Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Tokyo 194-8543, Japan.
Drug Metab Pharmacokinet. 2009;24(6):549-52. doi: 10.2133/dmpk.24.549.
Trimethylaminuria is caused by excessive malodorous trimethylamine excreted via urine and body secretion by decreased hepatic flavin-containing monooxygenase 3 (FMO3) metabolic capacity for transforming non-odorous trimethylamine N-oxide. This study investigates foodstuff first in healthy volunteers for palliative care for self-reported Japanese trimethylaminuria subjects. Urinary excretion of total trimethylamine in volunteers was determined by gas chromatography under daily food intake or after ingestion of selected fish premeasured for total trimethylamine content. Frequency of individuals showing apparently <40% FMO3 metabolic capacity was 3.8% in 365 Japanese volunteers who suffered from self-reported malodor. Bonitos, especially red flesh, had the lowest total trimethylamine content (approximately 1 micromol per g tissue) among salmon, tuna, swordfish, sea bream or cod in this study. Mean excretion ratio of total trimethylamine in 8 h-urines from six healthy volunteers was approximately 90% after loading test by ingesting bonito (200 g) resulting in less than 2 micromol of free trimethylamine/mmol creatinine excreted in volunteers harboring high FMO3 metabolic capacity, in contrast to approximately 40% after ingestion of 200 g cod. These results in healthy volunteers suggest that bonito may be one of the best nutrient sources and palliative care for self-reported Japanese trimethylaminuria subjects.
三甲基胺尿症是由肝脏黄素单加氧酶 3（FMO3）代谢能力下降，导致无法将无臭的三甲基胺 N-氧化物转化为过多恶臭的三甲基胺，从而通过尿液和身体分泌物排出引起的。本研究首先在健康志愿者中调查食物，以寻找针对自述有日本三甲基胺尿症的患者的姑息治疗方法。志愿者的总三甲基胺排泄量通过气相色谱法在日常食物摄入或摄入预先测量总三甲基胺含量的选定鱼类后确定。在 365 名自述有异味的日本志愿者中，表现出明显的 FMO3 代谢能力<40%的个体频率为 3.8%。在本研究中，鲣鱼，尤其是红肉，总三甲基胺含量最低（约每克组织 1 微摩尔），其次是三文鱼、金枪鱼、箭鱼、真鲷或鳕鱼。六位健康志愿者在摄入鲣鱼（200 克）后进行负荷试验，8 小时尿液中的总三甲基胺排泄率约为 90%，而在高 FMO3 代谢能力的志愿者中，排泄的游离三甲基胺/mmol 肌酐量少于 2 微摩尔，相比之下，摄入 200 克鳕鱼后，排泄率约为 40%。这些健康志愿者的结果表明，鲣鱼可能是自述有日本三甲基胺尿症的患者的最佳营养来源和姑息治疗方法之一。
