Dietary serine and cystine attenuate the homocysteine-raising effect of dietary methionine: a randomized crossover trial in humans.
BACKGROUND
A high plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease. The increase in tHcy induced by methionine, the sole dietary precursor of homocysteine, might be modulated by other amino acids present in dietary proteins.


OBJECTIVE
Our objectives were to compare the postprandial effect of free and dietary methionine on plasma tHcy concentrations and to investigate whether serine and cystine modify the effect of free methionine on tHcy.


METHODS
We conducted a randomized crossover trial in 24 healthy men. Each subject ingested 4 meals on separate days, which were separated by 1 wk. tHcy concentrations were measured in the fasting state and at 2, 4, 6, 8, 10, and 24 h after meal ingestion. The meals were 1) a low-protein meal fortified with 30 mg methionine/kg body wt (reference, denoted by "Met"), 2) meal 1 additionally fortified with 60.6 mg serine/kg body wt (MetSer), 3) meal 1 additionally fortified with 12.3 mg cystine/kg body wt (MetCys), and 4) a protein-rich meal containing 30 mg methionine, 60.6 mg serine, and 12.3 mg cystine per kg body wt (Protein).


RESULTS
The mean (+/-SD) fasting tHcy concentration was 9.1 +/- 2.7 micromol/L. Mean peak tHcy concentrations were 17.9 +/- 4.5, 14.3 +/- 3.3, 14.8 +/- 3.9, and 11.2 +/- 3.1 micromol/L after Met, MetSer, MetCys, and Protein, respectively. Compared with the mean 24-h area under the tHcy-by-time curve after Met, the mean curves after MetSer, MetCys, and Protein were 37%, 32%, and 77% smaller, respectively (all P < 0.0005).


CONCLUSIONS
Dietary methionine increases tHcy much less than does free methionine. Serine and cystine attenuate the tHcy-raising effect of free methionine. Thus, dietary proteins with a high content of serine or cystine relative to methionine may lead to lower postprandial tHcy responses.
Verhoef
Petra
P
Wageningen Centre for Food Sciences, Nutrition and Health Programme, Wageningen, Netherlands. petra.verhoef@wur.nl
Steenge
Gery R
GR
Boelsma
Esther
E
van Vliet
Trinette
T
Olthof
Margreet R
MR
Katan
Martijn B
MB
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control; D018592:Cross-Over Studies; D003553:Cystine / Q000008:administration & dosage / Q000494:pharmacology*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology; D005215:Fasting / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000187:drug effects / Q000378:metabolism / Q000493:pharmacokinetics; D012694:Serine / Q000008:administration & dosage / Q000494:pharmacology*
D004044:Dietary Proteins; D006710:Homocysteine; D012694:Serine; D003553:Cystine; D008715:Methionine