Table 2.
Animal studies of chronic and acute administration of medium-chain triglycerides (MCTs) and their metabolites caprylic (C8) and capric (C10) medium-chain fatty acids and β-hydroxybutyrate.
| Object |
Model/
Condition |
Administered substance |
Administered
amount/ concentration |
Administration protocol |
Measured ketone body levels |
Measured MCFA levels |
Cerebral and Cognitive effects |
Metabolic effects |
Molecular effects /Mechanism of Action |
References |
|---|---|---|---|---|---|---|---|---|---|---|
| Beagle dog | Aged dogs (8–11 years) | AC-1203 MCT (95% C8 + 5% C10). | 2 g/kg Added to standard feed | 2 months | Not measured | Not measured | Not measured | Not measured | Increased in parietal cortex: Total phospholipid DHA (Docosahexaenoic acid) DPA (Docosapentaenoic acid) Total n-3 polyunsaturated fatty acid | (50) |
| Dog | Aged Beagle dogs | MCT (97% C8 + 3% C10) | MCT supplement, 5.5% w/w mixed into the food made by Nestle· Purina PetCare | 8 months | βHB in Blood: 0.11 mM | Not measured | Improved: Visuospatial function Learning Reversal learning Attention More difficult tasks showed more significant effects. | No change: Standard dog blood panel parameters | NA | (51) |
| Dog | Aged dogs with canine cognitive dysfunction syndrome (analogous to dementia in people) | MCT (FA content unspecified) | Standard diet containing 6.5% or 9% MCT | 3 months | βHB in Blood: No difference from control (measured fasting level) | Not measured | Decreased: Signs of cognitive dysfunction syndrome |
Increased in Blood: DHA (Docosahexaenoic acid) EPA (Eicosapentaenoic acid) total omega-3 polyunsaturated fatty acids omega-3/omega-6 ratio No change in Blood: Cholesterol Glucose Total triglycerides |
NA | (52) |
| Dog | Dogs diagnosed with idiopathic epilepsy | MCT (60–65% C8, 30–50% C10) | 9% of cal | 3 months supplementation 7 days washout 3 months supplementation | βHB in Blood: 0.070 mM (preprandial) 0.059 mM (postprandial) | Not measured | Decreased: Seizure frequency Seizure day frequency |
Decreased: Blood alkaline phosphatase activity No change: Body weight Blood glucose Pancreas lipase activity |
NA | (53) |
| Dog | Dogs diagnosed with idiopathic epilepsy | MCT (60–65% C8, 30–50% C10) | 9% of cal | 3 months supplementation 7 days washout 3 months supplementation | Not reported | Not measured | Improved: Spatial-working memory Problem-solving Owner-reported trainability | Not measured | Positive correlation: Problem-solving test results with the postprandial blood βHB | (54) |
| Rat | 2 m.o. Sprague Dawley rats Chronic hypoxia-induced stress | MCT (C8)-rich ketogenic diet (KD-MCT) 20g KetoCaNa in 100 ml MCT (C8) (KS) | KD-MCT: 27% w/w MCT(C8) added to standard feed (F/C/P: 77.0/0.5/22.5) KS: 10% (w/v) added to standard feed |
Chronic: 3 weeks transition into diets + 3 weeks ad libitum Acute: Single intragastric 10 g/kg KS |
βHB in Blood:
Acute: ~ 2.6 mM (peak at 1h) Chronic: ~ 1.3 mM (KD-MCT) ~ 0.5 mM (KS) βHB in Hippocampus: With no stress: ~ 0.9 mM (KD-MCT) ~ 0.9 mM (KS) ~ 0.9 mM (ctrl) Under stress: ~ 0.6 mM (KD-MCT) ~ 0.5 mM (KS) ~ 0.45 mM (ctrl) |
Not measured |
KD-MCT:
