Deficiencies as PD cause/Vitamin D

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The inhabitants of Alaska are in something of a ferment about Vitamin D [1]. They can’t get enough of it. A petition in March 2011 to the State legislature [2] calls upon them to “adopt a prevention model of public health by increasing awareness about vitamin D deficiency, testing and supplementation.” A Vitamin D Wiki has also been set up to achieve this and it includes a video debate on the subject.

Vitamins [3] are essential organic compounds, which are required as nutrients in tiny amounts by an organism, and trigger all sorts of metabolic activity. The first discovery was Vitamin A (Retinol) in 1913, and the last discovery was Vitamin B9 (Folic Acid) in 1941. Their function, daily recommended allowance and the health consequences of over or under intake are well documented. They are associated with a number of diseases.

For example too little of Vitamin A can result in Night Blindness or Hyperkeratosis or Keratomalacia. Too much of Vitamin B5 on the other hand can induce Diarrhoea or Nausea or Heartburn. The same cannot be said, however, about Vitamin D.

Vitamin D [4] was isolated by an American researcher, Elmer McCollum in 1921. He called it Vitamin D because it was the fourth such compound to be identified. Nutritionally it is found in fish (particularly salmon and tuna) and in dairy products. It is also uniquely synthesised by the action of Ultra- Violet rays from sunlight on the skin. This last aspect introduces a number of deficiency risk factors:-

  • Diet. (Low consumption of Vitamin D nutrients and consequently greater reliance on skin absorption.)
  • Body Mass Index. (Large people have more skin and, being better insulated, tend to wear less clothing.)
  • Latitude. (The nearer individuals live to a pole, the shorter their winter UV exposure.)
  • Skin colour. (Dark skinned races evolved nearer to the equator, where there is an abundant supply of UV sunlight). They carry an in-built sun-screen. Whereas fair skinned races, who evolved nearer to the poles where UV sunlight is scarcer, have developed an enhanced skin capacity to absorb it.
  • Life style. (UV absorption is regulated by how much time people spend indoors and how much of their skin they cover up when they are outdoors.)

There are more than enough variables here to generate a deficiency disease of a personal and sporadic nature.

There does not seem to be a scientific consensus on what Vitamin D does and how much of it you need.

Vitamin D prevents rickets in children and osteomalacia in adults, and, together with calcium, helps to protect older adults from osteoporosis. Vitamin D also affects neuromuscular function, inflammation, and influences the action of many genes that regulate the proliferation, differentiation and apoptosis of cells.

Source - Wikipedia

Despite the many claims of benefit surrounding vitamin D in particular, the evidence did not support a basis for a causal relationship between vitamin D and many of the numerous health outcomes purported to be affected by vitamin D intake. Although the current interest in vitamin D as a nutrient with broad and expanded benefits is understandable, it is not supported by the available evidence. The established function of vitamin D remains that of ensuring bone health, for which causal evidence across the life stages exists and has grown since the 1997 DRIs were established (IOM,1997). The conclusion that there is not sufficient evidence to establish a relationship between vitamin D and health outcomes other than bone health does not mean that future research will not reveal a compelling relationship between vitamin D and another health outcome. The question is open as to whether other relationships may be revealed in the future.

Source - The Institute of Medicine (1997)


Deluca et al [5] examined the relationhship between Vitamin D and neurological disorders:-

This review highlights the epidemiological, neuropathological, experimental, and molecular genetic evidence implicating vitamin D as a candidate in influencing susceptibility to a number of psychiatric and neurological diseases. The strength of evidence varies for schizophrenia, autism, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, and is especially strong for MS


Willis et al (2010) [6] conducted a serial cross-sectional study of US PD patients who were Medicare beneficiaries aged 65 and over. Using over 450,000 Parkinson’s disease cases per year, they calculated Parkinson’s disease prevalence and annual incidence by race, age, sex, and county.

They found that over the 10 year period from 1995 to 2005 the incidence and prevalence of PD was stable. The overall prevalence among people aged 65 and over was 1.6%. Prevalence increased with age with no sign of a plateau. The highest prevalence was for white males and the lowest for Asian females. White people stood a 50% greater chance of contracting the disease than blacks or Asians. The incidence and prevalence of the disease in the Midwest- and Northeast regions was 2 to 10 times higher than in the Western and Southern counties. Prevalence was greater in urban than rural environments.

