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Vitamin D Supplementation and Parkinson's Disease

A Report from PDF's Medical Policy Committee

Summary:  

Vitamin D is an essential vitamin supplied by the effects of sunlight on the skin and by dietary intake.  While vitamin D has been recognized as an essential contributor to bone health for many years, more recently, it has received attention as a potential treatment for Parkinson’s disease and other non-skeletal disorders.  

Vitamin D deficiency is common in Parkinson’s disease.  There is evidence that vitamin D is active in brain regions commonly affected in Parkinson’s disease and that vitamin D may reduce the toxicity of agents normally used to model PD in animals.  Despite this evidence, there is no convincing evidence in human studies that vitamin D supplementation reduces the risk of Parkinson’s disease or favorably alters progression of Parkinson’s disease disability over time. However, people with Parkinson’s disease may benefit from the effects of vitamin D on bone health and fracture risk. 

The following report of the PDF Medical Policy Committee analyzes the available data about vitamin D supplementation and Parkinson’s disease and makes two conclusions: 

  • The PDF Medical Policy Committee advises that people with Parkinson’s disease discuss the risks and benefits of vitamin D supplementation with their primary care physicians, who can best monitor for states of insufficiency and deficiency and correct low levels in the interest of bone health.    
  • At the present time, the PDF Medical Policy Committee does not have sufficient scientific information to comment on the role of vitamin D on the underlying brain impairments of PD itself.  

For additional information, browse the full report below, or call PDF's toll-free HelpLine at (800) 457-6676. Please note that this report was prepared by Kathleen Shannon, M.D., PDF Research Center at Rush University Medical Center, Chicago, IL, in conjunction and consultation with members of the PDF Medical Policy Committee led by Christopher Goetz, M.D., also at the PDF Research Center at Rush University Medical Center, Chicago, IL. See full list of reviewers at the end of this report.

Full report:

More than 50 percent of United States residents use vitamin supplements, and the supplements industry continues a pattern of increased strength, with $28 billion in annual sales in 2010.[1]  Vitamin D is an essential vitamin.  For more than a century, its role in the development and maintenance of bone has been recognized.  Deficiency early in life causes rickets, and later in life causes osteomalacia, loss of bone strength.  In older adults, vitamin D deficiency is thought to increase the risk of falls and fractures.[2]  Although it can be acquired through the diet, 80 percent of vitamin D is produced by exposure of the skin to ultraviolet B rays in sunlight, leading to its nickname, “the sunshine vitamin.”  Dietary sources include oily fish, egg yolks, food supplements and fortified margarine, milk and cereal. [3] People at high risk of vitamin D deficiency include: breastfed babies, older adults, those with dark skin or little exposure of the skin to sunlight, those who restrict fat intake or who poorly absorb fat, those who are obese or have had gastric bypass surgery or who are taking certain medications (steroids, orlistat, cholestyramine, phenobarbital and phenytoin).[4]  Vitamin D levels are measured in the blood using a test for 25-hydroxy-Vitamin D (25(OH)D).  Levels of 25(OH)D of less than or equal to 30 ng/mL are considered to reflect insufficiency, and levels of less than or equal to 20 ng/mL are considered to reflect deficiency.  [5] It has been estimated that as many as one billion of the world’s citizens may be Vitamin D deficient.  Unlike many other vitamin deficiency syndromes that are mostly isolated to third world environments, US adults also are at significant risk of vitamin D deficiency. [4]

In addition to its well-recognized role in bone health, more recent research has suggested vitamin D may be important in many other body tissues.  A number of studies have shown associations of low vitamin D levels with cancer, cardiovascular disease, diabetes and neurodegenerative disorders. [6, 7]  It is thought that Vitamin D may be important to brain development, to production of factors that support the health of and protect brain cells, and to chemical messenger production. [8]  

Several lines of evidence point to a possible role of Vitamin D in PD.  Studies of brain tissue show that receptors for vitamin D are widely distributed in brain areas affected by PD, suggesting an important role in normal function. [9] Some animal studies show protective effects of vitamin D against toxin-induced parkinsonism, the most widely used animal model of PD.  [10, 11]  Human studies suggest that differences in the genes that control vitamin D receptors may influence the risk of developing PD. [12] One Finnish study in healthy people suggested that those who developed PD over 29 years follow-up were more likely to have had low vitamin D levels at baseline than those that remained healthy.  In this study, people with the highest level of vitamin D developed PD only one-third as often as those with the lowest levels. [13] Several studies in people with PD have shown that 55-85 percent are vitamin D insufficient and 23 percent are vitamin D deficient.  [5,14] In addition, PD subjects, especially those who are vitamin D insufficient tend to have low bone mineral density and increased risk of bone fracture. [15] While such studies are intriguing, they fall short of proving that low vitamin D causes or directly contributes to the cause of PD, or that vitamin D supplementation will reduce the risk of PD or influence its progression.  These studies document an association of two findings (in this case low vitamin D and PD), but such this co-existence is not proof of causation.  One alternative explanation for such an association is that people with PD (even those very early in the development of the disease) get outside less frequently, thus have reduced sun exposure, resulting in low vitamin D.  Another possible explanation is that both low vitamin D and PD relate to a common underlying factor, yet to be defined.  In order to conclude that vitamin D deficiency is integral to the development or progression of PD, one would need to demonstrate that supplementation with the vitamin altered disease risk or progression, and convincing data do not yet exist.  There is only one published study comparing vitamin D to placebo (inactive tablets) in PD.  This study was small, but suggested that fewer vitamin D than placebo research subjects showed progression of disability over one year. [16] While interesting, such a finding requires replication in a larger group of people with Parkinson’s disease before any recommendations can be made.   

