Fasting Plasma Total Homocysteine Concentrations Research Articles

A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers

Background: A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine—the sole dietary precursor of homocysteine—may raise plasma tHcy concentrations. Objectives: We studied whether high intake of protein increases plasma concentrations of tHcy in the fasting state and throughout the day. Design: We conducted a randomized, dietary controlled, crossover trial in 20 healthy men aged 18–44 y. For 8 d, men consumed a controlled low-protein diet enriched with either a protein supplement [high-protein diet (21% of energy as protein)] or an isocaloric amount of short-chain glucose polymers [low-protein diet (9% of energy as protein)]. After a 13-d washout period, treatments were reversed. On days 1 and 8 of each treatment period, blood was sampled before breakfast (fasting) and throughout the day. Results: Fasting tHcy concentrations did not differ significantly after the 1-wk high-protein and the 1-wk low-protein diets. The high-protein diet resulted in a significantly higher area under the 24-h homocysteine-by-time curves compared with the low-protein diet, both on day 1 (difference: 45.1 h · μmol/L; 95% CI: 35.3, 54.8 h · μmol/L; P < 0.0001) and on day 8 (difference: 24.7 h · μmol/L; 95% CI: 15.0, 34.5 h · μmol/L; P < 0.0001). Conclusions: A high-protein diet increases tHcy concentrations throughout the day but does not increase fasting tHcy concentrations. As previously shown, the extent of the tHcy increase is modified by the amino acid composition of the protein diet. The clinical relevance of this finding depends on whether high concentrations of tHcy—particularly postprandially—cause cardiovascular disease.

A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers

A high plasma concentration of total homocysteine (tHcy) is associated with increased risk of cardiovascular disease. A high protein intake and hence a high intake of methionine--the sole dietary precursor of homocysteine--may raise plasma tHcy concentrations. We studied whether high intake of protein increases plasma concentrations of tHcy in the fasting state and throughout the day. We conducted a randomized, dietary controlled, crossover trial in 20 healthy men aged 18-44 y. For 8 d, men consumed a controlled low-protein diet enriched with either a protein supplement [high-protein diet (21% of energy as protein)] or an isocaloric amount of short-chain glucose polymers [low-protein diet (9% of energy as protein)]. After a 13-d washout period, treatments were reversed. On days 1 and 8 of each treatment period, blood was sampled before breakfast (fasting) and throughout the day. Fasting tHcy concentrations did not differ significantly after the 1-wk high-protein and the 1-wk low-protein diets. The high-protein diet resulted in a significantly higher area under the 24-h homocysteine-by-time curves compared with the low-protein diet, both on day 1 (difference: 45.1 h x micromol/L; 95% CI: 35.3, 54.8 h x micromol/L; P < 0.0001) and on day 8 (difference: 24.7 h x micromol/L; 95% CI: 15.0, 34.5 h x micromol/L; P < 0.0001). A high-protein diet increases tHcy concentrations throughout the day but does not increase fasting tHcy concentrations. As previously shown, the extent of the tHcy increase is modified by the amino acid composition of the protein diet. The clinical relevance of this finding depends on whether high concentrations of tHcy-particularly postprandially-cause cardiovascular disease.

Effect of supraphysiologic doses of testosterone on fasting plasma total homocysteine concentrations in men with Klinefelter's syndrome

Objective To examine the effect of supraphysiologic doses of testosterone (T) on plasma total homocysteine (tHcy) concentrations in patients with Klinefelter's syndrome (KS). Design Prospective clinical study. Setting University hospital. Patient(s) Thirty-two newly diagnosed male patients with KS, and 20 healthy, volunteer controls matched by age and body mass index. Intervention(s) Testosterone was administered IM every 2 weeks for 6 months. Initially, pretreatment fasting blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 7 days after the last injection. Main outcome measure(s) Plasma total homocysteine. Result(s) The KS patients had lower tHcy levels than the controls. However, plasma fasting tHcy concentrations increased in a statistically significant manner after 6 months of treatment. As compared with the levels among controls, pretreatment levels of the serum creatinine, hemoglobin, and hematocrit were significantly lower, and increased in a statistically significant way following treatment. Posttreatment levels of total cholesterol were statistically significantly higher than the baseline. The pretreatment folate and cobalamin levels also were statistically significantly higher in patients when compared with controls, and decreased significantly after treatment. The linear regression analysis showed that only creatinine, cobalamin, and folate were independently associated with plasma tHcy levels in patients before and after treatment. Conclusion(s) The patients with KS showed lower tHcy concentrations than healthy, age-matched male controls. Testosterone treatment increased plasma tHcy levels.