Increased (all regardless of the stress): Novel object exploration Spatial learning Spatial memory (MWM Probe trial) No change: Passive avoidance KS: Increased: Spatial learning (on day 4 impaired by stress) No change: Novel object exploration Passive avoidance Spatial memory (MWM Probe trial) |
KD-MCT:
Increased: Peripheral fat pad βHB Decreased: Body weight Glucose Insulin No change: Epydimal fat pad ACTH, CORT (basal and restrain stress-induced) KS: Increased: Peripheral fat pad Epydimal fat pad No change: Body weight Glucose βHB, Insulin ACTH, CORT (basal and restrain stress-induced) |
KD-MCT: Increased: BDH1 (vs ctrl & KS, stress-induced increase) Hippocampal ACAT1 Decreased: Hippocampal GLUT1 (vs ctrl & KS, no stress induced reduction) No change: Hippocampal βHB (but partially attenuated stress-induced reduction) Hippocampal BDNF Hippocampal GLUT3 (basal) KS: Increased: Hippocampal ACAT1 β-hydroxybutyrate dehydrogenase-1 (BDH1) Decreased: Hippocampal GLUT1 (no stress induced reduction) No change: Hippocampal βHB (stress induced reduction) Hippocampal BDNF Hippocampal GLUT3 (basal) |
(55) |
| Mouse | 78 w.o. C57BL/6 males | MCT (FA content unspecified) ketogenic diet | MCT diet: ketogenic diet with caloric proportion of 84% fat and 2% carbohydrate | High-fat-high-cholesterol (not ketogenic, 40% fat) diet: 16 days, after that for 8 weeks: high-fat-high-cholesterol diet or high-fat-high-cholesterol diet + metformin or MCT-rich diet |
βHB in Blood: ~5.5 (units unspecified; MCT group) ~2.6 (units unspecified; control group) |
Not measured | Improved: Spatial learning and memory |
No change in Blood: Glucose TG Total cholesterol Insulin AST activity (Aspartate aminotransferase) ALT activity (Alanine aminotransferase) |
Both MCT-enriched diet and adding Metformin to the high-fat-high-cholesterol diet: Reversed the high-fat diet-induced increase (to control levels) in protein levels of: cortical and hippocampal NF-κB, cortical TNF-α, cortical and hippocampal glial fibrillary acidic protein (GFAP), cortical and hippocampal glial phosphate tau phosphate tau amyloid protein precursor (APP). MCT feeding reversed the high-fat diet-induced decrease in cortical BDNF protein levels. |
(58) |
| Rat | 2–3 m.o. Wistar males Divided into Low and High Anxiety subgroups | MCT (40% C8 + 60% C10) | 5% MCT | Added to standard chow 8–15 days ad libitum | Blood: ~ 0.144–0.288 mM βHB | Not measured |
Decreased: Anxiety (Dark-Light Box); No change: Depressive-like behavior (FST). |
Increased: βHB in blood No change: Body weight Food intake |
Mitochondrial respiration: Decreased in mPFC No change in Nucleus accumbens Increased in mPFC: GLUT1 (only in High Anxiety group) GLT1 (EAAT2) (only in High Anxiety group) Na/K ATPase (only in High Anxiety group) Hexokinase mt/cyt (only in High Anxiety group) Decreased in mPFC: phospho-GSK-3α/GSK-3α (only in High Anxiety group) Hexokinase (only in Low Anxiety group) No change in mPFC: GLUT1 (only in Low Anxiety group) GLT1 (EAAT2) (only in Low Anxiety group) Na/K ATPase (only in Low Anxiety group) Hexokinase (only in High Anxiety group) phospho-GSK-3α/GSK-3α (only in Low Anxiety group) Hexokinase (only in Low Anxiety group) |
(59) |
