Nutr Res Pract.  2017 Apr;11(2):114-120. 10.4162/nrp.2017.11.2.114.

Association of serum carotenoid, retinol, and tocopherol concentrations with the progression of Parkinson's Disease

• Kim JH
• Hwang J
• Shim E
• Chung EJ
• Jang SH
• Koh SB

• KMID: 2412023
• DOI: http://doi.org/10.4162/nrp.2017.11.2.114

Abstract

BACKGROUND/OBJECTIVES
A pivotal role of oxidative stress has been emphasized in the pathogenesis as well as in the disease progression of Parkinson's disease (PD). We aimed at investigating serum levels of antioxidant vitamins and elucidating whether they could be associated with the pathogenesis and progression of PD.
MATERIALS/METHODS
Serum levels of retinol, α- and γ-tocopherols, α- and β-carotenes, lutein, lycopene, zeaxanthin and β-cryptoxanthin were measured and compared between 104 patients with idiopathic PD and 52 healthy controls matched for age and gender. In order to examine the relationship between antioxidant vitamins and the disease progression, multiple group comparisons were performed among the early PD (Hoehn and Yahr stage I and II, N = 47), advanced PD (stage III and IV, N = 57) and control groups. Separate correlation analyses were performed between the measured antioxidant vitamins and clinical variables, such as Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) motor score.
RESULTS
Compared to controls, PD patients had lower levels of α- and β-carotenes and lycopene. α-carotene, β-carotene and lycopene levels were significantly reduced in advanced PD patients relative to early PD patients and were negatively correlated with Hoehn and Yahr stage and UPDRS motor score in PD patients. No significant differences were found in serum levels of retinol, α- and γ-tocopherols, and other carotenoids between PD patients and controls. No significant correlations were found between these vitamin levels and clinical variables in PD patients.
CONCLUSIONS
We found that serum levels of some carotenoids, α-carotene, β-carotene and lycopene, were lower in PD patients, and that these carotenoids inversely correlated with clinical variables representing disease progression. Our findings suggest that decreases in serum α-carotene, β-carotene and lycopene may be associated with the pathogenesis as well as progression of PD.

Keyword

Parkinson disease; oxidative stress; carotenoids; disease progression

MeSH Terms

Carotenoids
Disease Progression
Humans
Lutein
Oxidative Stress
Parkinson Disease*
Tocopherols*
Vitamin A*
Vitamins
Zeaxanthins
Carotenoids
Lutein
Tocopherols
Vitamin A
Vitamins
Zeaxanthins

Figure

• 

  Fig. 1 Significant correlations between Hoehn and Yahr stages and serum carotenoids. Spearman's test, P < 0.05; A, α-carotene; B, β-carotene; C, lycopene.

• 

  Fig. 2 Significant correlations between UPDRS motor scores and serum carotenoids. Spearman's test, P < 0.05; A, α-carotene; B, β-carotene; C, lycopene.

Reference

1. de Rijk MC, Breteler MM, Graveland GA, Ott A, Grobbee DE, van der Meché FG, Hofman A. Prevalence of Parkinson's disease in the elderly: the Rotterdam study. Neurology. 1995; 45:2143–2146.

2. Kim HS, Lee KS, Bae HJ, Koh IS, Chang SH, Im DH, Heo JH. Changes in length of stay for neurological geriatric diseases in Korea between 2003 and 2007. J Clin Neurol. 2011; 7:148–155.

3. Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015; 386:896–912.

4. Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson's disease. Neurology. 1996; 47:S161–S170.

5. Craft NE, Haitema TB, Garnett KM, Fitch KA, Dorey CK. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging. 2004; 8:156–162.

6. Fiedor J, Burda K. Potential role of carotenoids as antioxidants in human health and disease. Nutrients. 2014; 6:466–488.

7. Ulatowski L, Parker R, Warrier G, Sultana R, Butterfield DA, Manor D. Vitamin E is essential for Purkinje neuron integrity. Neuroscience. 2014; 260:120–129.

8. de Rijk MC, Breteler MM, den Breeijen JH, Launer LJ, Grobbee DE, van der Meché FG, Hofman A. Dietary antioxidants and Parkinson disease. The Rotterdam study. Arch Neurol. 1997; 54:762–765.

9. Golbe LI, Farrell TM, Davis PH. Follow-up study of early-life protective and risk factors in Parkinson's disease. Mov Disord. 1990; 5:66–70.

10. Miyake Y, Fukushima W, Tanaka K, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M. Fukuoka Kinki Parkinson's Disease Study Group. Dietary intake of antioxidant vitamins and risk of Parkinson's disease: a case-control study in Japan. Eur J Neurol. 2011; 18:106–113.

11. Zhang SM, Hernán MA, Chen H, Spiegelman D, Willett WC, Ascherio A. Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology. 2002; 59:1161–1169.

