Two Faces of Catechol-O-Methyltransferase Inhibitor on One-Carbon Metabolism in Parkinson's Disease: A Meta-Analysis.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Parkinson Disease*/drug therapy ; Catechol O-Methyltransferase Inhibitors*/therapeutic use; Humans ; Carbon/metabolism ; Folic Acid/therapeutic use ; Homocysteine ; Levodopa/pharmacology ; Vitamin B 12/therapeutic use ; Vitamins/therapeutic use

Levodopa (L-dopa) and catechol-O-methyltransferase (COMT) inhibition are widely used therapeutics in Parkinson's disease (PD). Despite their therapeutic effects, it was raised that nutrients involved in one-carbon metabolism can be deteriorated by PD therapies. The aim of this meta-analysis was to investigate the impact of L-dopa and COMT inhibitors on levels of homocysteine (Hcy), vitamin B 12 and folate in patients with PD. A total of 35 case-control studies from 14 different countries were selected through PubMed, MEDLINE and Google Scholar and were meta-analyzed. In the L-dopa group, the Hcy level was higher compared to the PD without L-dopa group (SMD: 5.11 μmol/L, 95% CI: 3.56 to 6.66). Moreover, vitamin B 12 and folate levels in the L-dopa group were lower compared to the healthy control (SMD: -62.67 pg/mL, 95% CI: -86.53 to -38.81; SMD: -0.89 ng/mL, 95% CI: -1.44 to -0.33, respectively). The COMT inhibitor group showed lower levels of Hcy (SMD: -3.78 μmol/L, 95% CI: -5.27 to -2.29) and vitamin B 12 (SMD: -51.01 pg/mL, 95% CI: -91.45 to -10.57), but higher folate levels (SMD: 1.78 ng/mL, 95% CI: -0.59 to 4.15) compared to the L-dopa group. COMT inhibitors may ameliorate L-dopa-induced hyper-homocysteine and folate deficiency but exacerbate vitamin B 12 deficiency.

Clin Neurol Neurosurg. 2020 Jan;188:105587. (PMID: 31733593)
Nutrients. 2016 Jan 27;8(2):68. (PMID: 26828517)
Nat Rev Drug Discov. 2018 Nov;17(11):804-822. (PMID: 30262889)
Neuromolecular Med. 2012 Mar;14(1):84-90. (PMID: 22354693)
J Neurol Sci. 2009 Dec 15;287(1-2):64-8. (PMID: 19786283)
Clin Chem. 2001 Jun;47(6):1102-4. (PMID: 11375298)
Fundam Clin Pharmacol. 2015 Dec;29(6):522-8. (PMID: 26376956)
Neurol Res. 2006 Dec;28(8):853-8. (PMID: 17288745)
Lancet. 1999 Jul 10;354(9173):126-7. (PMID: 10408491)
Medicine (Baltimore). 2021 Aug 20;100(33):e26875. (PMID: 34414939)
Neurosci Lett. 2006 Aug 14;404(1-2):56-60. (PMID: 16787708)
Nutr J. 2015 Jan 10;14:6. (PMID: 25577237)
Nutr J. 2020 Oct 4;19(1):111. (PMID: 33012287)
J Neurol Sci. 2006 Oct 25;248(1-2):56-61. (PMID: 16774768)
Acta Neurol Scand. 2013 Aug;128(2):73-82. (PMID: 23432663)
Front Public Health. 2021 Dec 07;9:776847. (PMID: 34950630)
Nutr Metab (Lond). 2017 Dec 22;14:78. (PMID: 29299040)
Cell Death Discov. 2021 Jun 28;7(1):151. (PMID: 34226525)
Parkinsonism Relat Disord. 2005 Jun;11(4):253-6. (PMID: 15878587)
BMJ. 2002 Nov 23;325(7374):1202. (PMID: 12446535)
Mov Disord. 2004 Dec;19(12):1403-8. (PMID: 15390053)
Eur J Neurol. 2005 May;12(5):365-8. (PMID: 15804266)
Molecules. 2017 Dec 25;23(1):. (PMID: 29295587)
Eur J Clin Pharmacol. 2006 Jun;62(6):447-50. (PMID: 16758261)
Parkinsonism Relat Disord. 2005 Mar;11(2):131-3. (PMID: 15734674)
Lancet Neurol. 2018 Nov;17(11):939-953. (PMID: 30287051)
Mov Disord. 2005 Jan;20(1):69-72. (PMID: 15390046)
Nutr Res Rev. 2019 Dec;32(2):218-230. (PMID: 31303188)
Neurology. 2000 Aug 8;55(3):437-40. (PMID: 10932284)
BMC Neurol. 2017 Oct 6;17(1):192. (PMID: 28985720)
BMC Musculoskelet Disord. 2021 Apr 17;22(1):364. (PMID: 33865356)
J Neurosci. 2002 Mar 1;22(5):1752-62. (PMID: 11880504)
Parkinsons Dis. 2019 May 29;2019:3124295. (PMID: 31275543)
Mov Disord. 2009 May 15;24(7):1028-33. (PMID: 19353704)
Ann Clin Transl Neurol. 2020 Nov;7(11):2332-2338. (PMID: 33085841)
Neuromolecular Med. 2003;3(2):119-28. (PMID: 12728194)
Pract Lab Med. 2015 Mar 26;1:35-41. (PMID: 28932797)
Front Pharmacol. 2022 Apr 07;13:805388. (PMID: 35462934)
Eur Neurol. 2007;58(2):96-9. (PMID: 17565222)
J Neurol Neurosurg Psychiatry. 2003 Apr;74(4):549. (PMID: 12640094)
Parkinsonism Relat Disord. 2009 Jul;15(6):477-8. (PMID: 19028438)
Front Neurol. 2021 Sep 24;12:707723. (PMID: 34630283)
J Neural Transm (Vienna). 2002;109(1):69-75. (PMID: 11793163)
Curr Nutr Rep. 2018 Sep;7(3):70-84. (PMID: 30099693)
J Clin Neurosci. 2021 Jun;88:226-231. (PMID: 33992189)
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17495-500. (PMID: 23045670)
Neuromolecular Med. 2007;9(3):249-54. (PMID: 17914182)
Arch Neurol. 2004 May;61(5):657-60. (PMID: 15148140)
J Clin Neurosci. 2005 Aug;12(6):669-72. (PMID: 16040247)
BMJ. 2003 Sep 6;327(7414):557-60. (PMID: 12958120)

2022M3A9B6017813 National Research Foundation of Korea; NRF-2017R1A5A2014768 National Research Foundation of Korea

Keywords: Parkinson’s disease; folate; homocysteine; levodopa; meta-analysis; one-carbon metabolism; vitamin B

7440-44-0 (Carbon)
935E97BOY8 (Folic Acid)
0LVT1QZ0BA (Homocysteine)
46627O600J (Levodopa)
P6YC3EG204 (Vitamin B 12)
0 (Vitamins)
0 (Catechol O-Methyltransferase Inhibitors)

Date Created: 20230225 Date Completed: 20230228 Latest Revision: 20230301

20240829

PMC9964466

10.3390/nu15040901

36839259