Parkinson’s Disease

Parkinson’s disease (PD) is a progressive, degenerative disorder of the brain that is associated with a loss of dopaminergic neurons in the substantia nigra; neurodegeneration in other areas of the central nervous system (CNS), such as the locus coeruleus and the cerebral cortex; and the presence of Lewy bodies.[1] Loss of dopamine stimulation causes an imbalance between excitation and inhibition pathways of the basal ganglia (which coordinate motor activity), resulting in impairment in the voluntary control of movement.

Hallmarks of the disease include muscular (“cogwheel”) rigidity, resting (“pill-rolling”) tremor that decreases or disappears with movement, bradykinesia, and an unstable, flexed posture.[2] Patients exhibit a narrow-based, shuffling gait and usually show progressive difficulties with activities of daily living (e.g., eating, dressing, writing). Micrographia may be present; therefore, in assessing disease progression, it is helpful to compare the patient’s previous handwriting samples to a recent sample.

Depression is the most common psychiatric complaint, and hallucinations may appear with more advanced disease, sometimes as an adverse side effect of medications used to treat the condition.[3][4] Dementia occurs in about one-third of cases and presents with personality changes, psychomotor retardation, and memory problems. Anxiety, sleep problems, fatigue, and autonomic dysfunction, including postural hypotension, are also common late in the course of disease.[3][5][6][7]

Risk Factors

Family history. Several studies have shown that one of the strongest risk factors is a family history of PD or tremors.[8] Specific gene mutations have also been associated with PD.[9]

Age. About 1% of Americans over age 60 are affected, and prevalence increases with age. Typical age of onset is the 70s and early 80s, with less than 5% of cases presenting before age 40.[10][11][12]

Environmental factors, such as pesticides and heavy metals, are being studied for possible roles in PD, especially because specific toxins are known to target the substantia nigra.[13][14] The risk of PD is also increased among individuals with high dairy consumption.[15]

Head trauma and low vitamin D levels are additional risk factors.[16][17] The use of postsynaptic dopamine-receptor blockers (antiemetics, antipsychotics) may lead to parkinsonism.


Diagnosis is generally made using a thorough history and a complete physical examination, including a neurologic examination, showing at least 2 or more of the characteristic clinical findings of PD (bradykinesia, resting tremor, rigidity, postural instability). Presentation is often unilateral or asymmetric, especially at disease onset.[18]

Although there are no commonly available laboratory tests or imaging modalities, clinical response to a dopamine agonist is strong supportive evidence for the diagnosis.

Brain imaging with CT or MRI and/or laboratory testing may be indicated in equivocal cases to rule out other diagnoses (e.g., Wilson’s disease, Huntington’s disease, cerebrovascular disease, normal pressure hydrocephalus, mass lesions). However, imaging is generally indicated only if the presentation is atypical or if focal symptoms are present.


PD follows a progressive course. The disease advances in all cases, but the rate of progression varies, with younger patients often progressing more rapidly. While there is no cure, medical treatment can alleviate many of the symptoms and help improve quality of life. Medications should be used at their lowest effective dose.

Adjuvant Therapies

Physical, occupational, and speech therapies are often beneficial, and social work consultation can help make daily living at home easier. Exercise has been shown to be beneficial at all stages of the disease and can help both mood and mobility. Exercises should focus on conditioning, strengthening, and stretching (20 minutes at least 3 times weekly is a reasonable target).[19] As balance worsens, appropriate precautions must be taken.


Medications that may cause parkinsonian symptoms should be discontinued if possible. Treatment is primarily aimed at increasing the availability of dopamine to the CNS and reducing symptoms. To date, there are no proven methods to stop disease progression. Some evidence suggests that exercise and deep brain stimulation may slow progression.

The combination of levodopa (a dopamine metabolic precursor) plus carbidopa (which antagonizes the dopa decarboxylase enzyme that would otherwise convert levodopa to dopamine prior to reaching the brain) has proven to be the most effective therapy to improve symptoms, and is usually used first-line.[20] Concern about potentially speeding Parkinson’s deterioration by early use of levodopa is probably unfounded.[21] Side effects are more common with increased dose and frequency, and may include nausea and dizziness, hallucinations, motor complications, and orthostatic hypotension.[22]

Dopamine agonists (pramipexole, ropinirole, and rotigotine) improve symptoms and may be used as monotherapy for early disease. Apomorphine, an injectable, is used as a rescue therapy for patients with sudden akinesia.[23] Side effects are similar to those seen with levodopa/carbidopa. Bromocriptine is used most commonly as an adjuvant to levodopa.