| Mouse | 7–8 w.o. CD1 males Seizure model | MCT (C8) MCT (C10) | 35% of cal | Added to standard chow 10 days ad libitum |
Blood: 0.5–1 mM βHB Brain: 175 nmol/g βHB |
Blood: 0.033 mM C8 (MCT(C8)) 0.076 mM C10 (MCT(C10)) Brain: 2.88 nmol/g C8 (MCT(C8)) 1.17 nmol/g C10 (MCT(C10)) |
Increased: Seizure threshold (6-Hz) [MCT(C10)] Tolerance to fluorothyl [MCT(C10)] |
Increased: Plasma reducing capacity (anti-oxidant effect) [MCT(C10)] No change: Body weight Blood βHB Brain βHB Blood glucose |
Increased: Hippocampal mRNA levels of heme oxygenase 1 and FoxO [MCT(C10)]. No change: mRNA levels of FoxO3, FoxO6, Sirt1 mRNA levels of Ucp2, Ucp3, Ucp4 and Ucp5 Catalase and superoxide dismutase activities in the hypothalamus Proton leak in the mitochondria isolated from the hippocampus |
(74) |
| Rat | Adult Wistar males | 3HB-BDE (R-3-hydroxybutyrate-R-1,3-butanediol monoester) | 30% of cal | Added to standard chow 14 days ad libitum | Blood: 2.8 mM βHB | Not measured | Not measured |
Increased: Blood ketone bodies Decreased: Food intake Blood glucose Blood insulin Blood leptin No change in blood: total fatty acids stearic acid pH |
Increased in the whole brain: malonyl-CoA UCP4 and UCP5 protein [NAD+]/[NADPH] ratio Decreased in the whole brain: 3-phosphoglycerate l-lactate l-glutamate GABA No change in the whole brain: TCA cycle intermediates ATP hydrolysis |
(85) |
| Mouse | 12 m.o. C57BL/10Tar males MPTP model of Parkinson's Disease | C8 | 0.15 g/kg |
Intragastric gavage: single (1.5 h before MPTP) repeated (3 days, 1.5 h before MPTP and 2 consecutive days) |
Not measured | Not measured | Not measured | NA | Increased in striatum: Dopamine (acute and repeated C8 vs. MPTP) DOPAC (3,4-Dihydroxyphenylacetic acid) (acute and repeated C8 vs. MPTP) HVA (Homovanillic acid) (acute and repeated C8 vs MPTP) PGC-1α mRNA (Peroxisome proliferator-activated receptor-γ coactivator) (acute C8 vs. ctrl, 1.5 h post-gavage) PEPCKc mRNA (Phosphoenolpyruvate carboxykinase, Cytosolic) (acute C8 vs. ctrl, 1.5 h post-gavage) PEPCKm mRNA (Phosphoenolpyruvate carboxykinase, Mitochondrial) (acute C8 vs. ctrl, 1.5 h post-gavage) | (88) |
| Mouse | 6 w.o. C57Bl/6J males | MCT (C8) | 10% of cal | Single intragastric gavage | Not measured | Not measured | Not measured | Decreased: Food intake |
Increased in PVH (paraventricular nucleus of hypothalamus): α-MSH (alpha melanocyte-stimulating hormone) c-fos (marker of neuronal activity) |
(96) |
| Mouse | 6 w.o. C57Bl/6J males | C8 | NA | Labeled C8 was administered: - ICV: 2 μL of 1 mCi/mL - via carotid artery: 5 min (40 μL/min) - oral gavage: 100 μM | Not measured | Not measured | Not measured |
Increased in hypothalamus (30 min after ICV administration, 15 min after administration
via
the carotid artery, 60 min after oral gavage): FA oxidation FA oxidation to storage ratio |
NA | (96) |
| Rat | Wistar Han male. | High-fat diet | High-fat diet (42% fat) | Ad libitum 20 weeks | Not measured | Blood: ~ 0.003 mM C8 CSF: ~ 0.0024 mM C8 | Not measured | No change: Total FA levels. Plasma FA levels are 2.5-fold higher than in CSF. MCFA/Total FA proportion: 1% in plasma, 4% in CSF. Among the MCFAs, 78% was C8 in both plasma and CSF. | NA | (96) |
