Search

Adhering to the ketogenic diet can reduce or stop seizures, even when other treatments fail, via mechanism(s) distinct from other available therapies. These results have led to interest in the diet for treating conditions such as Alzheimer’s disease, depression and schizophrenia. Evidence points to the neuromodulator adenosine as a key mechanism underlying therapeutic benefits of a ketogenic diet. Adenosine represents a unique and direct link among cell energy, neuronal activity, and gene expression, and adenosine receptors form functional heteromers with dopamine receptors. The importance of the dopaminergic system is established in addiction, as are the challenges of modulating the dopamine system directly. A mediator that could antagonize dopamine’s effects would be useful, and adenosine is such a mediator due to its function and location. Studies report that the ketogenic diet improves cognition, sociability, and perseverative behaviors, and might improve depression. Many of the tr

It is frequently claimed that a VLCARB sets the stage for a significant loss of muscle mass as the body recruits amino acids from muscle protein to maintain blood glucose via gluconeogenesis. It is true that animals share the metabolic deficiency of the total (or almost total) inability to convert fatty acids to glucose [18]. Thus, the primary source for a substrate for gluconeogenesis is amino acid, with some help from glycerol from fat tissue triglycerides. However, when the rate of mobilization of fatty acids from fat tissue is accelerated, as, for example, during a VLCARB, the liver produces ketone bodies. The liver cannot utilize ketone bodies and thus, they flow from the liver to extra-hepatic tissues (e.g., brain, muscle) for use as a fuel. Simply stated, ketone body metabolism by the brain displaces glucose utilization and thus spares muscle mass. In other words, the brain derives energy from storage fat during a VLCARB.

https://doi.org/10.1186/1743-7075-3-9 Full paper

Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing prope

Very-low-calorie diets (VLCDs) are used to treat obesity, often in a non-clinical setting, and the typical formulation of a minimum of 50 g carbohydrates daily can induce a mild dietary ketosis. This clinically benign state is sometimes confused with the non-metabolically adapted state of ketoacidosis, and this misunderstanding may lead to the rejection of VLCDs as a suitable obesity treatment. This paper summarises and discusses the difference between physiological ketosis and pathological ketoacidosis, the benefits of ketosis-inducing weight-loss regimen such as VLCDs and why ketoacidosis should never be the diagnosis in a non-type 1 diabetic on a carbohydrate-restricted diet.

Paper https://doi.org/10.1111/j.1467-3010.2011.01916.x

Full Paper on scihub

TLDR: People don't need carbohydrates, ketosis isn't dangerous.

It is pertinent to briefly discuss the enduring misconception that glucose itself represents an “absolutely essential”, “universal fuel” in human physiology, which requires nuanced definition and gradation, but has been perpetuated verbatim and may have been incorporated into the physiology education of currently practicing healthcare professionals [1-7].

We must first address the distinction between endogenous and exogenous sources of glucose. Clinical trials and epidemiological studies of very low to zero carbohydrate diets support the statement of the US National Academies of Sciences that “the lower limit of dietary carbohydrate compatible with life apparently is zero, provided that adequate amounts of protein and fat are consumed” [8-11]. Even so, despite seemingly safe and increasingly popular, the long-term effects of a truly “zero” carbohydrate diet (without micronutrient supplementation) are difficult to as

TLDR - If you are a ketogenic lean mass hyper responder with high LDL, insist on imaging to determine your atherosclerotic risk, as this study indicates the LDL and ApoB by itself doesn't indicate a growth in plaque.

Background - Changes in low-density lipoprotein cholesterol (LDL-C) among people following a ketogenic diet (KD) are heterogeneous. Prior work has identified an inverse association between body mass index and change in LDL-C. However, the cardiovascular disease risk implications of these lipid changes remain unknown.

Objectives - The aim of the study was to examine the association between plaque progression and its predicting factors.

Methods - One hundred individuals exhibiting KD-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglycerides ≤80 mg/dL were followed for 1 year using coronary artery calcium and coronary computed tomography angiography. Plaque progression predictors were assessed with linear regression and Bayes factors. Die

TLDR: Keto is good for you, and not bad for you. Despite what some agenda based people say the evidence is in favor of keto as good for you, yes even you.

As the prevalence of chronic diseases persists at epidemic proportions, health practitioners face ongoing challenges in providing effective lifestyle treatments for their patients. Even for those patients on GLP-1 agonists, nutrition counseling remains a crucial strategy for managing these conditions over the long term. This paper aims to address the concerns of patients and practitioners who are interested in a low-carbohydrate or ketogenic diet, but who have concerns about its efficacy, safety, and long-term viability. The authors of this paper are practitioners who have used this approach and researchers engaged in its study. The paper reflects our opinion and is not meant to review low-carbohydrate diets systematically. In addressing common concerns, we hope to show that this approach has been well researched and can no longer

