Parkinson’s Disease

Parkinson’s disease results from progressive damage to the nerves in the area of the brain responsible for controlling muscle tone and movement. The damaged cells are those needed to produce a neurotransmitter (chemical messenger in the brain) called dopamine, so people with Parkinson’s disease manufacture inadequate amounts of dopamine. Parkinson’s disease occurs primarily, but not exclusively, in the elderly. Parkinson-like symptoms can also be caused by prescription and illicit drugs.

Checklist for Parkinson’s Disease

Rating Nutritional Supplements Herbs
1Star 5-HTP (with Sinemet®)
D-phenylalanine
L-tyrosine
Methionine
NADH
Phosphatidylserine
Vitamin B6 (with Sinemet® or selegiline)
Vitamin C and vitamin E (in combination)
Vitamin D		 Mucuna prurient
Psyllium husks (for constipation)
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

What are the symptoms of Parkinson’s disease? Symptoms include a fixed facial expression, wide-eyed stare with infrequent blinking, fluttering of the eyelids, drooling, illegible handwriting, monotone voice, and rhythmic movement of the fingers, hand, foot, or arm when at rest. People with Parkinson’s disease often have difficulty getting out of bed or a soft chair, and may tend to stand stooped over and walk leaning forward with limited arm-swing and small, shuffling steps. Depression and decreased mental functioning are also common symptoms in advanced stages.

How is it treated? There is no known cure for Parkinson’s, but symptoms are often improved by drug therapy. The most commonly used drug is Sinemet®, which contains both levodopa and carbidopa, which cause more L-dopa to be converted to dopamine within the brain. Other drugs used include selegiline (Eldepryl®, Atapryl®), bromocriptine (Parlodel®), amantadine (Symadine®, Symmetrel®), pergolide (Permax®), pramipexole (Mirapex®), ropinirole (Requip®). All of these drugs can deplete or interact with essential nutrients. Refer to the individual drug for information on its interactions with supplements and herbs.

In some cases, surgery to destroy specific areas of the brain is recommended. Physical therapy, speech therapy, and aids to daily living, such as railings, non-slip mats, and special chairs, may also be suggested in advanced cases.

Dietary changes that may be helpful: Clinical studies have shown that one can enhance the action of L-dopa and improve the symptoms of Parkinson’s disease by consuming nearly all of the day’s protein intake at dinner, while keeping the protein content of breakfast and lunch extremely low.1 2 3 This dietary approach is now well-accepted, but must be carefully monitored by a qualified healthcare professional in order to avoid deficiencies of protein and certain vitamins and minerals.

Consumption of large amounts of fava beans (Vicia faba), also known as broad beans, might increase the action of L-dopa and possibly lead to L-dopa overdose. Parkinson’s disease patients should, therefore, talk with a doctor before adding broad beans to their diet.

A preliminary study found that higher coffee and caffeine intake is associated with a significantly lower incidence of Parkinson’s disease in older persons.4 These findings do not mean that coffee or caffeineated beverages can be used as a treatment for Parkinson’s disease, but simply that caffeine may in some way help to prevent the development of the disease in its early stages. Until more is known, increasing caffeine consumption is not recommended, even in people with a family history of Parkinson’s disease.

Doctors recommend that people with Parkinson’s disease supplement with fiber and maintain adequate fluid intake to reduce constipation associated with this disease.5 See the discussion about psyllium seed below in “Herbs that may be helpful.”

Lifestyle changes that may be helpful: People with Parkinson’s disease are at higher than normal risk for osteoporosis and vitamin D deficiency. Regular weight-bearing exercise, exposure to sunlight, and a variety of supplements and dietary changes may be helpful in preventing osteoporosis.

A twice-weekly, 14-week program of intensive exercise has been shown to significantly improve the signs and symptoms of Parkinson’s Disease.6 Athletic training included resistance exercises in water to increase strength, as well as exercises increasing flexibility and balance.