| Rat | 7 m.o. Wistar males | MCT (60% C8 + 40% C10) | 2 g/kg/day | Intragastric daily gavage + fasting 6 h/day 4 weeks | Not measured | Not measured | Increased: Spontaneous alternations in Y-maze Time in target quadrant in MWM probe trial | Not measured | Increased in mPFC: GluN2a mRNA (NMDA receptor subunit 2A) GluN2b mRNA (NMDA receptor subunit 2B) GluA1 mRNA (AMPA receptor subunit 1) GluA2 mRNA (AMPA receptor subunit 2) | (100) |
| Rat | 7 m.o. Wistar males | MCT (60% C8 + 40% C10) | 2 g/kg/day | Intragastric daily gavage + fasting 6 h/day 4 weeks | Not measured | Not measured | Increased: Spontaneous alternations in Y-maze Time in target quadrant in MWM probe trial | Not measured | NA | (101) |
| Mouse | Adult naïve Albino Swiss males 25–30 g Seizure tests | C8 | 5 mmol/kg 10 mmol/kg 20 mmol/kg 30 mmol/kg | Single dosage C8 was suspended in a 0.5% aqueous solution of methyl cellulose and administered by gastric gavage (10 ml/kg) 30 min before the test. | Blood (20 mmol/kg C8): 0.9 mM βHB | Dose-dependent increase. Blood: 0.18 to 0.51 mM C8 (5-30 mmol/kg C8) Brain: 0.11 to 0.25 mM C8 (5-30 mmol/kg C8) |
Increased (dose-dependently): seizure threshold (PTZ: myoclonic twitch and clonus) seizure threshold (6-Hz) No change: seizure threshold (PTZ: tonus) seizure threshold (MEST) C8 increased anticonvulsant potency of valproic acid (VPA) in the 6-Hz and MES seizure tests. |
Decreased in blood: Glucose (20 mmol/kg C8) No change in blood: pH (20 mmol/kg C8) |
NA | (102) |
| Mouse | Adult naïve Albino Swiss males 25–30 g Seizure tests | C10 | 10 mmol/kg 30 mmol/kg 50 mmol/kg | Single dosage C10 was suspended in a 0.5% aqueous solution of methyl cellulose and administered by gastric gavage (10 ml/kg) 30 min before the test. | Blood (30 mmol/kg C10): 1.66 mM βHB |
Blood: 0.41 mM C10 (30 mmol/kg) Brain: 0.24 mM C10 (30 mmol/kg) |
Increased: Seizure threshold (6-Hz) (dose-dependently, 10 and 30 mmol/kg) Seizure threshold (MEST) (dose-independently, 50 mmol/kg) No change: Seizure threshold (PTZ) |
Increased in blood: βHB (30 mmol/kg) Decreased in blood: pH (30 mmol/kg) Glucose (30 mmol/kg) |
NA | (103) |
| Rat | 10 m.o. Wistar Albino Glaxo/Rijswijk males | MCT (60% C8 + 40% C10) + Ketone Salt (Na/K-βHB) (1:1; KSMCT) | 2.5 g/kg/day | Intragastric gavage 7 days | βHB in Blood: 1.8 mM (day 1) 1.9 mM (day 7) | Not measured | Decreased: Spike-wave discharges (SWD) (between days 3 and 7 of gavage) | Increased: Blood βHB | Inhibition of Adenosine receptor A1: abolished the anti-seizure effect of KSMCT. The SWD number and βHB levels returned to the baseline levels on the first day without ketone supplementation. | (107) |
| Rat | 8 m.o. Wistar Albino Glaxo/Rijswijk males | MCT (60% C8 + 40% C10) + Ketone Salt (Na/K-βHB) (1:1; KSMCT) | 2.5 g/kg/day | Intragastric gavage 7 days | βHB in Blood: 1.23 mM (day 1) 1.23 mM (day 7) | Not measured | Decreased: Anxiety (Elevated plus maze) |
Increased: Blood βHB Decreased: Blood glucose No change: Body weight |
Inhibition of Adenosine receptor A1: did not change blood βHB levels modified (abolished) the anti-anxiety effect of KSMCT | (108) |