The relevance of this to Vitamin D is the indication that latitude and skin colour might be implicated as causative factors.

de Pedro-Cuesta et al (2009) [7] plotted the prevalence of PD in Spain. The resultant map showed a notable similarity to the one prepared by Willis et al for the United States, with a marked gradient running from north to south.

Alaska has to endure a long, dark, Arctic winter and has therefore an interest in settling the matter. The index to the Vitamin D [8] wiki links the compound to almost every known disease and it will be of no surprise to find that Parkinson’s Disease is listed. [9] .

Is there any scientific evidence to support the contention?

Wermouth et al (2004) [10] noted the high incidence of PD in the Faroe Islands (209 per 100,000 inhabitants) and in Greenland (187.5 per 100,000 inhabitants).

The hypothesis that Vitamin D deficiency and PD might be connected was proposed by Newmark and Newmark (2007) [11], and states:-

We hypothesize, based upon several lines of evidence, that documented chronically inadequate vitamin D intake in the United States, particularly in the northern states and particularly in the elderly, is a significant factor in the pathogenesis of PD. This hypothesis implies that dietary aid for prevention and therapy for PD is possible.

Vitamin D deficiency diseases are also of concern to the people of Finland. A Health Survey, Knecht et al(2008) [12] was conducted in 1997/98 and a cohort of 3,173 people between the ages of 59 and 79 years and free of PD selected for a follow-up survey. During the next 29 years 50 of them were diagnosed with PD. Frozen serum samples taken at the baseline date were then assessed for Vitamin D levels. A key paragraph in the paper is:-

The vitamin D receptors and an enzyme responsible for the formation of the active form 1,25-hydroxyvitamin D have been found in high levels in the substantia nigra, the region of the brain affected most by Parkinson disease. This raises the possibility that chronic inadequacy of vitamin D leads to the loss of dopaminergic neurons in the substantia nigra region and further Parkinson disease.

The conclusions of the study were:-

Individuals with higher serum vitamin D concentrations showed a reduced risk of Parkinson disease. The relative risk between the highest and lowest quartiles was 0.33 (95% confidence interval, 0.14-0.80) after adjustment for sex, age, marital status, education, alcohol consumption, leisure-time physical activity, smoking, body mass index, and month of blood draw. The results are consistent with the suggestion that high vitamin D status provides protection against Parkinson disease. It cannot, however, be excluded that the finding is due to residual confounding and further studies are thus needed.

Evatt et al (2008) [13]selected three cohorts – 100 with PD, 100 with AD and 100 without either. They found that more than half of the PD participants (55%) had vitamin D insufficiency compared with approximately a third of the controls. ‘Vitamin D insufficiency’ was defined as less than 30 nanograms per millilitre of blood of the 25-hydroxy form (the major storage form) of the vitamin and ‘deficiency’ as less than 20 nanograms per millilitre.

Their report states:-

The prevalence of vitamin D deficiency (25[OH]D, <20 ng/mL) in our PD cohort (23%) was slower than that previously observed in a Japanese PD cohort (50 of 71 patients with PD[85%]). Both insufficiency (36%) and deficiency (10%) in our control cohort were also less prevalent than reported in controls from a study of prostate cancer risk 20 (58% insufficient[<32 mg/mL] and 16% deficient [<20 ng/mL]). Because all our study participants resided in southern latitudes and were predominantly white and a greater proportion of our samples were collected in the summer to fall, a lower prevalence of hypovitaminosis D in all our cohorts is not unexpected. Also, the Japanese participants were drawn from a hospital population, whereas participants in this study were recruited from an outpatient clinic. Previous studies indicate that hospitalized patients have lower mean vitamin D levels than age matched participants recruited from the community. The higher prevalence of insufficiency in the PD cohorts compared with the control cohort is not unexpected given that PD may cause patients to have decreased activity levels and lower sunshine exposure.

Evatt et al (2011) [14] tested whether or not the high prevalence of Vitamin D deficiency in PD patients was the result of having a chronic disease causing reduced mobility. They examined 157 diagnosed PD patients in the early non-disabling stags of the disease. Their finding was :-

The prevalence of vitamin D insufficiency in patients with early PD was similar to or higher than those reported in previous studies. Vitamin D concentrations did not decline during progression of PD.

