Several major studies from the early 2000s have cast serious doubt on the safety of antioxidant supplements, spotlighting the likelihood that taking antioxidant and vitamin supplements probably does real harm.1-7
These studies were systematic reviews or meta-analyses of all published randomized controlled trials (RCTs) on multivitamins and antioxidant supplements as they affect various diseases and overall mortality.
(Meta-analysis is considered the highest form of medical evidence. Researchers analyze pooled data from all comparable trials. Larger patient numbers increase the likelihood of identifying real effects, rather than those caused by chance.)
Four major studies
Let’s look at some of these meta-analyses:
- Vivekananthan’s 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 beta-carotene supplementation resulted in a 7% increase in deaths overall, and a 10% increase 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 They examined trials involving more than 170,000 people and found no benefit from vitamins A or E or beta-carotene in reducing the incidence of these cancers. However, they did find an increase in the overall death rate among people who took these supplements versus those who took a placebo. For beta-carotene and vitamin A combination supplements, there was a 29% increase in death rate, and for beta-carotene together with vitamin E there was a 10% increase
- Miller and colleagues at the Johns Hopkins School of Medicine examined nearly 136,000 people in 19 clinical trials who were taking either vitamin E alone or in combination with other supplements.4 They found an increase in the overall death rate among those taking high doses of vitamin E (400IU or more per day), with a clear dose-response relationship; i.e., the higher the dose, the more likely that death was the outcome. There were an extra 39 deaths per 10,000 people taking the supplements, compared to those not taking vitamin E
- Lawson from the National Cancer Institute at Bethesda, MD, looked at the relationship between multivitamin use and the five-year risk of prostate cancer in more than 295,000 men who were cancer-free when they enrolled in the National Institutes of Health Diet and Health Study in 1995 and 1996.7 They found a 32% increase in the risk of advanced prostate cancer, and a 98% increase in the 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
Risks of antioxidants
The risk of taking antioxidant vitamin supplements was characterized further by Bjelakovic’s group from Copenhagen in 2007.6 This major meta-analysis (with nearly a quarter of a million participants) looked at death rates from all causes for people taking antioxidant supplements versus no treatment in 68 trials. 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 the use of vitamin and mineral supplements continues to increase in most western countries.
In his editorial, Bjelakovic answers the utopian lament “Why is it not possible to take a vitamin pill to obtain the same effect as a balanced diet?” as follows: “Antioxidant supplements in pills are synthetic, factory processed, and may not be safe compared with their naturally occurring counterparts.” 8 He hypothesized that the increase in death rates may be because these antioxidant supplements were given to people in middle- and high-income countries who already enjoy diets rich in vitamins and trace elements.
Spotlight on specific supplements
Swank placed all of the people in his low saturated fat studyon a multivitamin supplement. But that was before definitive evidence was available about their unexpected negative effects on health. The evidence is now clear: multivitamins, particularly vitamins A and E and beta-carotene, cannot be considered beneficial or safe; they should be avoided by people consuming a healthy diet. On the OMS diet, these and other essential vitamins should be readily available in the food itself.
According to available evidence, a number of individual supplements may be of value in MS. Let’s look at those.
An extremely important nutrient, vitamin B12 is found primarily in meat, especially liver, and in eggs and dairy products. No plant foods can be relied on as a definite source of B12. You need it to maintain a healthy nervous system, and it’s key in the metabolism of fatty acids, which are essential for the maintenance of myelin.
Prolonged B12 deficiency can lead to nerve degeneration and irreversible neurological damage. But deficiency is more commonly caused by failure to absorb B12 from the intestine, rather than by a dietary deficiency.
People with low levels of stomach acid are susceptible to B12 deficiency, which is also known to occur in vegans. In people taking drugs that lower stomach acid (such as ranitidine or omeprazole), a vegan diet increases the risk of B12 deficiency – though it may take years for deficiency disease to develop after changing to a diet low in B12.
This deficiency is surprisingly common, even among non-vegans and people with normal stomach acid levels. One Australian study showed that about a quarter of people over the age of 50 had low B12 levels.9
Fortunately, B12 is completely non-toxic, so it can do no harm. People with MS on vegan diets like the one OMS recommends should consider taking 250 to 1,000 micrograms of B12 per week, although many find that regular testing does not reveal any deficiency (particularly for those who consume seafood frequently). Contrary to popular belief, B12 oral supplements are very effective, so injections are not necessary.10-12 Also, B12 is quite cheap.
MS and B12 deficiency are pretty similar in terms of their inflammatory and neurodegenerative processes. It’s hard to tell them apart sometimes, owing to similarities in their clinical features and MRI findings. Also, decreased B12 levels are fairly common in people with MS.
In addition to its role in myelin formation, B12 has important immunomodulatory and neurotrophic effects, a bit like vitamin D. Researchers have raised the possibility that B12 deficiency causes MS, suggesting close monitoring of B12 levels in people with MS, as well as B12 supplementation.13
In general, the B group vitamins are extremely important for normal brain function. They are inexpensive and easily absorbed. Higher doses may be needed when alcohol intake is high. The B group also includes folate. Folate deficiency has most recently been linked to Alzheimer’s Disease.
