24.2 — Vitamins, Minerals and Deficiency Disease

In 1747, a Scottish naval surgeon called James Lind divided twelve sailors dying of scurvy into six pairs and gave each pair a different treatment: cider, vinegar, seawater, a spice paste, dilute sulphuric acid, or two oranges and a lemon.

The pair given citrus recovered within days. One returned to duty.

It was one of the first controlled clinical trials ever conducted, and it identified the cure for a disease that had killed more sailors than combat.

It took the Royal Navy 42 years to act on it.

And nobody knew what vitamin C was for another 180 years.

What a vitamin is

An organic compound the body needs in small amounts and cannot make — or cannot make enough of.

Which is why the definition is species-specific. Most animals make their own vitamin C. Humans, other primates, guinea pigs and bats carry a broken version of the gene for the final enzyme in the pathway (Chapter 3.6) — which is why we get scurvy and dogs do not.

Fat-soluble: A, D, E, K. Stored in the liver and fat, so deficiency takes longer to develop — and toxicity is possible.

Water-soluble: the B vitamins and C. Not stored to any great extent, so they need regular intake, and excess is mostly excreted — which is where the observation about expensive urine comes from.

B12 is the exception among the water-soluble vitamins: the liver stores several years' worth.

The vitamins

Vitamin A

Does: vision — it forms rhodopsin, the light-detecting pigment in the retina (Chapter 11.11); immune function; skin; and cell differentiation.

From: retinol in liver, dairy and eggs; and beta-carotene in orange and dark green vegetables, which the body converts.

Deficiency: night blindness first, then dryness of the eye surface, then corneal damage and blindness. Vitamin A deficiency remains a leading cause of preventable childhood blindness worldwide, and it also markedly increases death from infections such as measles. Supplementation programmes save a substantial number of lives.

Excess: liver damage, bone problems, and — critically — birth defects. High-dose retinol supplements and liver are avoided in pregnancy, and isotretinoin for acne requires strict pregnancy prevention for the same reason (Chapter 4.6).

Beta-carotene does not cause this, because conversion is regulated — excess simply turns the skin slightly orange, which is harmless.

And one important negative finding: beta-carotene supplements increased lung cancer in smokers in two large trials, which is the standard cautionary example against assuming a nutrient in a pill behaves like the nutrient in a carrot.

Vitamin D

Does: calcium and phosphate absorption from the gut, bone mineralisation, muscle function, and immune modulation (Chapter 12.3).

From: sunlight, primarily. UVB converts a cholesterol derivative in skin into vitamin D3. Also oily fish, egg yolk, and fortified foods.

And the reason deficiency is so common: at latitudes above roughly 37 degrees, sunlight in winter contains too little UVB to make any vitamin D at all. Darker skin needs considerably longer exposure, because melanin absorbs UVB. Older skin makes less. Sunscreen, clothing and indoor living all reduce it further.

Deficiency: rickets in children — soft bones, bowed legs, delayed growth. Osteomalacia in adults — bone pain, muscle weakness, and fractures. And low-grade deficiency is extremely common.

Supplementation: 10 micrograms (400 IU) daily is the standard recommendation in many countries during autumn and winter, and year-round for people with limited sun exposure, darker skin, or who are housebound.

And the honest note: vitamin D corrects bone disease reliably, and the large trials of supplementation in people who were not deficient failed to show benefit for cancer, cardiovascular disease or overall mortality. Correcting a deficiency helps. Taking more when you are not deficient does not appear to.

Toxicity is possible at very high doses, causing high calcium levels.

Vitamin E

An antioxidant protecting cell membranes. From vegetable oils, nuts and seeds.

Deficiency is rare except in fat malabsorption.

And high-dose supplements have been associated with increased mortality in meta-analyses, which is another entry on the list of antioxidant supplements that did not do what was expected.

Vitamin K

Does: activates clotting factors — the K is from the German Koagulation — and is needed for bone proteins (Chapter 7.1).

From: green leafy vegetables, and bacterial synthesis in the colon.

Deficiency: bleeding.

And newborns are given vitamin K at birth, because they are born with very low stores and gut bacteria have not yet colonised. Without it, a small number develop haemorrhagic disease of the newborn, including bleeding into the brain. It is one of the highest-value routine interventions in newborn care.