Collectively these findings mirror the analysis carried out by Simpson et al (2011) [15] who demonstrated a clear relationship between the prevalence of multiple sclerosis and latitude, which they attributed to Vitamin D creation.

Ramagopalan et al (2010) [16] published the results of a genomic study of Vitamin D. They used new DNA sequencing technology to create a map of vitamin D receptor binding across the human genome. The vitamin D receptor is a protein activated by vitamin D, which attaches itself to DNA and thus influences what proteins are made from the genetic code.

They found 2,776 binding sites for the vitamin D receptor along the length of the genome. These were unusually concentrated near a number of genes associated with susceptibility to autoimmune conditions such as MS, Crohn's disease, systemic lupus erythematosus (or 'lupus') and rheumatoid arthritis, and to cancers such as chronic lymphocytic leukaemia and colorectal cancer.

They also showed that vitamin D had a significant effect on the activity of 229 genes including IRF8, previously associated with MS, and PTPN2, associated with Crohn's disease and type 1 diabetes.

The results appear to show that Vitamin D deficiencies coupled with variations in an individual’s genetic make-up have the capacity to initiate a number of sporadic disease conditions. 20 Vitamin D receptors were identified which had previously been shown by gene associaton tests to have a high risk for PD.

Derex and Trouillas (1997) [17] describe the case of a 50 year old man who had been diagnosed with Parkinson’s Disease 13 years previously.

The disease had progressed to the point where he was admitted to hospital. His symptoms included “a slate of akinetic mutism, deep hypokinesia, masklike facies, extreme rigidity, inexhaustible blink reflex, and permanent severe resting tremor of four limbs.” The paper goes on to describe the treatment and outcone.

After the addition of 25-(OH) vitamin D3 (4,000 1U daily) and calcium supplements (1 g daily) to the ongoing conventional anti parkinsonian therapy, serum and urinary calcium and phosphorus values progressively normalized as well as serum 25-(OH) and 1,25-(OH)T vitamin D,.

The parkinsonism improved significantly during, the following year with decreased rigidity and akinesta and the antiparkinsonian drugs could be restricted to levodopa 375 mg daily. At 1-year follow-up, neurological examination revealed moderate rigidity without tremor.


Gordon, P.H. et al [18] calculated the prevalence of PD among American Indians and Alaskan Natives using data from 2002 to 2009. They found a crude prevalence of 143.8/100,000 – much higher than the national average. Prevalence increased with age through 84 years. The age-adjusted rate was 355.7 and was higher among men than women.

Khan and Lan [19] evaluated the role of Vitamin D in Parkinson’s disease.

Recent studies have highlighted a possible relationship between vitamin D and PD. Vitamin D may be beneficial in PD patients, as one patient showed improved rigidity and akinesia and was able to decrease their levodopa dosage after vitamin D therapy. Genetic studies have provided opportunities to determine what proteins may link vitamin D to PD pathology. Vitamin D can also act through a number of nongenomic mechanisms, including effects on protein expression, oxidative stress, inflammation, and cellular metabolism. Among the many forms of vitamin D, calcitriol (1,25-dihydroxyvitamin D3) is an attractive therapeutic candidate, because it is a particularly active metabolite, and its receptor is expressed in the CNS.


There is a growing number of indications that Vitamin D deficiency and the incidence and prevalence of Parkinson’s Disease are linked, but there is some polarisation of views as to whether this is a cause or an effect. To try to settle the matter a clinical study has been initiated by the Department of Veteran Affairs (USA), commencing in 2011 with the recruitment of a substantial cohort of PD patients [20]. Participants will be given Vitamin D supplements or placebos and measurements taken of balance, gait, falls, strength, and cognition. The results are due to be published in 2015.

Further Reading and Viewing[edit]

< Outdoor Trades much less likely to get Parkinson disease>

< Video Dr. Marion Evatt on the relationship of Vitamin D levels to skin colour and latitude.>

< Video Dr. Marion Evatt on Finnish studies of Vitamin D.>

< Video Dr. Hollick on Vitamin D deficiencies.>

< Video Dr. Cannell on recent Vitamin D research>

< Press ReleaseDigital Journal 29 May 2014 Is inadequate Vitamin D implicated in Fibromyalgia, Multiple Sclerosis and Parkinson's?

