Characterizing the Influence of Exogenous Ketosis on Circulating and Hepatic Metabolism in a Postprandial and Postabsorptive State in Adults Free From Metabolic Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Plasma glucose kinetics
研究概览
简要总结
The kinetics of circulating βHB following ingestion of the ketone monoester are dependent on several variables that determine the balance between appearance into, and disappearance from, the bloodstream. These dynamics have been well characterised in fasted humans but in the real world the ketone monoester is likely to be ingested in a fed state, pertinently within athletic spheres consumption would proceed a substantial high-carbohydrate meal. Within this, it is unclear how metabolism under exogenous ketosis might be affected in a fed versus fasted state.
This four-arm crossover study looks to characterise the relationship between feeding status, βHB pharmacokinetics, and resting metabolism.
As exogenous ketosis is known to reduce circulating glucose levels, this study will also explored if hepatic metabolism - for example, de novo lipogenesis - might consequently be altered, with implications for metabolic disease states such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and type II diabetes.
Participants will be asked to consume either the ketone monoester drink or a placebo drink when fasted and when having previously consumed a meal.
详细描述
Adults free from metabolic disease will be recruited for this randomised-counterbalanced crossover study. Participants will attend four study visits.
Participants will consume a prescribed isocaloric high-carbohydrate diet for two days prior to each visit to standardise dietary intake.
For two of these visits participants will remain 'fasted' throughout, and for the two 'fed' visits they will consume a mixed-nutrient breakfast meal. The breakfast for the 'fed' visits will provide 2g∙kg-1 bodyweight of carbohydrate.
Heavy water (D2O) will be consumed the evening preceding, and during, each fed study visit to achieve ~0.4% plasma enrichment, in order to quantify the contribution of hepatic de novo lipogenesis to VLDL-TG.
At these visits they will consume either a ketone monoester (KME) or taste/volume-matched placebo (PLA) drink. The nature of this drink will be single blinded and consumed after the breakfast meal during the 'fed' visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Habitually consuming a mixed macronutrient diet
- •Fluent in English, no communication impairments, willing & able to give informed consent for participation in the study
- •Not currently taking any medication (except the contraceptive pill)
- •No food allergies incompatible with the supplement drinks or with the standardised breakfast where a suitable substitution cannot be practically made
- •Female-only - on contraception (pill/implant/coil/etc); not pregnant/currently breastfeeding; pre-menopausal; not undertaking hormone replacement therapy (HRT)
- •In the investigator's opinion - able and willing to comply with all study requirements
排除标准
- •Significant cardiovascular disease or metabolic risk factors, or family history of it, on health screening questionnaire
- •Food allergies incompatible with the supplement drinks or standardised breakfast
- •Having been on a ketogenic diet in the 6 months prior to enrolment
- •Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study/the participant's ability to participate in the study
- •Concurrently a participant in any other dietary intervention study/have taken part in one within 1 month of enrolment
- •Pregnant or breastfeeding
- •Known history of moderate-to-severe motion sickness
研究组 & 干预措施
Fed - Ketone Monoester
Ketone monoester drink (573 mg∙kg-1 body weight) provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal
干预措施: Ketone Monoester (Dietary Supplement)
Fed - Placebo
Placebo drink provided 1 hour after a 2 g∙kg-1 bodyweight of carbohydrate mixed nutrient breakfast meal
干预措施: Placebo (Dietary Supplement)
Fasted - Ketone Monoester
Ketone monoester drink (573 mg∙kg-1 body weight) provided whilst fasted
干预措施: Ketone Monoester (Dietary Supplement)
Fasted - Placebo
Placebo drink provided whilst fasted
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Plasma glucose kinetics
时间窗: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Changes in concentration of plasma glucose (mM) over the post-drink time period
Plasma β-hydroxybutyrate (βHB) kinetics
时间窗: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
Changes in concentration of plasma βHB (mM) over the post-drink time period
Postprandial de novo lipogenesis (DNL)
时间窗: 7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink)
DNL in the fed visits - quantified as the incorporation of deuterium from heavy water into newly synthesised palmitate within very low-density lipoprotein-triglyceride (VLDL-TG)
次要结局
- Subjective measures of appetite(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Very low-density lipoprotein-triglyceride (VLDL-TG) fatty acid composition(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Breath acetone(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Urine composition(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Subjective measures of gastrointestinal distress(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Indirect calorimetry(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Urine volume(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))
- Plasma biochemistry(7 hours (fasted arrival through to 6 hours after consumption of the KME or PLA drink))