Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson’s disease patients: A randomized controlled study

Anamnart, Chumpol; Kitjarak, Ram

doi:10.1016/j.jocn.2021.03.047

Cited by 19 publications

(10 citation statements)

References 29 publications

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“…In addition to affecting HCY metabolism, FA and vitamin B12 play an important role in the production of tetrahydrofolate (THF) and tetrahydrobiopterin (BH4) (Figure 1) (Stoll et al., 2010). FA is the raw material of THF, vitamin B12 is the catalyst for THF generation and sufficient THF is the basis for maintaining BH4 levels (Anamnart & Kitjarak, 2021). Adequate BH4 can increase the affinity of NADPH oxidase to eNOS, promote the oxidation of L‐arginine to L‐guanidine and provide electrons for NO production.…”

Section: Discussionmentioning

confidence: 99%

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction—A cross‐sectional study

et al. 2021

Andrologia

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To evaluate the relationship between serum levels of folic acid (FA), homocysteine (HCY), vitamin B12 (B12) and erectile dysfunction (ED) and to explore their internal relationships. The study included 134 ED patients and 50 healthy controls. ED was assessed using IIEF-5 scores. ED group had lower median FA (6.08 versus 10.21; p < .001) and B12 (256.0 versus 337.5; p < .001) levels, and higher median HCY (11.4 versus 7.95; p < .001) levels, and these differences seemed to be more pronounced in the younger participants (age < 35 yr). FA decreased with the severity of ED (7.52 versus 6.15 versus 5.49 versus 3.97; p < .001), while HCY increased (10.35 versus 11.8 versus 12.9 versus 15; p < .001). Smoking and shift work were associated with lower FA levels. Multivariate analysis showed that serum FA and HCY revealed significant relation with ED. ROC analysis showed that FA ≤ 8.84 and HCY ≥ 10.35 were the best cut-off values for ED diagnosis. Both FA (r = −0.703, p < .001) and B12 (r = −0.576, p < .001) were negatively correlated with HCY. In conclusion, low FA levels and high HCY levels might be independent risk factors for ED. Low serum FA and B12 levels might co-cause high HCY levels and lead to ED.

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Section: Discussionmentioning

confidence: 99%

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction—A cross‐sectional study

et al. 2021

Andrologia

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“…In addition to Hcy, vitamin B 12 or folate can be found as methyl donors in one-carbon metabolism or the folate–methionine cycle [ 14 ]. Thus, deficiencies in folate and vitamin B 12 can interfere with DNA synthesis or replication, subsequently contributing to cell death or the development of diseases such as cancer [ 54 , 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, in the presence of COMT, S-adenosylmethionine provides its methyl group to L-dopa to produce S-adenosylhomocysteine (SAH) [ 13 ]. SAH is rapidly hydrolyzed to Hcy, which is elevated in patients with PD [ 14 ]. Therefore, the side effects of L-dopa in patients with PD might be closely related to the dysregulation of Hcy, vitamin B 12 and folate.…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Jin

et al. 2023

Nutrients

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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 B12 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 B12 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 B12 (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 B12 deficiency.

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“…Considering this, vitamin B12 and folate are essential, given that they act as cofactors for the remethylation of homocysteine in methionine, which can be used for SAM production [ 22 ]. Thus, a possible strategy to counteract homocysteine accumulation is by supplementing the diet with essential elements for the optimal functioning of this cycle, such as vitamin B12 and folic acid [ 28 , 30 , 94 , 95 , 96 , 97 ].…”

Section: Discussionmentioning

confidence: 99%

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and Kynu Expression in an Animal Model of Parkinson’s Disease

Kretzschmar

Targa

Soares-Lima

et al. 2022

Genes

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Parkinson’s disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra pars compacta of rats using the neurotoxin rotenone. In the sequence, the animals were supplemented with folic acid and vitamin B12 for 14 consecutive days and subjected to the object recognition test. We observed an impairment in object recognition memory after rotenone administration, which was prevented by supplementation (p < 0.01). Supplementation may adjust gene expression through efficient DNA methylation. To verify this, we measured the expression and methylation of the kynureninase gene (Kynu), whose product metabolizes neurotoxic metabolites often accumulated in PD as kynurenine. Supplementation prevented the decrease in Kynu expression induced by rotenone in the substantia nigra (p < 0.05), corroborating the behavioral data. No differences were observed concerning the methylation analysis of two CpG sites in the Kynu promoter. Instead, we suggest that folic acid and vitamin B12 increased global DNA methylation, reduced the expression of Kynu inhibitors, maintained Kynu-dependent pathway homeostasis, and prevented the memory impairment induced by rotenone. Our study raises the possibility of adjuvant therapy for PD with folic acid and vitamin B12.

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Effects of vitamin B12, folate, and entacapone on homocysteine levels in levodopa-treated Parkinson’s disease patients: A randomized controlled study

Cited by 19 publications

References 29 publications

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction—A cross‐sectional study

Association between folic acid, homocysteine, vitamin B12 and erectile dysfunction—A cross‐sectional study

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

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and Kynu Expression in an Animal Model of Parkinson’s Disease

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