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Recent meta-analyses, meaning studies of groups of studies, have suggested no benefit for multivitamins, and even, in some cases, the potential for harm. Should you be concerned and stop taking multivitamins?
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Patrick Holford, world-renowned nutrition expert, provides the following insight into the use of multivitamins:
Before I examine these studies to help you decide what’s right for you, there are a few points worth bearing in mind.
Firstly, doing a meta-analysis on ‘multivitamins’ is like doing a meta-analysis on ‘drugs’. It tells you very little.
In fact, if you were to do so you’d find that the total number of deaths per year caused by prescribed medication given and taken in the right dose, is in excess of 10 000. One might therefore, erroneously, conclude that all drugs increase risk of death and all drugs should be avoided.
Secondly, we need to look at what multivitamins are being studied. Is it the RDA-level multivitamins or optimal amounts of nutrients (which I call ODAs – for Optimal Daily Amounts)?
Thirdly, there’s the issue of who is being studied? Is it apparently healthy people with the aim of preventing illness (‘primary prevention’)? Or is it sick people in which vitamins are given in the hope of reducing further sickness or extending life (‘secondary prevention’)?
This second group is always complicated by consideration that a) such people are usually on medication or other treatment that may interfere with the effects of certain nutrients; and b) in some cases advanced diseases simply can’t be reversed.
Then there’s the question of whether the study is an actual controlled intervention, i.e. 1 000 people who have had heart attacks are given vitamin E or placebo pills. What’s the outcome? Or is it simply a survey, looking at associations?
One such study I refer to later found that people with aggressive prostate cancer took more selenium pills. So, selenium is associated with aggressive prostate cancer, but there is no evidence that it causes advanced prostate cancer.
A far more logical explanation, given that there is a relationship between family history of prostate cancer and severity, is that men in these groups are far more likely to be fearful and taking selenium supplements.
The main ingredients in a multivitamin, or daily supplement programme, are B vitamins, antioxidants, vitamins A, D and E and minerals. So, let’s look at these:
B vitamins – do they boost memory and reduce stroke and heart attack risk?
The most research has been carried out on folic acid (called folate in food), B12 and B6. The FSA now consider folic acid deficiency to be a major cause of birth defects and has recommended mandatory supplementation via fortified flour.
Controlled studies, not surveys, have consistently shown a significant reduction in stroke risk in those who have not had a stroke. A recent meta-analysis of eight studies, published in the Lancet, involving more than 15 000 subjects taking folic acid either on its own or with other B vitamins showed that those taking B vitamin supplements cut the chances of a stroke by an average of 18 percent – 29 percent, almost a third, if folic acid had been supplemented for more than three years.
Studies giving folic acid, sometimes with B6 and B12, have been inconsistent in those who have cardiovascular disease. Some studies have shown a reduced risk of heart attack, others no change, and one study found a slight increase.
There is no doubt that having high homocysteine levels means greater risk of both heart attacks and strokes, even if lowering it doesn’t confer protection from heart attacks.
One critique of these trials is that they generally reported very small changes in homocysteine (for example, a 2-3 point drop) and little change in heart attack risk. The sensible advice is to check your homocysteine level and, if it is raised, ensure you are receiving an optimal intake of these B vitamins.
Most experts in this field are giving 400 to 1 000mcg of folic acid (the RDA is 300mcg), 10 to 500mcg of B12 (the RDA is 1mcg), and 20 to 100mg of B6 (the RDA is 2mg).
So, you can see that the level that might be considered health promoting is much higher than the basic RDAs. These kinds of levels can drop a high homocysteine level (e.g. of 20) by over 10 points in eight weeks.
In children, high homocysteine is associated with worse school grades, and eleven out of13 studies have shown non-verbal IQ increases in those given supplements. The best results to date, reporting a 7-point increase in IQ on supplements versus placebo was in the Lancet study that I was involved in, which used optimal levels, not RDA levels of nutrients.