Monoamine oxidase inhibitors (type B) (Selegiline and Rasagiline) impede the breakdown of dopamine and may also prolong the action of levodopa.

Catecholamine-O-methyl-transferase (COMT) inhibitors (entacapone, tolcapone) may slow the breakdown of dopamine by enhancing the effect and half-life of levodopa.[24]

Amantadine (an antiviral medication) may be useful not only for its mild anti-Parkinson’s effects, but also as a mild psychostimulant and as treatment for severe dyskinesia.[25]

Some evidence suggests that low-dose estrogen might be helpful in reducing motor symptoms in postmenopausal women taking anti-Parkinson’s medications. Further study is warranted.[26]

Hallucinations may be treated with medication dose reduction, clozapine or quetiapine, tremor with benztropine or trihexyphenidyl, and depression with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or tricyclic antidepressants.


Surgical approaches (deep brain stimulation, or on rare occasions, thalamotomy or pallidotomy) may have a role in advanced disease, especially in patients with severe intractable dyskinesia, tremor, or rigidity.[27]

Nutritional Considerations

Observational studies have found associations between elements of plant-based diets and reduced risk of developing PD. In addition, some evidence suggests that diet changes may be useful in its treatment.[28] This may be due to protection against oxidative stress, which has emerged as a significant factor through the evidence on the roles of high-fat diets, uric acid, and plant components (e.g., flavonoids) in the risk for PD.

Evidence implicates dairy products and high-fat diets as contributors to risk. Flavonoids, caffeine, alcohol, and adequate vitamin D status have emerged as protective factors, although evidence is stronger in men than in women. Established roles for diets that are low in protein or redistribute protein to evening meals have also been confirmed as useful for many patients. These factors are discussed below.

Low-fat diets. Previous evidence suggested that the prevalence of PD correlated with intake of animal fat and total and saturated fat.[29][30][31] A more recent review and a meta-analysis concluded that the intake of polyunsaturated fat was significantly protective against PD.[32][33] Another meta-analysis found an inverse association between the intake of alpha-linolenic acid and risk for PD.[34]

Minimizing dairy products. A meta-analysis found an overall 40% higher risk for PD in individuals consuming the most dairy products compared with the lowest intake category. The effect was more pronounced among men than women.[35] One suggested mechanism for this association is the presence of organochlorine pesticides in milk. Organochlorines may increase the susceptibility of dopaminergic neurons to cell death, and have been found to a greater extent in the substantia nigra of PD sufferers.[36] The ability of higher dairy consumption to lower uric acid (a protective antioxidant) levels may also play a role in the association with PD. Serum uric acid, versus intracellular uric acid, which has pro-oxidative properties and is associated with CVD, HTN, and oxidative stress, is a known biomarker of PD severity and progression, and is found in lower levels in the substantia nigra of PD sufferers compared to normal individuals.[37]

There are other mechanisms where dairy is thought to increase PD risk. Dairy increases insulin resistance. There is an area of research that points to insulin resistance as factor in neurogenerative diseases like PD and is referred to as type 3 diabetes. Lactose intolerance can lead to intestinal inflammation and increased gut permeability. Bovine microbiota from dairy can lead to methane dominant small intestinal bacteria overgrowth.[38]

High intake of flavonoids. Widely distributed in plant-based foods and beverages, flavonoids have multiple functions. They interact with neuronal signaling pathways that are critical in controlling neuronal survival and differentiation, modulate the activity and expression of several antioxidant enzymes, and impact mitochondrial function and neuroinflammation. In the Health Professionals’ Follow-Up and Nurses Health’ Studies, men consuming the most flavonoids had a 40% lower risk for PD compared to those consuming the least.[39] Food sources that contain high levels of flavonoids include tea, berry fruits, apples, red wine, and orange/orange juice.[36]

Caffeinated beverages. A meta-analysis found a 25% lower risk for PD for individuals in the highest compared with lowest level of caffeine intake, an association that was more significant for men than for women.[40]