12. Logroscino G, Marder K, Cote L, Tang MX, Shea S, Mayeux R. Dietary lipids and antioxidants in Parkinson's disease: a population-based, case-control study. Ann Neurol. 1996; 39:89–94.

13. Johnson CC, Gorell JM, Rybicki BA, Sanders K, Peterson EL. Adult nutrient intake as a risk factor for Parkinson's disease. Int J Epidemiol. 1999; 28:1102–1109.

14. Morens DM, Grandinetti A, Waslien CI, Park CB, Ross GW, White LR. Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake. Neurology. 1996; 46:1270–1274.

15. Anderson C, Checkoway H, Franklin GM, Beresford S, Smith-Weller T, Swanson PD. Dietary factors in Parkinson's disease: the role of food groups and specific foods. Mov Disord. 1999; 14:21–27.

16. Hellenbrand W, Boeing H, Robra BP, Seidler A, Vieregge P, Nischan P, Joerg J, Oertel WH, Schneider E, Ulm G. 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. 1996; 47:644–650.

17. Nicoletti G, Crescibene L, Scornaienchi M, Bastone L, Bagalà A, Napoli ID, Caracciolo M, Quattrone A. Plasma levels of vitamin E in Parkinson's disease. Arch Gerontol Geriatr. 2001; 33:7–12.

18. Sohmiya M, Tanaka M, Tak NW, Yanagisawa M, Tanino Y, Suzuki Y, Okamoto K, Yamamoto Y. Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson's disease. J Neurol Sci. 2004; 223:161–166.

19. Ahlskog JE, Uitti RJ, Low PA, Tyce GM, Nickander KK, Petersen RC, Kokmen E. No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease. Mov Disord. 1995; 10:566–573.

20. Sudha K, Rao AV, Rao S, Rao A. Free radical toxicity and antioxidants in Parkinson's disease. Neurol India. 2003; 51:60–62.

21. Férnandez-Calle P, Molina JA, Jiménez-Jiménez FJ, Vázquez A, Pondal M, García-Ruiz PJ, Urra DG, Domingo J, Codoceo R. Serum levels of alpha-tocopherol (vitamin E) in Parkinson's disease. Neurology. 1992; 42:1064–1066.

22. Foy CJ, Passmore AP, Vahidassr MD, Young IS, Lawson JT. Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease. QJM. 1999; 92:39–45.

23. Buhmann C, Arlt S, Kontush A, Möller-Bertram T, Sperber S, Oechsner M, Stuerenburg HJ, Beisiegel U. Plasma and CSF markers of oxidative stress are increased in Parkinson's disease and influenced by antiparkinsonian medication. Neurobiol Dis. 2004; 15:160–170.

24. Jiménez-Jiménez FJ, Molina JA, Fernández-Calle P, Vázquez A, Cabrera-Valdivia F, Catalán MJ, García-Albea E, Bermejo F, Codoceo R. Serum levels of beta-carotene and other carotenoids in Parkinson's disease. Neurosci Lett. 1993; 157:103–106.

25. Verhage BA, Aben KK, Straatman H, Verbeek AL, Beaty TH, Kiemeney LA. Spouse controls in family case-control studies: a methodological consideration. Fam Cancer. 2003; 2:101–108.

26. Smith DS, Fillenbaum GG. Comparison of spouse and nonkin controls: the experience of the Consortium to Establish a Registry for Alzheimer's disease (CERAD). Aging (Milano). 1994; 6:151–157.

27. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999; 56:33–39.

28. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967; 17:427–442.

29. Yeum KJ, Ahn SH, Rupp de Paiva SA, Lee-Kim YC, Krinsky NI, Russell RM. Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer. J Nutr. 1998; 128:1920–1926.

30. Sopher BL, Fukuchi K, Kavanagh TJ, Furlong CE, Martin GM. Neurodegenerative mechanisms in Alzheimer disease. A role for oxidative damage in amyloid beta protein precursor-mediated cell death. Mol Chem Neuropathol. 1996; 29:153–168.

31. Kontush K, Schekatolina S. Vitamin E in neurodegenerative disorders: Alzheimer's disease. Ann N Y Acad Sci. 2004; 1031:249–262.

32. Delanty N, Dichter MA. Antioxidant therapy in neurologic disease. Arch Neurol. 2000; 57:1265–1270.

33. Johnson EJ, Vishwanathan R, Johnson MA, Hausman DB, Davey A, Scott TM, Green RC, Miller LS, Gearing M, Woodard J, Nelson PT, Chung HY, Schalch W, Wittwer J, Poon LW. Relationship between serum and brain carotenoids, alpha-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. J Aging Res. 2013; 2013:951786.

