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Vitamin D and Its Effects on Multiple Sclerosis:
An Annotated Bibliography
by:
Katherine Venegas
National College of Natural Medicine
Goldberg P, Polaroid Corp; Fleming MC, Tufts-New England Medical Center and St. Elizabeth’s
Hospital; Picard EH, Massachusetts General Hospital. Multiple Sclerosis: Decreased relapse
rate through dietary supplementation with calcium, magnesium, and vitamin D. Med Hyp.
1984;21:193-200.
This study was one of the first trials to be ever be conducted on the effects of vitamin D
supplementation and MS relapse rates. The study created by a group of doctors who specialized in
MS. They recruited MS patients for a self-pairing study where trial outcomes were compared to
each individual’s past medical history. Patients were given calcium, magnesium, and vitamin D
supplement in weight-relative amounts for a healthy population. After one year of taking the
supplements, exacerbations decreased by over one half than the hypothesis. However, the study
had a couple of limitations. Researchers wanted to look at patients with an extreme frequency of
relapses, which reduced the number of eligible participants. The sample size was small, consisting
of only sixteen patients. Then, six patients dropped out due to their dislike of cod liver oil. Using
capsules or giving out recipes to cover the fishy taste could have been a solution to this problem.
Thirdly, compliance was self-reported, which may lead to discrepancies. Although the 6-month
follow -up blood tests showed supplemented serum levels of vitamin D. Overall, this was an early
study with fairly reliable statistics from which other studies have been developed.
Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of
multiple sclerosis in monozygotic twins. Mult Scler. 2005;11:500-3.
This study looked at differences of childhood sun exposure in monozygotic twins when one twin
had MS and is unaffected. Participates were found through the International Twin Study database.
The monozygotic twins were asked questions about which twin spent more time sun tanning, going
to the beach and participating in team sports. Only twins in agreement were included in the data
analysis. After adjusting the data analysis for multiple confounding factors, this study concludes
that there is an inverse relationship between the frequency of sun exposure and the development
of MS in monozygotic twins. This evidence supports the findings of an article published by van der
Mei, et al. two years previous. Both studies recognize that adequate sun exposure before the age
of 15 is critical to the preventing the development of MS. Since both studies found the same
evidence in different parts of the world, it is entirely possible that this is a sound and reliable
conclusion. This paper was published by a group of doctors from the Department of Preventative
Medicine at the University of Southern California for a group of their scientific peers.
Souilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, and Mononen I. A
longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels
indicate the importance of vitamin D and calcium homeostasis regulation in multiple
sclerosis. J. Neurol. Neurosurg. Psychiatry. 2008 Feb;79:152-7.
This was the first longitudinal study that compared vitamin D and calcium serum levels of multiple
sclerosis patients versus a group of healthy subjects. Two forms of vitamin D were measured
25(OH)D and intact parathyroid hormone (iPTH). 25(OH)D is found in the blood. iPTH is known for
its accuracy in measuring vitamin D levels. MS patients and healthy subjects had almost identical
levels of serum 25(OH)D with vitamin D deficiency occurred in half of all participants. This may be
because the study took place in Finland, a country with limited sunlight. Therefore, natural vitamin
D synthesis is limited. Relapses often occur in the early spring, which ties in with the findings that
MS patients have lower levels of iPTH and serum calcium in the fall and winter months. It was also
discovered that relapses always occur when there are low 25(OH)D levels and high iPTH serum
levels. Interestingly enough, no relapses took place at high 25(OH)D levels. It is unknown whether
increasing vitamin D reduces the risk of a relapse, or if the relapse itself causes a decrease in
serum vitamin D. These results suggest that vitamin D deficiency is not a risk factor for MS, but
that high doses should be investigated for relevance in relapse prevention or disease treatment.
This conclusion is in accordance with the articles written by Goldberg, et al. and Munger et al. This
study also shows that iPTH levels are better indicators of MS relapse than monitoring 25(OH)D.
Further studies relating iPTH and multiple sclerosis should be conducted in the future. The authors
of this study are researchers from the Departments of Neurology, Virology, and Biochemistry of the
University of Turku, Finland along with the Turku University Hospital. This journal article was
written for a group of scientific peers.
Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake
and incidence of multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-5
This is a cohort study that used the Nurses’ Health Study (NHS) and Nurses’ Health Study II
participates as a pool of initial subjects. The purpose of this research was to find out if vitamin D
protects against developing MS. Dietary assessments were taken every 4 years before MS
diagnosis to establish the average dietary amount of vitamin D consumed, and after highly specific
inclusion criteria were met, data was collected and analyzed with regard to relative risk and age of
participants. The data was separated and analyzed in quintiles; it showed that women who had a
higher vitamin D intake at the baseline had a 40% lower risk of developing MS than those who had
lesser intakes. Women who take a multivitamin that contains vitamin D also had an inverse risk for
MS. These results did not change when the data was adjusted for two other known contributing
factors, smoking and latitude of birth. It was also found that there is no correlation between dietary
vitamin D intake and MS risk. The main limitation of the study was that vitamin D could not be
addressed independently of all the other nutrients in the multivitamins; the others do comment on
that and recognize that other nutrients like vitamin E, folic acid, zinc and various B vitamins may
also decrease MS risk. This study was written in collaboration with doctors at Harvard University,
the University of California at Irvine, Women’s Hospital in Boston, the Multiple Sclerosis Center and
Channing Laboratory.
Van der Mei IA, Ponsonby AL, Dwyer T, et al. Past exposure to sun, skin phenotype, and risk of
multiple sclerosis: case-control study. BMJ 2003;327:316.
It is well known that sunlight enables dermal vitamin D synthesis. This study looks at the
correlation between sunlight exposure and how it affects the risk of developing MS. All MS
diagnosis were confirmed via magnetic resonance imaging, spinal cord abnormalities and
neurological disability lasting more than one year. Climate and regional specific questions about
how much time was spent in the sun as a teenager, and how often other contributing factors were
involved in the subjects from age 10-15, like sunblock, vitamin D supplementation and history of
immunizations and infections. Silicone hand casts were used to measure actinic damage to most
accurately calculate lifetime sun exposure and a spectrophotometer was used to record cutaneous
melanin. This study found that increased actinic damage led to a decreased risk of MS. It was
also discovered that sun exposure before the age of 15 has protective effects against MS. Disease
duration was not influenced by actinic damage, but low melanin density subjects had a strong
tendency to develop MS earlier on in life. This was a case-control study conducted by contributors
associated with a University or Hospital in Australia including a biostatistician, a professor, a Ph.D.
student, and a neurologist. This article’s intended audience was a group of scientific peers.

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Vitamin D and Multiple Sclerosis - An Annotated Biography

  • 1. Vitamin D and Its Effects on Multiple Sclerosis: An Annotated Bibliography by: Katherine Venegas National College of Natural Medicine Goldberg P, Polaroid Corp; Fleming MC, Tufts-New England Medical Center and St. Elizabeth’s Hospital; Picard EH, Massachusetts General Hospital. Multiple Sclerosis: Decreased relapse rate through dietary supplementation with calcium, magnesium, and vitamin D. Med Hyp. 1984;21:193-200. This study was one of the first trials to be ever be conducted on the effects of vitamin D supplementation and MS relapse rates. The study created by a group of doctors who specialized in MS. They recruited MS patients for a self-pairing study where trial outcomes were compared to each individual’s past medical history. Patients were given calcium, magnesium, and vitamin D supplement in weight-relative amounts for a healthy population. After one year of taking the supplements, exacerbations decreased by over one half than the hypothesis. However, the study had a couple of limitations. Researchers wanted to look at patients with an extreme frequency of relapses, which reduced the number of eligible participants. The sample size was small, consisting of only sixteen patients. Then, six patients dropped out due to their dislike of cod liver oil. Using capsules or giving out recipes to cover the fishy taste could have been a solution to this problem. Thirdly, compliance was self-reported, which may lead to discrepancies. Although the 6-month follow -up blood tests showed supplemented serum levels of vitamin D. Overall, this was an early study with fairly reliable statistics from which other studies have been developed. Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Mult Scler. 2005;11:500-3. This study looked at differences of childhood sun exposure in monozygotic twins when one twin had MS and is unaffected. Participates were found through the International Twin Study database. The monozygotic twins were asked questions about which twin spent more time sun tanning, going to the beach and participating in team sports. Only twins in agreement were included in the data analysis. After adjusting the data analysis for multiple confounding factors, this study concludes that there is an inverse relationship between the frequency of sun exposure and the development of MS in monozygotic twins. This evidence supports the findings of an article published by van der Mei, et al. two years previous. Both studies recognize that adequate sun exposure before the age of 15 is critical to the preventing the development of MS. Since both studies found the same evidence in different parts of the world, it is entirely possible that this is a sound and reliable conclusion. This paper was published by a group of doctors from the Department of Preventative Medicine at the University of Southern California for a group of their scientific peers. Souilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, and Mononen I. A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels
  • 2. indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2008 Feb;79:152-7. This was the first longitudinal study that compared vitamin D and calcium serum levels of multiple sclerosis patients versus a group of healthy subjects. Two forms of vitamin D were measured 25(OH)D and intact parathyroid hormone (iPTH). 25(OH)D is found in the blood. iPTH is known for its accuracy in measuring vitamin D levels. MS patients and healthy subjects had almost identical levels of serum 25(OH)D with vitamin D deficiency occurred in half of all participants. This may be because the study took place in Finland, a country with limited sunlight. Therefore, natural vitamin D synthesis is limited. Relapses often occur in the early spring, which ties in with the findings that MS patients have lower levels of iPTH and serum calcium in the fall and winter months. It was also discovered that relapses always occur when there are low 25(OH)D levels and high iPTH serum levels. Interestingly enough, no relapses took place at high 25(OH)D levels. It is unknown whether increasing vitamin D reduces the risk of a relapse, or if the relapse itself causes a decrease in serum vitamin D. These results suggest that vitamin D deficiency is not a risk factor for MS, but that high doses should be investigated for relevance in relapse prevention or disease treatment. This conclusion is in accordance with the articles written by Goldberg, et al. and Munger et al. This study also shows that iPTH levels are better indicators of MS relapse than monitoring 25(OH)D. Further studies relating iPTH and multiple sclerosis should be conducted in the future. The authors of this study are researchers from the Departments of Neurology, Virology, and Biochemistry of the University of Turku, Finland along with the Turku University Hospital. This journal article was written for a group of scientific peers. Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-5 This is a cohort study that used the Nurses’ Health Study (NHS) and Nurses’ Health Study II participates as a pool of initial subjects. The purpose of this research was to find out if vitamin D protects against developing MS. Dietary assessments were taken every 4 years before MS diagnosis to establish the average dietary amount of vitamin D consumed, and after highly specific inclusion criteria were met, data was collected and analyzed with regard to relative risk and age of participants. The data was separated and analyzed in quintiles; it showed that women who had a higher vitamin D intake at the baseline had a 40% lower risk of developing MS than those who had lesser intakes. Women who take a multivitamin that contains vitamin D also had an inverse risk for MS. These results did not change when the data was adjusted for two other known contributing factors, smoking and latitude of birth. It was also found that there is no correlation between dietary vitamin D intake and MS risk. The main limitation of the study was that vitamin D could not be addressed independently of all the other nutrients in the multivitamins; the others do comment on that and recognize that other nutrients like vitamin E, folic acid, zinc and various B vitamins may also decrease MS risk. This study was written in collaboration with doctors at Harvard University, the University of California at Irvine, Women’s Hospital in Boston, the Multiple Sclerosis Center and Channing Laboratory. Van der Mei IA, Ponsonby AL, Dwyer T, et al. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 2003;327:316.
  • 3. It is well known that sunlight enables dermal vitamin D synthesis. This study looks at the correlation between sunlight exposure and how it affects the risk of developing MS. All MS diagnosis were confirmed via magnetic resonance imaging, spinal cord abnormalities and neurological disability lasting more than one year. Climate and regional specific questions about how much time was spent in the sun as a teenager, and how often other contributing factors were involved in the subjects from age 10-15, like sunblock, vitamin D supplementation and history of immunizations and infections. Silicone hand casts were used to measure actinic damage to most accurately calculate lifetime sun exposure and a spectrophotometer was used to record cutaneous melanin. This study found that increased actinic damage led to a decreased risk of MS. It was also discovered that sun exposure before the age of 15 has protective effects against MS. Disease duration was not influenced by actinic damage, but low melanin density subjects had a strong tendency to develop MS earlier on in life. This was a case-control study conducted by contributors associated with a University or Hospital in Australia including a biostatistician, a professor, a Ph.D. student, and a neurologist. This article’s intended audience was a group of scientific peers.