Hyperhomocysteinemia and Vitamin Score: Correlations with Silent Brain Ischemic Lesions and Brain Atrophy

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B₁₂, folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 µM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.

A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels

ObjectiveTo assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DesignProspective, double-blind, double-dummy, placebo-controlled study. SettingOutpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. Patient(s)One hundred fifty-two healthy hysterectomized postmenopausal women. Intervention(s)Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17β-E2, 50 μg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 μg (n = 33), followed by four cycles of placebo in each group. Main outcome measure(s)Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. Result(s)Mean (±SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 ± 2.5 μmol/L vs. 8.2 ± 2.0 μmol/L; mean change, −7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 ± 1.6 μmol/L vs. 8.6 ± 2.0 μmol/L; mean change, −4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. Conclusion(s)Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

Homocysteine and thiol metabolites in vitamin B12 deficiency

Homocysteine metabolism is increasingly implicated in a diverse group of clinical disorders, including atheromatous vascular disease. We studied the disposition of homocysteine via the trans-sulphuration pathway, plasma glutathione peroxidase (GPx) activity and plasma levels of the sulphated hormone dehydro-epiandrosterone sulphate (DHEAS) in six vitamin B(12)-deficient human subjects before and after 2 weeks of vitamin B(12) repletion, both in the fasting state and following an oral methionine load (0.1 g/kg body weight). Fasting plasma total homocysteine concentrations fell (P=0.03) and total cysteine concentrations rose significantly (P=0.048) after treatment for 2 weeks with vitamin B(12) injections. The magnitude of the mean fall in the fasting concentration of homocysteine (38.8 micromol/l) was similar to the mean rise in cysteine levels (36.0 micromol/l) following vitamin B(12) therapy. Circulating levels of homocysteine were increased at 4 h after a methionine load when compared with fasting levels, both before and after vitamin B(12) repletion (P=0.003 for both). Total cysteinyl-glycine was lower post-methionine than in the fasting state following vitamin B(12) therapy (P=0.007). Fasting plasma GPx fell significantly after 2 weeks of vitamin B(12) therapy (P=0.05). The change in plasma GPx between the fasting state and 4 h after methionine loading was significantly different pre- and post-vitamin B(12) therapy (P=0.05). The present study provides indirect support to the hypothesis that defects in the trans-sulphuration and remethylation of homocysteine produce hyperhomocysteinaemia in vitamin B(12) deficiency in human subjects. Elevated homocysteine levels directly or indirectly may up-regulate GPx. Sulphation status, as measured by plasma DHEAS, was unchanged.

The Effect of Estrogen Replacement Therapy on Total Plasma Homocysteine in Healthy Postmenopausal Women

