A progressive neurological disorder of movement and mental function characterized by the following:
• “Pill rolling” motion of the thumb and forefinger
• Tremor (worst when the limb is at rest; diminishes with voluntary movement and sleep)
• Slow movement or inability to move; difficulties not only with execution of movement but also with planning and initiation of movement
• Postural instability; impaired balance leading to frequent falls
• Stooped posture
• Abnormal gait
• Reduced or fixed facial expressions (“masked face”), low-volume or monotone voice, or both
• Gastrointestinal symptoms: constipation (often one of the earliest symptoms), difficulty swallowing (later in the disease)
• Cognitive disturbances, including an inability to make decisions and adapt to new environments, poor problem solving, fluctuations in attention, and memory problems
• Behavior and mood alterations, including depression, apathy, and anxiety
Parkinson’s disease was first described by James Parkinson in 1817. Parkinson’s disease affects more than 7 million people worldwide and at least 1 million in the United States, where about 50,000 new cases are reported annually. These figures are expected to increase as the average age of the population rises. The average age of onset is approximately 60 and the prevalence increases with age.1
Parkinson’s disease is the result of damage to the nerves in the area of the brain that is responsible for controlling muscle tension and movement—the substantia nigra of the basal ganglia. The damaged cells are the ones needed to produce the neurotransmitter called dopamine.
The disease usually begins as a slight tremor of one hand, arm, or leg. In the early stages the tremors are more apparent while the person is at rest, such as while sitting or standing, and are less noticeable when the hand or limb is being used. A typical early symptom of Parkinson’s disease is “pill rolling,” in which the person appears to be rolling a pill back and forth between the fingers. As the disease progresses, symptoms often get worse. The tremors and weakness affect the limbs on both sides of the body. The hands and the head may shake continuously. The person may walk with stiff, shuffling steps. In many cases, the disease causes a permanent rigid, stooped posture and an unblinking, fixed expression.1
Parkinson’s disease is classified as a neurodegenerative disease, like Alzheimer’s disease, and shares with Alzheimer’s some underlying causes, such as oxidative damage, inflammation, and dysfunction of the mitochondria, the energy-producing parts of cells. Many of the underlying issues in Parkinson’s disease are discussed in the chapter “A Cellular Approach to Health,” and that chapter also provides a deeper understanding of the preventive and therapeutic strategies that are important in Parkinson’s disease.
The first biochemical abnormality in Parkinson’s disease is a decrease in the level of glutathione, the brain cell’s primary antioxidant. Low glutathione makes the cells more susceptible to oxidative damage, such as that caused by environmental toxins. This sets the stage for the destruction of the neuron.
The first hint that Parkinson’s disease may be related to an environmental toxin came from a report based on a series of patients who developed Parkinson’s disease after exposure to MPTP, a contaminant found in synthetic heroin.2 MPTP can freely cross the blood-brain barrier, is selectively taken up by the dopamine system cells of the substantia nigra, and inhibits mitochondrial energy production; this inhibition results in cell death. As of 2012, MPTP is the only environmental agent that has been directly linked to development of Parkinson’s disease, but there are many more suspects. Population-based studies and animal experimental models have identified an association between Parkinson’s disease and a number of environmental factors, including living in a rural area, farming, drinking well water, exposure to pesticides, and long-term occupational exposure to copper, iron, lead, and manganese.3–16 Additionally, it is possible that pesticides and metals act synergistically with other neurotoxins to increase the risk of Parkinson’s disease. In other words, it may be the total load of neurotoxins—instead of any single agent—that matters in the development of Parkinson’s.
What all of these environmental toxins have in common is that they cause depletion of glutathione and disruption of the mitochondrial function.17 That is a one-two punch that ultimately destroys the brain cell. By the time Parkinson’s disease is typically diagnosed, more than 50% of the substantia nigra has been destroyed.
Therapeutic Considerations
At this point in time, Parkinson’s disease is best treated with drug therapy along with key dietary, nutritional, and herbal recommendations to address the underlying disease process and/or enhance the effectiveness of drug therapy.
The most popular drug used in Parkinson’s disease is Sinemet, which contains two key ingredients: levodopa and carbidopa. Levodopa, or L-dopa, is the “middle step” in the conversion of the amino acid tyrosine into dopamine. L-dopa, but not dopamine, crosses the blood-brain barrier. Carbidopa is a drug that works by ensuring that more L-dopa is converted to dopamine within the brain, where it is needed, and not within the other tissues of the body. Other drugs used include Eldepryl (selegiline or deprenyl), bromocriptine, and amantadine.
