Nutritional habits, risk, and progression of Parkinson disease

  • Roberto Erro
  • Francesco Brigo
  • Stefano Tamburin
  • Mauro Zamboni
  • Angelo Antonini
  • Michele Tinazzi


Parkinson disease (PD) is a multifactorial disease, where a genetic predisposition combines with putative environmental risk factors. Mounting evidence suggests that the initial PD pathological manifestations may be located in the gut to subsequently affect brain areas. Moreover, several lines of research demonstrated that there are bidirectional connections between the central nervous system and the gut, the “gut–brain axis” that influences both brain and gastrointestinal function. This opens a potential therapeutic window suggesting that specific dietary strategies may interact with the disease process and influence the risk of PD or modify its course. Dietary components can also theoretically modulate the chronic activation of the inflammatory response that is associated with aging, the strongest risk factor for PD, that has been suggested to hasten the underlying neurodegenerative process in PD. Here, we reviewed the evidence supporting an association between certain dietary compound and either the risk or progression of PD and have provided an overview of the possible pathomechanisms linking nutrition and neurodegeneration. The results of our review would not support a clear role for any dietary components in reducing the risk or progression of PD. However, the evidence favouring a connection between gut abnormalities, inflammation, and neurodegeneration in PD have become too compelling to be ignored, so that further research, also in the field of nutritional genomics, is highly warranted.


Parkinson Risk Food Diet Nutrition Microbiota Nutraceutic 


  1. 1.
    Pringsheim T, Jette N, Frolkis A, Steeves TD (2014) The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 29:1583–1590PubMedCrossRefGoogle Scholar
  2. 2.
    Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3:17013PubMedCrossRefGoogle Scholar
  3. 3.
    Erro R, Picillo M, Amboni M, Moccia M, Vitale C, Longo K, Pellecchia MT, Santangelo G, Martinez-Martin P, Chaudhuri KR, Barone P (2015) Nonmotor predictors for levodopa requirement in de novo patients with Parkinson’s disease. Mov Disord 30:373–378PubMedCrossRefGoogle Scholar
  4. 4.
    Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Santangelo G, Pellecchia MT, Barone P (2016) The non-motor side of the honeymoon period of Parkinson’s disease and its relationship with quality of life: a 4-year longitudinal study. Eur J Neurol 23:1673–1679PubMedCrossRefGoogle Scholar
  5. 5.
    O’Toole PW, Jeffery IB (2015) Gut microbiota and aging. Science 350:1214–1215PubMedCrossRefGoogle Scholar
  6. 6.
    Felice VD, Quigley EM, Sullivan AM, O’Keeffe GW, O’Mahony SM (2016) Microbiota-gut-brain signalling in Parkinson’s disease: implications for non-motor symptoms. Parkinsonism Relat Disord 27:1–8PubMedCrossRefGoogle Scholar
  7. 7.
    O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res 277:32–48PubMedCrossRefGoogle Scholar
  8. 8.
    Mayer EA (2011) Gut feelings: the emerging biology of gut–brain communication. Nat Rev Neurosci 12:453–466PubMedCrossRefGoogle Scholar
  9. 9.
    Collins SM, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10:735–742PubMedCrossRefGoogle Scholar
  10. 10.
    Houser MC, Tansey MG (2017) The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis 3:3PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167:1469PubMedCrossRefGoogle Scholar
  12. 12.
    Wang L, Fleming SM, Chesselet MF, Taché Y (2008) Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein. NeuroReport 19:873–876PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Hallett PJ, McLean JR, Kartunen A, Langston JW, Isacson O (2012) alpha-Synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits. Neurobiol Dis 47:258–267PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A (2011) Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS One 6:e28032PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A, Ohno K, Hirayama M (2015) Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PLoS One 10:e0142164PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Salat-Foix D, Tran K, Ranawaya R, Meddings J, Suchowersky O (2012) Increased intestinal permeability and Parkinson disease patients: chicken or egg? Can J Neurol Sci 39:185–188PubMedCrossRefGoogle Scholar
  17. 17.
