Chapter 21

Vitamin D Deficiency
And
Neurologic Diseases

Vitamin D is an important hormone for normal brain development. In addition, it is also important for the normal functioning of the brain.

Is there any evidence to link vitamin D deficiency to neurologic disorders? There is strong, clinical evidence for the relationship between vitamin D deficiency and Multiple Sclerosis (M.S.),as I explained in Chapter 10. Let’s explore if there is any credible evidence to link vitamin D deficiency to other neurologic diseases such as Dementia, including Alzheimer’s disease, Parkinson’s disease and Autism.

Vitamin D Deficiency And Dementia

An interesting study (1) from the University of Angers, France was published in 2011 in Dementia and Geriatric Cognitive Disorders . In this study, investigators divided 40, high functioning women into two groups Those who had 25 (OH) vitamin D level of less than10 ng/ml and those who had 25 (OH) vitamin D level of more than10 ng/ml. After a 7-year follow-up period, women who had severe vitamin D deficiency (level less than10 ng/ml) at baseline were more likely to develop dementia.

The same authors from France published another study (2) in 2013 in the journal of Alzheimers’ Disease. They performed an analysis of pooled data (meta-analysis) from nine case-control studies. They concluded that the patients with Alzheimer’s disease had lower levels of vitamin D than their matched-control group.

A study (3) from McMaster University in Hamilton, Canada was published in Neurology in 2012. These authors also did a meta-analysis of thirty-seven studies and concluded that low vitamin D was associated with the risk of developing Alzheimers’ disease

Then, there was another study (4), published in 2012 in Cognitive and Behavioral Neurology from the same researchers in France. In this interesting study, there were three groups: those treated with memantine (brand name Namenda) alone, those treated with Vitamin D alone, and those treated with a combination of Memantine and vitamin D. At six months, the combination treatment group performed better on a cognition test, called Mini-Mental State Examination (MMSE). Interestingly, the vitamin D alone group did as well as the Memantine alone group. These findings suggest a potential role of vitamin D in treating patients with Alzheimer’s disease.

Vitamin D Deficiency And Parkinson’s Disease

Parkinson’s disease is a degenerative disease of the brain. Usual symptoms of Parkinson’s disease include tremors, muscle rigidity, difficulty walking and changes in speech. So far all the medicines to treat Parkinson’s disease actually simply control the symptoms, while the disease itself continues to progress with time.

Can vitamin deficiency be playing a role in the causation of Parkinson’s disease. The answer is perhaps! There is some experimental evidence to link vitamin D deficiency to Parkinson’s disease. Researchers from Rutgers, the State University of New Jersey, published an article (5) in the Journal of Movement Disorder in 2007. They believe that vitamin D deficiency may be playing a significant role in causing Parkinson’s disease.

An excellent study (6) came in 2014 from Harbin Medical University, China. These researchers found the risk of Parkinson’s disease to be low in people who are regularly involved in outdoor activities and/or take vitamin D.

Due to difficulty in walking that occurs as a result of Parkinson’s disease itself, these people are at high risk for falling and fracturing their already weakened bones due to vitamin D deficiency. These patients can benefit tremendously from properly building up their vitamin D levels, which have been shown to strengthen muscles and bones and decrease the risk of fractures.

Vitamin D Deficiency And Autism

An interesting study (7) was published in 2012 in the Journal of Neuroinflammation . These researchers from King Saud University in Riyadh, Saudi Arabia measured 25 (OH) vitamin D and anti-myelin-associated glycoprotein (anti-MAG) auto-antibodies in autistic children. Myelin is an insulating material that form sheaths around the nerve fibers, and is crucial for the normal functioning of the brain. They discovered that 25 (OH) vitamin D was less than 30 ng/ml in 48% of autistic children. Increased levels of anti-MAG auto-antibodies were found in 70% of autistic children. Interestingly, vitamin D level had an inverse correlation with the level of anti-MAG auto-antibodies. In other words, the lower the vitamin D level, the higher the level of anti-MAG auto-antibodies. It does make sense. Vitamin D deficiency is now an established factor in causing autoimmune diseases. Can vitamin D deficiency lead to an immune-mediated attack on myelin and induce neurologic changes of autism?

A clinical review article (8) was published in 2012. These authors from the University of Glasgow, UK concluded there is some evidence to link vitamin D deficiency during pregnancy or early childhood to trigger autism in genetically susceptible individuals. Certainly more research is needed in this area.

