MATERIALS & METHODS

The analysis process utilized to write the review is described in the Academy of Nutrition and Dietetics (AND) 2012 Evidence Analysis Manual [28]. During September 2019, PubMed and EbscoHost were searched for literature utilizing 42 search words related to nutrition and lifestyle AND/OR Parkinson resulting in 42 individual searches (Table 1). Database filters consisted of human studies, English language, and primary research/peer publications. The exclusion criteria included animal or in vitro studies, case studies, narrative reviews, gene therapy, risk of developing PD, and pharmaceutical research. Each article meeting the inclusion criteria was assessed for quality utilizing the AND checklists; those graded as negative quality were also excluded. The research articles were then grouped into categories, and each category was assigned a grading of recommendations assessment, development and evaluation (GRADE) with a definition and conclusion statement (Figure 1). There was only one reviewer evaluating the quality of each individual research article, grouping the positive and neutral quality articles into categories and arbitrarily assigning a GRADE to each category based on the quantity and quality of the research.

RESULTS

Utilizing key words AND Parkinson produced 6,045 publications, of which 56 were considered relevant, with 41 assigned a neutral or positive quality rating; these were then grouped into the categories of diet patterns, vitamin D, omega-three fatty acids (n-3), B vitamins, coenzyme Q10 (CoQ10), probiotics, physical activity (PA), sleep, and stress. Research on stress management with regard to PD was lacking, with only one study utilizing yoga as the intervention.

The collection of research related to diet patterns was assigned a GRADE of fair (II) due to utilizing study designs that are less appropriate for interventions (cohort, crossover) and small sample sizes. However, designing ethical nutrition and health research is difficult, and studies regarding diet patterns and organic plant-based food items are compelling [29-31]. The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet, studied to reduce neurodegenerative changes, was associated with a 13% reduction in the risk of developing PD or the progression of symptoms. It is a Mediterranean-type plant-based anti-inflammatory diet consisting of vegetables, fruits, legumes, whole grains, nuts, small wild fish, and small amounts of farm raised poultry and red meats low in saturated fats [31]. Considering that PD is related to toxic burden, a plant-based diet, which is high in vegetables and some fruits, should consist mostly of organic foods. Lu et al. [30] conducted a study to determine the contribution of pesticide intake from vegetables and fruits in American children at a private school. The pesticides malathion dicarboxylic acid and malathion tricholoro-2 pyridinol were detected in the children’s urine on days they were fed their usual diet but not the days they were fed an organic diet.

Organic plant-based diets tend to be lower in protein due to limiting or excluding animal foods; therefore, supplementing with a protein powder may be necessary to meet protein requirements. Supplementing with 20 g of organic whey protein powder daily has been shown to improve motor function, reduce homocysteine related to inflammation, and increase glutathione synthesis necessary for detoxification in those with PD [32]. Higher protein diets such as a ketogenic or gluten-free diet have been proposed as interventions for PD, as studies show improvements in motor function due to better glycemic control and reduced toxicity associated with food intolerances [33,34].

Several nutrition supplements related to PD have been investigated, but there was a lack of high-quality studies utilizing vitamin D. Vitamin D supplementation research provides conflicting results regarding PD, which may be related to the dose provided and the length of the studies. A prospective cohort in China found that 43% of participants with PD had lower serum levels than controls, which trended towards a positive correlation with disease duration [35]. Hiller et al. [36] reported significant improvements in balance when participants with PD were supplemented with 10,000 IU vitamin D daily. Another trial supplementing 1,200 IU daily for 12 months in those with serum levels of 22.5 ± 9.7 ng/mL reported improved PD symptoms when serum levels reached 41.7 ± 12.6 ng/mL [37].

There are only two trials with the same small sample utilizing 1,000 mg of n-3s from flaxseed oil for 12 weeks. These studies reported a reduction in inflammatory markers and increased antioxidative capacity and glutathione production, reducing PD symptoms [38,39].

