Parkinson's Disease
Updated: 06/16/2006

Parkinson’s disease is a devastating brain disorder that gradually robs people of the ability to control their own movements. While the causes and cure of this affliction remain elusive, progressive scientists are continuing to unravel this disease.

During Parkinson’s, cells in the parts of the brain that control movement and regulate mood are gradually destroyed. The primary defect in Parkinson’s is a loss of dopaminergic neurons (such as dopamine-producing neurons) in a part of the brain called the substantia nigra. Dopamine is a neurotransmitter that modulates movement (Purves D et al 2001). In Parkinson’s disease, the dopamine-producing nerve cells are destroyed by high levels of oxidative damage (Atasoy HT et al 2004; Ross GW et al 2004). There is evidence that this oxidative damage is, in turn, caused by defects in the cells’ mitochondria, or power-generating centers.

The ideal treatment for Parkinson’s disease would be a neuroprotective agent— a treatment that protects the brain. While no neuroprotective prescription agent has been found, studies suggest that high-dose coenzyme Q10 (CoQ10), a natural agent, may have neuroprotective properties. CoQ10 is known to support mitochondria by enhancing energy levels in the brain, as well as by acting as a powerful antioxidant. In one phase 2 clinical trial, CoQ10 significantly slowed the progression of Parkinson’s disease (Beal MF 2003).

Conventional therapy for Parkinson’s disease focuses on increasing the production and utilization of dopamine. Levodopa, which is the precursor to dopamine, has been the mainstay of Parkinson’s disease therapy since its discovery in the early 1960s. Today, levodopa remains the foundation of Parkinson’s therapy. However, after 5 years, levodopa begins to lose its effectiveness in patients with Parkinson’s disease. If used as the sole treatment, levodopa must then be prescribed in higher and higher doses, leading to more adverse effects and more intense symptoms. Other drugs that target other parts of dopamine production and the utilization cascade are now increasingly prescribed. When used early enough, these drugs can help postpone levodopa therapy.

By supporting the mitochondria with CoQ10, reducing oxidant stress, and enhancing production of dopamine with supplements and alternative prescription agents, the Life Extension Foundation program for Parkinson’s described here may help slow the progression of the disease. Later on in this chapter, the Life Extension Foundation presents a unique program that will enhance the effectiveness of levodopa therapy.

Problems with Diagnosing Parkinson’s Disease

Parkinson’s disease is not uncommon. It is estimated that Parkinson’s disease affects about 1 out of 250 people older than 40 years of age and 1 out of 100 people older than 65. Approximately 50,000 new cases are diagnosed annually. Men are affected slightly more often than women. However, after menopause or after having a hysterectomy, the risk increases in women. Parkinson’s disease is rarely diagnosed before age 40 (Fishman PS et al 2002).

Unfortunately, it is difficult to diagnose Parkinson’s disease in its early stages. A diagnosis of Parkinson’s disease is based on the presence of symptoms, some of which occur in elderly people who do not have Parkinson’s. There is no lab test or imaging study that can accurately diagnose Parkinson’s.

In general, you have to exhibit two of the three following symptoms to be diagnosed with Parkinson’s disease:

• Tremor at rest (including nodding or shaking of the head)—the classic symptom of Parkinson’s, present in about 85 percent of cases (Kasper DL et al 2004)
• Rigidity
• Abnormally slow movements and reflexes (bradykinesia)

Although a number of tests may be conducted (such as magnetic resonance imaging [MRI] and positron emission tomography [PET]) to rule out other diseases, most diagnoses of Parkinson’s disease aren’t made until the disease has fairly well progressed. This is a problem, because many studies have shown that early intervention is especially valuable to postpone levodopa therapy. The recommended supplements have minimal adverse effects and are beneficial for even a healthy person. (However, the suggested prescription drugs discussed in these pages should not be taken unless you are under the supervision of a physician.)

