Multiple Sclerosis

"Vitamin D and Multiple Sclerosis," Hayes CE, et al, PSEBM, 1997;216:21-27; Vitamin D - It has been shown that 1,25- dihydroxyvitamin D3, the hormonal form of vitamin D3, can completely prevent experimental autoimmune encephalomyelitis, a widely accepted mouse model of multiple sclerosis (MS).  The authors hypothesize that one crucial environmental factor is the degree of sunlight exposure catalyzing the production of vitamin D3 in the skin, and that the hormonal form of vitamin D3 is a selective immune system regulator inhibiting this autoimmune disease.  Under low-sunlight conditions, insufficient vitamin D3 is produced, limiting the production of 1,25- dihydroxyvitamin D3 and increasing the risk for MS.  This theory can explain the remarkable geographic distribution of MS, which is nearly zero in equatorial regions and increases dramatically with latitude in both hemispheres.  In Switzerland, there is a high MS rate at low altitudes and a low MS rate at high altitudes.  In Norway, there is a high MS prevalence inland and a lower MS prevalence along the coast. Ultraviolet light intensity is greater at high altitudes, resulting in an increased vitamin D3 synthetic rate, which accounts for the low MS rates at higher altitudes.  On the Norwegian coast, fish is consumed at high rates and fish oils are rich in vitamin D3.  It is possible that 1,25-dihydroxyvitamin D3 or its analogs may have great therapeutic potential in patients with MS.  This also opens up the possibility that MS may be preventable in genetically susceptible individuals with early intervention strategies that provide adequate levels of hormonally active 1,25-dihydroxyvitamin D3 or its analogs.

This model of MS conclusions makes perfect sense and the suggestion that there may be definite preventive strategies for MS is encouraging. It also mentions the potential benefit in treating MS patients with 1,25-dihydroxyvitamin D3, which is the most hormonally-active form of vitamin D. At the very least, we can obtain vitamin D levels in MS patients. Consider Bio-D Mulsion (D3, cholecalciferol emulsified) with 400 IU per drop. It would be good if some intervention trials could be started soon, since MS has no known curative therapy, and vitamin D3 could be given safely. Other things that seem to help MS patients are vitamin B1, B12 and folic acid, sometimes food elimination diets, a low saturated fat diet rich in omega 3 fatty acids, antioxidants and treatment of the gut for yeast or abnormal bacterial pathogens. Heavy metals and mercury evaluation are also warranted.  A low saturated fat diet along with an increase in omega-3 fatty acids over the long run has been shown to help multiple sclerosis symptoms and affect the condition on the cellular level. Consider B12 Folate, Biomega-3 or Flax Seed Oil. Also call for further information on what the Balancing Body Chemistry clinicians have found to be useful, i.e. Iron/Copper Free Multi-Plus, Bioctasol Forte, Nuclezyme Forte, Neonatal Multi-Gland, etc.

"Are We Really Dying for a Tan?" Ness AR, et al, B M J, July 10, 1999;319:114-116.  Several studies have shown that vitamin D, which is a marker for sunlight exposure, is protective for cardiovascular disease. It has been shown that elevated 25-hydroxycholecalciferol concentrations equal to or above the median reduce the incidence of myocardial infarction. Although these findings are not conclusive, coronary death is such a significant cause of death, that even a modest protective effect could result in a substantial reduction in mortality. Mental health may be improved in individuals by relaxing and enjoying the sun, and sun exposure may help prevent seasonal affective disorder. Sunlight may help with psychiatric illness. Other diseases such as childhood rickets may be reduced with sun exposure as well as osteomalacia and fractures in adulthood. Psoriasis can be improved with sun exposure, and there may be a relationship between reduced sun exposure and the incidence of multiple sclerosis. In conclusion, there is evidence that the potential benefits of exposure to sunlight may outweigh the widely publicized adverse effects on the incidence of skin cancer. The authors note that in one study, the use of sunscreens was associated with reduced vitamin D concentrations. The risk/benefit ratio should be studied and made more public since individuals may have different risk factors that may make it advantageous to get sun exposure versus not. "Nonburning" exposure to sunlight, slow and gradual without sunburn, is essential to most for good health.

