Supplement shelves can give the impression that almost everyone needs something. Yet for generally healthy adults, a review of 84 studies found that routine vitamin and mineral supplements offered little or no protection against cardiovascular disease, cancer or early death.

Taking a supplement without a clear reason may also cause harm. High doses of some water-soluble vitamins can cause harm, and too much vitamin B6, for example, has been linked to nerve damage. Some fat-soluble vitamins, particularly vitamin A, can accumulate and cause toxicity when taken in excess.

A diagnosed deficiency is one reason to take a supplement. Other evidence-based reasons include folic acid before and during early pregnancy, vitamin B12 for people who cannot obtain enough from food and the ten micrograms of vitamin D that UK guidance recommends people consider during autumn and winter.

Once there is a sound reason to take a supplement, timing can sometimes affect absorption. Usually, “timing” concerns meals, drinks and other medicines rather than a perfect hour on the clock.

Iron: the fussiest supplement

Iron supplements are used to treat iron deficiency anaemia. Because iron deficiency can be caused by blood loss and poor absorption, including conditions affecting the gut, it should be confirmed and its cause considered rather than self-treated on the basis of tiredness alone.

Coffee can substantially reduce iron absorption. In a small study of 34 iron-depleted women, coffee taken with a 100mg iron supplement reduced absorption by 54% compared with water. Taking the supplement with breakfast reduced absorption by 66%, even though the meal included orange juice.

The same study found that 80mg of vitamin C increased iron absorption by 30%, while 500mg offered no further improvement. It also suggested that absorption was 37% lower in the afternoon than in the morning. The result fell just outside the usual threshold for statistical significance, so it cannot support a firm rule about taking iron in the morning.

Improved absorption does not always produce better clinical results. In a randomised trial involving 440 adults with iron deficiency anaemia, iron alone was as effective as iron combined with vitamin C at improving haemoglobin and iron stores.

Calcium can reduce iron absorption over a single meal or dose, particularly in large amounts. However, the same systematic review of human studies found that its effect on long-term iron status was small. If you have been advised to take both calcium and iron, ask a pharmacist whether to separate them.

Iron is generally absorbed better on an empty stomach but can cause nausea, constipation, diarrhoea or stomach pain. Taking it with food may make treatment easier to tolerate. NHS advice is to take ferrous sulfate 30 minutes before eating or two hours afterwards where possible, but with or after food if it upsets your stomach. Following the instructions for your preparation is more useful than pursuing perfect absorption and repeatedly missing doses.

Vitamin D: take it with a meal

Vitamin D is fat-soluble. A randomised study found that vitamin D3 was absorbed better with a meal containing fat than with a fat-free meal. This supports taking tablets or capsules with a main meal. The study compared the fat content of meals, so it cannot tell us whether breakfast is better than dinner.

Some medicines can affect how the body absorbs or processes vitamin D. These include orlistat, a medicine used to treat obesity by reducing fat absorption, and corticosteroids such as prednisolone, which are used to reduce inflammation. Moving the supplement to another hour may not solve the problem. Keep taking prescribed medicine and ask a healthcare professional whether your vitamin D intake or levels need reviewing.

Vitamin B12: the cause is more important than the clock

Vitamin B12 supports red blood cell production and the nervous system and is obtained from animal-derived or fortified foods. A systematic review and meta-analysis, which brought together relevant studies and combined their results, found that vegans who did not supplement had poorer B12 status than people who ate animal products. Supplements improved their blood markers of B12 status.

For most B12 products, the underlying reason for taking them matters more than the time of day. Metformin and acid-suppressing medicines such as omeprazole can reduce B12 absorption or levels over time. Simply separating the doses may not prevent this effect. For prescribed cyanocobalamin tablets, a manufactured form of vitamin B12, the NHS advises taking them on an empty stomach. Follow the packet instructions for products bought over the counter.

Where deficiency is caused by poor absorption, treatment may involve high-dose tablets or injections. A review of the available clinical trials found low-quality evidence that high-dose oral B12 and injections produced similar short-term changes in B12 levels, so treatment should be chosen according to the cause, symptoms and clinical advice.

Before adding a supplement

Ask whether you have an evidence-based reason to take it and whether the dose is appropriate. Check for the same ingredient in other products, as multivitamins, energy drinks and “wellness” powders can overlap. If you use prescribed medicines, ask a pharmacist about interactions and spacing. Then follow the label or prescription.

For some supplements, the surrounding meal or drink can make a measurable difference. Where no timing effect has been shown, follow the recommended dose and instructions at a time you can remember.