch early.

Don't be confused: folate can mask B12 deficiency. High folate intake corrects the anaemia of B12 deficiency without touching the neurological damage, so the blood count looks normal while nerve damage progresses silently. This is the main argument raised against high-dose folic acid fortification, and it is why B12 status should be assessed rather than assumed when folate is high.

Liver stores are large, typically 2 to 5 mg against a daily need of about 2.4 µg, so deficiency after switching to a vegan diet may take 2 to 5 years to appear. This delay is exactly why it catches people out. Anyone eating a vegan diet needs a reliable B12 source, either a supplement or consistently fortified foods. This is not negotiable and it is the single most important supplementation fact in this book.

Folate (B9)

What it does: carries one-carbon units for DNA synthesis and methylation. Rapidly dividing cells need it most, which is why deficiency shows up in blood cells and in a developing embryo.

Neural tube defects. The neural tube closes by day 28 after conception, which is often before a woman knows she is pregnant. Adequate folate at that moment substantially reduces the risk of spina bifida and anencephaly. The MRC Vitamin Study of 1991 demonstrated a roughly 70 percent reduction in recurrence with supplementation, and it is one of the cleanest findings in nutritional science.

The public health consequence: over 80 countries mandate folic acid fortification of flour or grain, and neural tube defect rates fell sharply where it was implemented, by roughly 25 to 50 percent. The UK announced mandatory fortification of non-wholemeal wheat flour in 2021 after decades of debate. Recommended supplementation is 400 µg daily for anyone who could become pregnant, from before conception through the first trimester, and higher doses (typically 5 mg) for those with previous affected pregnancies, diabetes, obesity, or on certain anti-epileptic drugs.

Don't be confused: folate and folic acid are not the same molecule. Folate is the natural form in food; folic acid is the synthetic, more stable, more bioavailable form used in supplements and fortification. Folic acid must be reduced by the enzyme DHFR before use, and that step is slow in humans, which is why unmetabolised folic acid appears in blood at high intakes. Methylfolate supplements avoid this step and are useful for people with certain MTHFR gene variants, though the clinical significance of common MTHFR variants is more modest than supplement marketing implies.

The rest of the B group, briefly

Thiamine (B1). Deficiency causes beriberi: wet (heart failure) or dry (peripheral neuropathy). Historically caused by polished white rice, which removes the thiamine-rich bran, and the discovery that unpolished rice cured it was a founding moment for the whole vitamin concept. Today the important context is alcohol: chronic heavy drinking impairs absorption and depletes stores, and acute deficiency causes Wernicke's encephalopathy (confusion, eye movement abnormalities, ataxia), which if untreated progresses to Korsakoff's syndrome, a permanent and profound memory disorder. This is why intravenous thiamine is given before glucose to anyone with alcohol dependence presenting confused: giving glucose first consumes the last of the thiamine and can precipitate the disaster.

Riboflavin (B2). Deficiency causes cracks at the corners of the mouth, sore tongue, and eye symptoms. Notable trivia with a practical edge: it is bright yellow and the excess is excreted, which is why high-dose B supplements turn urine fluorescent yellow within hours. That is harmless, and it is not evidence the supplement is "working."

Niacin (B3). Deficiency causes pellagra: the four Ds, dermatitis (a distinctive sun-exposed rash), diarrhoea, dementia, and death. It devastated the American South in the early twentieth century, where a maize-based diet was the cause. The reason is elegant: maize contains niacin in a bound, unavailable form, and traditional Mesoamerican nixtamalisation (soaking maize in alkaline lime water) releases it. Cultures that adopted maize without adopting the processing got pellagra; those that kept the processing did not. Joseph Goldberger established the dietary cause in the 1910s against fierce resistance from those insisting it was infectious.

B6 (pyridoxine) is the water-soluble vitamin that is genuinely toxic in excess. Chronic intakes above roughly 100 to 200 mg daily cause sensory peripheral neuropathy: numbness, tingling, and unsteadiness, which may be only partially reversible. High-dose B6 supplements are sold widely for premenstrual symptoms and morning sickness, and this risk is under-communicated. Several countries have restricted maximum doses in supplements as a result.

