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Long-term effect of betaine on risk factors associated with the metabolic syndrome in healthy subjects.
Schwab, U, Alfthan, G, Aro, A, Uusitupa, M
European journal of clinical nutrition. 2011;(1):70-6
Abstract
BACKGROUND/OBJECTIVES To examine the effects of betaine on serum lipid profile, plasma homocysteine concentration and hemostatic factors in healthy subjects. SUBJECTS/METHODS Altogether, 63 volunteers (27 ± 8 years, body mass index 22.6 ± 2.4 kg/m(2)) participated in a placebo-controlled, randomized, parallel double-blinded study. The intervention lasted for 6 months during which the subjects consumed mineral water 500 ml/day with (betaine group, n = 32) or without (control group, n = 31) a 4-g betaine supplementation. RESULTS There was a significant interaction of time and group (general linear model) in serum total and low-density lipoprotein (LDL)-cholesterol concentrations and total-to-high-density lipoprotein (HDL)-cholesterol ratio without a significant difference between or within the groups. Concentrations of serum HDL-cholesterol, triglycerides or oxidized LDL did not change during the study. Plasma homocysteine concentration did not change in either of the groups. Plasma plasminogen activator inhibitor 1 concentration increased in the betaine group (P = 0.028) and decreased in the control group (P = 0.006). There was a significant interaction of time and group (general linear model) in plasma fibrinogen and blood hemoglobin concentration without a significant difference between or within the groups. There were no changes in parameters regarding the function of the liver or kidney. CONCLUSIONS Betaine had no effect on serum lipid profile in long term in young healthy subjects. The lowering effect on plasma homocysteine concentration was weak.
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Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine.
Lever, M, George, PM, Slow, S, Elmslie, JL, Scott, RS, Richards, AM, Fink, JN, Chambers, ST
Cardiovascular drugs and therapy. 2009;(5):395-401
Abstract
PURPOSE Betaine is an osmolyte, supplies methyl groups, and controls plasma homocysteine. Abnormal urinary loss of betaine is common in patients with the metabolic syndrome or diabetes mellitus. These patients are often treated with fibrates which alter renal function and raise plasma homocysteine concentrations. We suggest there is a connection between fibrate treatment and betaine excretion. METHODS We identified 32 fibrate-treated patients in several studies (total of 740 subjects) and compared the betaine excretion by these with the excretion by other patients, both in the separate studies and in the combined group. We investigated the correlation of betaine excretion with homocysteine in these groups. RESULTS Patients taking bezafibrate had higher betaine excretion than patients not taking fibrates, p < 0.00001 in some studies with n < 10. Of 32 patients taking bezafibrate, 20 had abnormal (>97.5 %-ile) betaine excretion. Plasma homocysteine correlated positively with betaine excretion in male patients with lipid disorders who were not taking fibrate (n = 68, p = 0.043), but the relationship was stronger if patients taking bezafibrate were included (n = 76, p < 0.00001). In elderly (>65 years) subjects with hypertension there was a similar correlation (n = 19, p = 0.047), which was stronger when a subject taking bezafibrate was included (n = 20, p = 0.013). CONCLUSIONS Abnormal betaine excretion is common in patients treated with bezafibrate. Bezafibrate appears to exacerbate betaine loss, which will cause a rise in plasma homocysteine. Betaine supplementation could be considered in conjunction with fibrate therapy.
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Effects of two different oral contraceptives on homocysteine metabolism in women with polycystic ovary syndrome.
Cagnacci, A, Tirelli, A, Renzi, A, Paoletti, AM, Volpe, A
Contraception. 2006;(4):348-51
Abstract
PURPOSE This study was conducted to evaluate the effects of two different oral contraceptives (OCs) on homocysteine (Hcy) metabolism in 20 women with polycystic ovary syndrome (PCOS). METHODS Women were randomly allocated to receive either the biphasic OC containing 40/30 mug ethynylestradiol (EE)+25/125 mug desogestrel (DSG; n=10) or the monophasic OC containing 35 mug EE and 2 mg cyproterone acetate (CPA; n=10). Investigations were performed before and after 6 months of treatment. Fasting vitamin B(12), folate, Hcy and insulin sensitivity (SI), and glucose utilization independent of insulin (Sg), by the minimal model method, were evaluated. RESULTS Folate and vitamin B(12) were not significantly modified by either OC. EE/DSG decreased SI (2.53+/-0.35 vs. 1.68+/-0.45; p<.05), without modifying Hcy (9.54+/-0.7 micromol/L vs. 9.18+/-0.6 micromol/L). EE/CPA improved SI (1.47+/-0.38 vs. 3.27+/-0.48; p<.04) and decreased Hcy (9.8+/-1.9 micromol/L vs. 7.9+/-0.9 micromol/L; p<.05). This study indicates that in women with PCOS, EE/CPA, but not EE/DSG, improves IS and decreases fasting Hcy.
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Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study.
Kilicdag, EB, Bagis, T, Zeyneloglu, HB, Tarim, E, Aslan, E, Haydardedeoglu, B, Erkanli, S
Human reproduction (Oxford, England). 2005;(4):894-9
Abstract
BACKGROUND Elevated levels of plasma homocysteine (Hcy) have been implicated as a significant risk factor for cardiovascular disease. Although long-term treatment with metformin can increase Hcy levels in patients with type II diabetes mellitus or coronary heart disease, it is becoming an increasingly accepted and widespread medication in polycystic ovary syndrome (PCOS). In the literature, only one study has demonstrated that metformin increases Hcy levels in PCOS patients, but the effect of other insulin sensitizers on Hcy levels have not been reported previously in women with PCOS. We aimed to assess the effects of metformin and rosiglitazone on plasma Hcy levels in patients with PCOS. METHODS Thirty women were randomized to two groups: 15 women in group 1 received 850 mg of metformin twice daily for 3 months. In group 2, 15 women received 4 mg of rosiglitazone for 3 months. In both groups, body mass index, menstrual pattern, and plasma total Hcy, insulin, glucose and lipid metabolism parameters were recorded at baseline and at 3 months. RESULTS Hcy levels increased from 8.93+/-0.49 to 11.26+/-0.86 micromol/l (P = 0.002) and from 10.70+/-0.86 to 12.36+/-0.81 micromol/l (P = 0.01) in the metformin and rosiglitazone groups, respectively. Apolipoprotein (Apo) A1 levels increased from 127.10+/-6.85 to 145.7+/-7.18 mg/dl (P = 0.018) in the metformin group. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) and Apo B levels decreased in the metformin group, but the change was not significant. Total-C levels decreased from 161.15+/-8.94 to 150.23+/-8.73 mg/dl (P = 0.026), HDL-C decreased from 43.13+/-2.65 to 39.15+/-2.52 mg/dl (P = 0.005) and LDL-C levels decreased from 93.83+/-6.06 to 80.7+/-2.30 mg/dl (P = 0.021) in the rosiglitazone group. CONCLUSION Treatment with insulin sensitizers in women with PCOS may lead to increases in Hcy levels.
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Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia.
Setola, E, Monti, LD, Galluccio, E, Palloshi, A, Fragasso, G, Paroni, R, Magni, F, Sandoli, EP, Lucotti, P, Costa, S, et al
European journal of endocrinology. 2004;(4):483-9
Abstract
OBJECTIVE The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. DESIGN AND METHODS A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month. RESULTS In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables. CONCLUSIONS Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors.