Vitamin D intake and incidence of multiple sclerosis
George C.Ebers, University of Oxford
A. D. Sadovnick and Reinhold Veith
Published February 19, 2004
We read with interest the article by Munger et al. A protective effect of sunlight on MS risk was first suggested by
Acheson. [1] Vitamin D is a potential mediator of this relationship. We are sympathetic to the hypothesis being tested [2] by Munger et al. but have the following concerns:
1) NHS studied women age >30, but more than half of females with
MS have onset below this age. Of those accrued, some 50,000 were excluded
from analysis. [3] Was this done before testing the vitamin D hypothesis?
What were the characteristics, when known, of exclusions for calculated
vitamin D estimates compared to those retained? Perhaps MS risk can be
altered after age 30, but earlier ages are implicated from migration
studies.
2) 61 and then 130 questions were asked in the NHS and NHS II
questionnaires. Was correction made for multiple analyses?
Could the authors explain the assumptions and approach used to calculate
the "p trend" statistic that forms the basis of this report?
3) The apparent association of low MS risk with intake of <_400 units="units" of="of" vitamin="vitamin" d="d" from="from" supplements="supplements" per="per" day="day" seems="seems" at="at" odds="odds" with="with" the="the" recent="recent" report="report" that="that" those="those" intakes="intakes" have="have" minimal="minimal" effects="effects" on="on" _25ohd="_25ohd" levels.="levels." furthermore="furthermore" young="young" women="women" who="who" took="took" multivitamins="multivitamins" were="were" more="more" likely="likely" to="to" exercise="exercise" outdoors.="outdoors." multivitamin="multivitamin" use="use" correlated="correlated" better="better" summer="summer" levels="levels" than="than" winter="winter" _4.="_4." production="production" in="in" skin="skin" requires="requires" uvb="uvb" is="is" not="not" intense="intense" enough="enough" latitudes="latitudes"/>30 for at least one month
each winter.
4) The association of MS with latitude seems unambiguous from
Kurtzke’s US veteran’s studies and from Australia.[5] The lack of
interaction with latitude in this study [3] is surprising if vitamin D intake
in adulthood is causally related to MS risk, since D levels and putative
functional effects are dependent on latitude related UVB.
5) We note that the NHSII cohort had more MS “cases /person –y”
(97/7.5x10 5) compared to the NHS cohort (76/1.5x106). These data are
difficult to compare. As age specific incidences seem less in NHSII3, is
there evidence for a decreasing incidence or prevalence in the areas
surveyed?
6) How does the nurses’ D intake relate to that in the general
population? Vitamin intake could vary by ethnicity. Did the definition
of “white” include ethnic groups known to be resistant to MS? Recall bias has been reported within weeks of illness associated
events. Has the accuracy of four yearly reports been validated for the
measures in this paper?
References
1. Acheson ED, Bachrach CA, Wright FM. Some comments on the
relationship of the distribution of multiple sclerosis to latitude, solar
radiation and other variables. Acta Psychiat (Scand.) 1960; 35 Suppl 147:
132.
2. Steckley J, Dyment D, Sadovnick D, Risch N, Hayes C, Ebers GC and
the Canadian Collaborative Study Group. Genetic analysis of vitamin D
related genes in multiple sclerosis patients. Neurology 2000; 54:729-732.
3. Hernan MA, Olek MJ, Ascherio A. Geographic variation of MS
incidence in two prospective studies of US women. Neurology 1999; 53:1711
-1718.
4. Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Wintertime
vitamin D insufficiency is common in young Canadian women, and their
vitamin D intake does not prevent it. Eur J Clin Nutr 2001; 55:1901-1097.
5. Hammond SR, English DR, McLeod JG. The age-range of risk of
developing multiple sclerosis: evidence from a migrant population in
Australia. Brain 2000; 123:968-974.
We read with interest the article by Munger et al. A protective effect of sunlight on MS risk was first suggested by Acheson. [1] Vitamin D is a potential mediator of this relationship. We are sympathetic to the hypothesis being tested [2] by Munger et al. but have the following concerns:
1) NHS studied women age >30, but more than half of females with MS have onset below this age. Of those accrued, some 50,000 were excluded from analysis. [3] Was this done before testing the vitamin D hypothesis? What were the characteristics, when known, of exclusions for calculated vitamin D estimates compared to those retained? Perhaps MS risk can be altered after age 30, but earlier ages are implicated from migration studies.
2) 61 and then 130 questions were asked in the NHS and NHS II questionnaires. Was correction made for multiple analyses? Could the authors explain the assumptions and approach used to calculate the "p trend" statistic that forms the basis of this report?
3) The apparent association of low MS risk with intake of <_400 units="units" of="of" vitamin="vitamin" d="d" from="from" supplements="supplements" per="per" day="day" seems="seems" at="at" odds="odds" with="with" the="the" recent="recent" report="report" that="that" those="those" intakes="intakes" have="have" minimal="minimal" effects="effects" on="on" _25ohd="_25ohd" levels.="levels." furthermore="furthermore" young="young" women="women" who="who" took="took" multivitamins="multivitamins" were="were" more="more" likely="likely" to="to" exercise="exercise" outdoors.="outdoors." multivitamin="multivitamin" use="use" correlated="correlated" better="better" summer="summer" levels="levels" than="than" winter="winter" _4.="_4." production="production" in="in" skin="skin" requires="requires" uvb="uvb" is="is" not="not" intense="intense" enough="enough" latitudes="latitudes"/>30 for at least one month each winter.
4) The association of MS with latitude seems unambiguous from Kurtzke’s US veteran’s studies and from Australia.[5] The lack of interaction with latitude in this study [3] is surprising if vitamin D intake in adulthood is causally related to MS risk, since D levels and putative functional effects are dependent on latitude related UVB.
5) We note that the NHSII cohort had more MS “cases /person –y” (97/7.5x10 5) compared to the NHS cohort (76/1.5x106). These data are difficult to compare. As age specific incidences seem less in NHSII3, is there evidence for a decreasing incidence or prevalence in the areas surveyed?
6) How does the nurses’ D intake relate to that in the general population? Vitamin intake could vary by ethnicity. Did the definition of “white” include ethnic groups known to be resistant to MS? Recall bias has been reported within weeks of illness associated events. Has the accuracy of four yearly reports been validated for the measures in this paper?
References
1. Acheson ED, Bachrach CA, Wright FM. Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiat (Scand.) 1960; 35 Suppl 147: 132.
2. Steckley J, Dyment D, Sadovnick D, Risch N, Hayes C, Ebers GC and the Canadian Collaborative Study Group. Genetic analysis of vitamin D related genes in multiple sclerosis patients. Neurology 2000; 54:729-732.
3. Hernan MA, Olek MJ, Ascherio A. Geographic variation of MS incidence in two prospective studies of US women. Neurology 1999; 53:1711 -1718.
4. Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr 2001; 55:1901-1097.
5. Hammond SR, English DR, McLeod JG. The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia. Brain 2000; 123:968-974.