There is substantial preliminary evidence that exposure to certain organochlorine insecticides (e.g., lindane [Kwell®, Kildane®, Scabene®] and dieldrin [Dieldrite]) may contribute to the development of Parkinson’s disease.7 8 9 In California, death from Parkinson’s disease increased by about 40% in all Californian counties reporting use of restricted agricultural pesticides since the 1970s compared with those reporting none.10 Avoiding contact with pesticides and pesticide residues may be an important preventive measure for Parkinson’s and other diseases. Interestingly, consumption of the fat substitute olestra appears to increase elimination of certain organochlorine pesticides in the feces.11 12 However, no scientific studies have tested olestra as a possible treatment or preventive measure against Parkinson’s disease. Moreover, since olestra consumption may be associated with other health risks, such as depletion of beta-carotene, people with Parkinson’s should consult with their doctor before consuming products containing olestra.

Nutritional supplements that may be helpful: Some preliminary studies have indicated that high dietary intakes of antioxidant nutrients, especially vitamin E, are associated with a low risk of Parkinson’s disease,13 14 even though Parkinson’s patients are not deficient in vitamin E.15 16 The correlation between protection from Parkinson’s and dietary vitamin E may be not be due to the vitamin E itself, however. Legumes (beans and peas) contain relatively high amounts of vitamin E. Independent of their vitamin E content, consumption of legumes has been associated with low risk of Parkinson’s disease.17 In other words, high vitamin E intake may be a marker for diets high in legumes, and legumes may protect against Parkinson’s disease for reasons unrelated to their vitamin E content.

Interest in the relationship between antioxidants and Parkinson’s disease led to a preliminary trial using high amounts of vitamin C and vitamin E in early Parkinson’s disease18 and to a large ten-year controlled trial of high amounts of vitamin E combined with the drug deprenyl.19 In the trial combining vitamins C and E, people with early Parkinson’s disease given 750 mg of vitamin C and 800 IU of vitamin E four times each day (totaling 3,000 mg of vitamin C and 3,200 IU of vitamin E per day) were able to delay the need for drug therapy (i.e., L-dopa or selegiline) by an average of about two and a half years, compared with those not taking the vitamins.20 The ten-year controlled trial used 2,000 IU of vitamin E per day found no benefit in slowing or improving the disease.21 The difference in the outcomes between these two trials might be due to the inclusion of vitamin C and/or the higher amount of vitamin E used in the successful trial. However, the difference might also be due to a better study design in the trial that found vitamin E to be ineffective.

The amounts of vitamin E used in the above trials were very high, because raising antioxidant levels in brain tissue is quite difficult to achieve.22 In fact, some researchers have found that even extremely high intakes of vitamin E (4,000 IU per day) failed to increase brain vitamin E levels.23 The difficulty in increasing brain vitamin E levels may explain the poor results of the large, controlled trial.

Although vitamin B6 was reported many years ago in preliminary research to improve symptoms of Parkinson’s disease,24 it must not be used by people taking L-dopa alone. Taking vitamin B6 with L-dopa increases the conversion of L-dopa to dopamine outside the brain, thereby reducing delivery of dopamine to the brain.25 26 However, vitamin B6 can be used in conjunction with L-dopa plus carbidopa (Sinemet®) or selegiline (Eldepryl, Atapryl).27

Preliminary trials have suggested that the amino acid, methionine (5 grams per day), may effectively treat some symptoms of Parkinson’s disease.28 However, use of a related supplement, S-adenosylmethionine (SAMe), may be detrimental in people with Parkinson’s disease. Animal studies indicate that excessive methylation (methylation is one of the biochemical reactions promoted by SAMe) is associated with Parkinson’s disease,29 and SAMe has caused Parkinson’s disease-like effects in animal studies.30 Both animal and human studies indicate that increased methylation can cause the depletion of dopamine and block the effects of L-dopa31 32 33 —changes that in theory should exacerbate symptoms of Parkinson’s disease. Preliminary evidence indicates that SAMe may improve the emotional depression and the impaired mental function that is often associated with Parkinson’s disease.34 Nonetheless, many healthcare professionals recommend that people with Parkinson’s disease avoid SAMe until more is known.