Recommendation: Supplement these kinds of levels of B vitamins, as well as eating a whole food diet.
Antioxidants and vitamin C
The most controversial meta-analysis was that of Bjelakovic, published this February in the Journal of the American Medical Association. This was a study of studies which looked at all-cause mortality in association with supplementation of the antioxidants vitamin A, beta-carotene, vitamin E and vitamin C.
The summary of this study says ‘treatment with beta-carotene, vitamin A, and vitamin E may increase mortality’, creating the impression that these antioxidants are no good.
What it failed to say in the summary, all of which are clearly shown in the results, is that ‘vitamin C given singly, or in combination with other antioxidants did not affect mortality, and selenium given singly or in combination with other antioxidant supplements may reduce mortality’.
It also fails to say that ‘beta-carotene or vitamin A did not show increase in mortality if given in combination with other antioxidants’, or that ‘vitamin E given singly or combined with 4 other antioxidants did not significantly influence mortality’.
Furthermore, most of the studies included in this analysis were in sick people, so you can’t extrapolate these findings to the public at large. Indeed, many studies that have looked at the effects of supplementing antioxidants in healthy people have shown significant reduced risk of, for example, cancer, heart disease and death.
The lead author of this study had previously done a meta-analysis of antioxidants in relation to cancer. In this review, there was a clear reduction in cancer risk in four out of five studies giving selenium.
In addition, the one study, by a Dr Correa from the pathology department at the Louisiana State University Health Sciences Centre, that apparently skewed results for antioxidants overall towards a negative, showed a clear protective effect of antioxidant supplements against gastrointestinal cancer.
I decided to contact Dr Correa and he was ‘amazed’, he said, because his research, ‘far from being negative, had shown clear benefit from taking vitamins.’
Correa told us that there was no way the study could show anything about mortality. ‘Our study was designed for evaluation of the progress of precancerous lesions,’ he said. ‘It did not intend, and did not have the power, to study mortality and has no value to examine mortality of cancer.
Beta-carotene – good or bad?
There’s no doubt that eating foods rich in beta-carotene, an antioxidant nutrient found in most orange-coloured foods, reduces risk of cancer. It’s been well researched – 7 000 studies in all, 2 000 of which relate to cancer.
There’s also no doubt that having a higher beta-carotene level in your bloodstream is good news.
In 2005, a ten-year study of several thousand elderly people in Europe, conducted by the Centre for Nutrition and Health at the National Institute of Public Health and the Environment in the Netherlands, found that the higher the beta-carotene level, the lower the overall risk of death, especially from cancer.
Eating probably the equivalent of a carrot a day (raising blood level by 0.39mcmol/l) meant cutting cancer risk by a third.
All this good evidence has led to trials over the past 20 years in which people have been given beta-carotene supplements, sometimes in combination with other antioxidant nutrients. Many have proven protective. For example, research on 1 954 middle-aged men showed beta-carotene as having a protective effect against lung cancer.
But what about the bad news that tends to make the headlines, such as the ones that found an increased risk of cancer with beta-carotene?
If you analyse the studies this scare is based on, you find that the claim boils down to the fact that one smoker out of a thousand who takes beta-carotene on its own and takes no other anti-oxidant supplement, and keeps on smoking, will have a slightly raised risk of cancer.
Most anti-vitamin reports refer to a study by the National Cancer Institute in the US that gave smokers beta-carotene and reported a 28 percent increased incidence in lung cancer in those who continued to smoke.
Headlines such as ‘vitamins cause cancer’ ensued, but a closer look at the figures shows a rather different picture. In fact, the difference between those getting beta-carotene and those getting the placebo was not big enough to reach ‘statistical significance’; it was only a ‘trend’ and therefore could be coincidental.