Folate is intimately related to normal nerve cell development, as shown by the reduced incidence of spina bifida in babies born to mothers taking folate supplements.14 B group vitamins form an optional part of the OMS Recovery Program.
You can get large amounts of this major antioxidant from a vegan diet, particularly from fresh fruit and vegetables. There is little evidence from large-scale clinical trials that supplementation has any benefit for a variety of different diseases. But many authorities report striking improvements in individual patients in conditions such as cancer, particularly when the vitamin is given intravenously.
On the basis of the above meta-analyses, and unlike the other antioxidants, vitamin C appears to be safe, even in doses of up to two grams per day. However, the Mayo Clinic reports that in some cases, amounts above that, known as megadoses, may cause unpleasant side effects.
To supplement with iron or not to supplement? Many people are concerned that they will become iron-deficient on a vegan plus fish diet. This risk is really theoretical, because a good vegan diet includes a reasonable amount of iron. For women, particularly those with heavy periods, iron may be an issue. It is possible to get iron levels checked periodically. Because excess iron is very toxic, it’s better to take a smaller amount.
US researchers have noted that abnormal iron accumulation is common in a variety of neurodegenerative diseases, including MS, and evidence suggests that iron plays a role in promoting inflammation.15 They showed that the common Th1 pro-inflammatory cytokines were more toxic to nerve cells when loaded with iron.
Glucosamine, an extract from the shells of shellfish, is sold in capsule form at most health food shops. Recently it has been shown in experimental animals to produce a shift in the balance of the Th1/Th2 immune response toward a suppressive Th2 response, and to significantly suppress EAE (the animal form of MS) in the laboratory.16
The authors suggested a potential use for glucosamine, either alone or in combination with disease-modifying drugs, to enhance their benefit and reduce their doses in MS and possibly other autoimmune disorders. N-acetyl glucosamine appears to be the most helpful form.
The antioxidant alpha-lipoic acid (LA) has been shown to produce favorable immune effects in the laboratory17; to suppress and treat EAE (the animal form of MS)18; and to stabilize the blood-brain barrier in an animal model.19 LA has been further studied in humans.20 In a 14-day placebo-controlled study, investigators found that LA inhibited enzymes responsible for helping T cells get access to the CNS. They postulated that it may prove useful in treating MS, and noted that patients generally tolerated oral LA well. LA may ultimately be a useful treatment for MS.
There is no evidence that antioxidants improve the outcome in MS. The influential Nurses’ Health Studies I and II in the US, looking at the development of MS in groups of more than 176,000 US nurses, found no association between the development of MS and the consumption of vitamins C or E or dietary carotenoids (such as beta-carotene), whether taken as supplements or within food.21 Recent evidence has raised serious concerns about taking multivitamins regularly, on the basis that they increase overall death rates in controlled clinical trials.
Multivitamins should be avoided
Multivitamins are not recommended for people with MS, although individual supplements, including vitamin B12 and iron, may be necessary for people following a vegan plus fish diet. B group vitamins in general are thought to support optimal brain function, but people eating the OMS diet usually get plentiful amounts of the B group and other vitamins.
Supplements Overcoming MS does recommend:
- Omega 3 supplements 20 - 40 ml of cold-pressed flaxseed oil
- Vitamin D supplements up to 10,000 IU in the winter months
- B12 and Iron (if needed)
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. Bleys J, Miller ER, 3rd, Pastor-Barriuso R, et al. Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2006;
84:880-887; quiz 954-885
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. 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
8. Bjelakovic G, Gluud C. Surviving antioxidant supplements. J Natl Cancer Inst 2007; 99:742-743
9. Flood VM, Smith WT, Webb KL, et al. Prevalence of low serum folate and vitamin B12 in an older Australian population. Aust N Z J Public Health 2006; 30:38-41
10. Butler CC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract 2006; 23:279-285
11. Bial AK. Review: Limited evidence from 2 randomised controlled trials suggests that oral and intramuscular vitamin B12 have similar effectiveness for vitamin B12 deficiency. Evid Based Med 2006; 11:9
12. Rabunal Rey R, Monte Secades R, Pena Zemsch M, et al. [Should we use oral replacement for vitamin B12 deficiency as the first option of treatment?]. Rev Clin Esp 2007; 207:179-182
13. Miller A, Korem M, Almog R, et al. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci 2005
14. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007; 85:285S-288S
15. Zhang X, Haaf M, Todorich B, et al. Cytokine toxicity to oligodendrocyte precursors is mediated by iron. Glia 2005
16. Zhang GX, Yu S, Gran B, et al. Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response. J Immunol 2005; 175:7202-7208
17. Marracci GH, McKeon GP, Marquardt WE, et al. alpha lipoic acid inhibits human T-cell migration: Implications for multiple sclerosis. J Neurosci Res 2004
18. Morini M, Roccatagliata L, Dell’Eva R, et al. Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol 2004; 148:146-153
19. Schreibelt G, Musters RJ, Reijerkerk A, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J Immunol. 2006; 177:2630-7
20. Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 2005; 11:159-65
21. Zhang SM, Hernán MA, Olek MJ, et al. Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women. Neurology 2001; 57:75-80