Drug therapy for Parkinson’s disease has been reported to deplete vitamin B3 in humans.35 Vitamin B3 may be needed to decrease SAMe levels, and in so doing, may possibly help people with Parkinson’s disease. However, the two main forms of vitamin B3, niacin and niacinamide, when taken in combination with L-dopa, have demonstrated no benefit for people with Parkinson’s disease.36 Nicotinamide adenine dinucleotide (NADH)—the active form of vitamin B3 in the body—effectively raises the level of dopamine in the brain, making it potentially useful in the treatment of people with Parkinson’s disease. In preliminary research, NADH supplementation reduced symptoms and improved brain function in people with Parkinson’s disease.37 38 One researcher has recommended 5 mg taken twice per day for people with Parkinson’s disease.39 However, one small, double-blind, short-term trial using injections of NADH found no significant effects.40

In a preliminary report, 5-hydroxytryptophan (5-HTP) used in combination with Sinemet®, improved the emotional depression that is often associated with Parkinson’s disease.41 While 5-HTP may be helpful as a supplement to Sinemet® treatment for Parkinson’s, 5-HTP should never be used alone in Parkinson’s disease.42 43 44 5-HTP is converted to serotonin in the brain, and increasing serotonin without increasing dopamine can cause Parkinson’s symptoms, especially rigidity, to get worse.45 People taking selegiline should not take 5-HTP without a physician’s supervision, as this combination might raise serotonin to excessively high levels.46

L-tyrosine is the direct precursor to L-dopa. Theoretically, supplementing L-tyrosine could be an alternative to L-dopa therapy; however, L-tyrosine should not be taken with L-dopa as it may interfere with the transport of L-dopa to the brain.47 One small preliminary trial demonstrated that some people with Parkinson’s disease who supplemented with L-tyrosine (45 mg per pound of body weight) for three years had better clinical results and fewer side effects than did patients using L-dopa.48 Until these findings are confirmed, L-tyrosine should not be used as a replacement for, or in addition to, L-dopa.

In a small, four-week trial, D-phenylalanine (DPA) supplementation improved motor control and tremors in people with Parkinson’s disease.49 Additional research is needed before the benefits of this treatment can be considered proven. DPA should not be taken with L-dopa as it may interfere with the transport of L-dopa to the brain.50 People with Parkinson’s disease should consult with a physician before using DPA. Some commercially available phenylalanine products contain a 50:50 mixture of DPA and LPA, the form of phenylalanine that occurs naturally in food (these products are known as DLPA). People with Parkinson’s disease should consult a physician before using DPA or DLPA.

People with Parkinson’s disease treated with L-dopa have been reported to have reduced levels of the neurotransmitter phosphatidylserine.51 In one trial, supplementing with phosphatidylserine (100 mg three times daily) improved the mood and mental function in patients with Parkinson’s disease, but exerted no beneficial effects on muscle control.52 The phosphatidylserine used in this trial was obtained from cow brain. That product is not available in the United States, because of concern that an extract of cow brain could cause Creutzfeld-Jakob disease, the human variant of “mad cow” disease. The phosphatidylserine sold in the United States is manufactured from plant sources, and cow-brain phosphatidylserine.53

Vitamin D deficiency is common in Parkinson’s disease. People with Parkinson’s often get insufficient sun exposure and have reduced levels of activity that adversely affect calcium metabolism.54 Low vitamin D levels in Parkinson’s disease have been reported to increase the risk of hip fracture due to osteoporosis.55 This risk has been significantly reduced with the use of synthetic, activated vitamin D—a prescription drug.56 Whether the same effect could be achieved with supplemental vitamin D remains unknown, though some doctors recommend 400–1,000 IU vitamin D per day. People with Parkinson’s disease may wish to discuss the use of synthetic activated vitamin D with a healthcare professional.

