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Are multivitamins safe?

We have known for centuries that a diet rich in micronutrients, specifically vitamins, minerals and antioxidants is helpful in preventing a range of diseases, and slowing down the ageing process

We have known for centuries that a diet rich in micronutrients, specifically vitamins, minerals and antioxidants is helpful in preventing a range of diseases, and slowing down the ageing process.

It has not been clear however whether extracting those nutrients, concentrating them, and taking them in supplement form has any benefits. Like essential fatty acids, many of these compounds cannot be made in the body and must be ingested in the diet.

Eating a diet rich in vegetables, fruit, nuts, seeds and grains ensures a potent dietary mixture of these essential substances. It also ensures that they are in their natural state, balanced with other food factors essential for their optimal function.

The question is should we take vitamin and mineral supplements instead of, or in addition to getting them through our food. There has until recently been very little evidence, despite much interest and research in the area, that these compounds taken as supplements make any difference at all to health.

It was assumed that, even if they had no benefit, at least they were doing no harm, and so could be taken almost as a form of insurance against an unhealthy lifestyle. Several major well-conducted studies published in the early 2000s have cast serious doubt over this assumption, raising the likelihood that taking antioxidant and multivitamin supplements probably does very real harm.1-7

These studies were systematic reviews or meta-analyses of all the published randomized controlled trials (RCTs) on multivitamins and antioxidant supplements in various diseases, and their effect on overall mortality. Meta-analysis is considered the highest form of medical evidence.

Researchers analyse pooled data from all comparable trials. This means large patient numbers and greater likelihood of finding real effects rather than those caused by chance. Vivekananthan’ study from the Cleveland Clinic Foundation looked at seven RCTs of vitamin E and eight of beta-carotene supplementation versus placebo or no intervention in heart disease.1

These studies involved around 220,000 patients. There was no effect from vitamin E supplementation, but rather alarmingly, they found that beta-carotene supplementation resulted in a 7% increase (p=0.003) in deaths overall, and a 10% increase (p=0.003) in death from heart disease. Bjelakovic’s group from Copenhagen looked at various supplements in the prevention of cancers of the digestive system.2,3

hey examined trials involving over 170,000 people, and found no benefit of beta-carotene, vitamin A or vitamin E in reducing the incidence of these cancers. However, again, they found an increase in the overall death rate of the people who took these supplements versus those taking placebo.

For beta-carotene and vitamin A combination supplements there was a 29% increase in mortality, and for beta-carotene together with vitamin E there was a 10% increase. Miller and colleagues from the Johns Hopkins School of Medicine examined nearly 136,000 people in 19 clinical trials, taking either vitamin E alone or in combination with other supplements.4

They found an alarming increase in the overall death rate of those taking high dose vitamin E (400IU or more per day), with a clear dose-response relationship, that is, the higher the dose, the more likely that death was the outcome.

The size of the increase in risk was alarming, with an extra 39 deaths per 10 000 people (p=0.035) taking the high dose supplements compared with those not taking vitamin E. Lawson from the National Cancer Institute, Bethesda looked at the relationship between multivitamin use and the five year risk of prostate cancer in over 295 000 men in the National Institutes of Health Diet and Health Study who were cancer free at enrolment in 1995 and 1996.5

Alarmingly, they found a 32% increased risk of advanced prostate cancer, and a massive 98% increased risk of death in those men taking multivitamin supplements more than seven times a week. Because the study was very large, and was prospective, thus reducing bias from hindsight, the results were very likely to be accurate.

The risk of taking antioxidant vitamin supplements was characterized further by Bjelakovic’s group from Copenhagen in 2007.6 This major meta-analysis looked at death rate from all causes for people taking antioxidant supplements versus no treatment in 68 trials with nearly a quarter of a million participants.

They separated the trials into those of high and low quality. The high quality trials showed a clear increase in risk for those taking the supplements, with a 4% increase in death rate for those taking vitamin E alone, 7% increase for those taking beta-carotene, and 16% increase for those taking vitamin A.

These results are of great concern, particularly as it has been shown by the 1987, 1992, and 2000 National Health Interview Surveys that in the US, vitamin and mineral supplement use increased from just under a quarter of all adults in 1987 to over a third in 2000.7

This is probably similar in most developed countries. Bjelakovic’s editorial summed up the situation by asking ‘Why is it not possible to take a vitamin pill to obtain the same effect as a balanced diet?’8 He stated that ‘Antioxidant supplements in pills are synthetic, factory processed, and may not be safe compared with their naturally occurring counterparts’.

He hypothesized that one explanation for the increase in death rate due to supplementation was that these supplements were given to people in middle- and high-income countries who already have diets with plenty of vitamins and trace elements. The evidence is now clear.

Taking the antioxidant vitamins A (and its precursor beta-carotene) and E singly or in multivitamins is dangerous and should be avoided by people eating a healthy diet. On a diet like that recommended here, the intake of these and other important vitamins should be high, with no need for supplementation.


References:

  1. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361:2017-2023
  2. Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev 2004:CD004183
  3. Bjelakovic G, Nikolova D, Simonetti RG, et al. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004; 364:1219-1228
  4. Miller ER, 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142:37-46
  5. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007; 99:754-764
  6. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Jama 2007; 297:842-857
  7. Millen AE, Dodd KW, Subar AF. Use of vitamin, mineral, nonvitamin, and nonmineral supplements in the United States: The 1987, 1992, and 2000 National Health Interview Survey results. J Am Diet Assoc 2004; 104:942-950
  8. Bjelakovic G, Gluud C. Surviving antioxidant supplements. J Natl Cancer Inst 2007; 99:742-743
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