Vitamin B12 Protective Against Parkinson's Disease?

A high baseline intake of vitamin B12 is linked to lower risk of developing Parkinson's disease (PD), new research suggests.

"The results leave the door open for the possibility that vitamin B12 may have a beneficial effect in protecting against PD," lead author Mario H. Flores, PhD, a research fellow at Harvard T.H. Chan School of Public Health, Boston, Massachusetts, told Medscape Medical News.

The findings were presented at the International Congress of Parkinson's Disease and Movement Disorders (MDS) 2022.

B Vitamins and PD

Previous preclinical studies have suggested that B vitamins protect against PD by decreasing plasma homocysteine levels and through other neuroprotective effects.

However, there have only been two epidemiologic studies of B vitamins in PD — and their results were inconsistent, Flores noted.

The new study included 80,965 women from the Nurses' Health Study and 48,837 men from the Health Professionals Follow-up Study. All completed a food frequency questionnaire at baseline and every 4 years.

Researchers collected information on dietary, supplemental, and total intake of folate, vitamin B6, and vitamin B12 over the course of about 30 years up to 2012. They estimated hazard ratios and 95% CIs for PD according to quintiles of cumulative average intake.

During follow-up, 495 women and 621 men were diagnosed with PD.

The 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.

Analyses of cumulative average total folate, B6, and B12 intake were not associated with PD risk. "The results of the primary analysis of cumulative intake were not significant for any of the vitamins we looked at," said Flores.

Researchers also conducted secondary analyses, including assessment of how the most recent intake of B vitamins related to PD risk. This analysis also did not find a significant association.

However, when examining baseline intake of vitamin B12, "we saw some suggestion for a potential inverse association with PD," Flores said.

Among individuals with higher total intake of vitamin B12, there was 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, the investigators note.

Dietary sources of vitamin B12 include poultry, meat, fish, and dairy products; however, the main sources in this study were multivitamins/supplements and enriched foods such as cereals, said Flores.

Several Limitations

In an attempt to overcome risk for reverse causality, the researchers examined B12 intake during four lagged exposure periods: 8-, 12-, 16- and 20-year lags. They found a significant relationship between intake for the 20-year lag time and development of PD.

Overall, the study results provide support for a possible protective effect of early intake of vitamin B12 on the development of PD, Flores noted.

In addition to being involved in the regulation of homocysteine levels, vitamin B12 may help regulate leucine-rich repeat kinase 2 (LRRK2), an enzyme implicated in the pathogenesis of PD, he said.

However, the study did not examine how B12 deficiency might relate to risk for PD, which "is something worth looking at in future studies," said Flores.

He added that although findings from a single study cannot translate into recommendations on ideal vitamin B12 intake to prevent or delay PD onset, the median intake in the highest quintile that the study linked to less PD risk was 18 µg/d at baseline. The amount in multivitamins can vary from 5 to 25 µg.

Flores said a limitation of the study was that it included US healthcare professionals, "most of whom arguably have very good nutritional status."

As well, assessment of vitamin B intake was self-reported, so there might have been measurement error — and there may have been an unmeasured confounding factor that could explain the associations.

Flores also stressed that the effect of B12 on PD risk "was very modest," and the results need to be confirmed in other studies "ideally looking at circulating levels of vitamin B12."

Not Ready to Recommend

Commenting for Medscape Medical News, Michael S. Okun, MD, medical advisor at the Parkinson's Foundation and professor and director of the Norman Fixel Institute for Neurological Diseases at the University of Florida, Gainesville, noted that other recent studies have suggested high-dose B12 may be preventive and a possible treatment in PD.

"Although only a secondary aim of the current study, there was a reported potential benefit" in this new study, too, said Okun, who was not involved with the research.

However, the evidence is still not strong enough to change prescribing habits, he noted. "We do not recommend high-dose B12 either for those at genetic risk of Parkinson's or those already with the disease," Okun said.

He added that because multiple recent studies have questioned the beneficial effects for multivitamin combinations used to prevent neurologic diseases, "it wasn't surprising to see results showing a lack of protection against later-onset Parkinson's disease with [cumulative] folate, B6, and B12 intake" in the current study.

The study was supported by the NIH. Flores and Okun have reported no relevant financial relationships.

International Congress of Parkinson's Disease and Movement Disorders (MDS) 2022. Abstract 39. Presented September 15, 2022.

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Image 1: Mario H. Flores, PhD

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Cite this: Vitamin B12 Protective Against Parkinson's Disease? - Medscape - Sep 21, 2022.