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Food as Medicine: Diet’s Role in Parkinson’s Disease

Interest is growing in the role of nutrition as means of slowing, or even preventing, neurodegeneration in patients with Parkinson’s disease (PD).
For 15 years, John Duda, MD, national director of the VA Parkinson’s Disease Research, Education and Clinical Centers, has urged his patients to “keep waiting” for effective treatments to manage both motor and nonmotor symptoms of Parkinson’s disease.
However, Duda, who also serves as director of the Brain Wellness Clinic at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, recognized the persistent lack of effective drugs to address these symptoms. This prompted him to consider what other evidence-based strategies he could use to support his patients. 
“I recognized that nutritional approaches within a broader program that includes medication review, stress management, social connections, adequate sleep, and physical exercise could make a real difference,” he told Medscape Medical News.
Observational studies have shown an inverse association between dietary patterns and PD risk, age of onset, symptom severity, and mortality rates — particularly with the Mediterranean diet (MeDi) and the MIND diet, which combines elements of MeDi and the Dietary Approaches to Stop Hypertension (DASH) diet. Although randomized controlled trials are still limited, the epidemiologic evidence supporting dietary interventions is “compelling,” said Duda. 
For example, a cross-sectional study comparing 167 participants with PD vs 119 controls showed that later age of PD onset correlated with adherence to the MIND diet in women, with a difference of up to 17.4 years (P < .001) between low and high dietary tertiles. 
The MeDi was correlated with later onset in men, with differences of up to 8.4 years (P = .002). As previously reported by Medscape Medical News, a healthy diet emphasizing vegetables, fruits, nuts, and grains was inversely associated with prodromal features of PD, including constipation, excessive daytime sleepiness, and depression. In addition, lower rates of PD have been shown in populations following vegetarian and vegan dietary patterns. 
Does PD Start in the Gut?
PD is characterized by decreased short-chain fatty acid–producing bacteria and increased pro-inflammatory species linked to intestinal inflammation and a-synuclein aggregation. “There are reasons to believe that a-synuclein accumulation may start in the gut,” Duda noted.
Numerous studies implicate gut microbiome dysbiosis as a pathogenic mechanism in PD, with gastrointestinal symptoms often predating motor symptoms. Dysbiosis might result in a pro-inflammatory state potentially linked to the recurrent gastrointestinal symptoms. Fecal microbiota transplant may restore a healthier gut environment and beneficially affect PD symptoms, he said.
Some of the benefits conferred by the MeDi and other healthy diets may be mediated by improving the gut microbiome. Duda cited a study that showed that a 14-day ovo-lacto vegetarian diet intervention and a daily fecal enema for 8 days improved not only the microbiome but also Movement Disorder Society Unified Parkinson’s Disease Rating Scale—part III scores. 
Duda also reviewed the role of dietary interventions in addressing common PD symptoms, such as orthostatic hypotension. He recommended that PD patients with this condition should avoid eating large meals, increase dietary salt intake, increase fluid intake, and decrease alcohol intake.
Malnutrition affects close to 25% of those with PD, which is partially attributable to diminished olfaction. Because the experience of taste is largely driven by a sense of smell, patients may be less interested in eating. Duda recommended increasing herbs, spices, and other flavors in food. High caloric density foods, including nuts, nut butters, and seeds, can boost weight, he said. However, he added, any patient with significant weight loss should consult a nutritionist.
Constipation is one of the most debilitating symptoms of PD, affecting up to 66% of patients. Duda advised increasing fluid intake, exercise, and dietary fiber and use of stool softeners and laxatives. The MeDi may reduce symptoms of constipation and have a beneficial effect on gut microbiota. 
Coffee may be helpful for sleepiness in PD and may also confer neuroprotective, motor, and cognitive benefits. As an adjuvant treatment, caffeine may alter levodopa pharmacokinetics, reduce dyskinesia, improve gait in patients with freezing and may even reduce the risk of developing PD, with a maximum benefit reached at approximately three cups of coffee daily.
Problematic Foods
There is also a growing body of evidence regarding the deleterious effects of ultraprocessed foods (UPFs), Duda said. He noted that a recent systematic review and meta-analysis of 28 studies showed that higher UPF intake was significantly associated with an enhanced risk for PD (relative risk, 1.56; 95% CI, 1.21-2.02). As reported by Medscape Medical News, UPFs have been tied to a host of adverse neurologic outcomes, including cognitive decline and stroke. 
Although protein is a necessary nutrient, incorporating it into the diet of PD patients taking levodopa is complicated. Levodopa, a large neutral amino acid (LNAA), competes with other LNAAs for transport to the brain from the small intestine, Duda explained. 