Warfarin works by blocking vitamin K, which is why consistency of intake matters on that drug (Chapter 22.7).

The B vitamins

B1 — thiamine. Energy metabolism.

Deficiency: beriberi — wet beriberi affecting the heart, dry beriberi affecting the nerves.

And Wernicke's encephalopathy — confusion, unsteadiness and eye movement abnormalities — most commonly in alcohol dependence (Chapter 20.10). Untreated it progresses to Korsakoff syndrome, with permanent, profound memory loss.

Which is why thiamine is given before glucose in a malnourished or alcohol-dependent patient, since glucose consumes the remaining thiamine and can precipitate it.

B2 — riboflavin. Energy metabolism. Deficiency causes cracks at the corners of the mouth and a sore tongue.

B3 — niacin. Deficiency causes pellagra: the four Ds — dermatitis in sun-exposed areas, diarrhoea, dementia and death. Historically endemic where maize was the staple, because the niacin in maize is bound and unavailable unless the grain is treated with alkali — a processing step traditional Mesoamerican cultures had discovered and which was not exported along with the crop.

B6 — pyridoxine. Amino acid metabolism, and neurotransmitter synthesis.

Unusual in that both deficiency and excess cause neuropathy — high-dose supplements over long periods cause sensory nerve damage (Chapter 20.6).

B9 — folate. DNA synthesis and cell division.

Deficiency causes megaloblastic anaemia, and — critically — neural tube defects in early pregnancy.

400 micrograms daily before conception and for the first 12 weeks prevents the majority of neural tube defects (Chapter 4.6). Higher doses for women with diabetes, on antiepileptics, with a high BMI, or with a previous affected pregnancy.

Because the neural tube closes by around day 28 — frequently before a pregnancy is known — supplementation must start before conception. This is why flour fortification programmes exist, and where implemented they have reduced neural tube defects substantially.

B12 — cobalamin. Nerve function, red cell production, DNA synthesis.

Only in animal foods and fortified products — which makes it the one supplement that is genuinely non-negotiable on a vegan diet.

Absorption requires intrinsic factor, made by the stomach (Chapter 9.2). Which is why deficiency occurs in pernicious anaemia, after stomach surgery, and with long-term proton pump inhibitors or metformin.

Deficiency causes: anaemia; and neurological damage — numbness, tingling, unsteadiness, memory problems and mood change.

And a crucial point: the neurological damage can occur without anaemia and can become permanent. High folate intake can also mask the anaemia while the nerve damage continues, which is why B12 is checked alongside folate.

Absorption falls with age, so deficiency is common in older adults.

Vitamin C

Does: collagen synthesis — specifically the hydroxylation of proline, which stabilises collagen's triple helix; iron absorption; and antioxidant function.

Deficiency: scurvy. Because collagen holds tissue together, failing collagen produces bleeding gums, loose teeth, poor wound healing, old wounds reopening, bruising, joint pain and, eventually, death.

And scurvy still occurs — in people with very restricted diets, in alcohol dependence, in isolated older people, and occasionally in children with extremely selective eating. It is diagnosed late because nobody expects it.

Prevented by a very small amount — around 10 mg a day prevents scurvy, and recommendations of 40 to 90 mg allow a comfortable margin.

On the common cold: large trials show that routine supplementation does not prevent colds in the general population. It shortens duration slightly — around 8 percent in adults — and there is evidence of prevention in people under extreme physical stress, such as marathon runners and soldiers in subarctic conditions. That is the honest picture, and it is less than the reputation.

The minerals

Iron.

Carries oxygen in haemoglobin (Chapter 7.1).

Two forms: haem iron from meat, absorbed at around 15 to 35 percent; and non-haem iron from plants, absorbed at 2 to 20 percent.

Absorption is increased by vitamin C, so pairing beans or spinach with peppers, tomatoes or citrus makes a real difference. Reduced by tea, coffee and calcium taken at the same time.

Deficiency is the commonest nutritional deficiency in the world, particularly in menstruating women, pregnancy, and children.

Symptoms: fatigue, pallor, breathlessness, poor concentration, brittle nails, hair loss, and pica — craving non-food substances such as ice, which is a genuinely characteristic sign.

