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At the heart of general practice since 1960

Can nutritional supplements do any harm?

Why do patients want to take supplements and should you encourage them? Catherine Collins looks at the evidence

An orange the size of a football. Broccoli the size of a small bush. Four litres of orange juice. These are not portions that come to mind when recommending a Mediterranean-style diet for health. Yet each of these foodstuffs in such epic proportions provides 1,000mg of vitamin C, an amount commonly recommended by vitamin and mineral supplement manufacturers as a 'natural extension' to a healthy diet.

Vitamin C remains the most popular single-nutrient supplement, with sales estimated at 252 million tablets and capsules per annum, despite evidence that UK adults normally consume twice the reference nutrient intake – about equivalent to the EU-recommended daily allowance – from dietary sources alone.

That supplements are freely taken by those with little need bears testimony to current liberal legislation. In Britain, vitamin and mineral supplements are regulated by food law rather than the 1968 Medicines Act. Lack of regulatory control has allowed sales to progress unhindered to a market value of £326 million in 1999 (excluding internet sales and imports), with 40 per cent of women and 30 per cent of men reporting regular use.

In 2003, the Expert Group on Vitamins and Minerals published a report on the safety of micronutrient intakes. Sufficient clinical and scientific evidence existed to set safe upper limits (SULs, the daily nutrient intake an individual could consume daily over a lifetime without medical supervision) for just nine nutrients, with 'guidance levels' recommended for a further 22. Data was inadequate to set either SULs or guidance levels for five nutrients.

The expert group particularly highlighted the lack of robust, well-designed comparative human studies of significant duration for different levels of intake in health and disease, and concluded that evidence supporting the safety in use of vitamins and minerals is generally poor.

The UK is due to adopt an EU directive in preference to existing food law, which would limit the content and dose of vitamin and mineral supplements to low multiples of the EU-recommended daily allowance. This directive, which would seem prudent given the absent safety data and lack of central reporting of adverse effects, is being challenged by consumer and industry groups. They have successfully petitioned the High Court to refer this to the European Court of Justice.

When are supplements necessary?

Should GPs be concerned about the use of nutritional supplements by their patients? It is well-recognised that patients rarely disclose use of any complementary therapy unless specifically questioned.

The most recent National Diet and Nutrition Survey analysed dietary intakes from 1,700 UK adults aged 19-64. With the exception of a few nutrients (potassium intake across all groups, magnesium and copper intake in women, and iron intake in pre-menopausal women), nutrients were consumed at levels that met or exceeded the reference nutrient intake.

In considering whether to recommend vitamin and mineral supplements to patients, the following points should be considered.

Is the patient at nutritional risk?

According to the National Diet and Nutrition Survey, subjects in receipt of benefits have lower dietary intakes of iron, calcium, magnesium and potassium, which reflects dietary choices in low-income groups. Other patients at potential risk include those with:

lReduced intake (anorexia, early satiety)

lReduced absorptive capacity (small bowel surgery, age-related decline in intrinsic factor compromising vitamin B12 absorption)

lAbnormal losses

(B group vitamins in alcoholics, potassium and magnesium losses with diuretic therapy)

lIncreased requirements (calcium in adolescence, iron for menorrhagia)

l Abnormal metabolism (genetic polymorphisms such as the MTHFR gene and folate uptake)

l Inadequate synthesis (vitamin D in housebound individuals, lack of

exposure to UV light, use of high-factor sunblock).

Will supplements benefit the patient?

While unequivocal evidence supports the benefit of folic acid for prevention of neural tubal defects and protection of

bone by vitamin D supplementation, substantive evidence is lacking for other nutrients.

Supplementation with vitamin B6, B12 and folic acid successfully reduces hyperhomocysteinaemia but fails to translate biochemical benefit into a reduction in cardiovascular mortality in high-risk individuals. Homocysteine might therefore merely be a modifiable marker of disease.

Dietary vitamin E appears to reduce the risk of Alzheimer's disease, but supplements do not – nor do they reduce the risk of cardiovascular disease, whether as a single nutrient or combined with other anti-oxidant vitamins.

Topical application of vitamin

E-enriched cream worsens the appearance of surgical scars and increases the incidence of contact dermatitis. Zinc supplements fail to accelerate healing in venous leg ulcers unless a pre-existing zinc deficiency is present. Zinc lozenges are not proven to reduce either symptoms or duration of the common cold.

Could supplementation be harmful?

Absence of reports in the medical literature reflects lack of research into this question. However:

lHigh-dose vitamin A supplementation causes teratogenicity in the fetus (threshold 2,000 retinol equivalents per day) and promotes development of osteoporotic hip fractures in women. Routine 'overage' of vitamin A (to allow for losses during shelf-life) can increase retinol content 20- to 100-fold above the label specification.

l Beta-carotene supplementation is associated with a higher risk of lung cancer in susceptible individuals (smokers, prior exposure to asbestos).

lVitamin C enhances excessive iron absorption in haemachromatosis.

lLarge doses of oral zinc can cause thrombocytopaenia and neutrophilia.

lFolic acid supplementation in the presence of vitamin B12 deficiency can mask progressive irreversible neurological deficits.

Do supplements interfere with conventional medication/tests?

High-dose iron supplementation increases faecal losses and its pro-oxidant capacity is associated with an increased risk of colon cancer. Faecal iron excretion can also obscure the results of faecal occult bloods.

Vitamin K requirements are around 1mcg per kg body weight. Supplements providing reference nutrient intake can antagonise warfarin sufficiently to shorten INR.

