Our open-labelled, non-randomised cross-over trial is published.
We studied the effects of short-term ketosis-suppression in healthy women on long-standing ketosis.
Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). (66 days in total with a 6 month qualifying lead in)
Results:
Adherence to each phase was confirmed with daily capillary BHB tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 mmol/L).
Ketosis suppression significantly increased:
👉Insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) mmol/L (p = 0.0002)
👉IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045)
👉Glucose, 1.17-fold from 4.36 (± 0.53) to 5.12 mmol/L (± 0.59, P2; p = 0.0088)
👉Respiratory quotient, 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427)
👉PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428).
👉VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift.
👉Sustained ketosis showed no adverse health effects and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women.
Conclusions:
Evolutionary evidence suggests that ancestral populations were predominantly adapted to patterns of intermittent and time-restricted feeding, as opposed to continuous nutritional intake, rich in farinaceous and sucrose carbohydrates that stimulate bolus insulin secretion. The escalating prevalence of T2DM, obesity, CVD, AD, and cancer observed in populations adhering to multiple substantial carbohydrate-dominated meals in developed nations is a testament to this.
Individuals maintaining long-standing habitual NK, when subjected to 21 days of consuming carbohydrate to suppress ketosis, followed with restricting carbohydrate, reverted to an evolutionary ketotic state within one day, indicate metabolic flexibility and health.
The negative changes in biomarkers associated with chronic diseases and ageing, which occur from a one-time excursion in a 1-year period of 21 consecutive days of suppressing ketosis, are rapidly restored after restoring the baseline dietary lifestyle of carbohydrate restriction which does not overstimulate insulin demand and secretion.
Our data show that long-standing NK appears to provide major health benefits in the maintenance of euglycaemia, with low insulin and IGF-1, the triad of markers most strongly associated with chronic diseases and biological ageing. NK serves as a reliable surrogate marker for these parameters to understand an individual’s metabolic phenotype, and therefore risk.
This study was conducted to establish a detailed metabolic phenotype biomarker profile in a long-standing healthy ketosis cohort, providing a NK control group for other studies to establish metabolic phenotypes in people with cancer, CVD, AD, T2DM, and ageing, and to assess treatment efficacy using KMT in gaining better health.
Sustained NK may mitigate hyperinsulinemia without impairing metabolic flexibility and carbohydrate tolerance in metabolically healthy individuals. Maintaining low insulin requirement and IGF-1 levels through endogenous NK may offer lower chronic disease risk, resulting in benefits to both lifespan and healthspan.
https://t.co/aNCqk0phXJ
Awesome co-authors:
@Yvoni_Kyr@_kurtisedwards@_LucyPetagine@tnseyfried @TommyDeeMD @ascarbs@jacomesandra@AdrianSotoMota@kenbrookler@valennutrition@NovaesVanusa@Brads_science
Yes very much so. Patients are often sadly told Ketosis is dangerous and there’s no evidence it is safe. The #KetoSage trial provides a control group of healthy longstanding Ketosis (metabolic phenotype 1) people and what their biomarkers look like, which physicians and patients will be able to compare their own metabolic health and track their response to KMT for chronic diseases such as cancer, CVD, AD, PD, T2DM, NAFLD and ageing.
KetoSAge Trial: Adherence/compliance
For the duration of the 66 days trial, participants were required to monitor their capillary glucose and ketone BHB concentrations (mmol/L) at four time points throughout the day to ascertain compliance.
These time points were between:
7:30–9:30 a.m.,
11:30–13:30 p.m.,
15:30–17:30 p.m.,
21:30–23:30 p.m
252 capillary BHB concentrations: 84 tests across each of the 21-day phases.
Too many low carb/keto studies only measure morning capillary or urine BHB. Both of these are less reliable in ascertaining if participants are truly maintaining nutritional ketosis (NK), as morning readings are typically after an over night fast, where many individuals (even those with hyperinsulinaemia) may wake up with 0.3-0.5 mmol/L of BHB. This can lead to more noise in the results of studies, due to incorrectly classing participants as being in ketosis, when it is not truly known if they spend most of their 24 hour days in NK.