To clarify the effect of estrogen on total plasma homocysteine concentration and on the concentration of vitamins required for homocysteine metabolism (folate, vitamin B12, and vitamin B6). We measured total fasting plasma homocysteine in 16 healthy postmenopausal women before and 6 hours after a methionine load (100 mg/kg); fasting concentrations of folate, vitamin B12, vitamin B6, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were also determined. After 6 months of estrogen replacement therapy with estradiol, 2 mg daily, and 1 cycle of quarterly methoxyprogesterone acetate, 5 mg daily administered on the 91st through 100th days, measurements were repeated. There was no significant change in mean +/- SD fasting homocysteine concentration (8.8+/-2.5 vs 8.5+/-2.0 micromol/L; P=.30); homocysteine concentrations after methionine load increased from 38.8+/-12.3 to 51.1+/-12.5 micromol/L (P=.01). During this time period, no significant changes occurred in the concentrations of folate (11.7+/-4.4 vs 9.8+/-4.1 nmol/L; P=.06), vitamin B12 (394+/-182 vs 411+/-155 pmol/L; P=.40), or vitamin B6 (pyridoxal phosphate) (26+/-21 vs 36+/-25 nmol/L; P=.15). The mean +/- SD concentration of low-density cholesterol declined 20% (from 147+/-32 to 118+/-37 mg/dL) and high-density lipoprotein increased 16% (from 40+/-13 to 46+/-19 mg/dL) during the study period. Six months of estrogen replacement therapy did not lower fasting plasma total homocysteine concentrations and raised homocysteine concentrations following a methionine load. Lipid profiles improved significantly during the study period. A reduction in homocysteine concentrations is not likely to contribute to the reduction in cardiovascular events seen with estrogen replacement therapy.

Hormone replacement therapy and plasma homocysteine levels

Objective: To compare the effects of 4 and 12 weeks of combined estradiol-progestogen replacement with unopposed estradiol therapy on fasting plasma total homocysteine concentrations in healthy postmenopausal women. Methods: In this prospective, 12-week study in healthy postmenopausal women, we randomly assigned 59 women to sequentially combined daily 2 mg estradiol (E2) plus either trimegestone 0.5 mg daily or dydrogesterone 10 mg daily ( n = 28), or to unopposed daily 2 mg estradiol ( n = 16), or to placebo ( n = 15). Results: Fasting plasma total homocysteine concentrations decreased by 9.4% in the combined estradiol-progestogen group and by 5.1% in the estradiol-only group, and they increased by 2.4% in the placebo group (analysis of covariance: combined hormone replacement therapy compared with placebo ( P = .02); combined therapy compared with estradiol ( P = .23); and estradiol compared with placebo ( P = .26). Reductions were detectable after 4 weeks of combined estradiol-progestogen treatment. The data suggest an additional progestogen-related reduction in homocysteine levels of 0.7 μmol/L and 0.4 μmol/L after 4 and 12 weeks, respectively. Women with a baseline homocysteine concentration in the highest quartile had significantly greater reductions in homocysteine compared with women with an initial homocysteine value in the lowest quartile. Conclusion: Fasting total homocysteine concentrations were significantly reduced by combined estradiol-progestogen replacement. Women with high homocysteine levels at baseline benefit the most. The progestogens used in this study did not have an unfavorable effect on homocysteine metabolism.

A randomized controlled study of the effects of 17Beta-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women

Objective: To investigate the effects of oral 17β-estradiol (E2) -dydrogesterone on fasting plasma homocysteine concentrations in healthy postmenopausal women. Methods: We studied 27 postmenopausal women who were assigned randomly to either a treatment group ( n = 14) or a control group ( n = 13). During the first 12 months of the study, treatment consisted of oral E2, 1 mg daily, combined sequentially with dydrogesterone 5 or 10 mg (14 days per 28-day treatment cycle). Thereafter, women were treated with oral E2,2 mg daily, combined sequentially with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Fasting plasma total homocysteine concentrations were determined at baseline and 3, 12, and 15 months after study entry. Results: At baseline, plasma homocysteine levels did not differ between the groups. After 15 months of hormone treatment mean plasma homocysteine concentration was lowered by 12.6% compared with baseline ( P < .001; analysis of variance for repeated measures). Plasma homocysteine levels were not altered in the control group. The interaction between treatment and time for homocysteine levels was significantly different between the groups ( P < .001; analysis of variance for repeated measures). The decrease in plasma homocysteine levels correlated inversely with the increase in serum E2 levels after 3 and 12 months of hormone treatment ( r = −.54, P < .05 and r = −.56, P < .05, respectively). Conclusion: Plasma fasting homocysteine concentrations are lowered by E2-dydrogesterone therapy in postmenopausal women.