Parkinson's Disease: Critical Risk Factors and Treatment Alternatives

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While Parkinson's disease has no known cause or cure, a number of critical risk factors have been identified and advances have been made in alternative treatment options. Ultimately, increasing quality of life for those with Parkinson's disease is the goal

Parkinson's disease (PD) is a neurodegenerative disease, which means it kills neurons in the brain, affecting multiple body systems. An estimated 10 million people worldwide and 1 million in the U.S. suffer from PD.[i] "Predominantly perceived as a motor disease, it … has debilitating non-motor features, which are frequently missed and not treated," researchers wrote in the Journal of Ethnopharmacology.[ii]

Key characteristics of PD include progressive loss of dopamine neurons in the middle brain and a dramatic reduction in dopamine levels in the frontal brain.[iii] When cells that normally produce dopamine die, common symptoms of Parkinson's occur. These are different for each person and include:[iv]

1. Motor symptoms: tremors, stiffness, rigidity, slow movement, impaired balance and difficulty walking

2. Non-motor symptoms: fatigue, soft speech, drooling, constipation, sleep disturbances, anxiety, dementia and depression[v]

Critical Risk Factors

PD has no known identifiable causes. There are several risk factors for PD, however:

Environmental Toxins

Pesticides and herbicides including insecticides permethrin and beta-hexachlorocyclohexane (beta-HCH), the herbicides paraquat and organophosphorus, organochlorines, phenoxyacetic acids and triazine compounds areassociated with PD risk.[vi],[vii] Glyphosate, the active ingredient found in Roundup herbicide, is also linked to neurodegenerative conditions such as PD.[viii]

Gut Dysfunction

Parkinson's disease may start in the gut and travels to the brain via the vagus nerve.[ix] A link between gut bacteria called Helicobacter Pylori and PD has been uncovered.[x]

Neuron Transmission Disruption

Toxins hinder a key step in the transmission of neuronal signals -- the recycling of waste proteins (empty vesicle lipid membranes surrounding a neuron) essential for higher brain functioning.[xi],[xii] PD's earliest signs often display as sleep disorders, including a lower duration of sleep and deep sleep, which decrease recycling and restorative brain processes.[xiii],[xiv]

Oxidative Stress

Inflammation caused by free-radical damage in the brain is closely associated with several degenerative neurologic disorders, including PD, Alzheimer's and multiple sclerosis.[xv]

Latest Medical Treatments

While there is no known cure for PD, current conventional treatments include many drugs and a last-resort surgery option to alleviate symptoms:[xvi]

  • Carbidopa-levodopa (CD/LD): Levodopa is a chemical that passes into your brain and converts to dopamine. Combined with carbidopa, it lessens one of the biggest side effects of Parkinson's drugs -- nausea. Other side effects include lightheadedness and, after prolonged use, patients may develop dyskinesia (involuntary movements) and wearing-off of the drug.
  • Dopamine agonists: These mimic dopamine effects in your brain, last longer than CD/LD and are used for falling off periods. They cause many of thesame side effects as CD/LD but also may cause hallucinations, sleepiness and compulsive behaviors.
  • MAO B inhibitors: These elp prevent the breakdown of brain dopamine by inhibiting the brain enzyme monoamine oxidase B (MAO B), which metabolizes brain dopamine. Side effects include nausea, insomnia and hallucinations if combined with CD/LD.
  • Catechol O-methyltransferase (COMT) inhibitors: Entacapone (Comtan) mildly prolongs the effect of levodopa therapy by blocking an enzyme that breaks down dopamine. Side effects include dyskinesia and diarrhea.
  • Anticholinergics: These control PD tremors but present many side effects including impaired memory, confusion, hallucinations, constipation, dry mouth and impaired urination.
  • Amantadine: Used for short-term relief of symptoms of mild, early-stage PD, amantadine may also be given with CD/LD drugs to control dyskinesia. Side effects include purple mottling of the skin, ankle swelling and hallucinations.
  • Deep brain stimulation (DBS): For DBS, surgeons implant electrodes into your brain to decrease PD symptoms. Risks include infections, stroke and brain hemorrhage.

