Thursday, July 19, 2007

Daily rhythms in plasma levels of homocysteine

Daily rhythms in plasma levels of homocysteine

Background
There is accumulated evidence that plasma concentration of the sulfur-containing amino-acid homocysteine (Hcy) is a prognostic marker for cardiovascular morbidity and mortality. Both fasting levels of Hcy and post methionine loading levels are used as prognostic markers. The aim of the present study was to investigate the existence of a daily rhythm in plasma Hcy under strictly controlled nutritional and sleep-wake conditions. We also investigated if the time during which methionine loading is performed, i.e., morning or evening, had a different effect on the resultant plasma Hcy concentration.

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Results
In both the first and second experiments there was a significant daily rhythm in Hcy concentrations with a mid-day nadir and a nocturnal peak. Strikingly different 24-h patterns were observed in methionine, leucine, isoleucine and tyrosine. In all, the 24-h curves revealed a strong influence of both the sleep-wake cycle and the feeding schedule. Methionine loading resulted in increased plasma Hcy levels during both morning and evening experiments, which were not significantly different from each other.

Conclusions
There is a daily rhythm in plasma concentration of the amino acid Hcy, and this rhythm is independent of sleep-wake and food consumption. In view of the fact that increased Hcy concentrations may be associated with increased cardiovascular risks, these findings may have clinical implications for the health of rotating shift workers.

Experimental results accumulated in recent years have revealed that plasma concentration of the sulfur-containing amino-acid homocysteine (Hcy) is a prognostic marker for cardiovascular morbidity and mortality [1-5]. Plasma concentrations of Hcy in excess of 15 μmol/L under fasting conditions were associated with increased risk of cardiovascular mortality [6]. Furthermore, some patients having normal fasting levels of plasma Hcy were shown to have abnormally high levels of Hcy after methionine loading [7]. In most epidemiological studies, the differences between fasting concentrations of Hcy of cardiovascular patients and normal controls did not amount to more than 10–15%.

Studies conducted during the 1960s have demonstrated that plasma levels of several amino acids vary in a daily manner. Feigin, Klainer and Beisel [8] were the first to report on daily rhythms in serum levels of total amino acids in adult men. The peak levels of the total integrated amino acids occured between 1200 and 2000 with a minimum level at 0400. Wurtman, Chou and Rose [9] reported on a daily rhythm in plasma concentration of tyrosine with a nocturnal nadir and a morning peak, which represented a two-fold increase in plasma tyrosine level. This rhythm persisted when subjects were maintained on a two-week low protein diet. Subsequently, the same group [10] extended their findings to 15 additional amino acids. Tyrosine, tryptophan, phenylalanine, methionine, cysteine, and isoleucine, underwent the greatest daily changes while alanine, glycine and glutamic acid showed the least. Hussein et al [11] reported that the daily fluctuations of plasma free amino acids were significantly affected by the dietary conditions. In none of these studies, however, were the levels of amino acids determined during the sleep period or under uniform dietary conditions.

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