There are a limited number of studies utilizing individual B vitamins and deficiency states in PD. Thiamine (B1) deficiency has been linked with neuroinflammation and neurodegeneration, suggesting a role in the progression of PD [40]. An observational study found that 100 mg of B1 administered intramuscularly twice weekly improved PD symptoms within 3 months [40]. Coimbra et al. [41] conducted a study to determine the riboflavin (B2) status among participants with PD and found that people with PD had lower serum B2 levels compared to controls. After supplementation with 30 mg of B2 every eight hours, participants reported improved sleep, reasoning, and motivation and reduced depression within two weeks and improved motor function by 44–71% in three months. A deficiency in B vitamins is associated with neuroinflammation and oxidative stress, for which homocysteine is a biomarker [42]. Ozer et al. [43] found a negative correlation between homocysteine and visual-spatial tasks, learning, serum vitamin B12, and serum folate.

People with PD tend to be at greater odds of a CoQ10 deficiency, an antioxidant that is important for the detoxification system, which may be partially responsible for their toxic burden [44]. Several high-quality studies have shown that supplementation with 100–1,200 mg of CoQ10 daily, particularly larger dosages, reduces inflammatory markers and improves motor symptoms [45-49].

There is very little research regarding interventions to support a healthy microbiome in PD. A study with participants with PD utilizing fermented milk rich in probiotics combined with a prebiotic fiber reduced incomplete evacuation of stool and increased the frequency from 3 to 4.5 bowel movements weekly [50]. A trial conducted with probiotic supplements containing 8 × 109 CFU reduced inflammatory markers, but changes in PD symptoms were not tracked [51]. Abnormalities in the microbiota may extend to the esophagus and oropharyngeal cavity, which may be related to a higher number of alpha-synuclein mutations found in the oral cavity of subjects with PD [14]. It has been speculated that these abnormalities may be responsible for PD nonmotor symptoms, including changes in swallowing, taste, smell, salivation, and speech.

There was a wealth of publications related to PA. Many studies utilized the American College of Sports Medicine (ACSM) guidelines, suggesting that people engage in 150 minutes of moderate-intensity PA weekly or 75 minutes of high-intensity training or a combination of both [52]. Several studies with PA utilizing the ACSM guidelines found that higher intensity exercise improves motor function, balance, cognition, depression, sleep, and quality of life [53-58]. Two studies showed an improvement in inflammatory markers, and Landers et al. [59] reported improved motor and nonmotor skills and neuroplasticity [60]. Corcos et al. [61] reported that progressive weightlifting improved motor skills more than a nonprogressive program.

Other forms of exercise, such as yoga, tai chi (TC), and dance, have led to improvements in motor and nonmotor function. Yoga has been shown to improve sleep, depression, cognition, balance, motor skills, and quality of life [62-64]. TC improves not only motor skills but also flexibility, internal awareness, orientation, and proprioception [65-67]. Hackney and Earhart [68] reported that tango had a larger impact on motor skills than TC, which may be related to the impact of music and rhythm and the increased cognitive demands of memorizing steps and motor planning.

There was a lack of published research related directly to PD and sleep and stress. Inadequate or ineffective sleep impacts the brain and motor skills, which may be related to replenishing dopamine levels [69,70]. Research specifically related to PD and stress was limited to one small study with 10 participants with PD reporting a reduction in psychological stress and increased wellbeing [71].

DISCUSSION

The evidence suggests that nutrition and lifestyle interventions may reduce PD symptoms and possibly delay disease progression. Prescribing specific diet patterns and nutritional supplements has the potential to reduce inflammation and toxin exposure, support detoxification, heal the gut, and calm the immune system to reduce PD symptoms and promote health and wellbeing.

The research supports prescribing a Mediterranean-type diet pattern to reduce inflammation by focusing on whole foods that are low in toxins [31]. The diet pattern is high in vitamins, minerals, fiber, and antioxidants, including flavonoids, which are found in plant-based foods, particularly berries. Gao et al. [72] in their cohort study reported reduced risk and progression of PD with the consumption of flavonoids as these antioxidants cross the blood brain barrier, reduce inflammation, influence neural signaling, and improve the survival of dopamine neurons. Curcumin/turmeric should be included as a spice in cooking due to its antioxidant abilities that protect cells, restore cell morphological changes, increase cell survival, and reduce cell death by influencing gene expression [73,74].