34. Al-Delaimy WK, Ferrari P, Slimani N, Pala V, Johansson I, Nilsson S, Mattisson I, Wirfalt E, Galasso R, Palli D, Vineis P, Tumino R, Dorronsoro M, Pera G, Ocké MC, Bueno-de-Mesquita HB, Overvad K, Chirlaque M, Trichopoulou A, Naska A, Tjønneland A, Olsen A, Lund E, Alsaker EH, Barricarte A, Kesse E, Boutron-Ruault MC, Clavel-Chapelon F, Key TJ, Spencer E, Bingham S, Welch AA, Sanchez-Perez MJ, Nagel G, Linseisen J, Quirós JR, Peeters PH, van Gils CH, Boeing H, van Kappel AL, Steghens JP, Riboli E. Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Clin Nutr. 2005; 59:1387–1396.

35. Al-Delaimy WK, Slimani N, Ferrari P, Key T, Spencer E, Johansson I, Johansson G, Mattisson I, Wirfalt E, Sieri S, Agudo A, Celentano E, Palli D, Sacerdote C, Tumino R, Dorronsoro M, Ocké MC, Bueno-De-Mesquita HB, Overvad K, Chirlaque MD, Trichopoulou A, Naska A, Tjonneland A, Olsen A, Lund E, Skeie G, Ardanaz E, Kesse E, Boutron-Ruault MC, Clavel-Chapelon F, Bingham S, Welch AA, Martinez-Garcia C, Nagel G, Linseisen J, Quirós JR, Peeters PH, van Gils CH, Boeing H, van Kappel AL, Steghens JP, Riboli E. Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Clin Nutr. 2005; 59:1397–1408.

36. Borrelli E, Chambon P. Control of transcription and neurological diseases. Mol Psychiatry. 1999; 4:112–114.

37. Tafti M, Ghyselinck NB. Functional implication of the vitamin A signaling pathway in the brain. Arch Neurol. 2007; 64:1706–1711.

38. Ascherio A, Stampfer MJ, Colditz GA, Rimm EB, Litin L, Willett WC. Correlations of vitamin A and E intakes with the plasma concentrations of carotenoids and tocopherols among American men and women. J Nutr. 1992; 122:1792–1801.

39. Goodman DS. Overview of current knowledge of metabolism of vitamin A and carotenoids. J Natl Cancer Inst. 1984; 73:1375–1379.

40. Di Mascio P, Murphy ME, Sies H. Antioxidant defense systems: the role of carotenoids, tocopherols, and thiols. Am J Clin Nutr. 1991; 53:194S–200S.

41. Martini MC, Campbell DR, Gross MD, Grandits GA, Potter JD, Slavin JL. Plasma carotenoids as biomarkers of vegetable intake: the University of Minnesota Cancer Prevention Research Unit Feeding Studies. Cancer Epidemiol Biomarkers Prev. 1995; 4:491–496.

42. Scheider WL, Hershey LA, Vena JE, Holmlund T, Marshall JR, Freudenheim JL. Dietary antioxidants and other dietary factors in the etiology of Parkinson's disease. Mov Disord. 1997; 12:190–196.

43. Anglade P, Vyas S, Hirsch EC, Agid Y. Apoptosis in dopaminergic neurons of the human substantia nigra during normal aging. Histol Histopathol. 1997; 12:603–610.

44. Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence. Free Radic Biol Med. 2014; 66:3–12.

45. Herrera E, Barbas C. Vitamin E: action, metabolism and perspectives. J Physiol Biochem. 2001; 57:43–56.

46. Stahl W, Sies H. Antioxidant activity of carotenoids. Mol Aspects Med. 2003; 24:345–351.

47. Pappert EJ, Tangney CC, Goetz CG, Ling ZD, Lipton JW, Stebbins GT, Carvey PM. Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients: dose-response study and correlations with plasma levels. Neurology. 1996; 47:1037–1042.

48. Dexter DT, Ward RJ, Wells FR, Daniel SE, Lees AJ, Peters TJ, Jenner P, Marsden CD. Alpha-tocopherol levels in brain are not altered in Parkinson's disease. Ann Neurol. 1992; 32:591–593.

49. Jiménez-Jiménez FJ, de Bustos F, Molina JA, Benito-León J, Tallón-Barranco A, Gasalla T, Ortí-Pareja M, Guillamón F, Rubio JC, Arenas J, Enríquez-de-Salamanca R. Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer's disease. J Neural Transm (Vienna). 1997; 104:703–710.

50. Tohgi H, Abe T, Saheki M, Hamato F, Sasaki K, Takahashi S. Reduced and oxidized forms of glutathione and α-tocopherol in the cerebrospinal fluid of parkinsonian patients: comparison between before and after L-dopa treatment. Neurosci Lett. 1995; 184:21–24.