DIABETES MELLITUS - Glucose Tolerance, Insulin, Vitamin D - One- hundred and forty-two elderly Dutchmen aged 70 to 88 years were evaluated for vitamin D status.  Thirty-nine percent were vitamin D depleted.  The 1-hour glucose test and area under the glucose curve were inversely associated with serum concentrations of 25- hydroxyvitamin D.  With the exclusion of newly diagnosed diabetic patients, total insulin concentration during the oral glucose tolerance test was also inversely associated with the concentration of 25-hydroxyvitamin D.  The authors conclude that hypovitaminosis D may be a significant risk factor for glucose intolerance. "Vitamin D, Glucose Tolerance and Insulinemia in Elderly Men," Baynes, K. C. R., et al, Diabetologia, 1997;40:344-347.  (Address: Dr. B. J. Boucher, Cellular Mechanisms Research Group, The Royal London School of Medicine and Dentistry, Whitechapel, London E1 1BB, United Kingdom)  26930/27328 [end] 

PEARL:  Vitamin D is a "sleeper" nutrient.  It is  frequently deficient and a very important nutrient with respect to immune function, bone loss and, in this case, possibly diabetes.  Vitamin D is one nutrient which may actually be classically deficient in the U.S. population, especially in the elderly.  It is a nutrient that many, including myself, have not supplemented many patients with due to a fear of an "irreversible" toxicity.  Many people are not getting moderate sun exposure, which increases their risk of vitamin D deficiency.  In one study, 36% of elderly men and 47% of elderly women in the general population had low vitamin D status. In the elderly, 800-1600 I.U. of vitamin D may be given, especially if vitamin D levels are low.  In those house-bound or institution- bound, or in those 60 years of age or older, assessment of serum 25-hydroxyvitamin D, which is the main storage form of vitamin D, should be recommended.  One can also assess status of 1,25- dihydroxyvitamin D, which is the most active metabolite.  The former is most important for assessment, however.  Vitamin D levels probably should be part of a normal chemistry screen in those greater than 50 years of age, especially those with a history of low sunlight exposure.  Thirty minutes of sunlight exposure 2 to 3 times a week may also help maintain adequate vitamin D status. Exposure to sunlight through windows does not activate vitamin D synthesis.  With regards to the above article this is really an important issue. If vitamin D is a critical nutrient in improving insulin sensitivity in peripheral tissues and in insulin secretion by the beta cells in the pancreas, then exposure to sunlight, food fortification and vitamin D supplementation are very important, especially for those at risk for adult onset diabetes.


Reinhold Vieth, Ph.D., F.C.A.C.B. Pathology and Laboratory Medicine Mt. Sinai Hospital 600 University Avenue Toronto, Ontario M5G 1X5, Canada (416) 586-5920 / (416) 586-8628 FAX / e-mail: 

"Vitamin D Supplementation, 25-Hydroxyvitamin D Concentrations, and Safety," Am J Clin Nutr 1999;69:842-856.#32120 

Kirk Hamilton: What is your educational background and current position? 

Reinhold Vieth:     I started my graduate training in 1974 at the Hospital for Sick Children in Toronto, with physicians who specialized in pediatric bone disease. After that, I did a residency in clinical chemistry and later was given a position as director of the Bone Mineral Laboratory, at the University of Toronto and at Mount Sinai Hospital. I specialize in biochemical tests related to osteoporosis. I am currently an associate professor at the University of Toronto and lecture to students in nutrition, pharmacy, medicine and at the postgraduate level. 

KH:  What are the possible beneficial roles of vitamin D in different conditions? 

RV:  From my point of view, vitamin D is the most misunderstood and underestimated of vitamins. Most professionals think it is only useful in the prevention of rickets, and more recently, they have come to appreciate that it may be helpful for those with osteoporosis. There is a great deal of evidence that vitamin D does other things as well. Vitamin D is the raw material for a hormone made by the kidney to regulate calcium, but other tissues have the capacity to make the vitamin D hormone and respond to it directly. Such local production and use of signal molecules is called paracrine activity. In some ways, vitamin D is like cholesterol. Cholesterol is the raw material for making steroid hormones including sex steroids and cortisol. However, unlike cholesterol, which is always present, the amount of vitamin D available for hormone production is minute and arbitrary, mainly dependent upon ultraviolet-B exposure, and to a lesser degree upon our dietary intake. There are several cancers whose prevalence increases as one heads north in latitude, these include breast, ovarian and prostate cancers. Similarly, multiple sclerosis is more common in regions with less ultraviolet light. Average blood pressure in populations increases the farther those populations are away from the Equator, and the percentage of adults in those populations diagnosed as having hypertension increases as well. It is likely that the progressive decline in the supply of vitamin D associated with northern latitudes contributes to these diseases. These other functions of vitamin D are supported only by circumstantial evidence and more research is needed. 