Vitamin D Deficiency And Amyotrophic Lateral Sclerosis (ALS)

An exciting study (9) from Mayo Clinic, Rochester, USA, was published in 2013 in the Journal of Clinical Neuroscience. Researchers checked vitamin D level in 37 patients with ALS. Eighty-one percent of patients had a vitamin D level lower than 30 ng/mL. Twenty patients were given 2000 I.U. of vitamin D daily. They followed these patients over a 9 month follow-up period for a change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score, and any side effects from vitamin D. ALSFRS-R scores were compared between patients who took vitamin D and those who did not. Amazing discovery. The ALSFRS-R score improved in patients taking vitamin D. No side effects secondary to vitamin D supplementation were reported. Researchers concluded that vitamin D supplementation at 2000 I.U. daily was safe over a period of 9 months and may have a beneficial effect on ALSFRS-R scores for patients with ALS.

Vitamin D Deficiency And Myotonic Dystrophy

Myotonic dystrophy is a chronic, slowly progressing disease which can affect various organs in the body. It is inherited with autosomal dominant pattern.

Myotonic dystrophy is characterized by wasting of the muscles, called muscular dystrophy. Also muscles are difficult to relax, called, myotonia. Two types of myotonic dystrophy exist, Type 1 and Type 2.

Could there be an association between vitamin D deficiency and muscular impairment in patients with muscular dystrophy? The answer is perhaps. A breakthrough study (10) from University of Milan, Italy, was published in 2013. Researchers assessed vitamin D level, Parathyroid Hormone (PTH) and muscle parameters in 31 males with Type 1 myotonic dystrophy, 13 males with Type 2 myotonic dystrophy and 32 healthy controls. Vitamin D level was low in 88% of myotonic dystrophy patients. Secondary hyperparathyroidism due to vitamin D deficiency was diagnosed in 18% of patients. Serum 25 (OH) vitamin D levels inversely correlated with PTH levels. In other words, the lower the vitamin D level, the higher the level of PTH. The levels of PTH positively correlated with muscle dysfunction. In other words, the higher the PTH level, the more significant muscle dysfunction. It is likely that vitamin D deficiency may be responsible for muscular dysfunction by causing an elevation in PTH level.

Future Direction

In a recently published provocative experimental study (11), researchers from Aix-Marseille University in Marseille, France demonstrated that vitamin D can repair damaged neurons. They treated rats with an injured nerve of the lower leg, with vitamin D3 or vitamin D 2 at the dose of 100 or 500 I.U./kg/day. They observed that vitamin D3 is more efficient than Vitamin D2 and when delivered at a high dose (500 I.U./kg/day), vitamin D3 induces a significant locomotor and electrophysiological recovery in rats with injured nerve in the legs. A truly breakthrough research finding, which has huge implications for treating neurologic diseases.

References:

1.   Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet O. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dement Geriatr Cogn Disord . 2011;32(4):273-8

2.   Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis . 2013;33(3):659-74

3.   Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology . 2012 Sep 25;79(13):1397-405. 2.

4.   Annweiler C, Herrmann FR, Fantino B, Brugg B, Beauchet O. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study. Cogn Behav Neurol. 2012 Sep;25(3):121-7

5.   Newmark HL, Newmark J. Vitamin D and Parkinson’s disease--a hypothesis. Mov Disord . 2007 Mar 15;22(4):461-8.

6.   Zhu D1 , Liu GY, Lv Z, Wen SR, Bi S, Wang WZ. Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson’s disease. J Zhejiang Univ Sci B . 2014 Oct;15(10):923-7.

7.   Mostafa GA, Al-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation . 2012 Aug 17;9:201

8.   Kočovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: clinical review. Res Dev Disabil . 2012 Sep-Oct;33(5):1541-50

9.   Karam C, Barrett MJ, Imperato T, Macgowan DJ, Scelsa S. Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis. J Clin Neurosci . 2013 Jun 28

10. Passeri E, Bugiardini E, Sansone VA, Valaperta R, Costa E, Ambrosi B, Meola G, Corbetta S. Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies. J Neurol Sci . 2013 Aug 15;331(1-2):132-5

11. Jean-Francois Chabas, Delphine Stephan, Tanguy Marqueste, Stephane Garcia, Marie-Noelle Lavaut, Catherine Nguyen, Regis Legre, Michel Khrestchatisky, Patrick Decherchi, and Francois Feron. Cholecalciferol (Vitamin D3 ) Improves Myelination and Recovery after Nerve Injury. PLoS One . 2013; 8(5)