The actual figures were 50 cancer cases out of some 10 000 in the placebo group and 65 cases out of 10 000 among those getting beta-carotene. Put another way, this means that for every five cases of cancer out of a thousand people taking the placebo there were 6,5 cases out of a thousand among those taking the beta-carotene supplement. And remember, both groups involved people who had smoked for years and probably had undetected cancer before starting the trial.
But how could such a result be seen as increasing cancer risk by 28 percent? This is the difference between absolute risk and relative risk. This way of interpreting results is also regularly used in drug trials to make a very small benefit look much more impressive.
Here 64 divided by 50 equals 1.28, or an increased relative risk of 28 percent. It sounds dramatic put this way but, as we’ve seen, it is actually not even statistically significant. The absolute risk, remember, is 6 cases per year in 1 000 for smokers taking beta-carotene, as compared to 5 cases in 1 000 for smokers on a placebo.
Vitamin E – good or bad?
The studies showing a negative effect for vitamin E can be easily explained. As with beta-carotene, almost 50 years of research into vitamin E has shown that the higher your intake, the lower your risk of a heart attack.
The recent Bjekaolovic study failed to include or mention the findings of the Women’s Health Study – the largest and longest primary prevention trial to have used vitamin E. The study shows that vitamin E supplementation significantly reduced cardiovascular deaths in women, especially older women.
This is consistent with the surveys, published in the New England Journal of Medicine, in which 87 200 nurses who had an average intake of 67mg of vitamin E per day, for more than two years, had a 40 percent drop in fatal and non-fatal heart attacks compared to those not taking vitamin E supplements.
In another study, 39 000 male health professionals taking 67mg of vitamin E for the same length of time and achieved a 39 percent reduction in heart attacks. This is ‘primary prevention’ – preventing a disease from developing.
Then a ‘secondary prevention’ study, giving vitamin E to people with cardiovascular disease to prevent further problems, came up trumps. The study, carried out by researchers at the UK’s Cambridge University Medical School in 1996, gave some 2 000 people vitamin E or a placebo.
Those given vitamin E had a 75 percent reduced risk of a non-fatal heart attack but, interestingly, no reduced risk of death from fatal heart attacks. The research showed vitamin E to be almost four times as effective as aspirin in reducing heart attacks.
Vitamin E’s reputation suffered, however, when an American study, the HOPE (Heart Outcomes Prevention Evaluation) trial, published in the New England Journal of Medicine, hinted at a slight increased risk of heart attack in heart patients who were on medication and taking vitamin E.
The trial was extended for a further 2,5 years and, in 2005, the results of what was called the HOPE2 trial were published in the Annals of Internal Medicine, showing a slight increased risk of heart attack in heart patients who were on medication and taking vitamin E. This prompted a review of all trials in which vitamin E had been given to people with cardiovascular disease.
The results showed that vitamin E, in higher doses, seemed to increase mortality, while at lower doses, seemed to decrease mortality. The overall conclusion was that ‘vitamin E supplementation did not affect all-cause mortality’ – in other words, the same number of people overall died in the group that took vitamin E as did in the group that didn’t.
But as with beta-carotene, there was a group that did slightly worse (those on a high dose, above 268mg), and a group that did slightly better (on a low dose, below 268mg).
Either way, though, the results looked pretty damning. The effect of taking vitamin E, for these people, was not that greatly positive or negative – and certainly not as positive as the preventive power of giving vitamin E to reasonably healthy people.
The question is why? And why the difference between the high and low doses?
The answer is likely to be linked to the other drugs that the patients were taking – specifically the statins which, it is well known, have an effect on the same antioxidant network that is central to the functioning of beta-carotene.
Statins not only block the enzyme that makes cholesterol, they also block the enzyme that makes co-enzyme Q10 - and vitamin E can’t work as an antioxidant without it. Just as beta-carotene needs support from other vitamins.
