13 research outputs found
La stimulation de la cétogenÚse chez l'humain par une supplémentation en triglycérides de moyennes chaßnes
Le vieillissement de la population est reliĂ© Ă lâaugmentation de la prĂ©sence de certaines maladies comme les dĂ©clins cognitifs ou les dĂ©mences de type Alzheimer. Chez les personnes Ă risques de dĂ©velopper ces dĂ©mences, une diminution prĂ©coce du mĂ©tabolisme cĂ©rĂ©bral du glucose peut ĂȘtre observĂ©e avant mĂȘme lâapparition des premiers symptĂŽmes. Ce dĂ©ficit Ă©nergĂ©tique pourrait expliquer la cascade qui mĂšne au dĂ©veloppement des dĂ©clins cognitifs. Les cĂ©tones sont des molĂ©cules produites par le corps Ă partir de la lipolyse des acides gras qui ont dĂ©jĂ dĂ©montrĂ© leur efficacitĂ© comme substrat Ă©nergĂ©tique de substitution pour le cerveau. Lâutilisation de triglycĂ©rides de moyennes chaĂźnes (MCT), des acides gras facilement absorbables et oxydables, est un moyen efficace pour augmenter les cĂ©tones rapidement mais transitoirement. Notre objectif Ă©tait de voir sâil Ă©tait possible dâaugmenter les cĂ©tones plasmatiques et de maintenir une concentration modĂ©rĂ©e sur 24 h avec une supplĂ©mentation quotidienne en MCT. Dix participants ont dâabord reçu une supplĂ©mentation de 2 semaines dâune Ă©mulsion de MCT (3 fois par jour). Leur concentration plasmatique de cĂ©tones mais aussi de glucose, de cholestĂ©rol, de triglycĂ©rides et dâacides gras libres Ă©tait mesurĂ©e au dĂ©but et Ă la fin de la supplĂ©mentation. Huit participants ont par la suite reçu une supplĂ©mentation de 4 semaines de lâĂ©mulsion de MCT (4 fois par jour). En plus des paramĂštres mentionnĂ©s prĂ©cĂ©demment, des mesures dâoxydation de MCT, Ă lâaide dâun traceur 13C-trioctanoate, dâoxydation des cĂ©tones, Ă lâaide dâun traceur de 13C-bĂȘta-hydroxybutyrate ((30Hb), et des mesures de composition corporelle Ă©taient effectuĂ©es. Dans les deux Ă©tudes, les analyses plasmatiques ont dĂ©montrĂ© une augmentation significative des cĂ©tones plasmatiques (jusquâĂ 0,47 ± 0 ,1 5 mM), qui semblait plus soutenue lors de la deuxiĂšme Ă©tude. Aucune autre modification nâa Ă©tĂ© observĂ©e dans les analyses plasmatiques. Une diminution de lâoxydation du traceur 13C-trioctanoate dans les heures suivant la prise puis une hausse Ă 24 h suivant la supplĂ©mentation montre un changement dans lâutilisation des MCT, donc une plus grande conversion en cĂ©tones. Aucun changement nâa Ă©tĂ© observĂ© avec le traceur 13C-(30Hb. Aucune variation de la composition corporelle nâa Ă©tĂ© observĂ©e. Ces Ă©tudes montrent la capacitĂ© des MCT Ă augmenter et Ă maintenir une concentration de cĂ©tones durant 24 h Ă des niveaux lĂ©gers chez un adulte en santĂ©.Abstract : Aging leads to the development of many diseases among which is cognitive decline associated with dementia and Alzheimer's disease (AD). In populations who are at risk of developing cognitive decline, it has been noted that a marked brain glucose hypometabolism precedes the onset of other clinical symptoms such as [beta]-amyloid accumulation. This hypometabolism could therefore be responsible for the development of AD. Ketone bodies are energetic molecules that are produced by the liver following the (3-oxidation of fatty acids. They already have been showed to be able to sustain brain metabolism as the principal energy source. Medium chain triglycerides (MCT) are easily absorbed and metabolised fatty acids. They can raise plasma ketones rapidly but transiently. Our objective was to determine whether it was possible to raise and maintain a moderate plasma ketone concentration over 24 h in healthy adults. Ten participants were first given a 2 week supplementation of MCT (3 times a day). Plasma ketone, glucose, cholesterol, triglyceride and free fatty acids were measured. Another 8 participants were given a 4 week supplementation of MCT (4 times a day). In addition to the measures taken in the first project, MCT