KH:  Would you consider that vitamin D is frequently a deficient nutrient? 

RV:  Based on objective, measurable criteria, vitamin D deficiency is by far the most common "nutritional" deficiency at Northern latitudes, particularly in people over 60 years of age. It is relatively difficult to become deficient in most nutrients, especially the ones people seem to worry about. Vitamin A and vitamin E are relatively abundant in the food supply, iron deficiency is not all that common and we do not need all that much of the B vitamins. When people consume conventional diets, it is very difficult for them to develop objectively measurable insufficiencies in these. The laboratory test used to measure vitamin D nutrition is a good one, but it is so rarely tested that when the news comes out that people are vitamin D deficient, it comes across as a surprise. We now recognize that there are milder degrees of vitamin D deficiency. Thus, the circulating vitamin D level we consider to be insufficient (note, this is not as bad as deficient) has been going up. When the decision point we use to classify a deficiency increases, more people fall into the category we call insufficient. In the winter, half of the people on my hospital's laboratory staff fall into the insufficient vitamin D category. This situation is at least as bad in the elderly. 

KH:  What is the best way to assess vitamin D nutritional status? 

RV:  When vitamin D enters the bloodstream, the liver metabolizes it to 25-hydroxy-vitamin D [25(OH)D], which we measure. 25(OH)D is the key indicator of vitamin D nutritional status. This 25(OH)D has a half-life of about 2 months, (after 2 months, half is left, after 4 months, 1/4 is left, etc.) And the long half-life would explain why we can survive without consuming vitamin D during the winter months. One frequent mistake is to assume it is better to measure the vitamin D hormone, 1,25(OH)2D. This hormone is really a measure of the kidney endocrine function, its levels in circulation are about one, one-thousandth of those of 25(OH)D, they fluctuate depending upon calcium requirements, and the 1,25(OH)2D levels decline only once vitamin D depletion is virtually complete. 

KH:  What are the best food sources of vitamin D? 

RV:  I contend that vitamin D is not a natural part of the human diet. It is not present in plants normally consumed by humans and the best dietary source would be fatty fish such as salmon, cod or halibut. I am sure that few prehistoric humans would have consumed these food sources. In essence, vitamin D is the sunshine vitamin. Most of the vitamin D that we do get from foods is artificially added to it. There is essentially no vitamin D naturally present in milk. 

KH:  Is sunlight exposure enough to maintain adequate vitamin D stores and if so, how does one get that amount of vitamin D with regard to exposure? 

RV:  Vitamin D is made in the skin as a byproduct of the skin's production of the cholesterol necessary for skin cell membranes. When ultraviolet light shines upon the cholesterol precursor, 7- dehydro-cholesterol, the molecule breaks open and automatically converts into vitamin D3 (vitamin D2 was a product conveniently synthesized from treated yeast fat extract, but which we have shown is probably only 1/4 as potent as vitamin D3). Exposure of all of the skin of an adult to a non-burning amount of ultraviolet light (15 minutes of summer sun for a white person), provides at least 10,000 IU of vitamin D. However, because the skin of people over 65 years of age produces less cholesterol, the same sunshine results in only about one-third the amount of vitamin D as would be made by a younger person. Lastly, as the sun sits lower in the sky during winter months, there is not enough ultraviolet in the light that reaches earth to generate vitamin D. In Toronto or Boston, we cannot make any vitamin D from October until late February and the situation is worse at the farther north latitudes of Europe. One thing that should indicate what a powerful influence vitamin D has had on humans is that it is probably the reason northern Europeans have fairer skin than people in the South. Skin pigmentation is beneficial because it protects against the harmful effects of ultraviolet light. However, the pigment acts as a sun block and thereby increases the time required to generate vitamin D. As humans first migrated northwards, there would have been a natural selection in favor of lighter skin. A dark-skinned girl would have been more likely to develop rickets, she would have developed a miss-shapen pelvis and as a woman would have miscarried. 