Food sensitivities and intolerances often go undetected, which may contribute to toxic burden, inflammation, and gut damage leading to excessive immune responses. There appears to be a connection between PD and celiac disease, suggesting the possibility of nonceliac gluten intolerance, which may cause cerebellar ataxia and neuropathy [34,75]. A systematic review conducted in 2018 suggested that gluten sensitivity should be considered for movement disorders owing to the connection with neurological dysfunction [76]. Therefore, an elimination diet should be tried for people with PD to identify any possible food sensitivities or intolerances that are contributing to symptoms. Once food sensitivities have been identified, a modified Mediterranean-type diet should be prescribed for long-term usage.

Avoiding processed foods, sugar and sugar substitutes will reduce inflammation and toxic burden and improve blood glucose in most individuals, which is essential for supporting neurological health [33]. Excess carbohydrate intake may also interfere with muscle protein synthesis, reducing muscle strength and function [77].

Obtaining adequate protein sources may be challenging due to locating organic meats and poultry and wild fish. Supplementing with 20 g of whey protein spread throughout the day preserves muscle mass and reduces oxidative stress and inflammation [32]. Whey protein is a good source of cysteine that is needed for glutathione production to support detoxification and reduce homocysteine. As glutathione appears to be ineffective as a supplement, food sources are required to increase its biosynthesis to reduce inflammation and oxidative damage to neurons [32].

Diet and gut health also play an important role in supporting detoxification and managing constipation [78]. Regular bowel movements prevent toxins from deconjugating and being freed within the lumen and reabsorbed in the presence of increased intestinal permeability [78,79]. Fiber binds toxins and influences tight junction proteins that support gut wall integrity to prevent increased intestinal permeability and toxin reabsorption [78-80]. Substances that alter the microbiome and damage the gut include medications, a low-fiber diet high in processed foods, infectious agents and food intolerances [81,82]. Gut dysbiosis is a result of consuming foods that are poorly tolerated or highly processed, leading to an overgrowth of gram-negative bacteria and their inflammatory byproducts. It has been well established that an altered microbiota is prevalent in PD [2,13,81].

PA is an important aspect of managing PD and should include a variety of activities. Most types of PA are beneficial, but the key is motivation; therefore, the activity chosen should be enjoyed [58]. Even though all forms of PA appear to improve PD, each type of activity has its own unique benefits. An exercise program that is guided by a professional to increase exertion over time is more effective at improving motor skills and balance compared to nonprogressive programs [53-61]. Interval training with high spurts of activity followed by lower exertion activities has the best outcomes, including neuroplasticity, which includes improving cognition and mental health [53,54]. An exercise routine of stretching, strength training and aerobic activity improves depression and quality of life, which might be related to increasing brain-derived neurotrophic factor and decreasing inflammation [57,59,60]. Strength training combined with an adequate intake of dietary protein is important not only for managing PD symptoms but also for reducing age-related sarcopenia associated with frailty [32,83].

Yoga, dance, and TC may be more enjoyable than regimented PA programs for some individuals and more appropriate for the elderly or those with limited motor function [62,64-67,84,85]. Yoga is beneficial for improving motor function, overall physical fitness, flexibility, strength, sleep, and stress [62,64,71]. Dancing provides not only a social experience but also improves intellectual function, flexibility, balance, strength, functional movements (including finger and hand dexterity), motor planning and memory in people with PD [84]. TC improves quality of life and depression [67].

Sleep is important for PD management as it improves motor function possibly by restoring dopamine levels [70,86]. Ineffective sleep also has a negative impact on brain and motor skills, worsening symptoms and quality of life. Although the effects of sleep on PD are not well studied, the research does support a positive effect of sleep on other neurological diseases and motor skill improvements even in healthy individuals [69,87].