Risk Factors for Parkinson’s Disease

A number of risk factors have been identified that increase the odds of contracting Parkinson’s. While the disease’s underlying causes have not been discovered, most researchers believe Parkinson’s is caused by overlapping environmental and genetic factors (Kasper DL et al 2004). Interestingly, both smoking and drinking coffee have been associated with a decreased risk of Parkinson’s disease (Deleu D 2001; Benedetti MD et al 2000; Smargiassi A et al 1998; Zuber M et al 1991).

Risk factors for Parkinson’s disease include:

Exposure to toxic metals. Parkinson’s disease is somewhat more common in rural areas and among people who work in agriculture and landscaping, suggesting that exposure to pollutants and toxic metals may be involved in the disease. A few heavy metals are known to be neurotoxic, including mercury, aluminum, copper, and iron (American Parkinson Disease Association 2006; Bardin JA 2000; Brown DJ 1998; Adams CR et al 1983). Metals (iron in particular) may cause some destructive effect through the production of reactive oxygen species (Zecca L et al 2004; Linert W et al 2000). Of course, iron is a necessary nutrient. Also, an iron deficiency can lead to increased absorption of more toxic metals including lead, cadmium, and aluminum (Goyer RA 1997).

Bacterial toxins. Another risk factor for Parkinson’s disease may be chronic exposure to toxins produced by intestinal bacteria (Clayman CB 1989). People with “leaky gut” syndrome may absorb excessive amounts of these toxins as the result of damage to the intestinal lining caused by other toxins and oxidants. Liver damage from alcohol and other toxins may further increase exposure to bacterial toxins (Philpott DJ et al 2001; Sullivan A et al 2001; Tancrede C 1992; Gentry LO 1991).

Poor diet. Poor nutrition in general, especially a low dietary intake of B vitamins and a high intake of simple sugars, has been associated with an increased risk of Parkinson’s disease and with more rapid progression of the disease in patients who already have it (Yapa SC 1992; Golbe LI et al 1988). High dietary intake of meat increases absorption of iron and animal fats, both of which are associated with an increased risk of Parkinson’s (Powers KM et al 2003; Logroscino G et al 1996).

Genetics. Although the cause of Parkinson’s disease is unknown in about 90 percent of cases, increasing numbers of genes have been identified that may increase the risk of Parkinson’s. According to the American Parkinson Disease Association, people who have a first-degree relative (such as a parent, sibling, or child) with Parkinson’s disease are about 50 percent more likely to develop the disease.

The Value of Early Intervention

The leading cause of dopamine-producing nigral cell death in the brain appears to be mitochondrial energy depletion, which contributes to the oxidative stress that hastens the disease (Beal MF 2003). Other causes of nerve cell death include inflammation and excitotoxicity (Koller WC et al 2004).

Energy Enhancers: CoQ10 and Acetyl-L-Carnitine

Mitochondria are known as the energy powerhouses of cells. They use glucose and fats, combined with oxygen, to produce energy. This process generates a steady stream of oxidative molecules that are normally neutralized by internal antioxidants. In Parkinson’s disease, however, the electron chain in the mitochondria is deficient, causing them to produce much higher levels of oxidative molecules. This steady oxidant stress damages mitochondria and eventually kills the host cells (Abraham S et al 2005; Mazzio E et al 2001; Linert W et al 2000). The holy grail of Parkinson’s disease research is a neuroprotective agent (one that reduces damage to mitochondria and cells). According to encouraging study results, CoQ10 may be this promising neuroprotective agent.

CoQ10. CoQ10 levels are about 35 percent lower in the mitochondria of Parkinson’s disease patients than in the mitochondria of control subjects of similar age and sex (Shults CW et al 1997), both in blood platelets and in the substantia nigra (Gotz ME et al 2000). CoQ10 supplementation seems to protect substantia nigra neurons against impaired mitochondrial energy production (Shults CW et al 1997) and against glutamate-related excitotoxicity (Mazzio E et al 2001).

