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Other Supplements

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 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.


Despite intensive research, it is unclear which particular constituents of fruits and vegetables might be beneficial for health, but the antioxidant vitamins and elements have been most studied. The focus has been on antioxidants because it has been assumed that antioxidants may prevent damage to cells from oxidation. We know that oxidation plays a role in aging and in many diseases, including cardiovascular diseases and cancer.

A diet rich in vegetables, fruit, nuts, seeds and grains ensures a potent dietary mixture of vitamins, minerals and antioxidants. It also ensures that these substances are in their natural state, balanced with other food factors essential for their optimal function.
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The Risks Associated With Antioxidant and Multivitamin Supplements

The whole MS multivitamin, MS antioxidant question is quite vexed. The question is could we take antioxidant and multivitamin supplements instead of or in addition to getting them through our food. Several major studies published in the early 2000s have cast serious doubt over the safety of such supplements, raising the likelihood that taking antioxidant and vitamin 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 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 They 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 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. There were 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 1996.7 They found a 32% increased risk of advanced prostate cancer, and a 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 2000.8 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?’9 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 antioxidant 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.
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Should We Take Antioxidant or Multivitamin Supplements?

Swank placed all of the patients in his low saturated fat study on a multivitamin supplement. But that was before definitive evidence was available about their unexpected negative effects on health. The evidence is now clear, taking multivitamins, particularly the antioxidants vitamin E and A and beta-carotene, cannot be considered beneficial, or even safe, and should be avoided by people eating a healthy diet. On a diet like that recommended here, the intake of these and other essential vitamins should be quite high.

There have been many recommendations to supplement with quite large doses of vitamin E to guard against lipid peroxidation for people taking unsaturated oil supplements. Besides the above research about increasing death rates from vitamin E supplementation, research is now coming out on fish oil plus vitamin E supplementation for a range of diseases, but mainly in the area of heart disease. While the studies show a very beneficial effect for fish oil supplementation alone, they show no additional benefit from supplementing with vitamin E.10

So there is good evidence to suggest that people with MS should not take antioxidants or multivitamins. However, there are a number of individual supplemental vitamins which may be of value in MS according to available evidence.
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Vitamin B12

Vitamin B12 is an extremely important nutrient. It is a B group vitamin found primarily in meat, especially liver, eggs and dairy products. No plant foods can be relied on as a definite source of vitamin B12. It is necessary for the maintenance of a healthy nervous system and plays a key role in the metabolism of fatty acids essential for the maintenance of myelin. Prolonged B12 deficiency can lead to nerve degeneration and irreversible neurological damage. Deficiency is more commonly caused by failure to absorb B12 from the intestine rather than a dietary deficiency.

People with low levels of acid in the stomach are susceptible to deficiency. Deficiency is well known to occur in vegans. As many people are taking drugs which lower stomach acid levels, like ranitidine or omeprazole, if they are also on a vegan diet, there is a real risk of B12 deficiency. It can take many years for deficiency disease to develop after changing to diets low in B12. B12 deficiency is surprisingly common, even in people who are not on vegan diets or have low acid levels in their stomachs. One Australian study showed that about 23% of people aged over 50 had low vitamin B12 levels.11

Fortunately vitamin B12 is completely non-toxic, so it is impossible to do any harm by taking supplements. People with MS on vegan diets like the one recommended here really should be taking regular vitamin B12 tablets, of the order of 250 to 1,000 micrograms per week. It is quite effective by mouth, and does not require injection12-14, contrary to popular belief, and is quite cheap.

MS and vitamin B12 deficiency are pretty similar diseases in terms of their inflammatory and neurodegenerative processes. It is actually hard to tell the difference between them sometimes, due to similarities in clinical features and MRI findings. In addition, decreased levels of vitamin B12 are fairly common in MS patients. In addition to its role in myelin formation discussed above, B12 has important immunomodulatory and neurotrophic effects, a bit like vitamin D. Researchers have raised the possibility of B12 deficiency causing MS, and suggested close monitoring of vitamin B12 levels in people with MS, as well as B12 supplementation.15

The B group vitamins in general are extremely important for normal brain function. They are quite cheap and readily absorbed. The dose may need to be increased this if alcohol intake is high. The B group also includes folate. Folate deficiency has most recently been shown to be involved in causing 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.16
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Vitamin C

One of the major antioxidants is Vitamin C. You can get large amounts of this vitamin 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 a number of authorities report quite striking improvements in individual patients in conditions such as cancer, particularly when it is given intravenously. On the basis of the above meta-analyses, unlike the other antioxidants, vitamin C appears to be safe, even in large doses.


The MS iron supplement question is also problematic. Many people are concerned that they will become iron deficient on a vegan plus fish diet. This is really a theoretical risk, as a good vegan diet has a reasonable amount of iron in it. It is more of an issue for women, particularly those who have heavy periods. If this applies, it is possible to get iron levels checked periodically, or to take a small supplement. Excess iron is actually quite toxic and it is certainly better to be getting a small amount rather than a lot. Indeed, US researchers have noted that abnormal iron accumulation is common in a variety of neurodegenerative diseases, including MS, and there is evidence that iron plays a role in promoting inflammation.17 They showed that the common Th1 pro-inflammatory cytokines were more toxic to nerve cells if they were loaded with iron.


Glucosamine is an extract from the shells of shellfish and is sold in capsule form from 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 towards a suppressive Th2 response, and to significantly suppress the animal form of MS, EAE, in the laboratory.18 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.

Alpha-lipoic acid

Alpha-lipoic acid (LA) is an antioxidant which has been shown to have favourable immune effects in the laboratory19, to suppress and treat the animal model of MS, EAE20, and to stabilise the blood-brain barrier in an animal model.21 It has been further studied in humans.22 In a 14 day placebo-controlled study, the investigators found that LA inhibited enzymes responsible for helping T cells get access to the CNS. They postulated that it may therefore prove useful in treating MS. They found that oral LA was generally well tolerated by patients. LA may ultimately be a useful treatment for MS.
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There is no evidence that antioxidants improve the outcome from MS. The very influential Nurses’Health Study in the US, looking at the development of MS in over 176 000 US nurses, found no association between the intake of the antioxidant vitamins C or E, or dietary carotenoids (such as beta carotene) and the development of MS, either taken as vitamin supplements, or calculated from the foods they ate.23 Recent evidence has raised serious concerns about taking multivitamins regularly on the basis that they increase overall death rates in controlled clinical trials. They are not recommended in MS, although individual vitamins may be necessary for people following a vegan plus fish diet, including vitamin B12 and iron. B group vitamins in general are thought to be helpful for optimal brain function.
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  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. 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
  9. Bjelakovic G, Gluud C. Surviving antioxidant supplements. J Natl Cancer Inst 2007; 99:742-743
  10. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002; 105:1897-1903.
  11. 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
  12. 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
  13. 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
  14. 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
  15. Miller A, Korem M, Almog R, et al. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci 2005
  16. Pitkin RM. Folate and neural tube defects. Am J Clin Nutr 2007; 85:285S-288S
  17. Zhang X, Haaf M, Todorich B, et al. Cytokine toxicity to oligodendrocyte precursors is mediated by iron. Glia 2005
  18. 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
  19. Marracci GH, McKeon GP, Marquardt WE, et al. alpha lipoic acid inhibits human T-cell migration: Implications for multiple sclerosis. J Neurosci Res 2004
  20. 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