oxidation; with [indice supĂ©rieur 13] C-trioctanoate, ketone oxidation; with [indice supĂ©rieur 13] C-beta-hydroxybutyrate and body composition were measured. In both projects, plasma ketone concentration were raised (to a maximum of 0.48 ± 0.15 mM) and appeared to be more stable in the second project. All other plasma measures were unchanged. Significantly lower [indice supĂ©rieur 13] C-trioctanoate oxidation was detected during the 2 to 5 hours following the tracer absorption after the supplementation and a marked augmentation was detected 24 h following the supplementation. This indicates a shift in MCT utilization by the body from immediate energy source to ketone precursor. No changes were noted in [beta]OHb oxidation or in body composition. These studies show the ability of MCT to raise and maintain a moderate level of ketones in plasma when taken daily in healthy adults
Study of a ketogenic stimulation in healthy adults : effect of ketosis on brain energy metabolism
Le cerveau humain est un organe trĂšs mĂ©taboliquement actif. Cet Ă©norme besoin Ă©nergĂ©tique lâexpose Ă un risque accru de dĂ©tĂ©rioration causĂ©e par un dĂ©rĂšglement de ce mĂ©tabolisme. Dans la phase prĂ©coce de la maladie dâAlzheimer, un hypomĂ©tabolisme cĂ©rĂ©bral du glucose est observĂ©. Cette carence Ă©nergĂ©tique serait Ă lâorigine des dĂ©tĂ©riorations observĂ©e lors du dĂ©veloppement de cette maladie. Le cerveau a accĂšs Ă une autre source endogĂšne dâĂ©nergie : les cĂ©tones. Les cĂ©tones sont particuliĂšrement importantes pour le cerveau puisquâil ne possĂšde pas la capacitĂ© dâutiliser les acides gras comme source Ă©nergĂ©tique Ă lâinstar des autres organes. Les cĂ©tones sont issues de la ÎČ-oxydation hĂ©patique des acides gras. Ils sont produits en situation de jeĂ»ne lorsque les niveaux circulants de glucose et dâinsuline sont bas. Les cĂ©tones se sont dĂ©jĂ montrĂ© efficaces dans le traitement de divers troubles neurologiques comme lâĂ©pilepsie. Par contre, outre les diĂštes cĂ©togĂšnes et le jeĂ»ne prolongĂ©, il nâexiste pas de traitement efficace pour maintenir une cĂ©tonĂ©mie modĂ©rĂ©e chez lâadulte. Le mĂ©tabolisme Ă©nergĂ©tique cĂ©rĂ©bral en situation de cĂ©tose modĂ©rĂ©e reste encore mal compris dans cette population. Les travaux de cette thĂšse se sont donc concentrĂ©s Ă Ă©tudier la possibilitĂ© dâune combinaison dâapproche nutritionnelle et pharmacologique afin de stimuler la cĂ©togenĂšse chez lâadulte. Ils ont aussi explorĂ© les changements de mĂ©tabolisme cĂ©rĂ©bral chez lâadulte durant une cĂ©tose modĂ©rĂ©e. Lâobjectif de la premiĂšre Ă©tude Ă©tait dâĂ©tudier le potentiel du bezafibrate Ă stimuler la cĂ©togenĂšse induite par une supplĂ©mentation en triglycĂ©rides de moyennes chaĂźnes (MCT). Cette premiĂšre Ă©tude a dĂ©montrĂ© que le bezafibrate avait peu dâeffet sur la stimulation de la cĂ©togenĂšse induite par les MCT et que le facteur limitant dans cette stimulation Ă©tait donc la disponibilitĂ© des substrats et non la capacitĂ© cĂ©togĂšne des cellules hĂ©patiques. Lâobjectif de la seconde Ă©tude Ă©tait dâĂ©tudier les changements de capture des cĂ©tones et du glucose au cerveau durant un Ă©tat de cĂ©tose modĂ©rĂ©e chez lâadulte. Les rĂ©sultats de cette deuxiĂšme Ă©tude ont montrĂ© que la capture des cĂ©tones au cerveau est directement proportionnelle Ă leur concentration plasmatique. Cette Ă©tude a aussi dĂ©montrĂ© que la capture cĂ©rĂ©brale des cĂ©tones Ă©tait directement reliĂ©e Ă leur concentration plasmatique alors que la capture cĂ©rĂ©brale du glucose est modulĂ©e par les besoins Ă©nergĂ©tiques du cerveau. Une stimulation cĂ©togĂ©nique chez des personnes atteintes de dĂ©clin cognitif pourrait donc aider Ă rĂ©tablir la balance Ă©nergĂ©tique et ralentir lâapparition des symptĂŽmes chez ces personnes mais cet effet devra ĂȘtre Ă©tudiĂ© dans une Ă©tude ultĂ©rieure.Abstract : The human brain is the most metabolically active organ of the body. This high need for