Vitamin D and Parkinson's Disease

Parkinson’s disease

Parkinson’s disease (PD) is a chronic progressive neurological disease. It is linked to decreased production of dopamine, a nerve transmitter. PD is marked by tremor of resting muscles, rigidity, slowness of movement, impaired balance, and shuffling gait. PD also impairs speech and other bodily functions. Approximately 500,000 people in the United States suffer from Parkinson’s, and 50,000 new cases are diagnosed each year.

Risk factors

There are a number of risk-modifying factors for Parkinson’s disease:

• Chemicals in the environment: Chemicals, such as pesticides, are associated with PD.
• Low uric acid levels in the blood: Uric acid acts as an antioxidant in the brain, where it could affect risk of PD.
• Red meat consumption: This food increases uric acids, which could reduce risk of PD.
• Milk consumption: Milk, especially milk protein (casein), increases the risk of PD. (Several studies have found lower uric acid levels associated with milk consumption.)

Sunlight exposure and PD risk

Solar ultraviolet-B (UVB) light from the sun is the most important source of vitamin D for many people. Thus, studies of sunlight exposure can indicate whether vitamin D reduces the risk of PD:

• A study in Denmark found that outdoor work and more time spent outdoors were associated with reduced risk of PD.
• In the United States, there is increased prevalence of PD at higher latitudes. There is less solar UVB in areas farther from the equator.

Vitamin D and Parkinson’s disease

Vitamin D levels

Two studies of vitamin D and PD indicate that:

• In southeastern United States, people with PD have lower vitamin D blood levels than those without PD.
• In Finland, higher vitamin D levels  were associated with reduced the risk of developing PD by two-thirds. This result was noted at a 29-year follow-up. However, the usefulness of a single blood measurement loses predictive value as time increases.

How vitamin D works

The mechanisms of how vitamin D lowers the risk of PD are not well understood. All cells in the body, including those in the brain, have vitamin D receptors (VDRs). VDRs are activated by calcitriol, the active form of vitamin D. When activated, VDRs control the expression of many genes or how genetic material is used. Vitamin D may also reduce inflammation in the brain.

Prevention

There are no reported studies using vitamin D to reduce the risk of PD. The effects of vitamin D may occur over the course of many years. This would make it difficult to determine the amount of vitamin D required. However, based on results for other diseases, it appears that keeping vitamin D levels above 40 ng/mL (100 nmol/L) would be beneficial. The rule of thumb is that vitamin D levels rise by 6–10 ng/mL (15–25 nmol/L) for each 1000 international units (IU) (25 mcg)/day of vitamin D3. Vitamin D3 is the active form of vitamin D that is produced by the skin. However, there is considerable person-to-person variability. Thus, vitamin D levels should be measured both before and three months after starting supplements.

Vitamin D and calcium

In France, a patient with PD and low vitamin D levels (13 ng/mL [33 nmol/L]) was treated with 4000 IU [100 mcg]/day vitamin D and 1000 mg/day calcium. As a result, PD symptoms were greatly reduced.

Treatment

Those with PD generally have lower bone mineral density and an increased risk of falls and hip fractures. It seems advisable that those with PD seek to raise vitamin D levels to those consistent with optimal health, greater than 40 ng/mL (100 nmol/L).

Acknowledgements

William B. Grant, Ph.D.
Sunlight, Nutrition, and Health Research Center (SUNARC)
P.O. Box 641603
San Francisco, CA 94164-1603, USA
www.sunarc.org
wbgrant@infionline.net

The summary was reviewed by:

• Cedric Annweiler <ceannweiler@chu-angers.fr>
• Marian L. Evatt <mevatt@emory.edu>

Complete bibliography of research used in this summary

The research we have cited in our summary is listed below, with links to PubMed abstracts and full-text for those who wish to explore further.

