Figure of mouse brain tissue from the substantia nigra; cells that are stained are dopamine producing.

Parkinson’s disease (PD) is a neurodegenerative disease, which means that the damage in the brain begins several decades before the symptoms appear. In PD, approximately 60% of a specific cell type in the brain dies before symptoms appear. The cells that die are dopamine-producing cells. Dopamine is a neurotransmitter, which is a chemical in the brain that help cells communicate with each other. Dopamine cells within the substantia nigra, an area of the brain, die in PD. In the figure above you can see dopamine-producing cells. PD was first described in 1817 by James Parkinson, and although the exact cause of PD still remains unknown, researchers and clinicians know that changes in our DNA play an important role. There is also an environmental component–for example, exposure to herbicides like paraquat induce PD in people. Another example of an environmental contributor is nutrition. 

Nutrition, specifically B-vitamins, have been implicated in the onset and progression of PD. Folic acid is an example of a B-vitamin, and it is well known for its role in preventing neural tube defects during early brain development. Additionally, folic acid also helps to lower levels of a chemical called homocysteine. High levels of homocysteine are present in PD patients who take levodopa (L-DOPA), a pharmaceutical drug that helps replenish dopamine in the brain. The breakdown of L-DOPA in the body requires methyl groups generated from folic acid, and this in turn increases levels of homocysteine.

Methylenetetrahydrofolate reductase (MTHFR) is a protein that breaks down folic acid to generate methyl groups, and people with reduced levels of this protein are reportedly more affected by PD. In a recent research study from our group we use a mouse model with reduced levels of MTHFR to study how the paraquat model of PD impacts onset and progression.

Our study found that reduced levels of MTHFR result in motor impairments in PD mice, and these impairments are characteristic of PD. Additionally, the PD mice were sick and had higher levels of inflammation in the substantia nigra. There were also high levels of oxidative stress, which is an imbalance of reactive oxygen and antioxidant production within a brain region closely connected to the substantia nigra. Higher levels of oxidative stress have been implicated in several neurodegenerative diseases. In terms of targeting oxidative stress through pharmaceuticals, there has not been much progress. Food stuffs such as red wine, green tea, and blueberries have been reported ro reduce levels of oxidative stress through their antioxidant properties, but more investigation is required.  

Nutrition is an important aspect of health. It is well documented that not all older adults absorb as many nutrients compared to their younger counterparts due to several factors, one being inflammation in the stomach. These recent research findings presented in this blog along with others suggest that adequate nutrition should be a component of health care for patients with PD.

By: Mary Scourboutakos

Neural tube defects are a type of birth defect—affecting the brain, spine or spinal cord—that result from suboptimal folate status.
Folate is a B vitamin that’s naturally found in legumes (like chickpeas, lentils, pinto and kidney beans), seeds, leafy greens (like spinach, collard greens and romaine lettuce) and other vegetables such as asparagus, brussels sprouts and broccoli.

The problem is, people don’t eat enough of these foods. As a result, for many years, pregnant women were at risk for folate deficiency and hence, neural tube defects.

Prenatal supplements were the original solution to this problem as one of their prime ingredients is folic acid, the synthetic form of folate. However, they’re not a fool proof solution because neural tube defects form within four weeks of conception, often before women know they’re pregnant, and thus, before they start taking their supplements.

As a result, in the late 1990s folic acid was mandatorily added to white flour and enriched grain products to ensure that pregnant women would get enough folate, irrespective of whether they take a supplement.

Problem solved? Sort of…

Back in the early 1990s when discussions regarding the addition of folic acid to the food supply were taking place, it was suggested that after fortification was implemented, the dose of folic acid in prenatal supplements should be revised to prevent excessive intakes. The new problem is…the doses were never revised.

Currently, marketed prenatal supplements usually contain 1000 micrograms of folic acid, which is the daily upper limit for folic acid. Meanwhile, it’s recommended that pregnant women should consume about 400 micrograms of folic acid per day for neural tube defect prevention.

With mandatory fortification, three-quarters of a cup of cereal can provide greater than 400 micrograms of folic acid. So if you add a prenatal supplement to a bowl of cereal at breakfast, some bread at lunch, and pasta for dinner, you’re consuming a lot of folic acid!

According to Dr. Deborah O’Connor, a Professor from the University of Toronto who has spent decades studying folate and infant health, this could be a problem. She explained that in animal models, it has been shown that folate can make changes to the genes that are transcribed during development. And while similar data have not been done on humans, she said “if you’re not getting any benefit from those high levels, it would be prudent to cut back given the current status…(because) if there’s no benefit, there’s only a risk.”

From a regulatory point-of-view, she says there’s nothing stopping the industry from changing the amount of folic acid in the supplements. She suggested that the industry’s reluctance to modify the dose in prenatal supplements is probably due to inertia and the fact that “with nutrition you’re always fighting against the more is better philosophy.”

In the meantime, what should women do? In their 2015 clinical practice guidelines, the Society of Obstetrics and Gynecologists recommended a multivitamin containing 400 to 1000 micrograms of folic acid. But currently, there are no prenatal vitamins available with less than 1000. Hence, Dr. O’Connor’s recommendation is “do not use the prenatal, just use a regular multi-vitamin and maybe add a little iron.” Furthermore, she added “care must be taken to ensure vitamin A intakes do not exceed 3,000 mcg retinol activity equivalents (RAE) or 10,000 IU during pregnancy.”

Alas, it’s a classic story, you try to fix one problem, but in doing so, you create another. Hopefully prenatal supplements will be adjusted soon, but in the meantime, prudent folic acid intakes are probably a good idea.