Trending Clinical Topic: Vitamin B12

Ryan Syrek


November 11, 2022

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The potential benefit of vitamins is always a hot topic. New findings that suggest vitamin B12 is associated with possible protection against Parkinson's disease, ALS progression, and fatty liver disease severity spiked recent interest. At the International Congress of Parkinson's Disease and Movement Disorders (MDS) 2022, researchers presented findings from a study that included more than 80,000 women and nearly 50,000 men. The analysis included information on dietary, supplemental, and total intake of folate, vitamin B6, and vitamin B12 over the course of about 30 years, until 2012 (see Infographic).

During follow-up, 495 women and 621 men were diagnosed with Parkinson's disease. Investigators adjusted for potential confounders, including age, year, smoking status, physical activity, intake of alcohol or caffeine, hormone use (in women), intake of dairy and flavonoids, and Mediterranean diet score. Participants with higher total intake of vitamin B12 had a lower risk for PD (pooled hazard ratio for top vs bottom quintile, 0.74; 95% CI, 0.60-0.89; P for trend, .001). Intake from both diet and supplements contributed to this inverse association. In an attempt to overcome risk for reverse causality, researchers examined vitamin B12 intake during four lagged exposure periods: 8, 12, 16, and 20 years. They found a significant relationship between intake for the 20-year lag time and development of Parkinson's disease. Overall, the results support a possible protective effect of early intake of vitamin B12 on the development of PD.

In a separate study from earlier in 2022, an ultrahigh-dose of methylcobalamin, an active form of vitamin B12 analogue, was found to slow functional decline by 43% in patients with early-stage amyotrophic lateral sclerosis (ALS). The 50-mg dose was administered twice-weekly via intramuscular injection. In the phase 3 study, efficacy was higher for participants who were also taking riluzole, which is approved by the US Food and Drug Administration to treat ALS. The study included ambulatory patients at 25 neurology centers in Japan who were diagnosed with definite or probable ALS and whose symptoms began within the previous year. After 12 weeks of observation, the 130 participants who remained ambulatory and had only a 1- or 2-point decrease in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score were entered into a 16-week treatment period.

These patients (mean age, 61 years; 56.9% men) were randomly assigned to receive 50 mg of methylcobalamin or placebo. The primary endpoint was change in ALSFRS-R total score. At 16 weeks, this total score was -2.66 in the methylcobalamin group and -4.63 in the placebo group (95% CI, 0.44-3.50; P = .01). In the 90% of patients also taking riluzole, the difference in favor of methylcobalamin was even greater (-2.11; 95% CI, 0.46-3.76; P = .01). The difference in ALSFRS-R total score between the active drug and placebo amounted to 43% in all patients and 45% in those using riluzole. Adverse events (AEs) were experienced by 62% of patients receiving the drug and 66% receiving placebo. AEs reported by at least 5% of patients in either group included constipation, nasopharyngitis, contusion, falls, back pain, and insomnia. No AEs resulted in drug discontinuation.

Another study found that vitamin B12 and folic acid may also play a role in preventing or delaying disease progression in nonalcoholic steatohepatitis (NASH). Researchers have found that elevated blood levels of homocysteine correlate strongly with disease severity. However, the precise relationship between hyperhomocysteinemia and NASH is poorly understood. In their new study, Singh and colleagues determined that as hepatic homocysteine levels increase, amino acid attaches to various liver proteins, changing their structure and impeding their functioning. In particular, when homocysteine attaches to the syntaxin 17 protein, it blocks the protein from transporting and digesting fat (a process known as autophagy). This, in turn, induces the development and progression of fatty liver disease to NASH. In preclinical models, investigators found that supplementing the diet with vitamin B12 and folic acid increases hepatic syntaxin 17 levels, restores its role in autophagy, and slows NASH progression and reverses liver inflammation and fibrosis.

From Parkinson's disease to ALS and NASH, recent studies suggesting the importance of vitamin B12 garnered much recent attention, leading to this week's top trending clinical topic.

Take a quiz about vitamin B12 use.


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