Riboflavin Is a Determinant of Total Homocysteine Plasma Concentrations in End-Stage Renal Disease Patients

Abstract

Abstract. The effect of thiamine (vitamin B 1 ) or riboflavin (vitamin B 2 ) availability on fasting total homocysteine (tHcy) plasma levels in end-stage renal disease patients is unknown. A cross-sectional study was performed in a population of nonvitamin supplemented patients maintained on continuous ambulatory peritoneal dialysis. Red blood cell availability of thiamine (␣-ETK) and of riboflavin (␣-EGR), along with other predictors of tHcy plasma levels, was considered in the analysis. There was a linear association of ␣-EGR with tHcy plasma concentrations (P ϭ 0.009), which was not observed for ␣-ETK. Among red blood cell vitamins, ␣-EGR was the only predictor of tHcy levels (P ϭ 0.035), whereas ␣-ETK, red blood cell pyridoxal-5-phosphate supply (␣-EGOT) and red blood cell folate levels had no effect. The risk for having a high tHcy plasma levels within the fourth quartile (plasma tHcy Ͼ38.3 mol/L) was increased by an ␣-EGR Ͼ median (odds ratio, 4.706; 95% confidence interval, 1.124 to 19.704; P ϭ 0.026). By way of contrast, ␣-ETK had no effect in these analyses. Independent predictors of tHcy plasma levels were serum albumin, ␣-EGR, red blood cell folate, and certain MTHFR genotypes. A logistic regression analysis showed that the MTHFR genotype is a predictor for having a tHcy plasma concentration within the fourth quartile. In summary, riboflavin availability, as measured by ␣-EGR, is a determinant of fasting tHcy plasma levels in peritoneal dialysis patients. This finding may have implications for tHcy lowering therapy in individuals with end-stage renal disease.The majority of patients with impaired renal function present elevated total homocysteine (tHcy) plasma levels (1). Established predictors of tHcy plasma levels in the renal failure population include serum albumin and serum creatinine levels, creatinine clearance, folate status, vitamin B 12 and vitamin B 6 levels, as well as genetic variants in enzymes involved in the folate cycle or in the remethylation of homocysteine (2-7). An elevated tHcy plasma level can indicate folate and/or vitamin B 12 deficiency (8) and is associated with a variety of pathologic conditions such as vascular disease (9 -11) or birth defects (12). Although genetic and nongenetic factors have been shown to determine tHcy concentrations of patients with renal insufficiency, the cause of hyperhomocysteinemia among these patients is not completely understood (13).The role of B-group vitamins other than vitamin B 6 or vitamin B 12 as determinants of hyperhomocysteinemia in the general population and in the setting of renal insufficiency is far from clear, although vitamin B 1 (thiamine pyrophosphate) and vitamin B 2 (riboflavin) are involved in the metabolism of methionine and homocysteine.We assumed that thiamine or riboflavin availability is a predictor of fasting tHcy plasma levels in end-stage renal disease (ESRD). To test this hypothesis, we performed a crosssectional study among a population of non-vitamin supplemented patients maintained on continuous ambulatory perito...

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects

“…Flavin adenine dinucleotide, a coenzyme of MTHFR, probably facilitates the reaction by which administered folic acid is converted to 5, 10-MTHF and then further to 5-MTHF. Unexpectedly, the folate increasing and tHcy lowering effects of riboflavin suggested by previous reports (Shimakawa et al, 1997;Hustad et al, 2000;Jacques et al, 2001;Skoupy et al, 2002) were not seen in the present study. Previous reports have demonstrated an inverse relation between riboflavin and tHcy in subjects with poor riboflavin status such as the elderly (Jacques et al, 2001) and those with genetic risk factors (Hustad et al, 2000).…”

“…Examining the effects of folic acid, riboflavin, and the MTHFR genotype on human lymphocytes grown in culture media, Kimura et al (2004) observed that the tHcy concentration decreased as the riboflavin concentration increased. An inverse association between plasma riboflavin and tHcy concentrations has also been suggested in epidemiological studies (Shimakawa et al, 1997;Hustad et al, 2000;Jacques et al, 2001;Skoupy et al, 2002), and riboflavin is recognized as a determinant of plasma tHcy concentrations. Subjects who frequently consume dairy products, which are typical sources of riboflavin, reportedly have low plasma tHcy concentrations (Gao et al, 2003).…”

Association between plasma homocysteine and riboflavin status in Acute Lymphoblastic Leukemia in children

“…Jacqus et al (10) studied 450 subjects from the Framingham offspring cohort and found an inverse association between plasma concentration of riboflavin and The relationship between plasma tHcy and riboflavin status has also been investigated in end-stage renal disease. (11).The authors found a positive association between EGRAC and tHcy, which is consistent with high tHcy when riboflavin status is low. Riboflavin was significantly related to plasma tHcy in multivariate models, which included folate and other B-vitamins.…”

Biologically active form of vitamin B1 in human peritoneal effluent

“…Only few studies have assessed vitamin B1 status in PD patients. [5][6][7][8][9][10] To the best of our knowledge, only 1 measured vitamin B1 peritoneal losses. 5 However, ThDP losses have not been assessed and reported yet.…”