KH:  Who should be screened for vitamin D deficiency? 

RV:  I think people with bone disease should certainly be tested for serum 25(OH)D levels. However, I feel strongly that our nutritional guidelines concerning vitamin D are way out of whack for adults. Cod-liver oil has been used for about 200 years to prevent rickets in babies, and the adult 200 IU RDA is equivalent to half a teaspoon of cod-liver oil. The adult intake was set arbitrarily and it does not stand up to any critical scrutiny. I don't think anyone would have to be screened if nutritional guidelines for vitamin D were set appropriately. 

KH:  What do you believe should be the daily intake of vitamin D for the average person? 

RV:  The strongest preparation available over-the-counter is 1000 IU pills. For the time being, I would suggest this to be a minimally adequate intake during the winter. I estimate that sailors in US submarines are deprived of the equivalent of about 2000 IU per day. Of course, if you live on the beach in California and take in its sunshine regularly, you probably do not need the vitamin D supplements. 

KH:  What is too high a dose of vitamin D? 

RV:  It was possible to purchase up to 50,000 unit doses over-the- counter into the early 1970s. This was too high, and the clear risk of toxicity gave vitamin D a bad rap. I am told by physicians that when they ask their patients to take 1000 IU of vitamin D, the patients are warned by pharmacists about vitamin D toxicity, because the dose exceeds the current RDA and the patients are afraid to take it. 

KH:  Is vitamin D supplementation something that should occur routinely in the elderly as well as assessment? 

RV:  Absolutely! There is essentially no vitamin D in the foods that we eat. The elderly generally avoid the sun, and even when they do get sunshine, their skin makes far less vitamin D than that of younger people. We now have results from large, placebo- controlled trials to show that moderately higher doses of vitamin D, when combined with calcium, preserves bone strength and reduces the likelihood of fractures. Note that the calcium and vitamin D combination products currently available do not contain the 700 units/day or more vitamin D needed to provide the bone-preserving benefit people expect the product to provide. Furthermore, there was a fine presentation at last year's American Society for Bone and Mineral Research meeting showing vitamin D supplementation lessened the body sway of elderly people - improved balance means less falls and less fractures. 

KH:  What are the side effects to vitamin D? 

RV:  I know that you are asking about the potential toxicity of vitamin D, and in severe cases (consuming more than 40,000 IU/day for many months) the circulating calcium levels increase. With this there is constipation, excessive urination, reduced reflexes and higher calcium in the urine. However, I would contend that the more harmful situation relates to the side effects of too low a level of vitamin D nutrition. 

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VITAMIN D - 25-Hydroxyvitamin D - Subjects received 260 nmol (equivalent to approximately 4,000 IU) of vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 days.  Vitamin D3 treatment resulted in serum 25-hydroxyvitamin D increasing from 41.3 to 64.6 nmol/l after supplementation.  With vitamin D2 supplementation, 25-hydroxyvitamin D levels increased from 43.7 to 57.4 nmol/l after treatment.  The increase in 25-hydroxyvitamin D with vitamin D3 supplementation was 1.7 times that obtained from vitamin D2.  The assumption that vitamin D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.  "Evidence That Vitamin D3 Increases Serum 25- hydroxyvitamin D More Efficiently Than Does Vitamin D2," Trang HM, et al, Am J Clin Nutr, 1998;68:854-858.  30832

Bone Loss - Calcium at 0.5-0.6 g bid with 400 IU vitamin D3      increased bone density. Lower doses of sodium fluoride at 50      mg/d along with 2000 mg of calcium and vitamin D2 at 50,000      IU weekly may be of greater benefit than higher fluoride      doses. In the Framingham Heart Study, men and women with the      highest intakes of potassium and magnesium had the strongest      bone density. In 25 premenopausal women, lifetime weight-      bearing exercise was significantly correlated with total and      peripheral bone mineral density.