Deficiencies in two B vitamins may play a role in Parkinson's disease

Parkinson's disease is the fastest growing neurodegenerative disorder in the world, with the World Health Organization estimating that more than 8.5 million people had the condition in 2019. Since 1990, the number of people with Parkinson's disease has doubled worldwide.

The risk of developing Parkinson's disease increases with age, and men are 50% more likely to develop the disease than women. Other risk factors include genetics, exposure to environmental toxins, and a history of head injury.

Symptoms occur when nerve cells in the basal ganglia, the area of the brain that controls movement, become damaged and die, stopping production of the neurotransmitter dopamine. This results in tremors, muscle stiffness, slow movements, loss of balance and coordination, emotional changes, and gastrointestinal symptoms.

Research suggests that an imbalance in the gut microbiota may contribute to the development of Parkinson's disease.

Now, a study across five countries analysing the microbiota of people with and without Parkinson's disease has found that those with the disease have significant reductions in bacterial genes responsible for producing riboflavin (vitamin B2) and biotin (vitamin B7).

The study, conducted by researchers from the Nagoya University Graduate School of Medicine in Japan, was published in the journal npj Parkinson's Disease.

Michael S. Okun, executive director of the Fixel Institute for Neurological Diseases, chair of the University of Florida's department of neurology and national medical director of the Parkinson's Foundation, who was not involved in the study, said:

"Interestingly, this small study of people with Parkinson's disease found decreased faecal biosynthesis of riboflavin and biotin, as well as differences according to location and diet."

Vitamin B2 and B7 Deficiency and Parkinson's Disease

The researchers used faecal analysis to study the genomes of gut bacteria in 94 people with Parkinson's disease and 73 controls in Japan. Using a method called whole-genome sequencing, they recorded the bacterial genomes. They then compared their results with data from studies in the United States, Germany, China and Taiwan.

They found differences in gut microbiota across countries and between people with and without Parkinson's disease.

Regardless of the type of bacteria in the gut microbiota, people with Parkinson's disease had significantly reduced levels of bacterial genes responsible for the biosynthesis of vitamins B2 and B7.

Both vitamins, riboflavin (B2) and biotin (B7), are necessary for the metabolism of carbohydrates, fats and proteins into glucose for energy, enhancing immune system function and have anti-inflammatory properties.

Microbiome Alterations May Increase Neuroinflammation

Neuroinflammation is a key feature of Parkinson's disease, and researchers have speculated that deficiencies in riboflavin and biotin may contribute to neuroinflammation. However, Tim Sampson, an associate professor of cell biology at Emory University School of Medicine who was not involved in the study, noted:

"It is important to note that this study did not measure levels of biotin or riboflavin in the stool or circulation. The authors simply found that the bacterial genes responsible for synthesizing these molecules were reduced."

"Thus, it is not clear from this study whether the decreased synthesis of these vitamins is related to vitamin deficiency in the body," he added.

The researchers found that a decrease in genes for vitamins B2 and B7 was strongly associated with a decrease in fecal short-chain fatty acids and polyamines in Parkinson's disease. Both substances are involved in the production of the intestinal mucus layer.

If the intestinal mucus barrier is compromised, the intestines become more permeable, allowing toxins to enter the bloodstream. Researchers speculate that this may increase neuroinflammation.

Sampson explained how these changes may contribute to the symptoms of Parkinson's disease:

"We are increasingly realizing that people with Parkinson's disease have increased inflammation, and some of this may be due to the state of the gut environment. While these vitamins are associated with beneficial immune responses, we don't know whether their absence contributes to inflammation in Parkinson's disease."

"It's a similar story with polyamines. There's evidence to support the idea that the gut becomes more permeable in Parkinson's disease. That could allow bacterial products to enter the circulation and stimulate immune responses and inflammation, which could contribute to the disease," he said.

Further evidence for the gut's role in Parkinson's disease

"The authors of this study speculate about the role of increased intestinal permeability and potential exposure to pesticides, herbicides and other toxins important in Parkinson's disease, but there are still more questions than answers in this area of research," said Michael Okun.

The study highlights the links between the gut microbiome, metabolism and the nervous system, but its findings are not enough to change clinical practice, such as prescribing B2 and B7 supplements, Sampson noted.

"These data are still too early for therapeutic interventions. They highlight one of many ways in which the gut microbiome may contribute to Parkinson's disease."

"But these are metabolic predictions based on microbiome genes. The researchers did not measure that microbiomes are directly involved in these processes or affect the levels of these metabolites," he added.

Okun said vitamin supplements may be helpful in treating Parkinson's disease, but they should only be taken when medically indicated:

"The most common treatment for Parkinson's disease is levodopa, and we know that levodopa causes blood homocysteine levels to increase. That's why many experts recommend taking a multivitamin a day, because when you're taking levodopa you'll probably need to supplement with vitamins B12, B6, and folate."

"Replacing vitamins can also lead to unexpected side effects, so this should be done under the guidance of a doctor. There are no specific current recommendations for replacing vitamins B2 and B7 in Parkinson's disease," he added.

However, Sampson welcomed the study as adding to the evidence base about the role of the microbiome in Parkinson's disease:

"These data provide some testable hypotheses and add to the growing knowledge that the gut microbiome may contribute to aspects of Parkinson's disease."