Latest Alternative Treatments

Alternative PD research is growing, and has compiled 497 abstracts related to PD research and enhancing quality of life for PD patients:

  • Mucuna pruriens (MP), also known as velvet bean, is a naturally occurring L-Dopa plant. MP powder, called HP-200, was examined in PD diagnosed patients (46 male and14 female) and significantly reduced symptoms. The group mean dose for optimal control of symptoms was 6 +/- 3 sachets (7.5 grams) in water taken orally.[xvii]

A blind clinical trial of eight PD patients showed faster action and longer time without an increase in dyskinesia, highlighting a distinct advantage over conventional CD/LD preparations. Similarly, MP performed better (i.e., was safer and more effective) in 16 PD patients when compared to L-dopa treatments.[xviii]

  • Black cumin (Nigella sativa L.) seed oil. Biochemical studies of black cumin seed oil revealed potential to control inflammation in the mix glial cells of rats, an important issue in PD.[xix],[xx]
  • Baicalein, a Chinese herbal medicine used for treating central nervous system diseases,[xxi] has been found to have neural protective characteristics beneficial for PD symptoms, by inhibiting nitric oxide's (NO) and free radicals' microglia damage.[xxii]
  • Movement and the arts. Exercise lowers neuron degeneration and reduces inflammation in the brain, reducing symptoms in Alzheimer's and PD.[xxiii] Music therapy, [xxiv] tai chi and qigong,[xxv] yoga, relaxation, massage[xxvi],[xxvii],[xxviii] and dancing[xxix] also help decrease PD symptoms.
  • Gingko biloba. Ginkgetin, a biflavonoid isolated from ginkgo biloba L. leaves, has many anti-inflammatory, anti-influenza virus and anti-fungal benefits, with mice research showing its significant neuroprotective ability.[xxx]
  • Coenzyme Q10. In 80 PD patients, the greatest benefit occurred in those taking 1,200 milligrams of CoQ10. The supplement proved to be both safe and effective in slowing PD function deterioration.[xxxi]

CoQ10 prevented neurotoxic impact of the pesticide paraquat on rats.[xxxii] Serum CoQ was associated with lower risk for dementia[xxxiii] and greater protection for neurons.[xxxiv] CoQ10 (ubiquitol 10 version) was very effective in helping with the falling off of CD/LD treatments for PD in rats.[xxxv]

  • Curcumin. Curcumin (and its compound metabolite tetrahydrocurcumin -- ThC) may help prevent neuron toxicity in PD-induced mice.[xxxvi] Research shows antioxidant, anti-inflammatory and neuroprotective properties of curcumin can highly benefit PD.[xxxvii]
  • Cannabis. Positive results were found for cannabis and cannabinoids on decreasing PD motor and non-motor symptoms.[xxxviii],[xxxix]

Although PD currently has no cure and no agreed-upon cause, research is helping to understand the disease and find alternative treatment options that can increase the quality of life for those with PD.


[i] Parkinson's Foundation, Statistics

[ii] Pathak-Gandhi,N. , Vaidya AD. Management of Parkinson's disease in Ayurveda: Medicinal plants and adjuvant measures. J Ethnopharmacol. 2017 Feb 2;197:46-51. doi: 10.1016/j.jep.2016.08.020. Epub 2016 Aug 17.

[iii] Jackson-Lewis V, Smeyne RJ. MPTP and SNpc DA neuronal vulnerability: Role of dopamine, superoxide and nitric oxide in neurotoxicity. Minireview. Neurotox Res. 2005;7(3):193-202.