Vitamin C can interfere with urinalysis for occult blood or glucose. High doses (>1g) of vitamin C and magnesium supplementation are common causes of diarrhoea, which may interfere with absorption of oral drugs.

Are supplements cost-effective?

A 2002 JAMA editorial tentatively recommended daily, broad-spectrum vitamin and mineral supplements as a simple, low-cost approach to ensuring dietary adequacy and possible protection against chronic disease. While there is no evidence that low-dose supplementation is harmful, neither is there much robust evidence of benefit.

Supplementation in the prevention of cardiovascular disease and age-related macular degeneration seems ineffective, although it appears to be effective in reducing infection risk in diabetics and

C-reactive protein levels (associated with background inflammation and vascular damage).

A general multivitamin and mineral complex remains the most efficient way of improving dietary quality. 'Functional' ingredients in price-premium supplements are unnecessary and quadruple the cost – a significant consideration for those on low income. Tailored supplements may be useful for specific conditions, such as folic acid in pregnancy planning, low-dose iron supplementation in 'tired all the time' patients, and vitamin D supplementation in high-risk groups.

Consumption of multiple supplements is common but it can increase the potential for toxic effects and should therefore be discouraged.

Why do patients take supplements?

Common themes in supplement users include the desire to improve the quality of their diet, or for prophylaxis or treatment of a particular health concern. The 'worried well' are the very group who least need further supplementation. They already take more than 'five a day', exercise regularly, eat a low-fat diet and maintain a healthy weight.

This group commonly take several supplements concurrently, usually suggested by their therapist. At best they are wasting money, at worst consuming nutrients at levels that could cumulatively carry health risks.

The 'vulnerable optimists' with chronic health problems typically believe nutritional nirvana can be achieved and/ or symptoms resolved by supplement use. Supplements are a tragic waste of money for those with advanced cancer, worsening rheumatoid arthritis or irritable bowel syndrome, especially if they are on low income.

The 'hedge-betters' can be on opposite ends of the age spectrum, with older people concerned about advancing years and impending mortality and anxious parents wanting to ensure their children have sufficient for optimum health. This group usually want to hedge their bets and think a general multinutrient supplement is a good idea. It probably is.

In conclusion

As highlighted in the recent expert group report, research supporting the benefits of nutrients obtained through supplement use is extremely limited. For patients wanting to take them, direction towards a general multinutrient is recommended for potential health benefits and minimal risk of adverse effects.

Particular nutrient selection may be appropriate at different life stages or in certain clinical conditions. Patients should rationalise supplement intake to avoid potential overdosage. With the exception of recognised single polymorphisms, there is no apparent benefit from hyper-supplementation.

Catherine Collins is chief dietician at

St George's Hospital, London

Effects of common supplements

Nutrient Comment

Vitamin A Significant 'overage' in

retinol conventional supplements;

teratogenicity at 2,000mcg retinol

equivalent per day threshold;

may accelerate lung cancer growth;

may potentiate intercranial

hypertension with tetracycline; may

antagonise vitamin K blood-clotting

function; may diminish vitamin C

storage; may impair iron absorption

and have an anti-thyroid effect

ß carotene Enhance lung cancer development;

discolouration of skin due to fat

deposits; two large-scale studies in

smokers showed increased lung

cancer in high-risk individuals at

20-30mg a day; heart protection

study of anti-oxidant nutrients at

20mg a day showed no difference at

up to five years

Vitamin B6 Overdosing can lead to loss of feeling in limbs: in some cases, effects are irreversible

Calcium Inclusion of dairy foods three portions a day meet nutritional needs; alternative sources are UK fortified white flour and products, fortified soya milks, tofu, and green leafy vegetables; supplementation for bone health without increase in weight-bearing activity is of little proven benefit; too much can cause stomach pains and diarrhoea

Vitamin C Low toxicity; enhanced non-haem iron absorption of concern in haemachromatosis, thalassaemia; absorption is dose related; interference with occult blood and glucose urinalysis; large amounts can cause stomach pain, diarrhoea and flatulence

Folate 400mcg in pregnancy or 5mg for women with previous NTD pregnancy; methotrexate, epilepsy and anti-inflammatory drugs may reduce efficacy of drug; B12 deficiency masking due to folate oversupply – less than 1mg a day does not mask folate deficiency, >5mg does, amount in-between not certain

Niacin Reduces plasma chl levels; 3000mg/d hepatotoxic effects; 50mg + flushing

Pantothenic No problems

acid

Riboflavin Reduces absorption of erythromycin, streptomycin, carbomycin, and tetracyclines

Pyridoxine Neuropathy associated with high doses or prolonged duration over 200mg a day

B12 Alcohol consumption reduces absorption; chloramphenicol antagonises haematopoietic response to B12

Vitamin E Exacerbates Vit K deficiency; associated with a small but significant increase in haemorrhage stroke in some studies; potentially antagonistic to warfarin

Copper Impairs absorption of dietary iron, magnesium, zinc

Magnesium Diarrhoea with increasing oral doses

Zinc Reduces amount of copper the body can absorb, leading to anaemia; thrombocytopaenia and neutrophilia with large doses

Chromium Possible impairment of iron metabolism and storage; hexavalent form more toxic than trivalent form, with exception of chromium picolinate; case reports of renal failure associated with hexavalent forms

Boron Interferes with calcium metabolism, significance unclear; pregnant women more at risk of toxicity

Germanium Not an essential nutrient and is a cumulative toxin

Further information

Expert Group on Vitamins and Minerals. Safe Upper Limits of Vitamins and Minerals 2003. available at www.foodstandards.gov.uk/multimedia/

pdfs/vitmin2003.pdf

American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements: www.guideline.gov

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