Vitamin E is a fat-based antioxidant, sacrificing itself to disarm an oxidant. In the process, vitamin E becomes oxidised and dangerous. Co-enzyme Q10 helps to recycle oxidised vitamin E so it can fight another battle.
As biochemist Angelo Azzi, quoted in the New Scientist, correctly points out: ‘It must be protected against oxidation.’ That’s what co-Q10 does, together with vitamin C, and that’s what statin drugs block.
So, giving a large amount of vitamin E to someone on a statin drug, without giving co-enzyme Q10, would be expected to increase oxidation, not decrease it. In other words, statin drugs could make high dose vitamin E worse for you.
Nutritionists are taught never to give high-dose vitamin E (above 250mg) to a person on statins without also giving 90mg or more of co-enzyme Q10. Yet, that is exactly what these trials have done.
The big question these trials raise is ‘Was vitamin E reducing oxidation, as would be predicted?’ This can be measured with a blood test but, unfortunately, this wasn’t done in these trials. Until that measurement is done, there are simply not enough facts to make a final verdict on high-dose vitamin E for those with cardiovascular disease.
Recommendation: Based on what we know already, supplementing around 50 to 250mg of vitamin E (5 to 20 times the RDA) seems to be nothing but good news. This kind of level, and possibly more, may also be good for people with cardiovascular disease, but only if taken with co-enzyme Q10 if you’re on statins.
Vitamin C – does it fight infections and keep colds at bay?
A recent article in the Guardian states “Fact: The human body can only absorb 500mg of vitamin C and excretes the excess.”
This is simply not true. Most people will have increasing plasma levels of vitamin C at 2 000mg a day, some at 5 000mg a day. We all excrete the excess, otherwise we’d be full of vitamin C. It’s the same for water. What it does in those few hours circulating your blood stream is what counts.
Recommendation: Take at least 1 gram a day, in divided doses since vitamin C is water soluble and is in and out of the body in 4 to 6 hours.
Vitamin D – why you need to double your intake
In recent years the amount of evidence in favour of supplementing vitamin D above that easily achieved by diet has become overwhelming, with clear benefits in reducing cancer risk and osteoporosis, as well as potentially helping reduce risk for asthma, schizophrenia and infections.
All this evidence suggests that the RDA is far too low, as is the ‘upper safety level’ for this fat-soluble vitamin.
Recommendation: Supplement around 10mcg a day and eat fish to aim to achieve the same again, or more, from your diet. This means fish three times a week, at least.
Zinc, magnesium, selenium and chromium – you probably don’t get enough
These four are the most commonly deficient minerals. The RDA for zinc, of 10mg, which few people achieve from their diet with an average intake of 7.6mg, is almost certainly not enough. I would estimate that a daily intake of 15mg is optimal for most people.
Magnesium is probably the most deficient mineral in our diet. The average intake in Britain is 272mg, along way short of the optimal intake of 500mg. This kind of level lowers blood pressure, cholesterol, triglycerides and reduces cardiovascular mortality.
As we saw earlier, studies giving selenium to sick people have consistently shown reduction in mortality, and reduction in certain cancers. But one of the most confused recent surveys on antioxidants and prostate cancer claimed that supplements actively increased aggressive prostate cancer.
However, there was no step-wise increase in risk – in fact, the more often you took supplements, up to 7 days a week, the lower your risk. But if you took supplements more than 7 times a week, your risk went up.
A much easier explanation is that people ‘at risk’ took more supplements, not that the supplements caused the prostate cancer. They also were more likely to be screened for prostate cancer.
In fact, the researchers admit ‘it is possible that the positive association with heavy use of multivitamins along with certain supplements was spurious because more intensive screening led to increased diagnosis of localized prostate cancer’.
Most studies show a protective effect with an intake of 100mcg a day, which is more than you are likely to eat.
Chromium supplementation has consistently been shown to help stabilize blood sugar at levels of 200mcg or more. Few people eat more than 50mcg.