References

1. Anderson, C. Checkoway, H. Franklin, G. M. Beresford, S. Smith-Weller, T. Swanson, P. D. Dietary factors in Parkinson’s disease: the role of food groups and specific foods. Mov Disord. 1999 Jan; 14 (1): 21-7.
2. Anderson, R. F. Harris, T. A. Dopamine and uric acid act as antioxidants in the repair of DNA radicals: implications in Parkinson’s disease. Free Radic Res. 2003 Oct; 37 (10): 1131-6.
3. Andreadou, E. Nikolaou, C. Gournaras, F. Rentzos, M. Boufidou, F. Tsoutsou, A. Zournas, C. Zissimopoulos, V. Vassilopoulos, D. Serum uric acid levels in patients with Parkinson’s disease: their relationship to treatment and disease duration. Clin Neurol Neurosurg. 2009 Nov; 111 (9): 724-8.
4. Annweiler, C. Schott, A. M. Berrut, G. Chauvire, V. Le Gall, D. Inzitari, M. Beauchet, O. Vitamin D and ageing: neurological issues. Neuropsychobiology. 2010 Aug; 62 (3): 139-50.
5. Ascherio, A. LeWitt, P. A. Xu, K. Eberly, S. Watts, A. Matson, W. R. Marras, C. Kieburtz, K. Rudolph, A. Bogdanov, M. B. Schwid, S. R. Tennis, M. Tanner, C. M. Beal, M. F. Lang, A. E. Oakes, D. Fahn, S. Shoulson, I. Schwarzschild, M. A. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol. 2009 Dec; 66 (12): 1460-8.
6. Barnum, C. J. Tansey, M. G. Modeling neuroinflammatory pathogenesis of Parkinson’s disease. Prog Brain Res. 2010; 184113-32.
7. Betemps, E. J. Buncher, C. R. Birthplace as a risk factor in motor neurone disease and Parkinson’s disease. Int J Epidemiol. 1993 Oct; 22 (5): 898-904.
8. Cekic, M. Cutler, S. M. Vanlandingham, J. W. Stein, D. G. Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats. Neurobiol Aging. 2009 May 29;
9. Chen, H. Mosley, T. H. Alonso, A. Huang, X. Plasma urate and Parkinson’s disease in the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol. 2009 May 1; 169 (9): 1064-9.
10. Chen, H. O’Reilly, E. McCullough, M. L. Rodriguez, C. Schwarzschild, M. A. Calle, E. E. Thun, M. J. Ascherio, A. Consumption of dairy products and risk of Parkinson’s disease. Am J Epidemiol. 2007 May 1; 165 (9): 998-1006.
11. Chen, H. Zhang, S. M. Hernan, M. A. Willett, W. C. Ascherio, A. Diet and Parkinson’s disease: a potential role of dairy products in men. Ann Neurol. 2002 Dec; 52 (6): 793-801.
12. Choi, H. K. Liu, S. Curhan, G. Intake of purine-rich foods, protein, and dairy products and relationship to serum levels of uric acid: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2005 Jan; 52 (1): 283-9.
13. Dahodwala, N. Siderowf, A. Xie, M. Noll, E. Stern, M. Mandell, D. S. Racial differences in the diagnosis of Parkinson’s disease. Mov Disord. 2009 Jun 15; 24 (8): 1200-5.
14. Dalbeth, N. Wong, S. Gamble, G. D. Horne, A. Mason, B. Pool, B. Fairbanks, L. McQueen, F. M. Cornish, J. Reid, I. R. Palmano, K. Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial. Ann Rheum Dis. 2010 Sep; 69 (9): 1677-82.
15. Derex, L. Trouillas, P. Reversible parkinsonism, hypophosphoremia, and hypocalcemia under vitamin D therapy. Mov Disord. 1997 Jul; 12 (4): 612-3.
16. Driver, J. A. Smith, A. Buring, J. E. Gaziano, J. M. Kurth, T. Logroscino, G. Prospective cohort study of type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care. 2008 Oct; 31 (10): 2003-5.
17. Ebadi, M. Sharma, S. K. Ghafourifar, P. Brown-Borg, H. El Refaey, H. Peroxynitrite in the pathogenesis of Parkinson’s disease and the neuroprotective role of metallothioneins. Methods Enzymol. 2005; 396276-98.
18. Evatt, M. L. Beyond vitamin status: is there a role for vitamin d in Parkinson disease?. Arch Neurol. 2010 Jul; 67 (7): 795-7.
19. Evatt, M. L. Delong, M. R. Khazai, N. Rosen, A. Triche, S. Tangpricha, V. Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol. 2008 Oct; 65 (10): 1348-52.
20. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005 Jan; 29 (1): 21-30.
