Serum S-adenosylmethionine, but not methionine, increases in response to overfeeding in humans.

BACKGROUND: Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high-energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding. METHODS: Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days. RESULTS: Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9±0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5±0.2 kg) did not (Pinteraction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, Pinteraction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL)-cholesterol. CONCLUSION: Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention.

Plasma sulfur amino acids and stearoyl-CoA desaturase activity in two Caucasian populations.

In rats, dietary restriction of the cysteine precursor methionine suppresses hepatic stearoyl-CoA desaturase (SCD)-1 expression and activity, whereas cysteine supplementation reverses these effects. In 2 independent cohorts: Hordaland Health Study (HUSK; N=2021, aged 71-74y), Norway, and Hoorn study (N=686, aged 50-87y), Netherlands, we examined the cross-sectional associations of plasma sulfur-containing compounds (SCC; methionine, S-adenosylmethionine, S-adenosylhomocysteine, homocysteine, cystathionine, total cysteine (tCys), glutathione and cysteinylglycine) with SCD-16 index (16:1n-7/16:0), estimated from fatty acid profiles of total plasma or serum lipids. Only tCys was consistently associated with SCD-16 index after adjustments for sex and age (HUSK: partial r=0.14; Hoorn: partial r=0.11, P<0.001 for both), and after further adjustments for other SCC, body fat, diet, exercise and plasma lipids (HUSK: partial r=0.07, P=0.004; Hoorn: partial r=0.12, P=0.013). Together with animal data showing an effect of dietary cysteine on SCD1, our results suggest a role for cysteine in SCD1 regulation in humans.

Associations of serum n-3 and n-6 polyunsaturated fatty acids with echocardiographic measures among older adults: the Hoorn Study.

BACKGROUND/OBJECTIVES: Lower circulating polyunsaturated fatty acids (PUFAs) may induce loss of heart function. We investigated whether lower concentrations of n-3 and n-6 PUFAs were associated with less favourable echocardiographic measures and higher heart rate in older Caucasians, cross-sectionally and after 7 years of follow-up. SUBJECTS/METHODS: We used data from the Hoorn Study, a population-based cohort. Cross-sectional data were available for 621 participants and longitudinal data for 336 participants. Mean age was 68.6±6.8 years at baseline. We performed linear regression analyses using n-3 and n-6 PUFAs quartiles-assayed by gas liquid chromatography-with left ventricular ejection fraction (LVEF), left ventricular mass index, left atrial volume index and heart rate. RESULTS: In multivariable analyses (regression coefficient (95% confidence interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles compared with the highest quartiles were cross-sectionally associated with lower LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend <0.001) and 3.4 b.p.m. (1.2, 5.6; P for trend 0.001), respectively. Multivariate longitudinal analyses showed a significant trend across quartiles for alpha-linolenic acid in relation to LVEF. The lowest linoleic acid quartile was significantly associated with a decreased LVEF of -4.0% compared with the highest quartile. CONCLUSIONS: This study found no strong evidence of longitudinal associations of eicosapentaenoic acid and docosahexaenoic acid with echocardiographic measures, however, lower concentrations of alpha-linolenic acid and linoleic acid were associated with decreased LVEF. These results provide evidence for a potential protective role of alpha-linolenic acid and linoleic acid in relation to systolic function.

The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins.

BACKGROUND AND AIM: Sulfur amino acids are recognized as potent modulators of lipid metabolism. Plasma total cysteine (tCys) is associated with fat mass, obesity and serum LDL-cholesterol and apolipoprotein (Apo)-B in large population studies. It is not known how fasting plasma concentrations of cysteine precursors and products relate to these associations in humans, given that sulfur-containing compounds (SCC) influence rodent weight gain and serum lipids. METHODS AND RESULTS: We investigated the cross-sectional associations of fasting plasma SCC (methionine, total homocysteine, cystathionine, tCys, taurine and total glutathione) with BMI and fasting serum lipids and apolipoproteins in 854 men and women with and without cardiovascular disease (CVD). In multiple linear regression analysis adjusted for age, gender, CVD and other SCC, neither methionine, taurine, nor total glutathione was associated with BMI. Plasma taurine was, however, inversely related to HDL-cholesterol (partial r = -0.12, p = 0.004) and its associated apoA1 (partial r = -0.18, p < 0.001). Plasma cystathionine correlated positively with triglycerides and BMI, while tCys positively correlated with total cholesterol, LDL-cholesterol (partial r = 0.20, p < 0.001) and its associated apoB. The associations of SCC with serum lipids were independent of BMI. tCys was also independently associated with BMI (partial r = 0.20, p < 0.001) after adjustment for other SCC, glucose, lipids and apolipoproteins. CONCLUSIONS: Fasting tCys is associated with BMI independently of metabolically related SCC. Elevation of plasma SCC is generally associated with an unfavorable lipid profile. The negative relations of plasma taurine with HDL-C and apoA1 deserve further investigation.