Vitamins C and E Linked to Reduced Risk for Parkinson's Disease

Erik Greb

January 12, 2021

Higher intake of vitamins C and E was associated with a reduced risk for Parkinson's disease (PD) in an analysis of a national cohort study. Higher intake of both vitamins, as opposed to one, strengthened the association with lower PD risk.

In addition, body mass index (BMI) and coffee consumption appeared to influence the magnitude of these vitamins' effect on PD risk. Dietary beta-carotene and dietary nonenzymatic antioxidant capacity (NEAC) had no effect on this risk, however.

Dr Essi Hantikainen

"Our findings suggest that the protective effect of dietary vitamins on Parkinson's disease risk might be limited to specific vitamins, such as vitamin E and C," Essi Hantikainen, PhD, a postdoctoral researcher at the University of Milano-Bicocca, Milan, Italy, told Medscape Medical News. "Therefore, implementing foods in the diet that are rich in vitamin E and C might help to prevent the development of Parkinson's disease," she said.

More research is needed to confirm these findings, she added. "In addition, it is not yet clear what are the most beneficial amounts of vitamin E and C intake to reduce the risk of Parkinson's disease."

The research was published online January 6 in Neurology.

National Cohort

Researchers theorize that oxidative stress contributes to the pathogenesis of PD and leads to the loss of dopaminergic cells. Also, with respect to oxidative stress, polyunsaturated fatty acids in the brain undergo lipid peroxidation and produce toxins. Dietary antioxidants scavenge reactive oxygen species and so may protect against neuronal damage.

For this analysis, Hantikainen and colleagues analyzed data from the Swedish National March Cohort to examine the effect of antioxidant intake on the risk for PD. The cohort includes 43,865 participants who responded to a 36-page questionnaire about lifestyle factors and medical history. The researchers excluded all participants who died, emigrated, or received a diagnosis of PD before the beginning of follow-up.

Because evidence about the association between single antioxidants and risk for PD is inconsistent, the researchers analyzed the relationship between total antioxidant capacity (also known as NEAC) of the diet and the risk for PD. NEAC takes into account interactions between antioxidants. "One hypothesis of ours was therefore that a single-nutrient approach might not capture biological interactions, which might have explained inconsistent findings from earlier studies," said Hantikainen. "We additionally compared different measures to estimate NEAC."

As part of the questionnaire, participants reported their average consumption of various foods and beverages during the previous year. The investigators linked participants' dietary information to the Swedish National Food Composition database and used these data to estimate total intake of dietary vitamin E, vitamin C, beta-carotene, and NEAC. They also used questionnaire responses to calculate participants' BMI and daily physical activity.

The investigators conducted follow-up by examining participants' data in Swedish national and demographic health registries. They followed patients from October 1, 1997, to December 31, 2016. Follow-up ended at diagnosis of PD, death, emigration, or on December 31, 2016, whichever occurred first.

The data were analyzed using Cox proportional hazards regression models. The investigators controlled for potential confounders, such as sex, BMI, total physical activity, education, smoking, and alcohol intake. They also conducted four sensitivity analyses.

The researchers included 41,058 participants in their analysis. Mean follow-up time was 17.6 years, during which time 465 incident cases of PD were detected. The mean age at diagnosis was 74.6 years.

Antioxidants Linked to Reduced Risk

Participants in the highest tertile of intake of vitamins and NEAC were generally older, more educated, and consumed greater amounts of fruit and vegetables. Participants in the lowest tertile were more likely to be smokers and had higher total dairy intake.

After adjusting the data for potential confounders, the researchers found that the risk for PD was 32% lower among people in the highest tertile of vitamin E intake, compared with those in the lowest tertile. Participants in the highest tertile of vitamin C intake, compared with those in the lowest tertile, also had a 32% lower risk for PD.

Furthermore, participants in the highest tertile of vitamin E and C intake had a 38% lower risk for PD compared with those in the lowest tertile. The researchers found no association, however, between dietary beta-carotene or NEAC and risk for PD.

Subgroup analyses indicated that vitamin E had a stronger effect on people who were overweight or obese. Such patients who were in the highest tertile of vitamin E intake had a 56% lower risk for PD.

In addition, among participants with low coffee consumption, those in the highest tertile of vitamin C intake had a 46% reduced risk for PD.

Among overweight and obese participants, those in the highest tertile of vitamin C intake had a 48% lower risk for PD.

None of the sensitivity analyses altered the researchers' findings.

Population Differences

Food frequency questionnaires are useful for measuring average long-term dietary intake in observational studies, but they have several drawbacks. "It is difficult for most people to exactly remember what we eat how often and how much," said Hantikainen. "In addition, questionnaires are mostly designed to include foods and beverages that represent dietary habits of the specific country or region of study. If someone is following another diet, for example, due to their cultural background or a broader access to international foods, some of these foods might not have been included in the questionnaire."

These factors could explain some of the inconsistencies in the results of previous studies that examined antioxidant intake and PD risk.

Dr Xiang Gao

The prospective study design and long follow-up period are major strengths of the study by Hantikainen and colleagues, Xiang Gao, MD, PhD, professor and director of the Nutritional Epidemiology Laboratory, Pennsylvania State University, University Park, Pennsylvania, told Medscape Medical News. But the study is limited by its lack of confirmation of PD cases through a review of medical records, he added. It also lacks detailed information about antioxidant intake from supplements.

The current study differs in various ways from previous research that did not find significant associations between antioxidant intake and PD risk. The Swedish study population, for example, has a lower vitamin E intake than populations in previous investigations. The population examined in this analysis also was younger at baseline than the populations in previous studies. This difference "may suggest that nutrition status in middle age could be particularly important," said Gao.

"Future studies should be conducted to examine specific foods which are rich in vitamin E and vitamin C, such as vegetable oils, nuts and seeds, and fruits and vegetables, and [their association with] Parkinson's disease risk," he added. "Also, it is important to focus on dietary intake in young adulthood and early middle adulthood, as Parkinson's disease has a very long preclinical stage, and pathological changes could happen many years before Parkinson's disease onset."

The study was supported by the Swedish Cancer Society, ICA, and Telefonaktiebolaget LM Ericsson. Hantikainen and colleagues and Gao have disclosed no relevant financial relationships.

Neurology. Published online January 6, 2021. Abstract

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