    Edelblum KL, Turner JR (2009) The tight junction in inflammatory disease: communication breakdown. Curr Opin Pharmacol 9:715–720PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Cardoso FL, Kittel A, Veszelka S, Palmela I, Tóth A, Brites D, Deli MA, Brito MA (2012) Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells. PLoS One 7:e35919PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Erickson MA, Hansen K, Banks WA (2012) Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood–brain barrier: protection by the antioxidant N-acetylcysteine. Brain Behav Immun 26:1085–1094PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Biesmans S, Meert TF, Bouwknecht JA, Acton PD, Davoodi N, De Haes P, Kuijlaars J, Langlois X, Matthews LJ, Ver Donck L, Hellings N, Nuydens R (2013) Systemic immune activation leads to neuroinflammation and sickness behavior in mice. Mediators Inflamm 271359Google Scholar
  21. 21.
    Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA, Balling R, Neumann H (2014) Neurodegeneration by activation of the microglial complement–phagosome pathway. J Neurosci 34:8546–8556PubMedCrossRefGoogle Scholar
  22. 22.
    Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Liu Y, Qin L, Wilson B, Wu X, Qian L, Granholm AC, Crews FT, Hong JS (2008) Endotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficits. Neurotoxicology 29:864–870PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, Bentivoglio AR (2013) The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 28:1241–1249PubMedCrossRefGoogle Scholar
  25. 25.
    Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF (2015) Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 14:625–639PubMedCrossRefGoogle Scholar
  26. 26.
    Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, Ng SW, Ang SP, Chow SK, Tan CT, Yong HS, Marras C, Fox SH, Lim SY (2014) Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord 20:535–540PubMedCrossRefGoogle Scholar
  27. 27.
    Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM (2015) Colonic bacterial composition in Parkinson’s disease. Mov Disord 30:1351–1360PubMedCrossRefGoogle Scholar
  28. 28.
    Van Felius ID, Akkermans LM, Bosscha K, Verheem A, Harmsen W, Visser MR, Gooszen HG (2003) Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis. Neurogastroenterol Motil 15:267–276PubMedCrossRefGoogle Scholar
  29. 29.
    Heiman ML, Greenway FL (2016) A healthy gastrointestinal microbiome is dependent on dietary diversity. Mol Metab 5:317–320PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69:S4–S9PubMedCrossRefGoogle Scholar
  31. 31.
    Frasca D, Blomberg BB (2016) Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology 17:7–19PubMedCrossRefGoogle Scholar
  32. 32.
    Giunta B, Fernandez F, Nikolic WV, Obregon D, Rrapo E, Town T, Tan J (2008) Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflamm 5:51CrossRefGoogle Scholar
  33. 33.
    Rocha NP, de Miranda AS, Teixeira AL (2015) Insights into neuroinflammation in Parkinson’s disease: from biomarkers to anti-inflammatory based therapies. Biomed Res Int 2015:628192PubMedPubMedCentralGoogle Scholar
  34. 34.
    Ticinesi A, Meschi T, Lauretani F, Felis G, Franchi F, Pedrolli C, Barichella M, Benati G, Di Nuzzo S, Ceda GP, Maggio M (2016) Nutrition and inflammation in older individuals: focus on vitamin D, n-3 polyunsaturated fatty acids and whey proteins. Nutrients. 8:186PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Baylis D, Ntani G, Edwards MH, Syddall HE, Bartlett DB, Dennison EM, Martin-Ruiz C, von Zglinicki T, Kuh D, Lord JM, Aihie Sayer A, Cooper C (2014) Inflammation, telomere length, and grip strength: a 10-year longitudinal study. Calcif Tissue Int 95:54–63PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Landgrave-Gómez J, Mercado-Gómez O, Guevara-Guzmán R (2015) Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci 9:58PubMedPubMedCentralGoogle Scholar
  37. 37.
    Hellenbrand W, Boeing H, Robra BP, Seidler A, Vieregge P, Nischan P, Joerg J, Oertel WH, Schneider E, Ulm G (1996) Diet and Parkinson’s disease. II: a possible role for the past intake of specific nutrients. Results from a self-administered food-frequency questionnaire in a case–control study. Neurology 47:644–650PubMedCrossRefGoogle Scholar
  38. 38.
    Kyrozis A, Ghika A, Stathopoulos P, Vassilopoulos D, Trichopoulos D, Trichopoulou A (2013) Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece. Eur J Epidemiol 28:201367–201377CrossRefGoogle Scholar
  39. 39.
    Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A (2003) Dietary intakes of fat and risk of Parkinson’s disease. Am J Epidemiol 157:1007–1014PubMedCrossRefGoogle Scholar
  40. 40.
    Medina-Remón A, Casas R, Tressserra-Rimbau A, Ros E, Martínez-González MA, Fitó M, Corella D, Salas-Salvadó J, Lamuela-Raventos RM, Estruch R, PREDIMED Study Investigators (2016) Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a sub-study of the PREDIMED trial. Br J Clin Pharmacol. doi:10.1111/bcp.12986 PubMedGoogle Scholar
  41. 41.
    Fitó M, Konstantinidou V (2016) Nutritional genomics and the Mediterranean diet’s effects on human cardiovascular health. Nutrients 8:218PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Gu Y, Brickman AM, Stern Y, Habeck CG, Razlighi QR, Luchsinger JA, Manly JJ, Schupf N, Mayeux R, Scarmeas N (2015) Mediterranean diet and brain structure in a multiethnic elderly cohort. Neurology 85:1744–1751PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Alcalay RN, Gu Y, Mejia-Santana H, Cote L, Marder KS, Scarmeas N (2012) The association between Mediterranean diet adherence and Parkinson’s disease. Mov Disord 27:771–774PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Behari M, Srivastava AK, Das RR, Pandey RM (2001) Risk factors of Parkinson’s disease in Indian patients. J Neurol Sci 190:49–55PubMedCrossRefGoogle Scholar
  45. 45.
    Sanyal J, Chakraborty DP, Sarkar B, Banerjee TK, Mukherjee SC, Ray BC, Rao VR (2010) Environmental and familial risk factors of Parkinsons disease: case–control study. Can J Neurol Sci 37:637–642PubMedCrossRefGoogle Scholar
  46. 46.
    Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A (2002) Diet and Parkinson’s disease: a potential role of dairy products in men. Ann Neurol 52:793–801PubMedCrossRefGoogle Scholar
  47. 47.
    Wang A, Lin Y, Wu Y, Zhang D (2015) Macronutrients intake and risk of Parkinson’s disease: a meta-analysis. Geriatr Gerontol Int 15:606–616PubMedCrossRefGoogle Scholar
  48. 48.
    Abbott RD, Ross GW, White LR, Sanderson WT, Burchfiel CM, Kashon M, Sharp DS, Masaki KH, Curb JD, Petrovitch H (2003) Environmental, life-style, and physical precursors of clinical Parkinson’s disease: recent findings from the Honolulu-Asia Aging Study. J Neurol 250(Suppl 3):iii30–iii39PubMedGoogle Scholar
  49. 49.
    Janssen CIF, Kiliaan AJ (2014) Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. Prog Lipid Res 53:1–17PubMedCrossRefGoogle Scholar
  50. 50.
    Wu A, Ying Z, Gomez-Pinilla F (2008) Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 155:751–759PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rao JS, Ertley RN, Lee HJ, DeMar JC Jr, Arnold JT, Rapoport SI, Bazinet RP (2007) N-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Mol Psychiatry 12:36–46PubMedCrossRefGoogle Scholar
  52. 52.
    Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F (2009) Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry 33:1401–1408PubMedCrossRefGoogle Scholar
  53. 53.
    Ji A, Diao H, Wang X, Yang R, Zhang J, Luo W, Cao R, Cao Z, Wang F, Cai T (2012) N-3 polyunsaturated fatty acids inhibit lipopolysaccharide-induced microglial activation and dopaminergic injury in rats. Neurotoxicology 33:780–788PubMedCrossRefGoogle Scholar
  54. 54.
    Cardoso HD, Passos PP, Lagranha CJ, Ferraz AC, Santos Júnior EF, Oliveira RS, Oliveira PE, Santos Rde C, Santana DF, Borba JM, Rocha-de-Melo AP, Guedes RC, Navarro DM, Santos GK, Borner R, Picanço-Diniz CW, Beltrão EI, Silva JF, Rodrigues MC, Andrade da Costa BL (2012) Differential vulnerability of substantia nigra and corpus striatum to oxidative insult induced by reduced dietary levels of essential fatty acids. Front Hum Neurosci 6:249PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Parain K, Murer MG, Yan Q, Faucheux B, Agid Y, Hirsch E, Raisman-Vozari R (1999) Reduced expression of brain-derived neurotrophic factor protein in Parkinson’s disease substantia nigra. NeuroReport 10:557–561PubMedCrossRefGoogle Scholar
  56. 56.