energy exposes it to an increase risk in case of hypometabolism. Such a glucose hypometabolism is seen during the early stages of Alzheimerâs disease. This factor is believed to be one of the cause of the disease. Ketones are the main alternate substrate for the human brain. Ketones are particularly important since, unlike other organs, the brain can not use fatty acids as alternative fuel. Ketones are mainly produce through ÎČ-oxidation of fatty acid by the liver. This happens mainly during fasting when circulating levels of glucose and insulin are low. Studies have shown that ketones can have a therapeutic effect in a variety of neurological diseases, mainly epilepsy and Alzheimerâs disease. Nevertheless, apart from ketogenic diet and prolonged fasting, there is currently no effective ways to induce and maintain moderate ketosis in adults. Brain energy metabolism under moderate ketosis remains also misunderstood in this population. This thesis aimed look at the effect of a combination of a pharmacological treatment and a nutritional supplementation to induce moderate sustain ketosis in adults. It also studied the effect of a moderate ketosis on brain energy metabolism in adults. The aim of the first study was to study the effect of a pharmacological treatment, bezafibrate, on the potentiation of the ketogenic effect induced by a medium-chain triglycerides (MCT) supplementation. The results of this study that bezafibrate had little effect on the ketosis induced by a MCT supplementation and, therefore, that the limiting factor in human ketosis was not the liver cells capacity to produce ketones but the availability of substrates for ketogenesis. The aim of the second study was to study the impact of a nutritional moderate ketosis on brain glucose and ketone uptake. The results of this study showed a direct correlation between brain ketone uptake and plasma ketone concentrations. This study also showed that brain ketone uptake is regulated by blood ketone concentration whereas brain glucose uptake is regulated by the brain energy needs. Further studies should then look if such a moderate ketosis induced in cognitively impaired patients could re-equilibrate the energy balance in the brain and then slow the apparition of clinical symptoms in this population
La stimulation de la cétogenÚse chez l'humain par une supplémentation en triglycérides de moyennes chaßnes
RĂ©sumĂ© : Le vieillissement de la population est reliĂ© Ă lâaugmentation de la prĂ©sence de certaines maladies comme les dĂ©clins cognitifs ou les dĂ©mences de type Alzheimer. Chez les personnes Ă risques de dĂ©velopper ces dĂ©mences, une diminution prĂ©coce du mĂ©tabolisme cĂ©rĂ©bral du glucose peut ĂȘtre observĂ©e avant mĂȘme lâapparition des premiers symptĂŽmes. Ce dĂ©ficit Ă©nergĂ©tique pourrait expliquer la cascade qui mĂšne au dĂ©veloppement des dĂ©clins cognitifs. Les cĂ©tones sont des molĂ©cules produites par le corps Ă partir de la lipolyse des acides gras qui ont dĂ©jĂ dĂ©montrĂ© leur efficacitĂ© comme substrat Ă©nergĂ©tique de substitution pour le cerveau. Lâutilisation de triglycĂ©rides de moyennes chaĂźnes (MCT), des acides gras facilement absorbables et oxydables, est un moyen efficace pour augmenter les cĂ©tones rapidement mais transitoirement. Notre objectif Ă©tait de voir sâil Ă©tait possible dâaugmenter les cĂ©tones plasmatiques et de maintenir une concentration modĂ©rĂ©e sur 24 h avec une supplĂ©mentation quotidienne en MCT. Dix participants ont dâabord reçu une supplĂ©mentation de 2 semaines dâune Ă©mulsion de MCT (3 fois par jour). Leur concentration plasmatique de cĂ©tones mais aussi de glucose, de cholestĂ©rol, de triglycĂ©rides et dâacides gras libres Ă©tait mesurĂ©e au dĂ©but et Ă la fin de la supplĂ©mentation. Huit participants ont par la suite reçu une supplĂ©mentation de 4 semaines de lâĂ©mulsion de MCT (4 fois par jour). En plus des paramĂštres mentionnĂ©s prĂ©cĂ©demment, des