People with Parkinson’s disease have shown both decreased and increased levels of zinc and copper.57 58 59 60 Both nutrients function in the antioxidant enzyme superoxide dismutase (SOD). SOD tends to be low in the area of the brain involved in Parkinson’s disease. In theory, therefore, low levels of zinc and copper could leave the brain susceptible to free radical damage. However, copper and zinc (as well as iron) taken in excess can also act as pro-oxidants, and all have been associated with an increased risk of developing Parkinson’s disease in preliminary research.61 62 Insufficient evidence currently exists for either recommending or avoiding supplementation with zinc and copper.

Are there any side effects or interactions? Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful: In preliminary research, an extract of Mucuna prurient (HP-200) was studied in people with Parkinson’s disease, 43% of whom were taking Sinemet® before HP-200 treatment; the remaining 57% were not medicated.63 Statistically significant reductions in symptom scores were seen from the beginning to the end of the 12-week trial. The amount used in the trial was 7.5 grams of the extract (dissolved in water) three to six times daily.

Other preliminary research has shown that psyllium seed husks improve constipation and bowel function in people with Parkinson’s disease and constipation.64 A typical recommendation for psyllium seed husks is 3 to 5 grams taken at night with a one to two glasses of fluid.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

References:

1. Karstaedt PJ, Pincus JH. Protein redistribution diet remains effective in patients with fluctuating parkinsonism. Arch Neurol 1992;49:149–51.

2. Carter JH, Nutt JG, Woodward WR, et al. Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson’s disease. Neurology 1989;39:552–6.

3. Pincus JH, Barry KM, Dietary method for reducing fluctuations in Parkinson’s disease. Yale J Biol Med 1987;60:133–7.

4. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000;283:2674–9.

5. Kempster PA, Wahlqvist ML. Dietary factors in the management of Parkinson’s disease. Nutr Rev 1994;52:51–8 [review].

6. Reuter I, Engelhardt M, Stecker K, Baas H. Therapeutic value of exercise training in Parkinson’s disease. Med Sci Sports Exerc 1999;31:1544–9.

7. Corrigan FM, Wienburg CL, Shore RF, et al. Organochlorine insecticides in substantia nigra in Parkinson’s disease. J Toxicol Environ Health 2000;59:229–34.

8. Fleming L, Mann JB, Bean J, et al. Parkinson’s disease and brain levels of organochlorine pesticides. Ann Neurol 1994;36:100–3.

9. Corrigan FM, Murray L, Wyatt CL, Shore RF. Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson’s disease. Exp Neurol 1998;150:339–42.

10. Ritz B, Yu F. Parkinson’s disease mortality and pesticide exposure in California 1984–1994. Int J Epidemiol 2000;29:323–9.

11. Geusau A, Tschachler E, Meixner M, et al. Olestra increases faecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Lancet 1999;354:1266–7.

12. Moser GA, McLachlan MS. A non-absorbable dietary fat substitute enhances elimination of persistent lipophilic contaminants in humans. Chemosphere 1999;39:1513–21.

13. de Rijk MC, Breteler MM, den Breeijen JH, et al. Dietary antioxidants and Parkinson disease. The Rotterdam Study. Arch Neurol 1997;54:762–5.

14. Scheider WL, Hershey LA, Vena JE, et al. Dietary antioxidants and other dietary factors in the etiology of Parkinson’s disease. Mov Disord 1997;12:190–6.

15. Molina JA, de Bustos F, Jimenez-Jimenez FJ, et al. Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Parkinson’s disease. J Neural Transm 1997;104:1287–93.

16. Federico A, Battisti C, Formichi P, Dotti MT. Plasma levels of vitamin E in Parkinson’s disease. J Neural Transm Suppl1995;267–70.