    Kalia LV, Kalia SK, Lang AE (2015) Disease-modifying strategies for Parkinson’s disease. Mov Disord 30:1442–1450PubMedCrossRefGoogle Scholar
  57. 57.
    de Lau LM, Bornebroek M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM (2005) Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. Neurology 64:2040–2045PubMedCrossRefGoogle Scholar
  58. 58.
    Gudala K, Bansal D, Muthyala H (2013) Role of serum cholesterol in Parkinson’s disease: a meta-analysis of evidence. J. Parkinsons Dis 3:363–370PubMedGoogle Scholar
  59. 59.
    Kuhn W, Roebroek R, Blom H, van Oppenraaij D, Muller T (1998) Hyperhomocysteinaemia in Parkinson’s disease. J Neurol 245:811–812PubMedCrossRefGoogle Scholar
  60. 60.
    Kuhn W, Roebroek R, Blom H, van Oppenraaij D, Przuntek H, Kretschmer A, Büttner T, Woitalla D, Müller T (1998) Elevated plasma levels of homocysteine in Parkinson’s disease. Eur Neurol 40:225–227PubMedCrossRefGoogle Scholar
  61. 61.
    Duan W, Ladenheim B, Cutler RG, Kruman II, Cadet JL, Mattson MP (2002) Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson’s disease. J Neurochem 80:101–110PubMedCrossRefGoogle Scholar
  62. 62.
    Postuma RB, Lang A (2004) Homocysteine and levodopa. Should parkinson disease patients receive preventative therapy? Neurology 63:886–891PubMedCrossRefGoogle Scholar
  63. 63.
    Müller T (2008) Role of homocysteine in the treatment of Parkinson’s disease. Expert Rev Neurother 8:957–967PubMedCrossRefGoogle Scholar
  64. 64.
    Zoccolella S, dell’Aquila C, Abruzzese G, Antonini A, Bonuccelli U, Canesi M, Cristina S, Marchese R, Pacchetti C, Zagaglia R, Logroscino G, Defazio G, Lamberti P, Livrea P (2009) Hyperhomocysteinemia in levodopa-treated patients with Parkinson’s disease dementia. Mov Disord 24:1028–1033PubMedCrossRefGoogle Scholar
  65. 65.
    Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS (1997) Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proc Natl Acad Sci USA 94:5923–5928PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP (2000) Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20:6920–6926PubMedGoogle Scholar
  67. 67.
    Mattson MP (2003) Will caloric restriction and folate protect against AD and PD? Neurology 60:690–695PubMedCrossRefGoogle Scholar
  68. 68.
    Hu XW, Qin SM, Li D, Hu LF, Liu CF (2013) Elevated homocysteine levels in levodopa-treated idiopathic Parkinson’s disease: a meta-analysis. Acta Neurol Scand 128:73–82PubMedCrossRefGoogle Scholar
  69. 69.
    Stocker P, Lesgards JF, Vidal N, Chalier F, Prost M (2003) ESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins. Biochim Biophys Acta 1621:1–8PubMedCrossRefGoogle Scholar
  70. 70.
    Wondrak GT, Jacobson EL (2012) Vitamin B6: beyond coenzyme functions. Subcell Biochem 56:291–300PubMedCrossRefGoogle Scholar
  71. 71.
    Ehrenshaft M, Bilski P, Li MY, Chignell CF, Daub M (1999) A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis. Proc Natl Acad Sci USA 96:9374–9378PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Mahfouz MM, Kummerow FA (2004) Vitamin C or vitamin B6 supplementation prevent the oxidative stress and decrease of prostacyclin generation in homocysteinemic rats. Int J Biochem Cell Biol 36:1919–1932PubMedCrossRefGoogle Scholar
  73. 73.
    Ullegaddi R, Powers HJ, Gariballa SE (2004) B-group vitamin supplementation mitigates oxidative damage after acute ischemic stroke. Clin Sci 107:477–484PubMedCrossRefGoogle Scholar
  74. 74.