And in adults, unexplained iron deficiency needs investigating for a source of bleeding, because it can be the first sign of bowel cancer.

Excess is harmful — the body has no mechanism to excrete iron, which is why haemochromatosis causes organ damage and why iron tablets are a leading cause of serious childhood poisoning (Chapter 23.6).

Calcium — bone, muscle contraction, nerve transmission, clotting.

Around 700 to 1,000 mg daily for adults, from dairy, fortified plant milks, tinned fish with bones, tofu set with calcium, and leafy greens — though spinach is a poor source despite its calcium content, because oxalate binds it.

Magnesium — over 300 enzyme reactions. In nuts, seeds, wholegrains and green vegetables. Deficiency causes cramps, fatigue and arrhythmias.

Potassium — nerve and muscle function, and blood pressure. Higher potassium intake lowers blood pressure, and most people get less than recommended. In fruit, vegetables, potatoes and legumes.

Sodium — necessary, and consumed in excess almost everywhere. Reducing intake lowers blood pressure measurably (Chapter 18.2). Around 75 percent of dietary sodium comes from processed food rather than the salt cellar.

Iodine — thyroid hormone (Chapter 21.4). Deficiency causes goitre and, in pregnancy, is the leading preventable cause of intellectual disability worldwide. Salt iodisation is one of the great public health successes. Worth noting: many plant milks are not iodine-fortified, unlike dairy milk, which is a real source of deficiency in people who have switched.

Zinc — immune function, wound healing, taste. Deficiency causes poor healing, hair loss, diarrhoea and impaired immunity. In meat, shellfish, legumes and seeds.

Selenium — antioxidant enzymes and thyroid hormone metabolism. Brazil nuts are extremely rich — two or three a day is plenty, and much more can cause toxicity.

Supplements — what is actually worth taking

And this is the section people want, so here it is plainly.

Genuinely recommended:

Folic acid — before conception and in early pregnancy. Not optional.

Vitamin D — in autumn and winter at higher latitudes, and year round for people with limited sun exposure, darker skin, or who are housebound. And for all infants and breastfed babies.

Vitamin B12 — for anyone on a vegan diet, and for people with absorption problems. Not optional on a vegan diet.

Iron — where deficiency is diagnosed, not speculatively.

Vitamin K at birth.

Iodine — where intake is inadequate, particularly in pregnancy.

Specific medical situations — after bariatric surgery, in malabsorption, in alcohol dependence, and for certain medications.

Reasonable in specific circumstances:

Omega-3 from algae for people who eat no fish.

Calcium and vitamin D for people with osteoporosis or at high fracture risk.

Creatine for people doing resistance training, where the evidence for strength and lean mass is among the strongest of any supplement.

Not supported by evidence for healthy people eating a reasonable diet:

Multivitamins. Large trials have consistently failed to show reduced mortality, cardiovascular disease or cancer.

High-dose antioxidants — and beta-carotene in smokers is actively harmful.

Most single vitamins in people who are not deficient.

And the general principle worth carrying: correcting a deficiency produces dramatic benefit. Taking more of something you already have enough of produces nothing, and occasionally harm.

The nutrients in food come packaged with fibre, other compounds, and a matrix that changes how they behave. Which is the most likely explanation for why "eat more fruit and vegetables" works in every study and "take the vitamins from fruit and vegetables in a pill" repeatedly does not.

Who is actually at risk of deficiency

Older adults — reduced appetite, reduced absorption, less sun exposure, and medications that interfere.

Pregnant and breastfeeding women — increased requirements.

Vegans — B12, and attention to iron, iodine, omega-3, zinc and calcium.

People with malabsorption — coeliac disease, Crohn's, pancreatic insufficiency, and after bowel or bariatric surgery.

People with alcohol dependence — particularly thiamine.

People on certain drugs — metformin and B12; proton pump inhibitors and B12, magnesium and calcium; long-term steroids and bone; some antiepileptics and vitamin D.

And people with very restricted eating — from poverty, from eating disorders, or from selective eating.

If you are in one of those groups, testing and targeted supplementation is worthwhile. If you are not, a varied diet almost certainly has it covered.

What the next page fixes

Chapter 24.3 covers how to read a food label — the numbers that matter, the ones designed to mislead, and how to work out in ten seconds whether something is what it claims to be.