In one small placebo-controlled, double-blind study of patients with Parkinson’s disease, 360 milligrams (mg) daily of CoQ10 for 4 weeks provided a significant (if somewhat mild) reduction in symptoms and a significant improvement in measures of disease progression (Muller T et al 2003). In a larger trial, CoQ10 was associated with a 44 percent reduction in the decline of motor function and activities of daily living, in comparison with a placebo (Shults CW et al 2002). Doses as high as 3000 mg/day have been well tolerated. Investigators have concluded that 2400 mg/day is the highest appropriate dosage (Shults CW et al 2004).

When Parkinson’s disease has been chemically induced in animals, CoQ10 seems to be protective in the disease’s early stages; however, CoQ10 may be less effective once dopamine depletion is severe. This suggests that supplements should be started as early as possible (Schulz JB et al 1995).

Based on these studies, patients with Parkinson’s disease might consider supplementation with 1200 mg (or possibly more) of CoQ10 daily. Laboratory monitoring of CoQ10 blood levels (Jimenez-Jimenez FJ et al 2000) may help determine optimal dose and response to treatment (Steele PE et al 2004).

Acetyl-L-Carnitine. Acetyl-L-carnitine (ALC) increases energy production by channeling fatty acids into mitochondria. It may also limit brain cell injury, thereby improving memory, motor skills, and possibly other brain functions. ALC also stimulates nerve cells to release dopamine, and it protects dopamine-containing neurons from destruction in animal models with Parkinson’s disease (Pettegrew JW et al 2000; Castorina M et al 1994).

Even at high dosages, toxicity with ALC has not been reported. Nausea and headache are infrequent and usually resolve with continued use or with dose reduction. Because ALC is a natural stimulant that typically increases energy levels and decreases fatigue, it is best taken in the morning. If taken before bedtime, it may interfere with sleep by suppressing serotonin and melatonin activity.

When ALC was regularly injected into the brains of infant rats, receptors for nerve growth factor increased in the striatum, where some dopamine-producing neurons reside (De Simone R et al 1991). ALC also increased nerve growth factor levels and utilization in the brains of older rats (Foreman PJ et al 1995; Taglialatela G et al 1994).

Antioxidant Therapy to Protect Neurons

While the underlying defect involves a defective mitochondrial electron transport chain, experts agree that most of the actual damage that occurs during Parkinson’s disease is caused by extremely high levels of oxidative stress. Not surprisingly, high levels of antioxidants, such as vitamin E and vitamin C, have been shown to relieve symptoms by protecting brain cells.

Experimental evidence showed that enrichment with vitamin E protected against oxidative stress in the substantia nigra (Roghani M et al 2001). Some scientists suggest that “chronic, high dose vitamin E dietary supplementation . . . may serve as a successful therapeutic strategy for the prevention or treatment of Parkinson’s disease” (Fariss MW et al 2003). Treatment with levodopa may be delayed for 2 years (or more) in newly diagnosed patients who receive large amounts of vitamins C and E (Fahn S 1992; Fahn S 1991).

Vitamin C may relieve the symptoms of Parkinson’s disease by neutralizing dopamine free radicals (Sakagami H et al 1998) and toxic quinones released from dopamine metabolism (Pardo B et al 1995), thereby protecting brain cells from levodopa-induced damage (Mytilineou C et al 1993). In the laboratory, bathing nerve cells in vitamin C enhanced dopamine synthesis (Seitz G et al 1998).

Bioflavonoids, which provide the red, pink, and purple colors in fruits and vegetables, are even stronger antioxidants than vitamin C. Most are water soluble and easily penetrate the brain. Suggested antioxidant supplements include grape seed extract. The herbal compound Ginkgo biloba contains numerous antioxidants, including proanthocyanins and flavonoids, which help maintain healthy brain function, circulation, and metabolism.