    Umeno A, Horie M, Murotomi K, Nakajima Y, Yoshida Y (2016) Antioxidative and antidiabetic effects of natural polyphenols and isoflavones. Molecules 21(pii):E708PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang SM, Hernán MA, Chen H, Spiegelman D, Willett WC, Ascherio A (2002) Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology 59:1161–1169PubMedCrossRefGoogle Scholar
  76. 76.
    Etminan M, Gill SS, Samii A (2005) Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson’s disease: a meta-analysis. Lancet Neurol 4:362–365PubMedCrossRefGoogle Scholar
  77. 77.
    de Lau LM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM (2006) Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease. Neurology 67:315–318PubMedCrossRefGoogle Scholar
  78. 78.
    Shen L (2015) Associations between B vitamins and Parkinson’s disease. Nutrients 7:7197–7208PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Takeda A, Nyssen OP, Syed A, Jansen E, Bueno-de-Mesquita B, Gallo V (2014) Vitamin A and carotenoids and the risk of Parkinson’s disease: a systematic review and meta-analysis. Neuroepidemiology 42:25–38PubMedCrossRefGoogle Scholar
  80. 80.
    Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M (2010) Serum vitamin D and the risk of Parkinson disease. Arch Neurol 67:808–811PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Shrestha S, Lutsey PL, Alonso A, Huang X, Mosley TH Jr, Chen H (2016) Serum 25-hydroxyvitamin d concentrations in mid-adulthood and Parkinson’s disease risk. Mov Disord 31(7):972–978PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Larsson SC, Singleton AB, Nalls MA, Richards JB, International Parkinson’s Disease Genomics Consortium (IPDGC) (2017) No clear support for a role for vitamin D in Parkinson’s disease: a Mendelian randomization study. Mov Disord. 32:1249–1252PubMedCrossRefGoogle Scholar
  83. 83.
    Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679PubMedCrossRefGoogle Scholar
  84. 84.
    Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 50:56–63PubMedCrossRefGoogle Scholar
  85. 85.
    Ascherio A, Chen H, Schwarzschild MA, Zhang SM, Colditz GA, Speizer FE (2003) Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology 60:790–795PubMedCrossRefGoogle Scholar
  86. 86.
    Palacios N, Gao X, McCullough ML, Schwarzschild MA, Shah R, Gapstur S, Ascherio A (2012) Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov Disord 27:1276–1282PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Qi H, Li S (2014) Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr Gerontol Int 14:430–439PubMedCrossRefGoogle Scholar
  88. 88.
    Rivera-Mancía S, Pérez-Neri I, Ríos C, Tristán-López L, Rivera-Espinosa L, Montes S (2010) The transition metals copper and iron in neurodegenerative diseases. Chem Biol Interact 186:184–199PubMedCrossRefGoogle Scholar
  89. 89.
    Berg D, Gerlach M, Youdim MB, Double KL, Zecca L, Riederer P, Becker G (2001) Brain iron pathways and their relevance to Parkinson’s disease. J Neurochem 79:225–236PubMedCrossRefGoogle Scholar
  90. 90.
    Andersen JK (2014) Iron dysregulation and Parkinson’s disease. J Alzheimers Dis 6(6 Suppl):S47–S52Google Scholar
  91. 91.
    Kaur D, Andersen J (2014) Does cellular iron dysregulation play a causative role in Parkinson’s disease? Ageing Res Rev 3:327–343CrossRefGoogle Scholar
  92. 92.
    Barnham KJ, Bush AI (2008) Metals in Alzheimer’s and Parkinson’s diseases. Curr Opin Chem Biol 12:222–228PubMedCrossRefGoogle Scholar
  93. 93.
    Barnham KJ, Bush A (2014) Biological metals and metal-targeting compounds in major neurodegenerative diseases. Chem Soc Rev 43:6727–6749PubMedCrossRefGoogle Scholar
  94. 94.
    Logroscino G, Gao X, Chen H, Wing A, Ascherio A (2008) Dietary iron intake and risk of Parkinson’s disease. Am J Epidemiol 168:1381–1388PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Afzal M, Safer AM, Menon M (2015) Green tea polyphenols and their potential role in health and disease. Inflammopharmacology 23:151–161PubMedCrossRefGoogle Scholar
  96. 96.
    Caruana M, Vassallo N (2015) Tea polyphenols in Parkinson’s disease. Adv Exp Med Biol 863:117–137PubMedCrossRefGoogle Scholar
  97. 97.