[v] Surrey Neuroplasticity Clinic, Parkinson's Disease

[vi] Geneviève Van Maele-Fabry, Perrine Hoet, Fabienne Vilain, Dominique Lison. Occupational exposure to pesticides and Parkinson's disease: a systematic review and meta-analysis of cohort studies. Environ Int. 2012 Oct 1 ;46:30-43. Epub 2012 Jun 13. PMID: 22698719

[vii] Sara Mostafalou, Mohammad Abdollahi. Pesticides: an update of human exposure and toxicity. Arch Toxicol. 2017 Feb ;91(2):549-599. Epub 2016 Oct 8. PMID: 27722929

[viii] Ya-Xing Gui, Xiao-Ning Fan, Hong-Mei Wang, Gang Wang, Sheng-di Chen. Glyphosate induced cell death through apoptotic and autophagic mechanisms. Neurotoxicol Teratol. 2012 Apr 4. Epub 2012 Apr 4. PMID: 22504123

[x] Gulsah Camci and Sidika Oguz. Association between Parkinson's Disease and Helicobacter Pylori. J Clin Neurol. 2016 Apr;12(2):147-50. Epub 2016 Feb 26. PMID: 26932258 PMCID: PMC4828559 DOI: 10.3988/jcn.2016.12.2.147

[xi] Kohgaku Eguchi, Zacharie Taoufiq, Oliver Thorn-Seshold, Dirk Trauner, Masato Hasegawa, Tomoyuki Takahashi. Wild-type monomeric α-synuclein can impair vesicle endocytosis and synaptic fidelity via tubulin polymerization at the calyx of Held. The Journal of Neuroscience, 2017; 0179-17 DOI: 10.1523/JNEUROSCI.0179-17.2017

[xiii] Valadas et al. ER lipid defects in neuropeptidergic neurons impair sleep patterns in Parkinson's disease. Neuron. 2018 Jun 27;98(6):1155-1169.e6. doi: 10.1016/j.neuron.2018.05.022. Epub 2018 Jun 7.

[xv] Liu B1, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS. Ann N Y Role of nitric oxide in inflammation-mediated neurodegeneration. Acad Sci. 2002 May; 962:318-31.

[xviii] Cilia R, Laguna J, Cassani E, Cereda E, Pozzi NG, Isaias IU, Contin M, Barichella M, Pezzoli G. Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study. Neurology. 2017 Aug 1;89(5):432-438. doi: 10.1212/WNL.0000000000004175. Epub 2017 Jul 5. PMID: 28679598; PMCID: PMC5539737.

[xix] Mobina Alemi, Farzaneh Sabouni, Forough Sanjarian, Kamahldin Haghbeen,corresponding author and Saeed Ansari. Anti-inflammatory Effect of Seeds and Callus of Nigella sativa L. Extracts on Mix Glial Cells with Regard to Their Thymoquinone Conten.t AAPS PharmSciTech. 2013 Mar; 14(1): 160-167. Published online 2012 Dec 19. doi: 10.1208/s12249-012-9899-8 PMCID: PMC3581679 PMID: 23255199

[xx] Saeed Samarghandian, Tahereh Farkhondeh. A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases. CNS Neurol Disord Drug Targets. 2018 07 1. Epub 2018 Jul 1. PMID: 29962349

[xxi] Yanwei Li, Jinying Zhao, Christian Hölscher. Therapeutic Potential of Baicalein in Alzheimer's Disease and Parkinson's Disease. CNS Drugs. 2017 Aug ;31(8):639-652. PMID: 28634902

[xxii] Li FQ1, Wang TPei ZLiu BHong JS. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J Neural Transm (Vienna). 2005 Mar;112(3):331-47. Epub 2004 Oct 22. PMID: 15503194 DOI:10.1007/s00702-004-0213-0

[xxiv] Natalia García-Casares, Julia Eva Martín-Colom, Juan Antonio García-Arnés. Music Therapy in Parkinson's Disease. J Am Med Dir Assoc. 2018 Dec ;19(12):1054-1062. PMID: 30471799

[xxv] Penelope J Klein, Joseph Baumgarden, Roger Schneider. Qigong and Tai Chi as Therapeutic Exercise: Survey of Systematic Reviews and Meta-Analyses Addressing Physical Health Conditions. Altern Ther Health Med. 2019 Jun 1. Epub 2019 Jun 1. PMID: 3122193