Polyphenols are antioxidants found in green tea, which are being investigated for their potential to protect against Parkinson’s disease (Weinreb O et al 2004). Polyphenols are also found in extracts of grape seeds and other plants. Like the bioflavonoids, they are powerful antioxidants. They may also inhibit the nerve cell damage in diseases such as Parkinson’s and Alzheimer’s.

It’s also important to support healthy levels of glutathione, the main mitochondrial antioxidant. Parkinson’s disease is characterized by a substantial depletion of mitochondrial glutathione, which further increases oxidative stress, decreases the electron chain transport activity and adenosine triphosphate production, and contributes to cell death (Khaldy H et al 2003). Supplements that can increase levels of glutathione include cysteine, N-acetyl-cysteine, selenium, lipoic acid, and garlic (Abdel-Wahab MH 2005; Abraham S et al 2005; Hsu M et al 2005; Soto-Otero R et al 2000). When taking L-cysteine, N-acetyl-cysteine, or glutathione, three times as much vitamin C should be taken at the same time to prevent these amino acid supplements from being oxidized in the body.

Although melatonin, a hormone produced in the pineal gland, reduces dopamine activity and release in the striatum, its potent antioxidant and mitochondrial-stimulating effects may protect against loss of dopamine-containing neurons (Zisapel N 2001). In rodents with chemically induced symptoms of Parkinson’s disease, melatonin prevented cell death and preserved enzyme activity in the substantia nigra (Antolin I et al 2002). Melatonin given orally easily reaches the brain and is well tolerated. Melatonin has been proposed as a potential therapy to prevent development or progression of Parkinson’s disease (Chen ST et al 2002) and to regulate disturbed sleep-wake cycles (Sandyk R 1992).

Melatonin has also been shown to work synergistically with deprenyl, a prescription drug that is frequently prescribed in the early stages of Parkinson’s disease (see below). In one animal study, a combination of melatonin and deprenyl was shown to protect mitochondria and simultaneously reduce the turnover in dopamine (Khaldy H et al 2003).

Amino Acids to Support Dopamine Production

The dietary amino acid tyrosine is converted in the brain to levodopa and then to dopamine. Phenylalanine, another dietary amino acid, can also be converted to tyrosine. Tyrosine and phenylalanine supplements therefore provide the brain with raw material to synthesize dopamine, and have been shown to increase dopamine formation in the brains of Parkinson’s disease patients (Growdon JH et al 1982). These supplements should not be taken in conjunction with deprenyl because of the risk of a hypertensive crisis.

B Vitamins

Dopamine synthesis requires vitamin B6 (pyridoxine) and its cofactor zinc, which should be provided in high amounts to overcome long-term deficiency symptoms and to stimulate dopamine production. Vitamin B6 (10 to 100 mg/day) decreased cramps, rigidity, and tremors, and also improved walking skills and bladder control (Sandyk R et al 1990).

Niacinamide (nicotinamide) enhances mitochondrial energy production and may help protect mitochondria from damage by toxins. A substance derived from nicotinamide, called nicotinamide adenine dinucleotide (NADH), is essential for cell development and energy production (Bender DA et al 1979). Animal studies suggest that protective effects from oral nicotinamide supplements are greatest when given early in the course of Parkinson’s disease, before dopamine is severely depleted. The benefits of NADH in Parkinson’s disease may result from its ability to reduce inflammation within the brain and from its effect on the immune system (Nadlinger K et al 2001).

Deficiency of the B vitamin folate may increase the risk of Parkinson’s disease by elevating levels of homocysteine, which makes dopamine-containing neurons more vulnerable to environmental toxins (Duan W et al 2002).

Abnormalities in riboflavin (vitamin B2) in Parkinson’s disease may be associated with glutathione depletion, mitochondrial DNA mutations, disturbed mitochondrial protein complexes, and abnormal iron metabolism. In one small study of patients with Parkinson’s disease, all of whom had abnormally low riboflavin levels, daily supplements of 90 mg of riboflavin and elimination of red meat from the diet led to improvement in motor function with minimal adverse effects (Coimbra CG et al 2003).

