Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females

Cooper, Isabella D.; Kyriakidou, Yvoni; Edwards, Kurtis; Petagine, Lucy; Seyfried, Thomas N.; Duraj, Tomas; Soto-Mota, Adrian; Scarborough, Andrew; Jacome, Sandra L.; Brookler, Kenneth; Borgognoni, Valentina; Novaes, Vanusa; Al-Faour, Rima; Elliott, Bradley T.

doi:10.3390/ijms242115621

Cited by 4 publications

(1 citation statement)

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“…These analyses emerged from a larger recently published study. Further methodological details can be found here (8).…”

Section: Methodsmentioning

confidence: 99%

Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model

Cooper,

Sanchez-Pizarro,

Norwitz

et al. 2023

Front. Endocrinol.

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IntroductionThere is a large heterogeneity in LDL-cholesterol change among individuals adopting ketogenic diets. Interestingly, lean metabolically healthy individuals seem to be particularly susceptible, with an inverse association between body mass index and LDL-cholesterol change. The lipid energy model proposes that, in lean healthy individuals, carbohydrate restriction upregulates systemic lipid trafficking to meet energy demands. To test if anthropometric and energy metabolism markers predict LDL-cholesterol change during carbohydrate restriction.MethodsTen lean, healthy, premenopausal women who habitually consumed a ketogenic diet for ≥6 months were engaged in a three-phase crossover study consisting of continued nutritional ketosis, suppression of ketosis with carbohydrate reintroduction, and return to nutritional ketosis. Each phase lasted 21 days. The predictive performance of all available relevant variables was evaluated with the linear mixed-effects models.ResultsAll body composition metrics, free T3 and total T4, were significantly associated with LDL-cholesterol change. In an interaction model with BMI and free T3, both markers were significant independent and interacting predictors of LDL-cholesterol change. Neither saturated fat, HOMA-IR, leptin, adiponectin, TSH, nor rT3 was associated with LDL-cholesterol changes.DiscussionAmong lean, healthy women undergoing carbohydrate restriction, body composition and energy metabolism markers are major drivers of LDL-cholesterol change, not saturated fat, consistent with the lipid energy model.

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“…These analyses emerged from a larger recently published study. Further methodological details can be found here (8).…”

Section: Methodsmentioning

confidence: 99%

Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model

Cooper,

Sanchez-Pizarro,

Norwitz

et al. 2023

Front. Endocrinol.

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Exploring diet-induced ketosis with exogenous ketone supplementation as a potential intervention in post-traumatic stress disorder: a feasibility study

Edwards,

Furuholmen-Jenssen,

Søegaard

et al. 2024

Front. Nutr.

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BackgroundPost-Traumatic Stress Disorder (PTSD) is a severe and pervasive mental disorder, and patients experience numerous distressing symptoms and impairments that significantly impact their lives. In addition to being a mental disorder, PTSD is strongly associated with a wide range of metabolic abnormalities that affect the entire body. Existing treatment options of psychotherapy and medications are often ineffective. Exploring other potential treatments is necessitated. The ketogenic diet has shown potential as a metabolic therapy in certain neurological and mental disorders and is a promising intervention in the treatment of PTSD.AimThis study aimed to examine if a 4 weeks ketogenic diet intervention supplemented with exogenous ketones was feasible in adult patients with PTSD, to what extent it was possible to recruit patients, attain and maintain ketosis, the occurrence of serious adverse reactions and adverse reactions to KD-KS, and acceptance of treatment. Our exploratory aims were changes in PTSD symptoms and health-related quality of life (QoL) from baseline to 4 weeks.MethodsPatients 18 ≤ 65 years old, diagnosed with PTSD, and receiving outpatient treatment for PTSD at Southern Oslo District Psychiatric Centre (DPC), Oslo University Hospital, Oslo, Norway, were included. The intervention consisted of a ketogenic diet supplemented with β-hydroxybutyrate salt (KD-KS) to obtain ketosis (plasma concentration of β-hydroxybutyrate (BHB) ≥ 0.5 mmol/L). PTSD symptoms were measured with the PTSD Checklist for DSM-5 (PCL-5) and QoL was measured with the RAND 36-Item Health Survey 1.0.ResultsDuring a 21 weeks inclusion period, three of four eligible patients (75% [95% CI: 30 to 95%]) were included. Two patients (67% [95% CI: 21 to 94%]) completed the 4 weeks intervention and one patient (33% [95% CI: 6 to 79%]) completed 2 weeks of intervention before discontinuing. Ketosis was achieved on day 1 in one patient, and on day 2 in two patients, and was maintained in 87% of the intervention. There were no serious adverse reactions. Adverse reactions were reported in a total of 70% of intervention days, the most frequent being headache followed by fatigue. The participant-perceived degree of adverse reactions was low to moderate. The treatment was accepted by patients on all intervention days. PCL-5 decreased by 20 points (70 to 50) in patient 1 and by 10 points (50 to 40) in patient 2, from baseline to 4 weeks, which is a reliable and clinically meaningful improvement. QoL improved in six of eight RAND-36 subscales in patient 1 and three of eight in patient 2. Patient 3 did not complete assessments after week 2.ConclusionTo the best of our knowledge, this feasibility study is the first study examining a ketogenic diet intervention in patients with PTSD. Three of four predefined feasibility criteria were achieved. Ketosis was attained fast and maintained, patients were compliant and there were clinically meaningful improvements in PTSD symptoms and QoL. Despite the small sample size, the knowledge obtained in this study is important for the planning of future studies with ketogenic diet interventions in this patient group. It is a first step for potential dietary and metabolic therapies in PTSD. Further feasibility and pilot studies with larger sample sizes are needed to determine feasibility and safety before planning future randomised controlled trials investigating an effect.Clinical trial registrationhttps://ClinicalTrials.gov, identifier NCT05415982.

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Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females

Cooper,

Kyriakidou,

Petagine

et al. 2024

Biomedicines

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Metabolic dysfunctions are among the best documented hallmarks of ageing. Cardiovascular disease, Alzheimer’s disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. We studied the effect of suppressing ketosis in 10 lean (BMI 20.5 kg/m2 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9 years) maintaining nutritional ketosis (NK) for an average of 3.9 years (± 2.3) who underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Ketosis suppression significantly increased insulin, 1.83-fold (p = 0.0006); glucose, 1.17-fold (p = 0.0088); homeostasis model assessment for insulin resistance (HOMA-IR), 2.13-fold (p = 0.0008); leptin, 3.35-fold (p = 0.0010); total osteocalcin, 1.63-fold (p = 0.0138); and uncarboxylated osteocalcin, 1.98-fold (p = 0.0417) and significantly decreased beta-hydroxybutyrate, 13.50-fold (p = 0.0012) and glucagon-like peptide-1 (GLP-1), 2.40-fold (p = 0.0209). Sustained NK showed no adverse health effects and may mitigate hyperinsulinemia. All biomarkers returned to basal P1 levels after removing the intervention for SuK, indicating that metabolic flexibility was maintained with long-term euketonaemia.

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Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females

Cited by 4 publications

References 147 publications

Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model

Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model

Exploring diet-induced ketosis with exogenous ketone supplementation as a potential intervention in post-traumatic stress disorder: a feasibility study

Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females

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