mesures dâoxydation de MCT, Ă lâaide dâun traceur 13C-trioctanoate, dâoxydation des cĂ©tones, Ă lâaide dâun traceur de 13C-bĂȘta-hydroxybutyrate ((30Hb), et des mesures de composition corporelle Ă©taient effectuĂ©es. Dans les deux Ă©tudes, les analyses plasmatiques ont dĂ©montrĂ© une augmentation significative des cĂ©tones plasmatiques (jusquâĂ 0,47 ± 0 ,1 5 mM), qui semblait plus soutenue lors de la deuxiĂšme Ă©tude. Aucune autre modification nâa Ă©tĂ© observĂ©e dans les analyses plasmatiques. Une diminution de lâoxydation du traceur 13C-trioctanoate dans les heures suivant la prise puis une hausse Ă 24 h suivant la supplĂ©mentation montre un changement dans lâutilisation des MCT, donc une plus grande conversion en cĂ©tones. Aucun changement nâa Ă©tĂ© observĂ© avec le traceur 13C-(30Hb. Aucune variation de la composition corporelle nâa Ă©tĂ© observĂ©e. Ces Ă©tudes montrent la capacitĂ© des MCT Ă augmenter et Ă maintenir une concentration de cĂ©tones durant 24 h Ă des niveaux lĂ©gers chez un adulte en santĂ©. // Abstract : Aging leads to the development of many diseases among which is cognitive decline associated with dementia and Alzheimer's disease (AD). In populations who are at risk of developing cognitive decline, it has been noted that a marked brain glucose hypometabolism precedes the onset of other clinical symptoms such as [beta]-amyloid accumulation. This hypometabolism could therefore be responsible for the development of AD. Ketone bodies are energetic molecules that are produced by the liver following the (3-oxidation of fatty acids. They already have been showed to be able to sustain brain metabolism as the principal energy source. Medium chain triglycerides (MCT) are easily absorbed and metabolised fatty acids. They can raise plasma ketones rapidly but transiently. Our objective was to determine whether it was possible to raise and maintain a moderate plasma ketone concentration over 24 h in healthy adults. Ten participants were first given a 2 week supplementation of MCT (3 times a day). Plasma ketone, glucose, cholesterol, triglyceride and free fatty acids were measured. Another 8 participants were given a 4 week supplementation of MCT (4 times a day). In addition to the measures taken in the first project, MCT oxidation; with [indice supĂ©rieur 13] C-trioctanoate, ketone oxidation; with [indice supĂ©rieur 13] C-beta-hydroxybutyrate and body composition were measured. In both projects, plasma ketone concentration were raised (to a maximum of 0.48 ± 0.15 mM) and appeared to be more stable in the second project. All other plasma measures were unchanged. Significantly lower [indice supĂ©rieur 13] C-trioctanoate oxidation was detected during the 2 to 5 hours following the tracer absorption after the supplementation and a marked augmentation was detected 24 h following the supplementation. This indicates a shift in MCT utilization by the body from immediate energy source to ketone precursor. No changes were noted in [beta]OHb oxidation or in body composition. These studies show the ability of MCT to raise and maintain a moderate level of ketones in plasma when taken daily in healthy adults
Study of a ketogenic stimulation in healthy adults : effect of ketosis on brain energy metabolism
Le cerveau humain est un organe trĂšs mĂ©taboliquement actif. Cet Ă©norme besoin Ă©nergĂ©tique lâexpose Ă un risque accru de dĂ©tĂ©rioration causĂ©e par un dĂ©rĂšglement de ce mĂ©tabolisme. Dans la phase prĂ©coce de la maladie dâAlzheimer, un hypomĂ©tabolisme cĂ©rĂ©bral du glucose est observĂ©. Cette carence Ă©nergĂ©tique serait Ă lâorigine des dĂ©tĂ©riorations observĂ©e lors du dĂ©veloppement de cette maladie. Le cerveau a accĂšs Ă une autre source endogĂšne dâĂ©nergie : les cĂ©tones. Les cĂ©tones sont particuliĂšrement importantes pour le cerveau puisquâil ne possĂšde pas la capacitĂ© dâutiliser les acides gras comme source Ă©nergĂ©tique Ă lâinstar