Further Research

Related Pages[edit]

Vitamin D,


  1. State of Alaska Epidemiology Bulletin
  2. Alaskan Petition
  3. Wikipedia – Vitamins
  4. Wikipedia – Vitamin D
  5. Deluca, G.C.; Kimball, S. M,; Kolasinski, J,; Ramagopalan, S. V, and Ebers, G.C. (2013) AbstractNeuropathol. Appl. Neurobiol.. Jan 21 The Role of Vitamin D in Nervous System Health and Disease.
  6. Willis, Allison Wright; Evanoff, Bradley A.; Lian, Min; Criswell, Susan R. and Brad A. Racette, Brad A.(2010) Neuroepidemiology. 34(3): 143–151.Geographic and Ethnic Variation in Parkinson Disease: A Population-Based Study of US Medicare Beneficiaries.
  7. de Pedro-Cuesta, Jesus; Rodriguz- Farré, Eduard and Lopez-Abente, Gonzalo (2009) BMC Public Health 9 445 Spatial distribution of Parkinson’s Disease mortality in Spain 1989-1998 as a guide for focused aetiological research or health care intervention
  8. Vitamin D wiki index
  9. Vitamin D wiki PD
  10. Wermuth, L.; Bünger, N.; von Weitzel-Mudersback, P.; Pakkenberg, H. and Jeune, B. (2004)</b. Mov. Disord. 19 (7) 821-824. Clinical characteristics of Parkinson's disease among Inuit in Greenland and inhabitants of the Faroe Islands and Als (Denmark)
  11. Newmark, H.L. and Newmark, J. (2007) Mov Disord. 22(4):461-8, Vitamin D and Parkinson's disease--a hypothesis.
  12. Knekt, Paul; Kilkkinenn, Annamari;Rissanen, Harri; Marniemi, Jukka; Sääksjärvi, Katri and Heliövaara, Markku. (2008) Arch. Neurol.67(7):808-811.Serum Vitamin D and the Risk of Parkinson Disease
  13. Evatt, Marin L.; DeLong, Mahlon R.; Khazai, Natasha; Rosen, Ami; Triche, Shirley and Tangpricha, Vin (2008)Italic text. Arch. Neurol. 65 910) 1348-1352. Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease.
  14. . Evatt, M.L.; DeLong, M.R.; Kumari. M.; Auinger P.; McDermott, M.P. and Tangpricha, V. (2011) 68 (30 314-319. High prevalence of hypovitaminosis D status in patients with early Parkinson disease.
  15. Simpson Jnr., Steve; Blizzard, Leigh; Otahal, Petre; Van der Mei, Ingrid and Taylor, Bruce J. Neurol. Neurosurg. Psychiatry (2011) 82; 1132-1141 Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis.
  16. Ramagopalan, Sreeram R.; Heger, Andreas, Berlanga, Antonio J.; Maugeri, Narelle J.; Lincoln, Matthew R.; Burrell, Amy; Handunnetthi, Lahiru; Handel, Adam E,; Disanto, Giulio; Orton, Sarah-Michelle; Watson, Corey T. ; Morahan, Julia M.; Giovannoni, Gavin; Ponting, Chris P.; Ebers, George C. And Knight, Julian C. ((2010) Genome Research 20 1952-1960. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution.
  17. Derex L, and Trouillas P.(date)</font)> Mov, Disord. 12 612-613. Reversible parkinsonism, hypophosphoremia, and hypocalcemia under vitamin D therapy.
  18. Gordon, P.H.; Mehal, J.M.; Holman, R.C.; Rowland, J.S. and Cheek, J.E. (2012) Abstract Mov Disord. 2012 Aug 14. doi: 10.1002/mds.25153. [Epub ahead of print] Parkinson's disease among American Indians and Alaska natives: A nationwide prevalence study.
  19. Khanh, Luong and Lan, Nguyen (2012) Full Text ISRN Neurol. 2012; 2012: 134289. Role of Vitamin D in Parkinson's Disease
  20. US National Institutes for Health – Clinical PD Trial.