Vitamin D as a Neuroprotective Agent for Amyotrophic Lateral Sclerosis

Share this content:
Vitamin D as a Neuroprotective Agent for Amyotrophic Lateral Sclerosis
Vitamin D as a Neuroprotective Agent for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis, which causes progressive loss of upper and motor neurons, has a median range of survival of only three years.1 The only approved drug used to treat amyotrophic lateral sclerosis (ALS) is riluzole, so it's not surprising that any new therapy that shows some promise is a welcome addition for those treating or suffering from ALS. But could a treatment as simple as vitamin D supplementation be beneficial?

A study published in the Journal of Clinical Neuroscience in 2013 suggested that daily supplementation with 2000 international units of vitamin D can improve ALS functional rating scores when taken for nine months. The study looked at vitamin D levels in 37 consecutive ALS patients, of which 81% had vitamin levels below normal range. Twenty of the patients received vitamin D and their functional scores declined less rapidly than those patients who did not receive supplements.3

“Our study was small and retrospective, but the findings are suggestive of a benefit,” said Stephen N. Scelsa, MD, director of the ALS Center at Mount Sinai Beth Israel in New York City, and professor of neurology at Icahn School of Medicine.

That benefit is apparent in other neurodegenerative disease too. ALS shares similar pathophysiologic pathways with multiple sclerosis, Alzheimer's disease, and Parkinson's disease. In both animal disease models and human patients, vitamin D has been shown to ameliorate these pathways.4

Additionally, severe vitamin D deficiency in ALS has been associated with a fourfold increase in the rate of functional decline and significantly shorter survival expectancy. The authors of the retrospective review, which was published in the journal Neurobiology of Aging in 2014, concluded that their findings supported a neuroprotective role for vitamin D and a role as a reliable prognostic marker of ALS.1

Vitamin D and Neurodegeneration

“Vitamin D has become a hot area of research in brain health. We now have a fair amount of research in vitro and epidemiologically associating low levels of vitamin D with neurodegenerative disease,” said James Leverenz, MD, director of the Center for Brain Health at the Cleveland Clinic.

Indeed, a study recently published in Neurology that looked at more than 1,650 adults aged older than 65 found that participants who had severe vitamin D deficiency were more than twice as likely to develop dementia and Alzheimer's disease.

However, unlike in multiple sclerosis or dementia, there has not been any evidence to support low vitamin D levels as a causative factor for ALS. “Low levels of vitamin D found in patients with ALS are not surprising,” said Scelsa. “Patients who are homebound and have limited sun exposure are at risk for low vitamin D. This is expected in any chronic disease.”

“When it comes to causation, I put my skeptic hat on,” said Leverenz. “Fatigue and lack of interest in activity may precede overt neurodegenerative disease symptoms by several years, so does low vitamin D cause the disease, or does early disease lead to low vitamin D? It's the chicken and the egg scenario.”

There are, however, some intriguing mechanisms by which vitamin D could be a neuroprotective factor in ALS, as well as in other neurodegenerative diseases. “The role of vitamin D as an anti-inflammatory substance in the brain and as a moderator of oxidative stress is becoming increasingly recognized. Vitamin D receptors have been found in neurons, so they must be there for a reason. There may be several ways in which vitamin D improves neuronal functions,” said Leverenz.

The mechanism of action for riluzole is unknown, but one theory is that it works by inhibiting the release of glutamate which may be toxic to neurons.2 Vitamin D may also act by protecting neurons from glutamate toxicity.4 Although the exact cause of ALS remains a mystery, excitotoxicity is one of the most prominent theories.3

“The theory is that vitamin D increases the concentration of calcium binding proteins in neurons and limits damage done by calcium influx into neurons,” Scelsa explained.

Where Do We Go From Here?

“I think you can make a case for checking vitamin D levels and correcting them to normal levels as a matter of brain health. But data on supplementation is not strong. We need to be careful about high doses of vitamin D. There is enough data to warrant more trials, but that work still needs to be done,” said Leverenz.

“At this point, most experts will say there is not enough evidence to support a neuroprotective role for vitamin D in ALS. We will need to see larger, well-designed, randomized trials to know more. The problem will be finding a way to fund those studies because there is no money to be made from vitamin D,” said Scelsa. “For now, I am comfortable telling my ALS patients that although there is no solid evidence to support vitamin D, it is not harmful and may be helpful.”

Chris Iliades, MD, is a full-time freelance writer based in Cape Cod, Massachusetts. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH.

References

  1. Camu W, Tremblier B, Plassot C, et al. Vitamin D confers protection to motoneurons and    is a prognostic factor of amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35(5):1198-205.
  2. Rilutek, United States Food and Drug Administration. Available here: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020599s011s012lbl.pdf
  3. 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;20(11):1550-3.
  4. Gianforcaro A, Hamadeh MJ. Vitamin D as a potential therapy in amyotrophic lateral sclerosis. CNS Neurosci Ther. 2014;20(2):101-11.
You must be a registered member of Neurology Advisor to post a comment.
close

Next Article in Neurodegenerative Diseases

Sign Up for Free e-newsletters



CME Focus