Unfortunately, although effective in the early stages of the disease in providing relief of symptoms, drug therapy does alter the disease progression and loses efficacy over time. Also, L-dopa and other drugs for Parkinson’s disease are associated with common side effects such as motor complications, nausea, vomiting, sedation, hallucinations, and delusions. The primary focus with naturopathic care is to reduce these side effects while protecting the neurons from further damage.1,18
There are preliminary studies of gene therapy, which involves the use of a noninfectious virus to shuttle a gene into a specific part of the brain. The goal is to set in motion a series of biochemical processes that will increase the amount of GABA, which helps to manage Parkinson’s disease symptoms. A more controversial therapy involves transplanting stem cells into the substantia nigra. Another therapy that is regaining traction is deep brain stimulation, which involves implanting a brain stimulator (a device similar to a heart pacemaker) in certain areas of the brain. All of these treatments are promising but still considered experimental.
A low-protein diet can enhance the action of L-dopa therapy. This simple dietary recommendation has been demonstrated to be extremely helpful in several clinical studies and is now a well-accepted supportive therapy. The usual recommendation is to eliminate as much protein as possible from breakfast and lunch while eating a typical dinner, so that total daily protein intake is less than 50 g per day for men and 40 g per day for women. This simple dietary practice can be effective in reducing tremors and other symptoms of Parkinson’s disease during waking hours.19
Since L-dopa absorption is delayed or diminished by the amino acids in protein, patients on L-dopa should take their medication with a high-carbohydrate meal.
Antioxidants
Given the abundance of data suggesting that an excessive free radical burden contributes to Parkinson’s disease, it is logical to consider that increasing antioxidant intake through dietary supplementation may offer some therapeutic benefit. Unfortunately, the research that exists on this line of therapy has focused on a rather limited number of antioxidant nutrients and the results have been rather disappointing. High supplemental dosages of vitamin E and C do not seem to affect Parkinson’s disease. However, population-based studies have mostly indicated that high dietary intakes of antioxidant nutrients, especially vitamin E, may prevent Parkinson’s disease.20,21 The results from these preliminary studies led to a trial of high-dose vitamins C and E in early Parkinson’s disease as well as a large study of high-dose vitamin E and the drug selegiline.22
In the double-blind study in patients with early Parkinson’s disease given 3,000 mg vitamin C and 3,200 IU of vitamin E each day for a period of seven years, the supplement group fared better than the placebo group.23 Although all patients eventually required drug treatment, the patients receiving the vitamins were able to delay the need for medication for up to two to three years longer. These results were quite promising, but a 10-year study of vitamin E only, at 2,000 IU per day, failed to show any real benefit in slowing or improving the disease.24 It is likely that a combination of nutrients and a very broad antioxidant supplement program may be required in order to see any significant benefit in preventing the progression of Parkinson’s disease.25
Coenzyme Q10 (CoQ10)
Given that CoQ10 is a powerful antioxidant and is also essential for the specific mitochondrial function that is damaged in Parkinson’s disease, it seems that CoQ10 should be helpful, but the research is not clear. Reduced levels of CoQ10 have been demonstrated in the platelets of individuals with Parkinson’s disease, and CoQ10 levels were strongly correlated with activity in mitochondrial energy production.26
Results of clinical trials have been inconsistent. In one trial of CoQ10 supplementation, progression of Parkinson’s disease was reduced by 44%.27 All of the patients had the three primary features of Parkinson’s disease—tremor, stiffness, and slowed movements—and had been diagnosed with the disease no more than five years before enrolling in the study. After an initial screening and baseline blood tests, the patients were randomly divided into four groups. Three of the groups received CoQ10 at different doses (300, 600, or 1,200 mg per day) while a fourth group received a placebo, for 16 months. The subjects who received the largest dose of CoQ10 displayed significant improvement in mental function, motor function, and ability to carry out activities of daily living, such as feeding or dressing themselves; the greatest effect was in activities of daily living. The subjects who received 300 mg per day and 600 mg per day developed slightly less disability than the placebo group, but the effects were less than those in the group that received the highest dosage of CoQ10. Average plasma levels of CoQ10 were approximately 1.8, 2.1, and 4.5 mcg/ml, respectively, for the 300-, 600-, and 1,200-mg dosages. These results indicate that the beneficial effects of CoQ10 in Parkinson’s disease may require adequate blood levels. It is important to point out that in this study CoQ10 was administered along with vitamin E at a dosage of 1,200 IU day, which may have prevented the achievement of higher levels of CoQ10. If vitamin E is not used, target CoQ10 levels may be reached at lower dosages. The researchers were aware of this issue but chose to include the vitamin E given its apparent protective role against Parkinson’s disease.