Recommendation: I recommend supplementing around 5-10mg of zinc, 100-200mg of magnesium, 35 to 100mcg of selenium and 35 to 400mcg of chromium – the higher levels being for people with specific disease states such as high blood pressure or diabetes.
What to look for in a multivitamin
On the basis of the evidence to date, I recommend everyone supplement a high-strength multivitamin providing the following:
400 to 800mcg of folic acid
10 to 500mcg of B12
10 to 100mg of B6
50 to 250mg of vitamin E
10mcg of vitamin D
5-10mg of zinc
100-200mg of magnesium
35 to 100mcg of selenium
35 to 400mcg of chromium
Vitamin C – 1 000 to 2 000 mg a day. Your multivitamin may give you 100 to 200mg, so that means supplementing 900 to 1 800mg a day.
References:
M Pirmohamed et al, ‘Adverse Drug Reactions In Hospitalised Patients’, British Medical Journal, (2004), vol 329, pages 15-19
W Xiaobin et al, ‘Efficacy of folic acid supplementation in stroke prevention: a meta-analysis’, The Lancet, (2007), vol 369, page 1876 .
D Benton ‘Micronutrient Supplementation and the Intelligence of Schoolchildren’, Neuroscience and Biobehavioural Reviews(2001), vol 25, pages 297-309
D Benton and G Roberts, ‘Effect of vitamin and mineral supplementation on the intelligence of a sample of schoolchildren’ The Lancet (1988) vol I, pages 140-3
G Bjelakovic et al, ‘Mortality in randomized trials of antioxidant supplements for primary and secondary prevention systematic review and meta-analysis, JAMA, (2007), vol 297, No. 8
G Bjelakovic et al, ‘Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis’, The Lancet (2004), vol 364, pages 1219-28
P Correa et al‘Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy’, (2000), J Natl Cancer Inst vol 92(23), pages 1881-8
Letter from Dr P. Correa
B. Buijsse et al, ‘Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA)’, Am J Clin Nutr, (2005), vol 82(4), pages 879-86
R. B. Shekelle et al, ‘Dietary vitamin A and risk of cancer in the Western Electric study’, The Lancet, (1981), vol 2(8257), pages 1185-90
G. Omenn et al, ‘The Beta-Carotene and Retinol Efficacy Trial (CARET)’, New England Journal of Medicine, (1996), vol 334, pages 1150–5
I M Lee et al, ‘Vitamin E in primary prevention of cardiovascular disease and cancer; the Womens Health Study: a randomised trial’, JAMA (2005), vol 294, pages 56-65
M. J. Stampfer et al, ‘Vitamin E consumption and the risk of coronary disease in women’, N Engl J Med, (1993), vol 328(20), pages 1444–9
E. B. Rimm et al, ‘Vitamin E consumption and the risk of coronary heart disease in men’, New England Journal of Medicine, (1993), vol 328(20), pages 1450–60
S. Yusuf et al, ‘Vitamin E Supplementation and Cardiovascular Events in High-Risk Patients’, N Engl J Med, (2000), vol 342, pages 154-60
E. Miller et al, ‘Meta-analysis: High Dose Vitamin E Supplementation May Increase All-Cause Mortality’, Annals of Internal Medicine, (2004), vol 142(1), pages 37-46
B. T. Altura and B. M. Altura, ‘Magnesium in cardiovascular biology’, Scientific American, (1995), pages 28-36
K A Lawson et al, Multivitamin use and risk of prostate cancer in the National Institues of Health – AARP Diet and Health Study, J Natl Cancer Inst (2007), vol 99, pages 754–64
C Leigh Broadhurst and P Domenico, Clinical studies on chromium picolinate supplementation supplementation in diabetes mellitus – a review’, Diabetes Technology and Therapeutics, (2006), vol 8 (6), pages 677-87
- (Issued on behalf of Bioharmony by AHOY! PR and Leap Communications, June 2007)
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