| Rat | 6 m.o. WAG/Rij males Isoflurane-induced anesthesia (immobility) Inhibition of Adenosine A1 receptor | MCT (60% C8 + 40% C10) + Ketone Salt (Na/K-βHB) (1:1; KSMCT) MCT (60% C8 + 40% C10) + Ketone Ester (1,3-butanediol - acetoacetate diester) (1:1; KEMCT) | 2.5 g/kg/day | Intragastric gavage 7 days After 7 days, isoflurane (3%) was administered for 5 min | Blood (day 7): 1.33 mM βHB (KSMCT) 2.14 mM βHB (KEMCT) | Not measured | Increased: Latency to isoflurane-induced immobility | No change: Body weight Blood glucose | Inhibition of Adenosine receptor A1: abolished MCT-evoked delay in the onset of isoflurane-induced anesthesia | (109) |
| Rat | 10 m.o. Wistar Albino Glaxo/Rijswijk males | KEKS food: 10% w/w KE/R,S-1,3-butanediol-acetoacetate diester + 10% w/w KS/Na+ and Ca2+-ketone salt mixed with standard chow 1% saccharine | 20% KEKS food | 10 days ad libitum | βHB in Blood: 1.25 mM (day 1) 1.35 mM (day 10) | Not measured |
Decreased: Spike-wave discharges (SWD) (between days 7 and 10 of treatment) Total time of SWD LPS-evoked increase in SWD number No change: Discharge frequency within SWD Average SWD duration Total time of sleep-waking stages |
Increased: Blood βHB No change: Blood glucose Body weight |
The SWD number and βHB levels returned to the baseline levels on the second day without ketone supplementation. | (110) |
| Rat | 10 m.o. Wistar Albino Glaxo/Rijswijk males | KEKS food: 10% w/w KE/R,S-1,3-butanediol-acetoacetate diester + 10% w/w KS/Na+ and Ca2+-ketone salt mixed with standard chow 1% saccharine | 20% KEKS food | 9 days ad libitum | βHB in Blood: 1.25 mM (day 1) 1.40 mM (day 9) | Not measured | Decreased: Spike-wave discharges (SWD) (between days 3 and 9 of treatment) LPS-evoked increase in SWD number |
Increased: Blood βHB No change: Blood glucose Body weight |
Inhibition of Adenosine receptor A1: abolished the alleviating effect of KEKS food on LPS-generated increases in the SWD number. Inhibition of Adenosine receptor A2A: did not significantly modify the alleviating effect of KEKS food on LPS-generated increases in the SWD number. |
(111) |
| Mouse | Adult naïve Albino Swiss males 25–30 g Inhibition of Adenosine A1 and A2a receptors | C8 | 20 mmol/kg 30 mmol/kg | Single dosage C8 was suspended in a 0.5% aqueous solution of methyl cellulose and administered by gastric gavage (10 ml/kg) 30 min before the test. | Blood (30 mmol/kg C8): ~ 2.5 mM βHB (non-fasted mice) ~ 3.8 mM βHB (fasted mice) | Not measured |
Increased: 6 Hz seizure threshold (30 mmol/kg) No change: 6 Hz seizure threshold (20 mmol/kg) |
Decreased in blood: Glucose (non-fasted mice) No change in blood: Glucose (fasted mice) pH (non-fasted and fasted mice) |
Inhibition of Adenosine receptors A1 or A2a abolished the anticonvulsant effect of C8 (30 mmol/kg). Combined administration of an adenosine transporter inhibitor dipyridamole and 20 mmol/kg caprylic acid raised the threshold for the 6 Hz-induced seizures. KATP channel blockage by glibenclamide did not abolish the anticonvulsant effect of C8 (30 mmol/kg). Glucose (2 g/kg) abolished the anticonvulsant effect of C8 (30 mmol/kg) in non-fasted but not in fasted mice. | (112) |
