Courchesne-Loyer Alexandre, Lowry Carolyn-Mary, St-Pierre Valérie, Vandenberghe Camille, Fortier Mélanie, Castellano Christian-Alexandre, Wagner J Richard, Cunnane Stephen C
Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Department of Pharmacology and Physiology, University of Sherbrooke, Sherbrooke, Quebec, Canada.
Curr Dev Nutr. 2017 Jun 21;1(7):e000851. doi: 10.3945/cdn.117.000851. eCollection 2017 Jul.
Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability () by 2- to 3-fold and decreased the number of side effects by ∼50%. Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.
在与衰老相关的认知衰退发生之前，大脑下部的葡萄糖摄取通常就已出现，这可能会增加患阿尔茨海默病的风险。酮类是大脑中葡萄糖的主要替代能量底物。中链甘油三酯（MCTs）能快速进行β氧化，具有生酮作用，但也有胃肠道副作用。我们评估了将MCT乳化到无乳糖脱脂乳基质中[乳化MCTs（MCT-Es）]与相同口服剂量的未乳化MCTs[未乳化MCTs（MCT-NEs）]相比，是否会改善生酮作用、减少副作用，或者两者兼具。我们的目的是表明，在健康成年人中，MCT-Es比MCT-NEs能诱导更高的酮血症，且副作用更少，并且MCT-NEs和MCT-Es对生酮作用和血浆中链脂肪酸（MCFAs）的影响将呈剂量依赖性。采用代谢研究日方案，10名健康成年人分别接受3种不同剂量（10、20或30克）的MCT-NEs或MCT-Es，同时搭配标准早餐或不接受任何治疗[对照组（CTL）]。在4小时内每隔30分钟采集一次血样，以测量血浆酮类（β-羟基丁酸和乙酰乙酸）、辛酸、癸酸及其他代谢产物。参与者在每个研究日结束时完成一份副作用问卷。与CTL相比，MCT-NEs使生酮作用增加了2倍，各剂量之间无显著差异。MCT-Es使血浆总酮类以剂量依赖性方式增加了2至4倍。与MCT-NEs相比，MCT-Es使血浆MCFA生物利用度提高了2至3倍，并使副作用数量减少了约50%。在匹配条件下，对于单剂量≤30克的MCTs，乳化以剂量依赖性方式增强了生酮作用并减少了副作用。需要进一步研究以确定乳化是否能维持生酮作用并将副作用降至最低，从而用作一种在较长时间内改变大脑酮类可用性的治疗方法。该试验已在clinicaltrials.gov上注册，注册号为NCT02409927。