Multiple tests, spread over the day, before consuming foods/drinks and at least 4 hours after a meal, enable confirmation that a persons lifestyle is truly supporting euketonaemia.
https://t.co/aNCqk0phXJ
@Yvoni_Kyr@_kurtisedwards@_LucyPetagine@tnseyfried @TommyDeeMD @AdrianSotoMota@ascarbs@jacomesandra@kenbrookler@valennutrition@NovaesVanusa@Brads_science
Our open-labelled, non-randomised cross-over trial is published.
We studied the effects of short-term ketosis-suppression in healthy women on long-standing ketosis.
Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). (66 days in total with a 6 month qualifying lead in)
Results:
Adherence to each phase was confirmed with daily capillary BHB tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 mmol/L).
Ketosis suppression significantly increased:
👉Insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) mmol/L (p = 0.0002)
👉IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045)
👉Glucose, 1.17-fold from 4.36 (± 0.53) to 5.12 mmol/L (± 0.59, P2; p = 0.0088)
👉Respiratory quotient, 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427)
👉PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428).
👉VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift.
👉Sustained ketosis showed no adverse health effects and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women.
Conclusions:
Evolutionary evidence suggests that ancestral populations were predominantly adapted to patterns of intermittent and time-restricted feeding, as opposed to continuous nutritional intake, rich in farinaceous and sucrose carbohydrates that stimulate bolus insulin secretion. The escalating prevalence of T2DM, obesity, CVD, AD, and cancer observed in populations adhering to multiple substantial carbohydrate-dominated meals in developed nations is a testament to this.
Individuals maintaining long-standing habitual NK, when subjected to 21 days of consuming carbohydrate to suppress ketosis, followed with restricting carbohydrate, reverted to an evolutionary ketotic state within one day, indicate metabolic flexibility and health.
The negative changes in biomarkers associated with chronic diseases and ageing, which occur from a one-time excursion in a 1-year period of 21 consecutive days of suppressing ketosis, are rapidly restored after restoring the baseline dietary lifestyle of carbohydrate restriction which does not overstimulate insulin demand and secretion.
Our data show that long-standing NK appears to provide major health benefits in the maintenance of euglycaemia, with low insulin and IGF-1, the triad of markers most strongly associated with chronic diseases and biological ageing. NK serves as a reliable surrogate marker for these parameters to understand an individual’s metabolic phenotype, and therefore risk.
This study was conducted to establish a detailed metabolic phenotype biomarker profile in a long-standing healthy ketosis cohort, providing a NK control group for other studies to establish metabolic phenotypes in people with cancer, CVD, AD, T2DM, and ageing, and to assess treatment efficacy using KMT in gaining better health.
Sustained NK may mitigate hyperinsulinemia without impairing metabolic flexibility and carbohydrate tolerance in metabolically healthy individuals. Maintaining low insulin requirement and IGF-1 levels through endogenous NK may offer lower chronic disease risk, resulting in benefits to both lifespan and healthspan.
https://t.co/aNCqk0phXJ
Awesome co-authors:
@Yvoni_Kyr@_kurtisedwards@_LucyPetagine@tnseyfried @TommyDeeMD @ascarbs@jacomesandra@AdrianSotoMota@kenbrookler@valennutrition@NovaesVanusa@Brads_science
We propose a criteria for establishing metabolic phenotypes and T2DM staging
The largest stage of T2DM is hyperinsulinaemia, increased levels of insulin that manages glycaemia
When overt hyperglycaemia presents, an individual is already at stage 3 T2DM https://t.co/zdpqI2icpd
@urbankitchen@MyNutriWeb @RachelC_WCRF It was a pleasure to attend to the webinar 🤗! My main take away points were the modifiable lifestyle risk factors, the inequalities on #breastcancer awareness, and the common myths about breast cancer.
How to deal with sugar cravings
1.Salt
2.Dark chocolate (70% cacao)
3.Nuts
4.Mineral water
5.Chromium
6.Remove junk food from the diet
7.Just eat real food
Excellent first session of the #jounalclub with @DrCEChilds and @MyNutriWeb about reading and reviewing a scientific paper!
Looking forward to the next one!