21. Fernandes de Abreu, D. A. Eyles, D. Feron, F. Vitamin D, a neuro-immunomodulator: Implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology. 2009 Jun 20;
22. Gao, X. Chen, H. Choi, H. K. Curhan, G. Schwarzschild, M. A. Ascherio, A. Diet, urate, and Parkinson’s disease risk in men. Am J Epidemiol. 2008 Apr 1; 167 (7): 831-8.
23. Gao, X. Chen, H. Fung, T. T. Logroscino, G. Schwarzschild, M. A. Hu, F. B. Ascherio, A. Prospective study of dietary pattern and risk of Parkinson disease. Am J Clin Nutr. 2007 Nov; 86 (5): 1486-94.
24. Gao, X. Simon, K. C. Han, J. Schwarzschild, M. A. Ascherio, A. Family history of melanoma and Parkinson disease risk. Neurology. 2009 Oct 20; 73 (16): 1286-91.
25. Ghadirian, P. Shatenstein, B. Verdy, M. Hamet, P. The influence of dairy products on plasma uric acid in women. Eur J Epidemiol. 1995 Jun; 11 (3): 275-81.
26. Grant, W. B. Dietary links to Alzheimer’s disease. Alz Dis Rev. 1997; 242-55.
27. Hernan, M. A. Takkouche, B. Caamano-Isorna, F. Gestal-Otero, J. J. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson’s disease. Ann Neurol. 2002 Sep; 52 (3): 276-84.
28. Hirtz, D. Thurman, D. J. Gwinn-Hardy, K. Mohamed, M. Chaudhuri, A. R. Zalutsky, R. How common are the “common” neurologic disorders?. Neurology. 2007 Jan 30; 68 (5): 326-37.
29. Hofman, A. Collette, H. J. Bartelds, A. I. Incidence and risk factors of Parkinson’s disease in The Netherlands. Neuroepidemiology. 1989; 8 (6): 296-9.
30. Holmoy, T. Moen, S. M. Assessing vitamin D in the central nervous system. Acta Neurol Scand Suppl. 2010; (190): 88-92.
31. Hu, G. Jousilahti, P. Bidel, S. Antikainen, R. Tuomilehto, J. Type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care. 2007 Apr; 30 (4): 842-7.
32. Invernizzi, M. Carda, S. Viscontini, G. S. Cisari, C. Osteoporosis in Parkinson’s disease. Parkinsonism Relat Disord. 2009 Jun; 15 (5): 339-46.
33. Jankovic, J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr; 79 (4): 368-76.
34. Jomova, K. Vondrakova, D. Lawson, M. Valko, M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010 Aug 22;
35. Kenborg, L. Lassen, C. F. Ritz, B. Schernhammer, E. S. Hansen, J. Gatto, N. M. Olsen, J. H. Outdoor work and risk for Parkinson’s disease: a population-based case-control study. Occup Environ Med. 2010 Sep 30;
36. Kim, J. S. Kim, Y. I. Song, C. Yoon, I. Park, J. W. Choi, Y. B. Kim, H. T. Lee, K. S. Association of vitamin D receptor gene polymorphism and Parkinson’s disease in Koreans. J Korean Med Sci. 2005 Jun; 20 (3): 495-8.
37. Knekt, P. Kilkkinen, A. Rissanen, H. Marniemi, J. Saaksjarvi, K. Heliovaara, M. Serum vitamin D and the risk of Parkinson disease. Arch Neurol. 2010 Jul; 67 (7): 808-11.
38. Kones, R. Parkinson’s disease: mitochondrial molecular pathology, inflammation, statins, and therapeutic neuroprotective nutrition. Nutr Clin Pract. 2010 Aug; 25 (4): 371-89.
39. Kuhn, D. M. Sakowski, S. A. Sadidi, M. Geddes, T. J. Nitrotyrosine as a marker for peroxynitrite-induced neurotoxicity: the beginning or the end of the end of dopamine neurons?. J Neurochem. 2004 May; 89 (3): 529-36.
40. Kurtzke, J. F. Goldberg, I. D. Parkinsonism death rates by race, sex, and geography. Neurology. 1988 Oct; 38 (10): 1558-61.
41. Kutzing, M. K. Firestein, B. L. Altered uric acid levels and disease states. J Pharmacol Exp Ther. 2008 Jan; 324 (1): 1-7.
42. Lorefalt, B. Toss, G. Granerus, A. K. Bone mass in elderly patients with Parkinson’s disease. Acta Neurol Scand. 2007 Oct; 116 (4): 248-54.
43. Lux, W. E. Kurtzke, J. F. Is Parkinson’s disease acquired? Evidence from a geographic comparison with multiple sclerosis. Neurology. 1987 Mar; 37 (3): 467-71.
44. Newmark, H. L. Newmark, J. Vitamin D and Parkinson’s disease–a hypothesis. Mov Disord. 2007 Mar 15; 22 (4): 461-8.