Adequate vitamin D status. Individuals with PD typically have lower circulating vitamin D levels than age-matched controls, along with lower bone mineral density and higher risk for both falls and fractures.[41] The incidence of PD was also found to be three times greater in individuals with the lowest (compared to highest) vitamin D blood levels.[42] A meta-analysis found that individuals with vitamin D blood levels in the deficient range had more than twice the risk for developing PD, compared with those in the normal range, while vitamin D supplementation was associated with a nearly 40% lower risk for this disease.[43] A controlled clinical trial of daily 1,200 IU of vitamin D supplements increased the blood level of vitamin D from a deficient to a normal range and significantly prevented the deterioration of the Hoehn and Yahr (HY) stage (a system for describing how the symptoms of PD progress) in patients with a vitamin D receptor phenotype (FokI TT) known to be associated with PD risk.[44]

Alcohol. A meta-analysis found a roughly 20% lower risk in individuals who consumed the most compared to the lowest amount of alcohol overall; however, the effect was most pronounced in male beer drinkers.[41]

Nutritional Factors in Treatment

The most immediate nutritional concerns in PD treatment include changes in the absorption rate, blood levels, and CNS uptake of L-dopa. The protein content of meals, and particularly the distribution of protein intake throughout the day, has emerged as an important consideration in the effectiveness of L-dopa for many patients. Improvement in clinical response varies from 30% with protein redistribution to 82% with low-protein diets.[45][46][47]

In a study of 1,053 patients with PD, a food frequency questionnaire revealed that higher consumption of fresh fruits, fresh vegetables, nuts and seeds, non-fried fish, olive oil, wine, coconut oils, and fresh herbs and spices were associated with a reduced rate of symptom progression. Foods associated with an increased rate of symptoms included canned fruits and vegetables, diet and non-diet soda, fried foods, beef, ice cream, yogurt, cheese, and iron supplements.[35] It should be noted that fish may contain heavy metals that are neurotoxins, potentially damaging the dopamine producing cells, increasing PD risk. Another study demonstrated that consuming foods high in the antioxidants vitamin E and beta-carotene significantly decreased PD risk.[48]

Up to 24% of PD patients may be classified with malnutrition, and thesepatients have a 4-fold increase in risk for weight loss of 10 lbs or more compared with age-matched controls.[49] Reasons for this include impaired sensory perception (e.g., anosmia, dysgeusia), dysautonomia (e.g., constipation), dysphagia, dyskinesias, depression, and cognitive impairment.[50] Conversely, excess weight gain may occur due to an increase in sedentary behavior.[51] Individuals with chewing or swallowing difficulties should be referred to a speech therapist for a swallowing study and recommendations for appropriate changes in diet texture and liquid thickness. Dysphagia is associated with a significant increased risk of malnutrition. The International Dysphagia Diet Standardization Initiative (IDDSI) developed a framework of various levels of texture of foods and thickness of liquids to improve safety and provide a continuum to individualize nutrition therapy to maximize nutrition and prevent unintended weight loss.[52]

There are eight levels:

  • Level 7: Regular
  • Level 6: Easy to chew
  • Level 5: Soft and bite-sized
  • Level 4: Extremely thick/pureed
  • Level 3: Moderately liquidized
  • Level 2: Mildly thick
  • Level 1: Slightly thick
  • Level 0: Liquid

A registered dietitian can work with a patient to develop an eating plan based on the speech therapist’s recommendations for IDDSI diet level to ensure adequate nutrition while helping families plan meals that are also adequate in fluid and fiber (particularly insoluble fiber), an important concern to prevent constipation.[48]

Timing of Protein Intake

Most patients do not note a major impact of food on their response to medication in terms of the onset of effect. Those who do may avoid problems by taking levodopa 30 minutes prior to eating, or at least 60 minutes after meals. However, some patients note that high-protein meals blunt the response to L-dopa, reflecting competition for neutral amino acid carriers across the blood-brain barrier. The beneficial effects (e.g., control of dyskinesias) on L-dopa bioavailability of a protein-reduced diet, or the redistribution of almost all protein to evening meals, have been demonstrated in patients who experience erratic responses to levodopa therapy.[27][28][29][30] In these studies, reducing protein intake to amounts as low as 0.5g/kg body weight resulted in an improved therapeutic response in many individuals, as shown by improvements in neurologic scoring.[44]