Two recent studies have cast doubt on the therapeutic efficacy of CoQ10 in Parkinson’s disease, however. In a German study, a highly absorbable form of CoQ10 at a dosage of 100 mg three times per day or a placebo was given to 131 patients with Parkinson’s disease for three months. Plasma levels of CoQ10 reached 4.6 mcg/ml in the treatment group, yet no effect on symptoms was seen. These results indicate that other factors may be responsible for determining the efficacy of CoQ10 in Parkinson’s disease beyond achieving effective plasma levels.
On May 27, 2011, the National Institute of Neurological Diseases and Strokes stopped a phase III study of coenzyme Q10 for treatment of early stage Parkinson’s disease.28 The study enrolled 600 patients with early Parkinson’s disease and randomly assigned them to receive 1,200 or 2,400 mg per day of active CoQ10 or a placebo. All subjects also received vitamin E at a dosage of 1,200 IU per day. While CoQ10 was shown to be extremely safe, results of an interim analysis showed that longer patient follow-up was not likely to demonstrate any statistically significant difference between active treatment and the placebo.
Despite this result, we recommend making CoQ10 a part of a comprehensive protocol for dealing with Parkinson’s disease because of its safety and the rationale for its use.
Reduced Nicotinamide Adenine Dinucleotide (NADH)
NADH is the active form of vitamin B3 that is required by the brain to make various neurotransmitters as well as chemical energy. Human studies indicate that NADH is effective in raising the level of dopamine within the brain. In two studies NADH has been shown to significantly increase brain dopamine levels in patients with Parkinson’s disease, reducing symptoms and improving brain function.29–31
Phosphatidylserine is the major phospholipid in the brain, where it plays a key role in determining the integrity and fluidity of cell membranes. Normally the brain can manufacture sufficient levels of phosphatidylserine, but there is evidence that insufficient production can lead to depression and/or impaired mental function, especially in people over the age of 50. In numerous double-blind studies phosphatidylserine supplementation has been shown to improve mental function, mood, and behavior in elderly subjects, including those with Parkinson’s disease.32
5-Hydroxytryptophan (5-HTP)
When used in combination with Sinemet, 5-HTP can alleviate the depression often associated with Parkinson’s disease.33 While it may be helpful as a supplement to Sinemet, 5-HTP should never be used alone in Parkinson’s disease.34–36 It is converted to serotonin in the brain, and increasing serotonin without increasing dopamine can worsen symptoms, especially rigidity. People taking Eldepryl should also not take 5-HTP unless under a physician’s care, since there is a significant risk that this combination can raise serotonin to excessively high levels.37
N-acetylcysteine
N-acetylcysteine (NAC) has shown promising results in animal models of Parkinson’s disease.38 It may work by increasing brain glutathione levels. Early research on intravenous glutathione showed some benefit, which lasted for several weeks even after treatment was stopped.39 Some nutritionally oriented doctors are reporting good results with both intravenous and intranasal glutathione. It is too early to make specific recommendations, but we hope these encouraging results will soon be followed up with rigorous research.
QUICK REVIEW
• Parkinson’s disease is the result of damage to the nerves in the area of the brain that is responsible for controlling muscle tension and movement
• The first biochemical abnormality in Parkinson’s disease is a decrease in the level of glutathione, the brain cell’s primary antioxidant
• Parkinson’s disease may be related to exposure to environmental toxins
• Parkinson’s disease is best treated with drug therapy along with key dietary, nutritional, and herbal recommendations to address the underlying disease process and/or enhance the effectiveness of drug therapy
• A low-protein diet can enhance the action of L-dopa therapy
• Results of clinical trials with supplemental dietary antioxidants have been inconsistent
• Phostphatidylserine has been shown in numerous double-blind studies to improve mental function, mood, and behavior in elderly subjects, including those with Parkinson’s disease
• Population-based studies consistently demonstrate that consumption of green tea offers protection against the development of Parkinson’s disease
• Velvet bean and fava bean are natural sources of L-dopamine
Green Tea
Population-based studies consistently demonstrate that consumption of green tea (Camellia sinensis) offers protection against the development of Parkinson’s disease. Specifically, green tea polyphenols may play a role in preventing and treating the oxidative stress underlying Parkinson’s disease. In cell cultures and animal models, green tea polyphenols have demonstrated an ability to protect brain cells against neurotoxins.40,41