des autres organes. Les cĂ©tones sont issues de la ÎČ-oxydation hĂ©patique des acides gras. Ils sont produits en situation de jeĂ»ne lorsque les niveaux circulants de glucose et dâinsuline sont bas. Les cĂ©tones se sont dĂ©jĂ montrĂ© efficaces dans le traitement de divers troubles neurologiques comme lâĂ©pilepsie. Par contre, outre les diĂštes cĂ©togĂšnes et le jeĂ»ne prolongĂ©, il nâexiste pas de traitement efficace pour maintenir une cĂ©tonĂ©mie modĂ©rĂ©e chez lâadulte. Le mĂ©tabolisme Ă©nergĂ©tique cĂ©rĂ©bral en situation de cĂ©tose modĂ©rĂ©e reste encore mal compris dans cette population. Les travaux de cette thĂšse se sont donc concentrĂ©s Ă Ă©tudier la possibilitĂ© dâune combinaison dâapproche nutritionnelle et pharmacologique afin de stimuler la cĂ©togenĂšse chez lâadulte. Ils ont aussi explorĂ© les changements de mĂ©tabolisme cĂ©rĂ©bral chez lâadulte durant une cĂ©tose modĂ©rĂ©e. Lâobjectif de la premiĂšre Ă©tude Ă©tait dâĂ©tudier le potentiel du bezafibrate Ă stimuler la cĂ©togenĂšse induite par une supplĂ©mentation en triglycĂ©rides de moyennes chaĂźnes (MCT). Cette premiĂšre Ă©tude a dĂ©montrĂ© que le bezafibrate avait peu dâeffet sur la stimulation de la cĂ©togenĂšse induite par les MCT et que le facteur limitant dans cette stimulation Ă©tait donc la disponibilitĂ© des substrats et non la capacitĂ© cĂ©togĂšne des cellules hĂ©patiques. Lâobjectif de la seconde Ă©tude Ă©tait dâĂ©tudier les changements de capture des cĂ©tones et du glucose au cerveau durant un Ă©tat de cĂ©tose modĂ©rĂ©e chez lâadulte. Les rĂ©sultats de cette deuxiĂšme Ă©tude ont montrĂ© que la capture des cĂ©tones au cerveau est directement proportionnelle Ă leur concentration plasmatique. Cette Ă©tude a aussi dĂ©montrĂ© que la capture cĂ©rĂ©brale des cĂ©tones Ă©tait directement reliĂ©e Ă leur concentration plasmatique alors que la capture cĂ©rĂ©brale du glucose est modulĂ©e par les besoins Ă©nergĂ©tiques du cerveau. Une stimulation cĂ©togĂ©nique chez des personnes atteintes de dĂ©clin cognitif pourrait donc aider Ă rĂ©tablir la balance Ă©nergĂ©tique et ralentir lâapparition des symptĂŽmes chez ces personnes mais cet effet devra ĂȘtre Ă©tudiĂ© dans une Ă©tude ultĂ©rieure.Abstract : The human brain is the most metabolically active organ of the body. This high need for energy exposes it to an increase risk in case of hypometabolism. Such a glucose hypometabolism is seen during the early stages of Alzheimerâs disease. This factor is believed to be one of the cause of the disease. Ketones are the main alternate substrate for the human brain. Ketones are particularly important since, unlike other organs, the brain can not use fatty acids as alternative fuel. Ketones are mainly produce through ÎČ-oxidation of fatty acid by the liver. This happens mainly during fasting when circulating levels of glucose and insulin are low. Studies have shown that ketones can have a therapeutic effect in a variety of neurological diseases, mainly epilepsy and Alzheimerâs disease. Nevertheless, apart from ketogenic diet and prolonged fasting, there is currently no effective ways to induce and maintain moderate ketosis in adults. Brain energy metabolism under moderate ketosis remains also misunderstood in this population. This thesis aimed look at the effect of a combination of a pharmacological treatment and a nutritional supplementation to induce moderate sustain ketosis in adults. It also studied the effect of a moderate ketosis on brain energy metabolism in adults. The aim of the first study was to study the effect of a pharmacological treatment, bezafibrate, on the potentiation of the ketogenic effect induced by a medium-chain triglycerides (MCT) supplementation. The results of this study that bezafibrate had little effect on the ketosis induced by a MCT supplementation and, therefore, that the limiting factor in human ketosis was not the liver cells capacity to produce ketones but the availability