There are no high-quality studies linking stress and PD, but it is well known that stress has a direct connection to developing chronic diseases, particularly those of the brain [88]. Chronic stress affects neuropeptide signaling, causing anxiety, depression, and inflammation related to disease. The dopaminergic nuclei are also inhibited by chronic stress, which may be related to the depressive symptoms common in PD. Depression may affect glutamate, which activates receptors and alters the hippocampal excitatory synapse, which affects cognition, another common feature of PD. Stress reduction should be addressed in the management of PD, as it has the potential to reduce symptoms and improve overall health and quality of life.

Research suggests that people with PD are deficient in CoQ10, glutathione and vitamins C and D [35,44,88,90]. Coenzyme Q10 at dosages of 300–1,200 mg daily may have a positive impact on motor neuron symptoms, finger dexterity, visual color acuity, and inflammation. Glutathione is not beneficial as a supplement, but its endogenous production relies on nutrients provided by a Mediterranean-type diet high in cruciferous and allium vegetables, citrus, and berries and possibly supplemental n-acetyl cysteine [91]. A small study administering large dosages of oral nacetyl cysteine (1,200 to 8,000 mg/day) to five participants with PD reported an increase in serum glutathione without adverse effects at a dose of 1,200 mg daily [92].

People with PD are at risk of vitamin D deficiency, but there is conflict in the research regarding the daily dose [35,36,93]. The impact of adequate vitamin D for good health is well established; therefore, serum levels should be tested and treated as needed [94]. To treat deficiencies, calculating a dose based on 40 IU for every 12 ng/mL for serum levels below 50 ng/mL may be the best approach [95].

Although there is no research related to PD and vitamin C supplementation, vitamin C is a powerful antioxidant that quenches reactive oxygen species developed during detoxification. Ide et al. [89] found an inverse relationship between serum vitamin C and the most severe stages of PD. As vitamin C supports detoxification, food sources would be included in the daily diet pattern.

Deficiencies in B vitamins are more prevalent with PD than in the healthy population [40,96]. Deficiencies in B1 are linked with neuroinflammation and neurodegeneration and B12, B6, and folate to elevated homocysteine. Correcting B1 deficiency may improve motor function, fatigue and cognition [96]. Motor symptoms, sleep, motivation, and depression improve with the correction of B2 deficiency [41]. Correcting B6, B12 and folate deficiencies has a positive effect on homocysteine, which tends to be high in those taking levodopa [97]. In clinical practice, biomarkers of B vitamins have several limitations for assessing nutrition status; therefore, a thorough nutrition-focused physical examination should be conducted to identify micronutrient deficiencies that should then be treated as needed [98,99].

Omega-three fatty acids reduce inflammation and may improve PD motor skills. Flaxseed is a source of n-3s, but the conversion of alpha-linolenic acid to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is very small; therefore, fish sources that are rich in EPA and DHA are recommended [100]. As fish are contaminated with methylmercury and polychlorinated biphenyl, prescribed n-3 supplements should be purified. The suggested dose is 1 g increasing to 4 g daily as tolerated [38,39].

Consuming probiotic supplements and prebiotics as food sources reduces inflammation and oxidative stress to heal the gut and correct the balance of microbes. As there is limited information regarding specific strains for PD, supplementation with 8 × 109 CFU live bacteria with a variety of species is a general recommendation based on the available research.

A systematic search of the literature has provided research regarding diet patterns, supplements, and PA, with limited research on probiotics, vitamin C, individual B vitamins and the impact of sleep and stress on PD. Another limitation of the literature review is that a single author evaluated the literature and assigned a GRADE to categories of research. Regardless of the limitations, the research suggests that providing nutrition and lifestyle interventions for people with PD or parkinsonism symptoms may be beneficial. Future research is needed to identify the potential benefits of nutrients with limited research identified in this review. A program including a Mediterranean-type diet, supplements, stress management and sleep hygiene needs to be developed and tested as a pilot program to determine the impact on quality of life and disease progression.

Notes

Conflicts of Interest

The authors have no financial conflicts of interest.

Acknowledgments

None.

Figure 1.

Grade definitions: strength of evidence for a conclusion statement. Adapted from Academy of Nutrition and Dietetics.[28]

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