[xxvi] A Mooventhan, L Nivethitha. Evidence based effects of yoga in neurological disorders. J Clin Neurosci. 2017 Jun 6. Epub 2017 Jun 6. PMID: 28599839

[xxvii] Ilana Schlesinger, Orna Benyakov, Ilana Erikh, Suheir Suraiya, Yitzhak Schiller. Parkinson's disease tremor is diminished with relaxation guided imagery. Mov Disord. 2009 Oct 30;24(14):2059-62. PMID: 19768725

[xxviii] Christopher Johns, Debbie Blake, Alan Sinclair. Can reflexology maintain or improve the well-being of people with Parkinson's Disease? Complement Ther Clin Pract. 2010 May;16(2):96-100. Epub 2009 Nov 4. PMID: 20347841

[xxix] Madeleine E Hackney, Gammon M Earhart. Effects of dance on balance and gait in severe Parkinson disease: a case study. Disabil Rehabil. 2010;32(8):679-84. PMID: 20205

[xxx] Y-Q Wang, M-Y Wang, X-R Fu, Peng-Yu, G-F Gao, Y-M Fan, X-L Duan, B-L Zhao, Y-Z Chang, Z-H Shi. Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron. Free Radic Res. 2015 ;49(9):1069-80. Epub 2015 Jul 1. PMID: 25968939

[xxxi] Clifford W Shults, David Oakes, Karl Kieburtz, M Flint Beal, Richard Haas, Sandy Plumb, Jorge L Juncos, John Nutt, Ira Shoulson, Julie Carter, Katie Kompoliti, Joel S Perlmutter, Stephen Reich, Matthew Stern, Ray L Watts, Roger Kurlan, Eric Molho, Madaline Harrison, Mark Lew,. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50. PMID: 12374491

[xxxii] Somayajulu-Niţu MSandhu JKCohen JSikorska MSridhar TSMatei ABorowy-Borowski HPandey S. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10. BMC Neurosci. 2009 Jul 27;10:88. doi: 10.1186/1471-2202-10-88. PMID: 19635141 PMCID: PMC2724477 DOI:10.1186/1471-2202-10-88

[xxxiii] Kazumasa Yamagishi, Ai Ikeda, Yuri Moriyama, Choy-Lye Chei, Hiroyuki Noda, Mitsumasa Umesawa, Renzhe Cui, Masanori Nagao, Akihiko Kitamura, Yorihiro Yamamoto, Takashi Asada, Hiroyasu Iso,. Serum coenzyme Q10 and risk of disabling dementia: the Circulatory Risk in Communities Study (CIRCS). Atherosclerosis. 2014 Dec ;237(2):400-3. Epub 2014 Sep 28. PMID: 25463064

[xxxiv] Frontiers in Physiology 2018; 9:44

[xxxv] Yoritaka AKawajiri SYamamoto YNakahara TAndo MHashimoto KNagase MSaito YHattori NRandomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease. Parkinsonism Relat Disord. 2015 Aug;21(8):911-6. doi: 10.1016/j.parkreldis.2015.05.022. Epub 2015 May 29. PMID: 26054881 DOI: 10.1016/j.parkreldis.2015.05.022

[xxxvii] R B Mythri, Mm Srinivas Bharath. Curcumin: A Potential Neuroprotective Agent in Parkinson's DiseaseCurr Pharm Des. 2012 Jan 1. Epub 2012 Jan 1. PMID: 22211691

[xxxviii] Tina Mainka, Jan Stork, Ute Hidding, Carsten Buhmann. Cannabis in Parkinson's Disease: Hype or help? Fortschr Neurol Psychiatr. 2018 Feb ;86(2):106-116. Epub 2018 Jan 11. PMID: 29325182

[xxxix] Nilson Carlos Ferreira Junior, Maurício Dos-Santos-Pereira, Francisco Silveira Guimarães, Elaine Del Bel. Cannabidiol and Cannabinoid Compounds as Potential Strategies for Treating Parkinson's Disease and L-DOPA-Induced Dyskinesia. Neurotox Res2019 Oct 22. Epub 2019 Oct 22. PMID: 31637586

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