45. Noonan, C. W. Reif, J. S. Yost, M. Touchstone, J. Occupational exposure to magnetic fields in case-referent studies of neurodegenerative diseases. Scand J Work Environ Health. 2002 Feb; 28 (1): 42-8.
46. Pacher, P. Beckman, J. S. Liaudet, L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan; 87 (1): 315-424.
47. Park, J. Yoo, C. I. Sim, C. S. Kim, H. K. Kim, J. W. Jeon, B. S. Kim, K. R. Bang, O. Y. Lee, W. Y. Yi, Y. Jung, K. Y. Chung, S. E. Kim, Y. Occupations and Parkinson’s disease: a multi-center case-control study in South Korea. Neurotoxicology. 2005 Jan; 26 (1): 99-105.
48. Park, M. Ross, G. W. Petrovitch, H. White, L. R. Masaki, K. H. Nelson, J. S. Tanner, C. M. Curb, J. D. Blanchette, P. L. Abbott, R. D. Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Neurology. 2005 Mar 22; 64 (6): 1047-51.
49. Sanchez, B. Relova, J. L. Gallego, R. Ben-Batalla, I. Perez-Fernandez, R. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res. 2009 Feb 15; 87 (3): 723-32.
50. Sato, Y. Honda, Y. Iwamoto, J. Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease. Neurology. 2007 Mar 20; 68 (12): 911-5.
51. Sato, Y. Honda, Y. Iwamoto, J. Kanoko, T. Satoh, K. Abnormal bone and calcium metabolism in immobilized Parkinson’s disease patients. Mov Disord. 2005 Dec; 20 (12): 1598-603.
52. Sato, Y. Iwamoto, J. Kanoko, T. Satoh, K. Alendronate and vitamin D2 for prevention of hip fracture in Parkinson’s disease: a randomized controlled trial. Mov Disord. 2006 Jul; 21 (7): 924-9.
53. Sato, Y. Kaji, M. Tsuru, T. Satoh, K. Kondo, I. Vitamin K deficiency and osteopenia in vitamin D-deficient elderly women with Parkinson’s disease. Arch Phys Med Rehabil. 2002 Jan; 83 (1): 86-91.
54. Sato, Y. Kikuyama, M. Oizumi, K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology. 1997 Nov; 49 (5): 1273-8.
55. Sato, Y. Manabe, S. Kuno, H. Oizumi, K. Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999 Jan; 66 (1): 64-8.
56. Schlesinger, I. Schlesinger, N. Uric acid in Parkinson’s disease. Mov Disord. 2008 Sep 15; 23 (12): 1653-7.
57. Schwartz, G. G. Multiple sclerosis and prostate cancer: what do their similar geographies suggest?. Neuroepidemiology. 1992; 11 (4-6): 244-54.
58. Schwarzschild, M. A. Schwid, S. R. Marek, K. Watts, A. Lang, A. E. Oakes, D. Shoulson, I. Ascherio, A. Hyson, C. Gorbold, E. Rudolph, A. Kieburtz, K. Fahn, S. Gauger, L. Goetz, C. Seibyl, J. Forrest, M. Ondrasik, J. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol. 2008 Jun; 65 (6): 716-23.
59. Smith, M. P. Fletcher-Turner, A. Yurek, D. M. Cass, W. A. Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res. 2006 Apr; 31 (4): 533-9.
60. Surmeier, D. J. Guzman, J. N. Sanchez-Padilla, J. Goldberg, J. A. What causes the death of dopaminergic neurons in Parkinson’s disease?. Prog Brain Res. 2010; 18359-77.
61. Tüchsen, F. Jensen, A. A. Agricultural work and the risk of Parkinson’s disease in Denmark, 1981-1993. Scand J Work Environ Health. 2000 Aug.; 26 (4): 359-62.
62. Tuohimaa, P. Keisala, T. Minasyan, A. Cachat, J. Kalueff, A. Vitamin D, nervous system and aging. Psychoneuroendocrinology. 2009 Dec; 34 Suppl 1S278-86.
63. van der Veen, R. C. Hinton, D. R. Incardonna, F. Hofman, F. M. Extensive peroxynitrite activity during progressive stages of central nervous system inflammation. J Neuroimmunol. 1997 Jul; 77 (1): 1-7.
64. Wang, J. Y. Wu, J. N. Cherng, T. L. Hoffer, B. J. Chen, H. H. Borlongan, C. V. Wang, Y. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001 Jun 15; 904 (1): 67-75.
65. Weisskopf, M. G. O’Reilly, E. Chen, H. Schwarzschild, M. A. Ascherio, A. Plasma urate and risk of Parkinson’s disease. Am J Epidemiol. 2007 Sep 1; 166 (5): 561-7.
66. Yanagihara, R. Garruto, R. M. Gajdusek, D. C. Tomita, A. Uchikawa, T. Konagaya, Y. Chen, K. M. Sobue, I. Plato, C. C. Gibbs, C. J., Jr. Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia. Ann Neurol. 1984 Jan; 15 (1): 42-8