Because falling is dangerous and common in PD, it is reasonable to examine the effect of vitamin D on falls.  One study found that vitamin D supplementation failed to prevent falls in subjects with PD. [17] In contrast, studies are more supportive of an effect of vitamin D supplementation on falls and fractures in elderly non-PD subjects.  One recent review of multiple studies suggested that vitamin D supplementation in a dose resulting in blood 25(OH)D levels greater than 24 ng/mL reduced falls by about 20 percent. The American Geriatrics Society has recommended vitamin D and calcium supplementation to prevent falls and fractures in the elderly.  They recommend that adults 65 years old and older should consume 1000 IU Vitamin D daily along with calcium 1000-1200 mg daily. [2] Given the propensity for falls in PD, this official advice logically extends to people with PD in the same age ranges, though primary care physicians will want to tailor the decision to each individual and consider the risk for kidney stones and other problems associated with high dose calcium supplementation.   The PDF Medical Policy Committee, however, is well-aware of a dissenting view represented in an editorial in the Annals of Internal Medicine.  Four prominent physicians decried the exuberant use of various supplements, including vitamin D, in the United States, and stated that its “widespread use is not based on solid evidence that benefits outweigh harms.”[1,18]   

Whereas the above American Geriatrics Society recommendations relate to falls and fractures, there is considerably less enthusiasm for vitamin D supplementation as a specific treatment for non-skeletal disorders including PD.  One large ongoing study, VITAL will assess whether vitamin D supplementation reduces the risk of developing a number of diseases (though not specifically PD) in more than 20,000 research subjects. [19] Clearly, large well-designed studies comparing vitamin D to placebo in PD are warranted, and only such trials will one day clarify whether supplementation has salutary effects on the PD risk, clinical manifestations, and progression. 

For now, it seems prudent that vitamin D levels be monitored in people with PD by their primary care physicians and that those who have insufficient or deficient levels be treated to prevent and treat bone problems, but not to treat brain function.  Supplementation should be geared towards optimization of general and bone health and is best managed by the primary care physician who can consider the risk and benefits of supplementation in the context of overall health and function, and who can monitor the effects of supplementation.

References cited:

  1. Guallar, E., et al., Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann Intern Med, 2013. 159(12): p. 850-1.
  2. American Geriatrics Society Workgroup on Vitamin D supplementation for older adults, Recommendations Abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc, 2013.
  3. Prentice, A., G.R. Goldberg, and I. Schoenmakers, Vitamin D across the lifecycle: physiology and biomarkers. Am J Clin Nutr, 2008. 88(2): p. 500S-506S.
  4. Hilger, J., et al., A systematic review of vitamin D status in populations worldwide. Br J Nutr, 2014. 111(1): p. 23-45.
  5. Evatt, M.L., et al., Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol, 2008. 65(10): p. 1348-52.
  6. Holick, M.F., Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr, 2004. 80(6 Suppl): p. 1678S-88S.
  7. Autier, P., et al., Vitamin D status and ill health: a systematic review. Lancet diabetes-endocrinology, 2014. 2: p. 76-89.
  8. DeLuca, G.C., et al., Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol, 2013. 39(5): p. 458-84.
  9. Eyles, D.W., et al., Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat, 2005. 29(1): p. 21-30.
  10. Wang, J.Y., et al., Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res, 2001. 904(1): p. 67-75.
  11. Cass, W.A., M.P. Smith, and L.E. Peters, Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine. Ann N Y Acad Sci, 2006. 1074: p. 261-71.
  12. Butler, M.W., et al., Vitamin D receptor gene as a candidate gene for Parkinson disease. Ann Hum Genet, 2011. 75(2): p. 201-10.
  13. Knekt, P., et al., Serum vitamin D and the risk of Parkinson disease. Arch Neurol, 2010. 67(7): p. 808-11.
  14. Zhao, Y., et al., Vitamin D levels in Alzheimer's and Parkinson's diseases: a meta-analysis. Nutrition, 2013. 29(6): p. 828-32.
  15. van den Bos, F., et al., Bone mineral density and vitamin D status in Parkinson's disease patients. J Neurol, 2013. 260(3): p. 754-60.
  16. Suzuki, M., et al., Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease. Am J Clin Nutr, 2013. 97(5): p. 1004-13.
  17. Sato, Y., et al., Vitamin D reduces falls and hip fractures in vascular Parkinsonism but not in Parkinson's disease. Ther Clin Risk Manag, 2013. 9: p. 171-6.
  18. Moyer, V.A., M.L. LeFevre, and A.L. Siu, Vitamin D and calcium supplementation to prevent fractures in adults. Ann Intern Med, 2013. 159(12): p. 856-7.
  19. Manson, J.E., et al., The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials, 2012. 33(1): p. 159-71.

Reference: Authored by Kathleen Shannon, M.D., Rush University Medical Center, on behalf of the PDF Medical Policy Committee (MPC). Reviewed by MPC members, including Christopher Goetz, M.D., Chair, Rush University Medical Center; Roy N. Alcalay, M.D., Columbia University Medical Center; Robert Burke, M.D., Columbia University Medical Center; Stanley Fahn, M.D., Columbia University Medical Center; Blair Ford, M.D., Columbia University Medical Center; Jennifer Goldman, M.D., Rush University Medical Center; Katie Kompoliti, M.D., Rush University Medical Center; Leo Verhagen, M.D., Ph.D., Rush University Medical Center; and Cheryl Waters, M.D., Columbia University Medical Center.  Published April 2014.