In Study 2 a Student's unequal variance t-test with equal SD was used to compare urine βHB concentrations. Additionally, a linear mixed effects model was constructed to estimate partitions of variance in R, using the lme4 and blme packages (Chung et al., 2013; Bates et al., 2015). Feeding state and visit number were fixed effects in this model, and inter-participant variability was a random effect. Inter-participant variability was calculated according to the adjusted generalized R2 metric (as proposed by Nakagawa and Schielzeth, 2013), to partition variance between the fixed effects of feeding, inter-participant variability, and residual variability. The coefficient of variation for βHB Cmax and AUC were calculated using the method of Vangel (1996).
Blood glucose concentrations are decreased during both exogenous and endogenous ketosis, although by different mechanisms. During endogenous ketosis, dietary carbohydrate deficit is the underlying cause of low blood glucose, along with reduced hepatic gluconeogenesis and increased ketone production (Cahill et al., 1966). With exogenous ketosis, carbohydrate stores are plentiful, yet ketones appear to lower blood glucose through limiting hepatic gluconeogenesis and increasing peripheral glucose uptake (Mikkelsen et al., 2015). One clinical use of the ketogenic diet is to improve blood glucose control, yet the elevated blood FFA may increase the risk of heart failure (Holloway et al., 2009). Thus, the ability of exogenous ketones to lower blood glucose without elevating blood FFA concentrations could deliver the desired effect of the diet, whilst also decreasing a potential risk.
Ketosis supplements made in poor quality, have proven to lead to side-effects such as constipation and increased levels of cholesterol and triglycerides in men, and women may also experience amenorrhea or other disruptions to the menstrual cycle. This is why it is really important to know what combination of compounds you are consuming, particularly while you are on this very strict diet because the wrong balance can really mess with you in the long term and won't give you the high performance that you are looking for.
Funding. This work supported by an Industrial DPhil Fellowship to BS from the Royal Commission for the Exhibition of 1851. JM was supported by the EPSRC Doctoral Training Centre and Prize Fellowship; Ref: EP/M508111/1. The funding sources were not involved in the design, conduct or analysis of this study. TΔS Ltd. provided the ketone ester, ΔG®, and NTT DOCOMO Inc. provided the acetone meter for the study.
These studies were approved by external Research Ethics Committees (London Queen's Square: 14/LO/0288 and South West Frenchay: 15/SW/0244) and were conducted in accordance with the Declaration of Helsinki (2008). Studies took place at the University of Oxford between September 2014 and September 2016. Participants were healthy, aged 21–57, non-smokers and had no history of major illness. Female participants were using oral contraception to minimize the effects of menstrual phase on results. Participants provided written informed consent prior to inclusion, and completed a confidential medical screening questionnaire to determine eligibility. Anthropometric characteristics are shown in Table Table1.1. Sample sizes were chosen following an estimated power calculation based on the effect size in previous work using KE drinks (Clarke et al., 2012b; Shivva et al., 2016).
BHB isn’t just an energy source for the brain–it has other effects which promote brain health. BHB can trigger the release of chemicals called neurotrophins, which support neuron function and synapse formation. One of these neurotrophins is called BDNF (brain-derived neurotrophic factor), which is a protein in the brain associated with cognitive enhancement, alleviation of depression and reduction of anxiety.10
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