    Jurado-Coronel JC, Ávila-Rodriguez M, Echeverria V, Hidalgo OA, Gonzalez J, Aliev G, Barreto GE (2016) Implication of green tea as a possible therapeutic approach for Parkinson disease. CNS Neurol Disord Drug Targets 15:292–300PubMedCrossRefGoogle Scholar
  98. 98.
    Basli A, Soulet S, Chaher N, Mérillon JM, Chibane M, Monti JP, Richard T (2012) Wine polyphenols: potential agents in neuroprotection. Oxid Med Cell Longev 2012:805762PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Gao X, Cassidy A, Schwarzschild MA, Rimm EB, Ascherio A (2012) Habitual intake of dietary flavonoids and risk of Parkinson disease. Neurology 78:1138–1145PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Tan LC, Koh WP, Yuan JM, Wang R, Au WL, Tan JH, Tan EK, Yu MC (2008) Differential effects of black versus green tea on risk of Parkinson’s disease in the Singapore Chinese Health Study. Am J Epidemiol 167:553–560PubMedCrossRefGoogle Scholar
  101. 101.
    Hernán MA, Chen H, Schwarzschild MA, Ascherio A (2003) Alcohol consumption and the incidence of Parkinson’s disease. Ann Neurol 54:170–175PubMedCrossRefGoogle Scholar
  102. 102.
    Zhang D, Jiang H, Xie J (2014) Alcohol intake and risk of Parkinson’s disease: a meta-analysis of observational studies. Mov Disord 29:819–822PubMedCrossRefGoogle Scholar
  103. 103.
    McCarty MF (2001) Does a vegan diet reduce risk for Parkinson’s disease? Med Hypotheses 57:318–323PubMedCrossRefGoogle Scholar
  104. 104.
    Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL (2000) d-[beta]-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci USA 97:5440–5444PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD, Naini A, Vila M, Jackson-Lewis V, Ramasamy R, Przedborski S (2003) d-[beta]-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson’s disease. J Clin Invest 112:892–901PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB (2005) Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 64:728–730PubMedCrossRefGoogle Scholar
  107. 107.
    Bonaventura J, Navarro G, Casadó-Anguera V, Azdad K, Rea W, Moreno E, Brugarolas M, Mallol J, Canela EI, Lluís C, Cortés A, Volkow ND, Schiffmann SN, Ferré S, Casadó V (2015) Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer. Proc Natl Acad Sci USA 112:E3609–E3618PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Petzer A, Pienaar A, Petzer JP (2013) The interactions of caffeine with monoamine oxidase. Life Sci 93(2013):283–287PubMedCrossRefGoogle Scholar
  109. 109.
    Petzer A, Grobler P, Bergh JJ, Petzer JP (2014) Inhibition of monoamine oxidase by selected phenylalkylcaffeine analogues. J Pharm Pharmacol 66:677–687PubMedCrossRefGoogle Scholar
  110. 110.
    Zeitlin R, Patel S, Burgess S, Arendash GW, Echeverria V (2011) Caffeine induces beneficial changes in PKA signaling and JNK and ERK activities in the striatum and cortex of Alzheimer’s transgenic mice. Brain Res 12:127–136CrossRefGoogle Scholar
  111. 111.
    Yaday S, Gupta SP, Srivastava G, Srivastava PK, Singh MP (2012) Role of secondary mediators in caffeine-mediated neuroprotection in maneb- and paraquat-induced Parkinson’s disease phenotype in the mouse. Neurochem Res 37:875–884CrossRefGoogle Scholar
  112. 112.
    LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM, 6002-US-005 Study Group (2008) Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial 6002-US-005. Ann Neurol 63:295–302PubMedCrossRefGoogle Scholar
  113. 113.
    Hauser RA, Shulman LM, Trugman JM, Roberts JW, Mori A, Ballerini R, Sussman NM, Istradefylline 6002-US-013 Study Group (2008) Study of istradefylline in patients with Parkinson’s disease on levodopa with motor fluctuations. Mov Disord 23:2177–2185PubMedCrossRefGoogle Scholar
  114. 114.
    Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M, Japanese Istradefylline Study Group (2010) Clinical efficacy of istradefylline (KW-6002) in Parkinson’s disease: a randomized, controlled study. Mov Disord 25:1437–1443PubMedCrossRefGoogle Scholar
  115. 115.