Early Intervention with Prescription Drugs

The ideal goal of early therapy is to slow disease progression and postpone levodopa therapy. A number of promising drugs have been identified that can be used alone (monotherapy) or in conjunction with the supplements mentioned here to control symptoms and enhance dopamine production.

In 2006, the US Food and Drug Administration (FDA) approved a new drug called rasagiline for early intervention of Alzheimer’s disease. In clinical trials, rasagiline was shown to block the breakdown of dopamine. Rasagiline belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. MAO acts in the brain to degrade dopamine. MAO inhibitors are especially helpful in younger patients, who are better able to tolerate their adverse effects (including high blood pressure, insomnia, and hallucinations). MAO inhibitors work by inhibiting dopamine breakdown in the brain. Another promising MAO inhibitor is selegiline. Some evidence derived from testing in animals suggests that selegiline and rasagiline have neuroprotective benefits, although this has not been demonstrated in clinical trials (Koller WC et al 2004).

Finally, some physicians recommend the use of dopamine agonists, which directly stimulate dopamine receptors. These drugs can be used as monotherapy early in the disease. Some of the more common dopamine agonists include ropinirole, pramipexole, and bromocriptine. Clinical trials have shown that these drugs can delay motor complications when used early in the disease, although they aren’t effective at long-term control (American Parkinson Disease Association 2006).

An interesting study reported in the New England Journal of Medicine involved 268 patients with Parkinson’s disease. Of these, 179 were randomly assigned to receive ropinirole; 89 received levodopa. Eighty-five patients in the ropinirole group and 45 patients in the levodopa group completed the 5-year study. After 5 years of treatment, patients taking ropinirole were significantly less likely to develop involuntary movements (dyskinesia). Only 20 percent in the ropinirole group developed dyskinesia, compared to 45 percent in the levodopa group. In addition, only 8 percent of patients taking ropinirole had severe dyskinesia, compared to 23 percent of those taking levodopa. Besides preventing dyskinesia, ropinirole helped control the symptoms of Parkinson’s disease about as well as levodopa. On a scale that measured how well participants were able to perform daily living tasks, there were no significant differences between the two groups. The adverse effects in both groups were also similar. Researchers concluded that “early Parkinson’s disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary” (Rascol O et al 2000).

Amantadine is also sometimes prescribed for patients with Parkinson’s disease, both early in the disease and in combination with levodopa. Amantadine does not slow disease progression, but has been shown to reduce dyskinesia by blocking N-methyl-D-aspartate (NMDA) receptors, which are responsible for the excitotoxicity associated with Parkinson’s.

Studies have also been conducted on drugs that reduce the activity of adenosine, a neurotransmitter that is known to inhibit the release of dopamine. One nonselective adenosine receptor antagonist is theophylline, which was studied in a small trial of 15 patients who had Parkinson’s disease. These patients were already taking levodopa, but couldn’t tolerate higher doses because of adverse effects. Shortly after beginning theophylline therapy, 11 patients reported moderate or marked improvement in their conditions, which lasted for 3 months (Mally J et al 1994).

Nondrug Treatment

Because drug treatment cannot cure Parkinson’s disease and can only partially ameliorate symptoms, nondrug approaches are of great interest. A number of problems common to Parkinson’s may respond to nondrug treatments, including constipation, speech, poor nutrition, poor sleep, depression, and motor problems. Patients with Parkinson’s disease may benefit from physical therapy, occupational therapy, exercise, and speech therapy.

One modality that is attracting attention is known as deep brain stimulation. During this treatment, a part of the brain known as the subthalamic nucleus is stimulated; this results in long-term benefits for patients with Parkinson’s disease. In one recent study, 71 patients were given deep brain stimulation. The patients were observed for up to 2 years. Researchers found that the patients’ quality of life was improved after the therapy, and that these improvements were maintained over the long-term (Lyons KE et al 2005).