Peters Brandilyn A, Hall Megan N, Liu Xinhua, Parvez Faruque, Siddique Abu B, Shahriar Hasan, Uddin Mohammad Nasir, Islam Tariqul, Ilievski Vesna, Graziano Joseph H, Gamble Mary V
Department of Environmental Health Sciences.
Department of Epidemiology, and.
J Nutr. 2015 Oct;145(10):2245-52. doi: 10.3945/jn.115.216739. Epub 2015 Aug 26.
Creatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats.
We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys.
Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA.
Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001).
Our findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556.
由胍基乙酸合成肌酸消耗了约50%的源自S-腺苷甲硫氨酸（SAM）的甲基，这占S-腺苷高半胱氨酸（SAH）和总同型半胱氨酸（tHcys）合成的相同比例。膳食肌酸会抑制胍基乙酸的合成，从而降低大鼠的血浆tHcys水平。
我们检验了以下假设：补充肌酸会降低血浆胍基乙酸水平、增加血液中的SAM、降低血液中的SAH并降低血浆tHcys水平。
将孟加拉国成年人随机分为4组，接受12周的4种治疗之一：安慰剂组（n = 101）、3克/天肌酸组（Cr；n = 101）、400微克/天叶酸组（FA；n = 153）或3克/天肌酸加400微克/天叶酸组（Cr+FA；n = 103）。在基线和第12周时，通过高效液相色谱法分析血浆胍基乙酸和tHcys以及全血SAM和SAH的结果。通过比较Cr组与安慰剂组以及Cr+FA组与FA组来检验补充肌酸的治疗效果。
Cr组血浆胍基乙酸下降了10.6%（95%置信区间：4.9，15.9），而安慰剂组无显著增加（3.7%；95%置信区间：-0.8，8.5）（组间差异P = 0.0002）。同样，Cr+FA组血浆胍基乙酸下降了9.0%（95%置信区间：3.4，14.2），而FA组有所增加（7.0%；95%置信区间：2.0，12.2）（组间差异P < 0.0001）。FA组和Cr+FA组的血浆tHcys分别下降了23.4%（95%置信区间：19.5，27.1）和21.0%（95%置信区间：16.4，25.2）（组间差异P = 0.41），安慰剂组或Cr组无显著变化（组间差异P = 0.35）。在Cr+FA组中，随着时间推移胍基乙酸的减少与tHcys的减少相关（β = 0.30；95%置信区间：0.17，0.43；P < 0.0001）。
我们的研究结果表明，虽然补充肌酸会下调内源性肌酸合成，但这可能并不会平均降低人体血浆tHcys水平。然而，在接受肌酸加叶酸补充的参与者中，当血浆胍基乙酸下降时，tHcys确实有所降低。该试验已在clinicaltrials.gov上注册，注册号为NCT01050556。