Ginkgo Biloba Extract
Ginkgo biloba extract has a number of beneficial effects that may help in Parkinson’s disease. In a one-year open trial of 25 patients with Parkinson’s disease who had signs of impaired mental function, it produced significant improvements in brain wave tracings, signifying improved brain metabolism.42 Ginkgo has also been shown to be useful in animal models of Parkinson’s disease and has demonstrated the ability to protect the substantia nigra from damage induced by the neurotoxin MPTP.43
Velvet Bean
The powdered seed of the velvet bean (Mucuna pruriens) has long been used in traditional ayurvedic medicine for Parkinson’s disease and other conditions. It is a rich natural source of L-dopamine, but other components also contribute to its medicinal actions. An extract of velvet bean (7.5 g of velvet bean extract dissolved in water, given three to six times per day) was studied in 60 patients with Parkinson’s disease (26 patients were taking Sinemet before treatment with the extract, and the remaining 34 were not taking any medication).44 Statistically significant reductions in symptom scores were seen from the beginning to the end of the 12-week study. In another study, eight Parkinson’s disease patients were given single doses of 200/50 mg L-dopa/carbidopa (LD/CD) and 15 and 30 g velvet bean preparation in randomized order at weekly intervals.45 Compared with standard LD/CD, the 30 g velvet bean preparation led to a considerably faster onset of effect (34.6 vs. 68.5 minutes), reflected in shorter times to peak L-dopa concentrations in the blood, and fewer side effects. The researchers felt that the velvet bean might possess advantages over conventional L-dopa preparations. This conclusion has been confirmed in various animal models.46,47 Individuals on medications such as Sinemet and L-dopa should be aware that velvet bean consumption may increase L-dopa levels too much.
Fava Bean
L-dopamine was also found in the fava or broad bean (Vicia faba) in 1913. Since then, anecdotal cases of symptomatic improvement after broad bean consumption have been described in patients with Parkinson’s disease. In one small clinical study, 250 g cooked broad beans produced a substantial increase in L-dopamine blood levels, which correlated with a significant improvement in motor performance.48 Individuals on medications such as Sinemet and L-dopamine should be aware that consumption of fava beans may increase L-dopamine levels too much.
TREATMENT SUMMARY
Treatment of Parkinson’s disease from a naturopathic perspective involves trying to address the underlying disease process by employing strategies to protect the neurons in the substantia nigra as well as support current drug therapy.
Follow the guidelines in the chapter “A Health-Promoting Diet,” along with the following recommendations:
• Eat a diet that is high in fiber, specifically from legumes and vegetables, and low in animal products.
• Eat antioxidant-rich foods: nuts and seeds, green leafy vegetables (bok choy, chard, etc.), beans, spices (turmeric, clove, cinnamon), coffee, and chocolate.
• Avoid pesticides by using organic produce when possible.
• To maintain bowel health and facilitate the liver’s detoxification processes, eat high-sulfur foods such as garlic, onions, and eggs, as well as soluble fiber such as guar gum, oat bran, pectin, and psyllium seed.
• For patients taking L-dopa, a lower protein intake is recommended (50 g per day for men and 40 g per day for women). They should take their medication with a high-carbohydrate meal and delay protein intake until the final meal of the day in an effort to optimize the medication’s therapeutic efficacy.
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures” (without iron)
• Vitamin D3: 2,000 to 4,000 IU per day (ideally, measure blood levels and adjust dosage accordingly)
• Fish oils: 1,000 to 3,000 mg EPA + DHA per day
• Specialty supplements:
N-acetylcysteine: 400 to 600 mg per day
NADH (Enada): 10 to 20 mg per day
CoQ10:
• Ubiquinone powder in hard gelatin capsule: 400 mg three times daily with meals
• Ubiquinone suspended in rice bran oil in soft gelatin capsule: 200 mg three times daily with meals
• Ubiquinone ==solubilized (e.g., Q-gel) in soft gelatin capsule: 100 mg three times daily with meals
• Ubiquinone nanonized in soft or hard gelatin capsule: 100 mg three times daily with meals
• Ubiquinone emulsified with soy peptide (BioQ10 SA) in soft or hard gelatin capsule: 100 mg twice daily with meals
• Ubiquinol in soft gelatin capsule: 100 mg twice daily with meals
• One of the following:
Green tea extract (90% polyphenol content): 150 to 300 mg per day
Grape seed extract (>95% procyanidolic oligomers): 150 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 150 to 300 mg per day
Ginkgo biloba extract (24% ginkgo flavonglycosides): 240 to 320 mg per day
• Velvet bean (Mucuna puriens): dosage equivalent to 30 g dried powdered seed