of substrates for ketogenesis. The aim of the second study was to study the impact of a nutritional moderate ketosis on brain glucose and ketone uptake. The results of this study showed a direct correlation between brain ketone uptake and plasma ketone concentrations. This study also showed that brain ketone uptake is regulated by blood ketone concentration whereas brain glucose uptake is regulated by the brain energy needs. Further studies should then look if such a moderate ketosis induced in cognitively impaired patients could re-equilibrate the energy balance in the brain and then slow the apparition of clinical symptoms in this population
Caffeine intake increases plasma ketones: an acute metabolic study in humans
Brain glucose uptake declines during aging and is significantly impaired in AlzheimerĂą s disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis/ lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of two doses of caffeine in healthy adults (2.5; 5.0 mg/kg) during a 4-hour metabolic study period. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined. NCT 02694601The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging
Brain energy metabolism in Alzheimerâs disease (AD) is characterized mainly by
temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a
consequence of the disease, i.e.
deteriorating neuronal function leading to lower demand for glucose. This review will
address deteriorating glucose metabolism as a problem specific to glucose and one that
precedes AD. Hence, ketones and medium chain fatty acids (MCFA) could be an alternative
source of energy for the aging brain that could compensate for low brain glucose uptake.
MCFA in the form of dietary medium chain triglycerides (MCT) have a long history in
clinical nutrition and are widely regarded as safe by government regulatory agencies. The
importance of ketones in meeting the high energy and anabolic requirements of the infant
brain suggest they may be able to contribute in the same way in the aging brain. Clinical
studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of
insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive
effects on cognition
Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging
Brain energy metabolism in Alzheimerâs disease (AD) is characterized mainly by
temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a
consequence of the disease, i.e.
deteriorating neuronal function leading to lower demand for glucose. This review will
address deteriorating glucose metabolism as a problem specific to glucose and one that
precedes AD. Hence, ketones and medium chain fatty acids (MCFA) could be an alternative
source of energy for the aging brain that could compensate for low brain glucose uptake.
MCFA in the form of dietary medium chain triglycerides (MCT) have a long history in
clinical nutrition and are widely regarded as safe by government regulatory agencies. The
importance of ketones in meeting the high energy and anabolic requirements of the infant
brain suggest they may be able to contribute in the same way in the aging brain. Clinical
studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of
insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive
effects on cognition
Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans: Protein, Carbohydrate, and Fat Metabolism
BACKGROUND: 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 ÎČ-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)]. OBJECTIVES: 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. METHODS: 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 (ÎČ-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. RESULTS: 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 (F) by 2- to 3-fold and decreased the number of side effects by âŒ50%. CONCLUSIONS: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs â€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