Similarly, redistributing all but 7 g of protein intake to the evening meal resulted in improvement in the Northwest Disability and AIMS Dyskinesia Scale. Both low-protein diets and diets reserving protein for evening meals were associated with significant reductions in the need for L-dopa.[43][44] A study that both decreased protein intake to the Recommended Daily Allowance (i.e., 0.8 g/kg body weight) and distributed almost all protein to the evening meal (through the use of special low-protein starches) demonstrated a similar benefit. Specifically, postprandial and total “off” phases (consisting of dyskinesias and complaints of pain, paresthesias, sweating, constipation, or shortness of breath) were reduced by 38%, from a mean of 79-49 minutes, while total “off” time was decreased by 39%, from a mean of 271-164 minutes by the protein redistribution diet.[28] In addition, the midday dosage of L-dopa was reduced in one-third of patients by an average of 9%. Caution may be required when redistributing most protein intake to the evening meal; this strategy can be so effective that an excess of L-dopa may enter the brain and trigger dyskinesia.[53]

In addition, PD patients who ate a plant-based diet experienced a significant reduction in the Unified Parkinson’s Disease Rating Scale (UDPRS) when compared with a similar group of patients eating an omnivorous diet.[25]

A decreased requirement for L-dopa induced by a protein-restricted diet may offer more than symptomatic benefit. It is well known that oxidative stress is central to the pathology of PD, and autoxidation of L-dopa increases oxidative stress in the substantia nigra.[54][55] In addition, higher cumulative levodopa doses have been associated with the earlier occurrence of motor complications.[56] Measures that reduce L-dopa dosages, therefore, may prolong the period during which patients benefit from drug therapy.

In addition, high-protein meals raise blood levels of total homocysteine, a known risk factor for vascular disease.[57] It is known to be elevated in PD patients as a side effect of L-dopa and contributes to dopaminergic cell death.[58][59] A meta-analysis found a significant relationship between plasma homocysteine and cognitive dysfunction, thereby suggesting a possible need for and benefit of testing for elevated levels and their treatment, respectively.[60] Metabolic B12 deficiency is a common cause of elevated homocysteine that is often missed and easily treated.[1]

High dose parenteral thiamine. Free thiamine levels in the cerebrospinal fluid of patients with PD are lower than controls, and PD sufferers have lower levels of thiamine-dependent glucose metabolism in the brain than individuals without PD. Studies show that higher concentrations of thiamine may reduce alpha-synuclein concentrations. Clinical data in PD patients given 100-200 mg/d of intramuscular thiamine have begun to support this notion, revealing significant improvement in typical PD symptoms.[61][62] Further studies are needed to confirm these initial clinical trials.

Oxidative Stress and Parkinson’s Disease

Several factors have led to the theory that oxidative stress contributes to the risk for development of PD, possibly by causing mitochondrial damage.[63][64] This has resulted in trials of both medications (e.g., entacapone) that inhibit oxidation and supplements (e.g., coenzyme Q10) that scavenge free radicals (see below).

Coenzyme Q10. The neuroprotective effects of coenzyme Q10 (CoQ10) have been under investigation for a potential role in PD treatment. A multicenter clinical trial in which patients were provided either 1,200 or 2,400 mg/d of CoQ10 in addition to 1,200 IU/day of vitamin E found no significant benefit.[65] However, a controlled trial with the reduced form of CoQ10 that has shown greater neuroprotective effects found a significant improvement in the UDPRS when compared with placebo.[12]


See Basic Diet Orders chapter.

A nutrition consultation would be appropriate to assist the patient in restricting protein prior to the evening hours.

What to Tell the Family

To minimize deconditioning, patients should maintain an active lifestyle as much as possible. Patients should be aware that PD often causes weight loss, which family members can help minimize by providing breakfast, lunch, and snacks that are high in calories from whole grains (e.g., oats, bulgur, barley, brown rice), fruits, nuts, and vegetables. The family should ensure proper nutrient intake and be advised that protein deficiency is unlikely if adequate calories are consumed. Family members can improve the effectiveness of L-dopa therapy by reserving high-protein foods for evening meals. A qualified nutrition professional (e.g., registered dietitian) may be helpful in accomplishing these aims.


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Last updated: July 31, 2023