Biotin (B7). Deficiency is rare, though it can be induced by eating large amounts of raw egg white, which contains avidin, a protein that binds biotin and blocks absorption (cooking denatures it). The important modern issue is different: high-dose biotin supplements, popular for hair and nails, interfere with many laboratory immunoassays, producing falsely high or low results for thyroid hormones and, dangerously, falsely low troponin, which is the test used to diagnose heart attacks. The FDA has issued specific safety communications about this. Tell your doctor if you take biotin.

Pantothenic acid (B5). Present in almost all foods, which is what its name means. Deficiency essentially does not occur.

Should you take a multivitamin?

In short: For most well-fed people, no measurable benefit has been shown; for specific groups, specific supplements have strong evidence.

The trial record for general multivitamin supplementation in well-nourished populations is consistently unimpressive. The US Preventive Services Task Force concluded in 2022 that there is insufficient evidence of benefit for cardiovascular disease or cancer prevention from multivitamins, and recommended against beta-carotene and vitamin E supplements specifically because of evidence of harm. Physicians' Health Study II found a small reduction in total cancer incidence with a daily multivitamin over 11 years, which is the most positive large result and is modest.

Meanwhile the cautionary results are notable:

• Beta-carotene: the CARET and ATBC trials both found increased lung cancer in smokers taking supplements. CARET was stopped early.
• Vitamin E: increased prostate cancer in SELECT.
• High-dose antioxidants may blunt some of the beneficial adaptations to exercise training, which is a small but well-replicated finding.
• Calcium supplements (not dietary calcium) have been associated with cardiovascular events in some analyses.

Where supplementation genuinely earns its place:

For everyone else, food remains the better delivery system, and not because of anything mystical. Food supplies vitamins in the forms, ratios, and matrices that absorption mechanisms evolved with, alongside fibre and the thousands of other compounds that isolated supplements do not contain.

The bottom line

• Thirteen vitamins: four fat-soluble that accumulate and can be toxic, nine water-soluble that mostly cannot, with B6 the notable exception.
• Vitamin D deserves supplementation in high-latitude winters, and the outcome claims beyond bone health have largely failed in large trials.
• B12 comes only from animal foods or fortification, and its deficiency causes nerve damage that can become permanent. Anyone eating vegan, and most older adults, need a source.
• Folic acid before conception prevents neural tube defects. This finding is as solid as nutrition gets and underpins fortification in over 80 countries.
• Multivitamins have repeatedly failed to show benefit in well-fed populations, and beta-carotene and high-dose vitamin E have shown harm. Target the specific gaps you actually have.

Sources and notes

Requirements, upper limits, and deficiency syndromes follow the US Institute of Medicine Dietary Reference Intakes, EFSA Dietary Reference Values, and the UK Scientific Advisory Committee on Nutrition reports. Vitamin D trials cited are VITAL (Manson et al., NEJM, 2019) and D2d; respiratory infection meta-analysis is Martineau et al., BMJ, 2017. Beta-carotene harm is the ATBC (1994) and CARET (Omenn et al., 1996) trials; vitamin E and prostate cancer is SELECT (Klein et al., JAMA, 2011). The Cochrane antioxidant supplement mortality review is Bjelakovic et al. Folic acid and neural tube defects is the MRC Vitamin Study, The Lancet, 1991, and the subsequent fortification literature. B12 absorption, atrophic gastritis, and metformin-associated deficiency follow standard haematology and the ADA standards of care. Vitamin C and colds is the Cochrane review by Hemila and Chalker. Pellagra history follows Goldberger's work and Kraut's biography. Thiamine, Wernicke, and the glucose-before-thiamine caution follow standard emergency medicine guidance. Biotin assay interference is the subject of an FDA safety communication, 2017 and 2019. The USPSTF multivitamin position is its 2022 recommendation statement.

Open questions. Optimal vitamin D status, as opposed to the level that prevents rickets, remains genuinely unsettled, and large trials have not supported the observational associations. Whether the unmetabolised folic acid seen at high fortification intakes matters clinically is unknown.

👉 Next: the minerals, where iron, calcium, iodine, and sodium each carry a different kind of trouble.