17. Morens DM, Grandinetti A, Waslien CI, et al. Case-control study of idiopathic Parkinson’s disease and dietary vitamin E intake. Neurology 1996;46:1270–4.

18. Fahn S. A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson’s disease. Ann Neurol 1992;32:S128–32.

19. Shoulson I. DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism. Ann Neurol 1998;44:S160–6.

20. Fahn S. A pilot trial of high-dose alpha-tocopherol and ascorbate in early Parkinson’s disease. Ann Neurol 1992;32:S128–32.

21. Shoulson I. DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism. Ann Neurol 1998;44:S160–6.

22. Vatassery GT, Fahn S, Kuskowski MA. Alpha tocopherol in CSF of subjects taking high-dose vitamin E in the DATATOP study. Parkinson Study Group. Neurology 1998;50:1900–2.

23. Pappert EJ, Tangney CC, Goetz CG, et al. Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson’s disease patients: dose-response study and correlations with plasma levels. Neurology 1996;47:1037–42.

24. Baker AB. Treatment of paralysis agitans with vitamin B6. JAMA 1941;116:2484.

25. Pfeiffer R, Ebadi M. On the mechanism of the nullification of CNS effects of L-DOPA by pyridoxine in Parkinsonian patients. J Neurochem 1972;19(9):2175–81.

26. Leon AS, Spiegel HE, Thomas G, Abrams WB. Pyridoxine antagonism of levodopa in parkinsonism. JAMA 1971;218(13):1924–7.

27. Mars H. Metabolic interactions of pyridoxine, levodopa, and carbidopa in Parkinson’s disease. Trans Am Neurol Assoc 1973;98:241–5.

28. Smythies JR, Halsey JH. Treatment of Parkinson’s disease with l-methionine. South Med J 1984;77:1577.

29. Charlton CG, Mack J. Substantia nigra degeneration and tyrosine hydroxylase depletion caused by excess S-adenosylmethionine in the rat brain. Support for an excess methylation hypothesis for parkinsonism. Mol Neurobiol 1994;9:149–61.

30. Crowell BG Jr, Benson R, Shockley D, Charlton CG. S-adenosyl-L-methionine decreases motor activity in the rat: similarity to Parkinson’s disease-like symptoms. Behav Neural Biol 1993;59:186–93.

31. Benson R, Crowell B, Hill B, et al. The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance. Neurochem Res 1993;18:325–30.

32. Cheng H, Gomes-Trolin C, Aquilonius SM, et al. Levels of L-methionine S-adenosyltransferase activity in erythrocytes and concentrations of S-adenosylmethionine and S-adenosylhomocysteine in whole blood of patients with Parkinson’s disease. Exp Neurol 1997;145:580–5.

33. Charlton CG, Crowell B Jr. Parkinson’s disease-like effects of S-adenosyl-L-methionine: effects of L-dopa. Pharmacol Biochem Behav 1992;43:423–31.

34. Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs 1994;48:137–52 [review].

35. Bender DA, Earl CJ, Lees AJ. Niacin depletion in Parkinsonian patients treated with L-dopa, benserizide and carbidopa. Clin Sci 1979;56:89–93.

36. Cotzias GC, Lawrence WH, Papavasiliou PS, Duby SE. Nicotinamide ineffective in parkinsonism. N Engl J Med 1972;287:147.

37. Birkmayer JGD, Vrecko C, Volc D, et al. Nicotinamide adenine dinucleotide (NAD). A new therapeutic approach to Parkinson’s disease. Comparison of oral and parenteral application. Neurol Scand 1993;87(Suppl 146):32–5.

38. Birkmayer JGD. Coenzyme nicotinamide adenine dinucleotide. New therapeutic approach to improving dementia of the Alzheimers type. Ann Clin Lab Sci 1996;26:1–9.

