By Jay Furst

Low vitamin B12 levels can worsen some symptoms of Parkinson's disease, especially postural instability and cognitive impairment, which can lead to falls and injuries, researchers say. Lower vitamin B12 levels also are associated with higher Hoehn-Yahr stage, the tool for assessing disease severity, and neuropathy in Parkinson's patients.

While it's not clear why, there may be a relationship between vitamin B12 and acetylcholine, a neurochemical that's believed to be a key to cognition and postural control. The neurons that make and use acetylcholine die during the course of the disease, says Mayo Clinic neurologist Rodolfo Savica, M.D., and one theory is that vitamin B12 deficiency may exacerbate that process.

Also relevant is that carbidopa/levodopa, the most commonly prescribed medication for Parkinson's, can reduce vitamin B12 levels, especially at high dosage, which is common later in the disease course as more medication is needed to manage tremor or slow movement.

"Currently, we do not have very effective therapies for these symptoms in Parkinson's disease, as they do not respond well to levodopa," says Stuart McCarter, M.D., a Mayo Clinic neurology resident who worked with Dr. Savica and colleagues at Mayo Clinic and the University of Minnesota on a recent study of vitamin B12 and Parkinson's.

The study, which was published in Mayo Clinic Proceedings in May, investigates the potential link between low vitamin B12, acetylcholine-related brain function, and disease severity. The study proposes that supplementing vitamin B12 could be helpful to improve cholinergic transmission and potentially motor and cognitive function.

Falls and the injuries that result are among the difficulties that face Parkinson's patients. Among the characteristics of the disease is freezing of gait -- a sudden inability to start or continue walking, especially when the person is changing directions or may be distracted, and contributes to fall risk. Cholinergic dysfunction may play a role in freezing of gait, and recent clinical trials suggest that anticholinesterase inhibitors, which increase acetylcholine, may decrease falls in Parkinson’s disease.

"Cognitive impairment with Parkinson's is multifactorial and is likely to be related to a combination of underlying issues," Dr. McCarter says. They include microvascular disease, Lewy body deposition, beta-amyloid plaques and tau neurofibrillary tangles, and dysfunction of multiple neurotransmitters. "Acetylcholine is just one part of the complex neuronal dysfunction that's associated with cognitive impairment. But there's evidence that it plays an important role."

Dr. Savica also says it's unlikely to be a "straightforward linear causal process" between vitamin B12 deficiency and cholinergic dysfunction, but it merits investigation. Among the challenges for researchers is that vitamin B12 is commonly measured as a total serum level, which lacks sensitivity and can be insufficient in measuring accurate B12 status, and seemingly normal lab values may not reflect vitamin B12 status in the brain.

Dr. Savica, who has more than 15 years of clinical as well as research experience in Parkinson's disease and related disorders, says he hopes the study in Proceedings will raise awareness about the potential importance of vitamin B12 status.

"It may not be well-known in the non-neurology setting that high doses of levodopa can decrease vitamin B12 levels, which in some cases leads to peripheral neuropathy and also worsen balance," he says.

Vitamin B12 levels should be checked in patients with Parkinson's disease and supplemented if low, he says. In Mayo's movement disorders practice, it's common to start patients who are on levodopa with a vitamin B12 supplement. "This is usually a combination pill with small amounts of vitamin B6 and folate," he says.

The cutoff for vitamin B12 deficiency varies between testing laboratories but is typically less than 200ng/L in the blood. However, given the inaccuracy of serum vitamin B12, impairment of vitamin B12-mediated function likely occurs at levels higher than 200 ng/L. Methylmalonic acid is another value that providers use to help determine severity of vitamin B12 deficiency and is more representative of true status.

Combination pills typically contain about 2.5mg of folate, 25mg of vitamin B6, and 1mg of vitamin B12, although there is no standardized recommendation of the amount of each vitamin required for beneficial effects. Important to note is that too much vitamin B6 can be toxic to the nervous system, so patients should exercise caution with vitamin B6 supplementation.

"The goal of vitamin supplementation currently is to avoid the complications induced by levodopa," Dr. McCarter says, especially when the patient is on high dosage and presenting with symptoms such as numbness and tingling in the hands and feet. “However, our study hopes to provide an additional rationale for the role of vitamin B12 in Parkinson’s disease.”

Next steps: Mayo Clinic researchers are working on a retrospective study to look for a connection between vitamin B12 deficiency and postural instability and cognitive impairment. They plan to complete this study by the end of 2019.

Watch the video about this study from Mayo Clinic Proceedings below.

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