Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90502, USA.
Nutr Cancer. 2011;63(6):950-9. doi: 10.1080/01635581.2011.590266. Epub 2011 Jul 20.
High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D(2) (PGD(2)). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD(2), niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E(2) (PGE(2)) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8-3.9). PGE(2) promotes tumors in the intestines, whereas PGD(2) may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc(Min/+) mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc(Min/+) mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc(Min/+) mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.
高剂量烟酸(烟碱酸)用于治疗血脂异常会引起潮红,这是由于前列腺素 D₂(PGD₂)水平升高所致。G 蛋白偶联受体 GPR109A 触发皮肤潮红。除了促进 PGD₂产生外,烟酸与 GPR109A 结合还会激活整个前列腺素级联反应。我们发现 GPR109A 存在于整个胃肠道中。在交替食用 1%烟酸饮食和对照饮食的小鼠中,当食用烟酸时,其尿液中前列腺素 E₂(PGE₂)代谢物水平更高(增加 2.8 倍;95%置信区间,1.8-3.9)。PGE₂促进肠道肿瘤,而 PGD₂可能具有相反的作用,我们的报告显示,转基因造血前列腺素 D 合酶可抑制 Apc(Min/+)小鼠的肠道腺瘤。为了确定肿瘤生长或肿瘤抑制是否占主导地位,我们给 Apc(Min/+)小鼠喂食 1%烟酸饮食并评估肿瘤发育情况。1%烟酸饮食并未影响 Apc(Min/+)小鼠在 14 周时组织学评分的肿瘤数量(烟酸组 33 只,对照组 33 只)。尽管烟酸刺激各种前列腺素的产生,但我们的结果支持这样一种解释,即在该模型中,非常高的烟酸摄入量与肠道肿瘤是安全的。