39. Wright JV. Interview: Alzheimer’s, Parkinson’s, NADH research. Jorg Birkmayer, M.D. Nutr Healing 1997;May:5–6.

40. Dizdar N, Kagedal B, Lindvall B. Treatment of Parkinson’s disease with NADH. Acta Neurologica Scand 1994;90:345–7.

41. Mayeux R, Stern Y, Sano M, et al. The relationship of serotonin to depression in Parkinson’s disease. Mov Disord 1988;3:237–44.

42. Bastard J, Truelle JL, Emile J. Effectiveness of 5 hydroxy-tryptophan in Parkinson’s disease. Presse Med 1976;5:1836–7.

43. Sano VI, Taniguchi K. L-5-hydroxytryptophan (L-5-HTP) therapy in Parkinson’s disease. MMWR 1972;114:1717–9.

44. Chase TN, Ng LK, Watanabe AM. Parkinson’s disease: modification by 5-hydroxytryptophan. Neurology 1972;22:479–84.

45. Chase TN, Ng LK, Watanabe AM. Parkinson’s disease. Modification by 5-hydroxytryptophan. Neurology 1972;22:479–84.

46. Mendlewicz J, Youdim MB. Antidepressant potentiation of 5-hydroxytryptophan by L-deprenil in affective illness. J Affect Disord 1980;2:137–46.

47. Wurtman RJ, Wurtman JJ, eds. Nutrition and the Brain, vol 7. New York: Raven Press, 1986.

48. Lemoine P, Robelin N, Sebert P, Mouret J. L-tyrosine: a long term treatment of Parkinson’s disease. C R Acad Sci III 1989;309:43–7.

49. Heller B, Fischer E, Martin R. Therapeutic action of D-phenylalanine in Parkinson’s disease. Arzneimittelforschung 1976;26:577–9.

50. Wurtman RJ, Wurtman JJ, eds. Nutrition and the Brain, vol 7. New York: Raven Press, 1986.

51. Riekkinen P, Rinne UK, Pelliniemi TT, Sonninen V. Interaction between dopamine and phospholipids. Studies of the substantia nigra in Parkinson disease patients. Arch Neurol 1975;32:25–7.

52. Funfgeld EW, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer’s type (SDAT). Prog Clin Biol Res 1989;317:1235–46.

53. Gaby AR. Don’t believe everything you read. Townsend Letter for Doctors and Patients 1997;July:125–6.

54. Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology 1997;49:1273–8.

55. Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology1997;49:1273–8.

56. Sato Y, Manabe S, Kuno H, Oizumi K. Amelioration of osteopenia and hypovitaminosis D by 1 a-hydroxyvitamin D3 in elderly patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;66:64–8.

57. Forsleff L, Schauss AG, Bier ID, et al. Evidence of functional zinc deficiency in Parkinson’s disease. J Altern Complement Med 1999;5:57–64.

58. Uitti RJ, Rajput AH, Rozdilsky B, et al. Regional metal concentrations in Parkinson’s disease, other chronic neurological diseases, and control brains. Can J Neurol Sci 1989;16:310–4.

59. Pall HS, Williams AC, Blake DR, et al. Raised cerebrospinal fluid copper concentration in Parkinson’s disease. Lancet 1987;2(8553):238–41.

60. Dexter DT, Carayon A, Javoy-Agid F, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain 1991;114:1953–75.

61. Dexter DT, Carayon A, Javoy-Agid F, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain 1991;114:1953–75.

62. Pall HS, Williams AC, Blake DR, et al. Raised cerebrospinal fluid copper concentration in Parkinson’s disease. Lancet 1987;2(8553):238–41.

63. An alternative medicine treatment for Parkinson’s disease: results of a multicenter clinical trial. HP-200 in Parkinson’s Disease Study Group. J Altern Complement Med 1995;1:249–55.

64. Ashraf W, Pfeiffer RF, Park F, et al. Constipation in Parkinson’s disease: objective assessment and response to psyllium. Mov Disord 1997;12:946–51.