| Rat | 21 m.o. Wistar males Aged animals | MCT (C8) MCT (C10) | 5% MCT | Added to standard chow 8 weeks ad libitum | Blood: ~ 0.3 mM βHB (MCT(C10)) ~ 0.25 mM βHB (MCT(C8)) | Blood: 0.0064 mM C8 (MCT(C8)) 0.0182 mM C10 (MCT(C10)) 0.002 mM C8 (MCT(C10)) 0.000 mM C10 (MCT(C8)) |
Increased: Social recognition Novel object recognition (MCT(C10)) Decreased: Locomotor activity (MCT(C8)) |
Decreased: Body weight Increased in blood: C8 (MCT(C8) vs ctrl and MCT(C10)) C10 (MCT(C10) vs ctrl and MCT(C8)) No change in blood: C8 (MCT(C10) vs ctrl) C10 (MCT(C8) vs ctrl) |
Increased: pIRS-1/IRS-1 (Insulin Receptor Substrate 1) in forebrain (MCT(C8)) pAkt/Akt (Serine/Threonine Kinase) in forebrain (MCT(C10)) SYP protein (Synaptophysin) in forebrain (MCT(C8)) UBE3A protein (Ubiquitin-protein ligase E3A) in forebrain (MCT(C8) and MCT(C10)) mRNA of plasticity-related early genes in mPFC (grin1, gba2) Decreased: pS6K/S6K (Ribosomal protein S6 kinase) in brain (MCT(C8) and MCT(C10)) mRNA of plasticity-related early genes in mPFC (arc, erg1, erg2, junb, plk3, nr4a1, fosb) No change: GDNF protein (Glial cell line-derived neurotrophic factor) in forebrain IGF-1 protein (Insulin-like growth factor 1) in forebrain VEGF protein (Vascular endothelial growth factor) in forebrain PSD-95 protein (Postsynaptic density protein 95) in forebrain mRNA of plasticity-related early genes in mPFC (jnk1, srf) |
(114) |
| Rat | Adult Wistar females and males Intracarotid infusion of C8 and C10 | C8 C10 | 0.043 mM C8 0.022 mM C10 | Intracarotid infusion Decapitation after 15 s | Not measured | NA | Not measured | Not measured | Brain uptake: 94% (C8) 88% (C10) | (125) |
| Rat | Adult Sprague Dawley males Intracarotid infusion of C8 | C8 | 220 mM | Intracarotid infusion (2.67 ml/h): Unlabeled C8 (30 min) and Labeled C8 ([2,4,6,8-13C4]octanoate) (105 min) | Blood: 0.1312 mM βHB + AcAc (0 min) 0.3574 mM βHB + AcAc (105 min) | Blood at 105 min: undetectable (unlabeled C8) 0.25 mM (labeled C8) | NA |
Increased in blood: ketone bodies (105 min vs 0 min) No change in blood: Glucose (105 min vs 0 min) |
Oxidation of 13C-octanoate in the brain accounted for ~20% of total brain oxidative energy production. | (127) |
| Rat | Adult Wistar males | MCT (70% C8 + 30% C10) | 8.55% C8 + 3.16% C10 | Added to standard chow 4 weeks (given daily at the beginning of the dark phase) | Not measured | Not measured | Not measured |
Increased: Apparent fat digestibility (vs ctrl & LCT) Liver weight (vs ctrl) Liver TG content (vs ctrl & LCT) Muscle TG content (vs ctrl) Decreased: Feed intake (vs ctrl & LCT) Blood TG (vs LCT) Blood free fatty acids (vs ctrl) Blood glucose (vs LCT) No change: Body weight (vs ctrl & LCT) Blood TG (vs ctrl) Blood glucose (vs ctrl) Blood insulin (vs ctrl & LCT) Liver weight (vs LCT) Muscle TG content (vs LCT) Wet weight of epididymal adipose tissue (vs ctrl & LCT) Wet weight of retroperitoneal adipose tissue (vs ctrl & LCT) |
No change: Skeletal muscle peroxisomal oxidation Liver peroxisomal oxidation Skeletal muscle CPT-1 and CPT-2 activity Liver CPT-1 and CPT-2 activity | (137) |
| Rat | Sprague Dawley males. Non-alcoholic steatohepatitis (NASH). | MCT (FA content unspecified) | 70% MCT | Added to chow 21 days ad libitum | Not measured | Not measured | Not measured |