“Some people notice that carbidopa-levodopa doesn’t work as well if taken with a high-protein meal.” He recommended taking carbidopa-levodopa 30 minutes before or 60 minutes after meals.
Rebecca Gilbert, MD, PhD, chief mission officer of the American Parkinson Disease Association, told Medscape Medical News that patients with PD might want to avoid eating protein during the day, concentrating instead on carbohydrates and vegetables and saving the protein for the evening, which is closer to bedtime. Some evidence also supports the use of protein redistribution diets to enhance the clinical response to levodopa and reduce motor fluctuations. 
What About Supplements? 
It’s “hard to prove that one specific supplement can be protective against PD because diet consists of many different components and the whole diet may be worth more than the sum of its parts,” Gilbert said. The evidence for individual supplements “isn’t robust enough to say they prevent or treat PD.”
Research on the role of specific nutrients in PD is conflicting, with no clear evidence supporting or refuting their benefits. For example, a study that followed participants for about 30 years showed no link between reduced PD risk and vitamin B or folate intake. 
On the other hand, there is research suggesting that certain vitamins may help reduce PD risk, although these nutrients do not operate in isolation. For instance, one recent study showed a connection between vitamins C and E and reduced PD risk, but factors such as body mass index and coffee consumption appeared to influence the strength of this association.
Consuming polyunsaturated fatty acids along with reducing saturated fatty acid intake has been tied to a reduced risk for PD. 
Additionally, certain foods may offer protective effects, including green and black tea, with consumption of three or more cups per day associated with a delay in motor symptom onset by 7.7 years. Foods high in nicotine content, such as those from the Solanaceae family — including peppers, tomatoes, tomato juice, and potatoes — have also been linked to potential protective benefits.
Diets rich in antioxidants, including carotenoids, lutein, and vitamins E and C, have been robustly linked to a reduced risk for parkinsonism and progression of parkinsonian symptoms in older adults.
Increasing the intake of dietary flavonoids, particularly tea, berry fruits, apples, red wine, and oranges or orange juice, can reduce PD risk. One study showed that male participants in the highest quintile of total flavonoid consumption had a 40% lower PD risk compared with those in the lowest quintile. Another study showed that flavonoid-rich foods were also associated with a lower risk for death in patients with PD. 
Food as Medicine 
Although recent research shows that the drug development pipeline for PD is robust, with a wide variety of approaches being developed and evaluated in phase 1 and 2, investigators note that only a limited number of disease-modifying treatments are transitioning to phase 3.
Duda noted that phytochemicals incorporated into the diet might target some of the same mechanisms that are targets of these drugs in development. 
“Flavonoids have been shown to stabilize alpha-synuclein in vitro,” he said. “Caffeine, curcumin, resveratrol, and eliminating meat and dairy inhibit mTOR [mammalian target of rapamycin], and mTOR inhibition results in increased autophagy that may help clear alpha-synuclein. Genestein, an isoflavone in soybeans, protects dopaminergic neurons by inhibiting microglia activation. Flavonoids inhibit inflammation by inhibiting release of NO [nitric oxide] and pro-inflammatory cytokines,” he noted. 
Ongoing studies of dietary interventions for PD are exploring various areas, including the potential role of the ketogenic diet in protecting the gut microbiome, optimizing protein intake for muscle preservation and sleep, the effects of psyllium and wheat bran on weight and constipation, and the impact of a gluten-free diet.
Practical Tips for Healthy Eating 
Gilbert emphasized that there are no medications or interventions currently available that can delay a PD diagnosis by up to 17 years, as some dietary patterns have been shown to do, and she noted that it’s not possible to replicate the MeDi diet in a pill. However, she recommended a practical approach to eating that includes a diet low in ultraprocessed foods and high in beneficial nutrients. She encouraged people to shop for “real food” and enjoy a variety of colorful fruits and vegetables.
Duda acknowledged that motivating patients to follow a healthy diet can be difficult. As a result, the focus often shifts to making small adjustments and modifications. For example, he suggested that instead of pairing meat with French fries, people could opt for vegetables or add greens to their meals. Similarly, instead of having eggs and bacon for breakfast, they might choose oatmeal.
Preparing whole-food, plant-based meals may take more time than patients are accustomed to, so Duda suggests that, if possible, patients involve loved ones in both the meal preparation and the meal itself. He explained that a healthy meal can become an opportunity for bonding and that the key is educating them about new meal-related concepts. 
Duda reports no relevant financial relationships with the pharmaceutical or food industries. He has received compensation from the Physicians Committee for Responsible Medicine for his lecture delivered at the conference and research grant support from the VA, National Institutes of Health, Michael J. Fox Foundation, and the Department of Defense, unrelated to this topic. Gilbert reports no relevant financial relationships. 
Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom(the memoir of two brave Afghan sisters who told her their story).
 
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