Serum Homocysteine: Relationship with Circulating Levels of Cortisol and Ascorbate

Cascalheira, José F.; Parreira, Mónica C.; Viegas, Andreza N.; Faria, Maria C.; Domingues, Fernanda

doi:10.1159/000158636

Cited by 17 publications

(8 citation statements)

References 58 publications

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“…Concerning folate and vitamin B 12 concentrations, no gender-related differences were found in this study, which is in accordance with data reported by Castro et al [35] and Cascalheira et al [36] in other Portuguese populations. On the contrary, men had higher vitamin B 6 levels than women, strongly suggesting that estrogens play a role on this vitamin concentration in plasma [16].…”

Section: Hyperhomocysteinemia and B-vitaminssupporting

confidence: 93%

Plasma Aminothiol Profile and Some of Its Determinants in Apparently Healthy Azorean Subjects

Lima

Ferin

Baptista

et al. 2014

ISRN Oxidative Medicine

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Objectives. To evaluate the plasma aminothiol profile (PAP) and serum gamma-glutamyltransferase (GGT) activity, as well as plasma folate, vitamin B 12 , and vitamin B 6 concentrations, in 326 apparently healthy subjects from the Azores archipelago (Portugal). Also eventual relationships of PAP with conventional risk factors for atherosclerosis were investigated, aiming at the finding of early blood markers of the disease. Design and Methods. This was an observational cross-sectional study, where participants were split into two groups: one with a normal and another with an altered PAP (at least one aminothiol out of its reference concentration range). Results. About 76% of subjects had an altered PAP, mainly due to low glutathione levels (<1.5 mol/L), mostly associated with normal GGT activity. Prevalence of hyperhomocysteinemia was 10%, where only 33% had some B-vitamin deficiency. The risk for atherosclerosis was more evidenced in subjects exhibiting both deficient GSH concentration and increased serum GGT activity.Conclusions. An altered PAP, namely, when caused by low GSH levels in the absence of alterations in the Hcy, or Cys, or Cys-Gly concentrations and in serum GGT activity, might reveal a subclinical stage of atherogenesis and should be explored as a potential early marker of atherosclerosis.

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Section: Hyperhomocysteinemia and B-vitaminssupporting

confidence: 93%

Plasma Aminothiol Profile and Some of Its Determinants in Apparently Healthy Azorean Subjects

Lima

Ferin

Baptista

et al. 2014

ISRN Oxidative Medicine

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“…In an observational study with 20 men and 40 women older than 50 years, serum Hcy correlated negatively with circulating levels of ascorbate (r = −0.30, p < 0.05) and folate (r = −0.31, p < 0.05) [33]. AA supplementation (500 mg/day) resulted in a significant 40% increase in erythrocyte folate in a study population comprising 65 male and 35 female Italian smokers without lowering Hcy levels [10].…”

Section: Discussionmentioning

confidence: 95%

Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts

et al. 2020

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Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings shed new light on the interaction of AA with the folate-mediated one-carbon cycle and partially explain clinical findings that AA supplementation enhances erythrocyte folate status and that it may decrease serum levels of homocysteine, which is considered as a biomarker of cardiovascular disease risk.

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“…In addition, depression is associated with higher levels of homocysteine 67 and elevated levels of cortisol 31,68 it may be that these two measures are related in part via their effects following dietary folate. Other reports show in a population of healthy middle-aged men and women, high cortisol levels were negatively associated with serum folate levels 69 , and positively associated with serum homocysteine levels. Elevated levels homocysteine and low folic acid are associated with depressive symptoms in middle-aged cohorts of both men and women 32,33 .…”

Section: Discussionmentioning

confidence: 70%

Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats

Qiu

Gobinath

Wen

et al. 2018

Preprint

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Folate is an important regulator of hippocampal neurogenesis, and in utero spinal cord development. Both high levels of folic acid and low levels of folate can be harmful to health, as low levels of folate have been linked to several diseases while high folic acid supplements can mask a vitamin B12 deficiency. Depressed patients exhibit folate deficiencies, lower levels of hippocampal neurogenesis, elevated levels of homocysteine, and elevated levels of the stress hormone, cortisol, which may be inter-related. Here, we are interested in whether different doses of natural folate or synthetic folic acid diets can influence neurogenesis in the hippocampus, levels of plasma homocysteine, and serum corticosterone in adult female rats. Adult female Sprague-Dawley rats underwent dietary interventions for 29 days. Animals were randomly assigned to six different dietary groups: folate deficient + succinylsulfathiazole (SST), low 5-methyltetrahydrofolate (5-MTHF), low 5-MTHF + (SST), high 5-MTHF + SST, low folic acid, and high folic acid. SST was added to a subset of the 5-MTHF diets to eliminate folic acid production in the gut. Before and after dietary treatment, blood samples were collected for corticosterone and homocysteine analysis, and brain tissue was collected for neurogenesis analysis. High folic acid and low 5-MTHF without SST increased the number of immature neurons (doublecortin-expressing cells) within the ventral hippocampus compared to folate deficient controls. Low 5-MTHF without SST significantly increased the number of immature neurons compared to low and high 5-MTHF + SST, indicating that SST interfered with elevations in neurogenesis. Low folic acid and high 5-MTHF+SST reduced plasma homocysteine levels compared to controls, but there was no significant effect of diet on serum corticosterone levels. Low folic acid and high 5-MTHF+SST reduced the number of mature new neurons in the ventral hippocampus (BrdU/NeuN-positive cells) compared to folate deficient controls. Overall, folic acid dose-dependently influenced neurogenesis, with low levels decreasing but high levels increasing, neurogenesis in the ventral hippocampus, suggesting this region, which is important for regulating stress, is particularly sensitive to folic acid in diets. Furthermore, the addition of SST negated the effects of 5-MTHF to increase neurogenesis in the ventral hippocampus.

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Serum Homocysteine: Relationship with Circulating Levels of Cortisol and Ascorbate

Cited by 17 publications

References 58 publications

Plasma Aminothiol Profile and Some of Its Determinants in Apparently Healthy Azorean Subjects

Plasma Aminothiol Profile and Some of Its Determinants in Apparently Healthy Azorean Subjects

Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts

Folic acid, but not folate, regulates different stages of neurogenesis in the ventral hippocampus of adult female rats

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