Increased: Blood adiponectin Decreased: Liver TG accumulation Blood leptin No change: Blood TG Blood insulin |
Decreased: Hepatic TNF mRNA and protein No change: Hepatic CYP2E1 protein (Cytochrome P450 2E1) |
(138) |
| Rat | Sprague Dawley males | MCT (FA content unspecified) | 25% Wt MCT (45% cal MCT) | Semiliquid MCT diet given via a gastrostomy tube twice a day for 6 weeks (first 3 weeks–gradually increasing dosage 17–30 ml/day) | Not measured | Not measured | Not measured |
Increased: Resting oxygen consumption Norepinephrine-stimulated oxygen consumption Decreased: Body weight Size of adipocytes Dissectible fat No change: Adipocyte density Liver fat Blood glucose |
NA | (139) |
| Rat | Sprague Dawley males Streptozotocin-induced diabetes | MCT (FA content unspecified) | 5%, 15%, 25% MCT | Added to standard chow Gradual increase: 5% for 14 days 15% for 12 days 25% for 12 days | βHB in Blood: Non-diabetics: ~ 0.11 mM (5% MCT) ~ 0.22 mM (15% MCT) ~ 0.48 mM (25% MCT) Diabetics: ~ 1 mM (5% MCT) ~ 8 mM (15% MCT) ~ 12 mM (25% MCT) | Not measured | Not measured |
Increased in Blood: Ketones (in non-diabetics vs ctrl non-diabetics) Decreased in Blood: TG (in non-diabetics vs ctrl non-diabetics) glycerol (in diabetics vs ctrl diabetics) |
NA | (140) |
| Rat | 3 w.o. Lewis males weighing ~50 g | MCT (FA content unspecified) | 23.4% C8, 16.9% C10 | Added to standard chow 6 weeks ad libitum | Not measured | Not detected | Not measured |
Decreased in Blood: TG Chylomicron VLDL No change in Blood: Cholesterol |
NA | (141) |
| Rat | Sprague Dawley males | MCT (65% C8 + 35% C10) BMS (Na/K-βHB mineral salt) + MCT | 5–10 g/kg/day | Daily intragastric gavage 28 days | Maximum βHB in Blood: ~3.8 mM (5 g/kg MCT, 1 h after gavage) ~5 mM (10 g/kg MCT, 1-8 h after gavage) ~2 mM (5 g/kg BMS+MCT, 4 h after gavage) ~3 mM (10 g/kg BMS+MCT, ~4-8 h after gavage) | Not measured | Not measured |
Increased: Blood βHB (acutely, MCT-containing supplements vs ctrl) Relative liver weight Decreased: Body weight (3-4 weeks, all supplements vs ctrl) Blood glucose (acutely, MCT-containing supplements vs ctrl) Blood HDL (after 28 days) Relative spleen weight No change: Blood total cholesterol Blood TG Blood LDL Relative weight of brain Relative weight of lungs Relative weight of kidneys Relative weight of heart |
NA | (142) |
AcAc, Acetoacetate; ACAT1, Acetyl-CoA acetyltransferase 1; ACTH, Adrenocorticotropic Hormone; BDH1, β-hydroxybutyrate dehydrogenase-1; BDNF, Brain derived neurotrophic factor; βHB, β-hydroxybutyrate; C10, capric acid; C8, caprylic acid; CORT, Corticosterone; CPT, carnitine palmitoyltransferase; EAAT2, Excitatory amino acid transporter 2; FA, Fatty acid; GLT1, Glutamate transporter 1; GLUT, Glucose transporter; GSK-3α, Glycogen synthase kinase-3 alpha; HDL, High density lipoprotein; KS, Ketone salt; LPS, Lipopolysaccharide; MCFA, medium-chain fatty acids; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NA, not applicable; SWD, Spike-wave discharges; TG, Triglycerides; TNF, Tumor necrosis factor; UCP, Uncoupling protein; VLDL, Very low density lipoprotein.