    Postuma RB, Lang AE, Munhoz RP, Charland K, Pelletier A, Moscovich M, Filla L, Zanatta D, Rios Romenets S, Altman R, Chuang R, Shah B (2012) Caffeine for treatment of Parkinson disease: a randomized controlled trial. Neurology 79:651–658PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Vorovenci RJ, Antonini A (2015) The efficacy of oral adenosine A(2A) antagonist istradefylline for the treatment of moderate to severe Parkinson’s disease. Expert Rev Neurother 15:1383–139015PubMedCrossRefGoogle Scholar
  117. 117.
    Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49:561–574PubMedCrossRefGoogle Scholar
  118. 118.
    Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, Gekeler F, Müller-Myhsok B, Gasser T, Tatsch K, Klopstock T (2006) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67:1262–1264PubMedCrossRefGoogle Scholar
  119. 119.
    NINDS NET-PD Investigators (2008) A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results. Clin Neuropharmacol 31:141–150CrossRefGoogle Scholar
  120. 120.
    Xiao Y, Luo M, Luo H, Wang J (2014) Creatine for Parkinson’s disease. Cochrane Database Syst Rev 6:CD009646Google Scholar
  121. 121.
    Liu J, Wang LN (2014) Mitochondrial enhancement for neurodegenerative movement disorders: a systematic review of trials involving creatine, coenzyme Q10, idebenone and mitoquinone. CNS Drugs 28:63–68PubMedCrossRefGoogle Scholar
  122. 122.
    Manyam BV, Dhanasekaran M, Hare TA (2004) Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters. Phytother Res 18:97–101PubMedCrossRefGoogle Scholar
  123. 123.
    Kasture S, Pontis S, Pinna A, Schintu N, Spina L, Longoni R, Simola N, Ballero M, Morelli M (2009) Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson’s disease. Neurotox Res 15:111–122PubMedCrossRefGoogle Scholar
  124. 124.
    Lieu CA, Kunselman AR, Manyam BV, Venkiteswaran K, Subramanian T (2010) A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias. Parkinsonism Relat Disord 16:458–465PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Yadav SK, Prakash J, Chouhan S, Westfall S, Verma M, Singh TD, Singh SP (2014) Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Neurochem Int 65:1–13PubMedCrossRefGoogle Scholar
  126. 126.
    HP-200 Study (1995) 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 1:249–255CrossRefGoogle Scholar
  127. 127.
    Katzenschlager R, Evans A, Manson A, Patsalos PN, Ratnaraj N, Watt H, Timmermann L, Van der Giessen R, Lees AJ (2004) Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry 75:1672–1677PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Agim ZS, Cannon JR (2015) Dietary factors in the etiology of Parkinson’s disease. Biomed Res Int 2015:672838PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Barichella M, Cereda E, Cassani E, Pinelli G, Iorio L, Ferri V, Privitera G, Pasqua M, Valentino A, Monajemi F, Caronni S, Lignola C, Pusani C, Bolliri C, Faierman SA, Lubisco A, Frazzitta G, Petroni ML, Pezzoli G (2016) Dietary habits and neurological features of Parkinson’s disease patients: implications for practice. Clin Nutr. doi:10.1016/j.clnu.2016.06.020 PubMedGoogle Scholar
  130. 130.
    Chen H, O’Reilly E, McCullough ML, Rodriguez C, Schwarzschild MA, Calle EE, Thun MJ, Ascherio A (2007) Consumption of dairy products and risk of Parkinson’s disease. Am J Epidemiol 165:998–1006PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Sääksjärvi K, Knekt P, Rissanen H, Laaksonen MA, Reunanen A, Männistö S (2008) Prospective study of coffee consumption and risk of Parkinson’s disease. Eur J Clin Nutr 62:908–915PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Neuroscience, Biomedicine and Movement ScienceUniversity of VeronaVeronaItaly
  2. 2.Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”University of SalernoSalernoItaly
  3. 3.Department of NeurologyFranz Tappeiner HospitalMeranoItaly
  4. 4.Section of Geriatrics, Department of Medicine, Division of GeriatricsUniversity of VeronaVeronaItaly
  5. 5.Parkinson Unit, IRCCS Hospital San Camillo and 1st Neurology ClinicAO Universitaria PaduaPaduaItaly

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