Recently we reported similar performances in both progressive tests to exhaustion (VO2max) and 5km running time trials (5KTT) after consuming low-carbohydrate, high-fat (LCHF) or high-carbohydrate, low-fat (HCLF) diets. Accordingly, we tested the null hypothesis that the metabolic responses during both tests would be similar across diets. In a randomized, counterbalanced, cross-over design, seven male athletes (VO2max: 61.9 ± 6.1 mL/kg/min; age: 35.6 ± 8.4 years; height: 178.7 ± 4.1 cm; mass: 68.6 ± 1.6 kg; body fat: 5.0 ± 1.3%) completed six weeks of LCHF (6/69/25% energy carbohydrate/fat/protein) and HCLF (57/28/15% energy carbohydrate/fat/protein) diets, separated by a two-week washout. Substrate utilization and energy expenditure were measured during VO2max tests and 5KTTs. The LCHF diet markedly increased fat oxidation and reduced carbohydrate oxidation, with no associated impairment in either the VO2max tests or the 5KTTs. Following the LCHF diet, athletes generated 50% or more

Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.

Many successful ultra-endurance athletes have switched from a high-carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of metabolic adaptations.

Twenty elite ultra-marathoners and ironman distance triathletes performed a maximal graded exercise test and a 180 min submaximal run at 64% VO2max on a treadmill to determine metabolic responses. One group habitually consumed a traditional high-carbohydrate (HC: n = 10, %carbohydrate:protein:fat = 59:14:25) diet, and the other a low-carbohydrate (LC; n = 10, 10:19:70) diet for an average of 20 months (range 9 to 36 months).

Peak fat oxidation was 2.3-fold higher in the LC group (1.54 ± 0.18 vs 0.67 ± 0.14 g/min; P = 0.000) and

TLDR: The take away from this paper is after a 6 week adaption phase a keto athlete had a higher time to exhaustion then a high carb athlete even with carb loading.

Very-low-carbohydrate diets (LCHF; <50 g/day) have been debated for their potential to lower pre-exercise muscle and liver glycogen stores and metabolic efficiency, risking premature fatigue. It is also hypothesized that carbohydrate ingestion during prolonged exercise delays fatigue by increasing carbohydrate oxidation, thereby sparing muscle glycogen. Leveraging a randomized crossover design, we evaluated performance during strenuous time-to-exhaustion (70% V̇o2max) tests in trained triathletes following 6-wk high-carbohydrate (HCLF, 380 g/day) or very-low-carbohydrate (LCHF, 40 g/day) diets to determine 1) if adoption of the LCHF diet impairs time-to-exhaustion performance, 2) whether carbohydrate ingestion (10 g/h) 6–12× lower than current CHO fueling recommendations during low glycogen availability (>15-h pre-exerci

TLDR: Type 2 Diabetes reversal using only ketosis

Aims: This study assessed the five-year effects of a continuous care intervention (CCI) delivered via telemedicine, counseling people with type 2 diabetes (T2D) on a very low carbohydrate diet with nutritional ketosis.

Results: Twenty percent (n = 24) of the five-year completers achieved remission, with sustained remission observed over three years in 15.8 % (n = 19) and four years in 12.5 % (n = 15). Reversal to HbA1c < 6.5 % without medication or only metformin was seen in 32.5 % (n = 39). Sustained improvements were noted in body mass (-7.6 %), HbA1c (-0.3 %), triglycerides (-18.4 %), HDL-C (+17.4 %), and inflammatory markers, with no significant changes in LDL-C and total cholesterol.

Conclusions: Over five years, the very low carbohydrate intervention showed excellent retention and significant health benefits, including diabetes remission, weight loss, and improved cardiometabolic markers.

Full Paper: https://pubmed.ncbi.

Rats addicted to cocaine - when giving the choice of cocaine or sugar, overwhelmingly chose sugar.

Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms and thus to lead to addiction.

Full Paper https://doi.org/10.1371/journal.pone.0000698

TLDR: Ketone levels above 2mmol/l show significant improvements in patients with Euthymic bipolar disorder.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). Fr

TLDR - Ketogenic diets are very safe, People taking SGLT2 inhibitors will need to be more diligent about monitoring their ketone levels.

Abstract Aims

Ketogenic diets are used by individuals with obesity and type 2 diabetes for improved glycaemic control, reduced appetite and weight loss. However, the risks associated with higher ketone levels, including diabetic ketoacidosis (DKA), in individuals with and without diabetes are not well-documented. Materials and Methods

We analysed real world data from a single-centre telemedicine clinic specializing in a very low carbohydrate ketogenic diet (VLCKD) as a lifestyle intervention. Illnesses associated with ketosis (IAK) were defined as beta-hydroxybutyrate (BHB) levels ≥3 mmol/L when patients sought in-person care. We estimated the IAK and DKA incidence rate in individuals with and without type 2 diabetes. Results

In 72 751 patient-years of follow-up, 86 people had IAK (incidence rate 1.18 per 1000 person-years). In 22 347 patie

Self insured company works with metabolic researchers to use TCF (total carbohydrate restriction / keto) and IF (intermittent fasting) to reduce their health care cost of chronic metabolic issues.

41 completed the one-year intervention. Mean weight loss for the 50 subjects in the intention-to-treat analysis was 19.5 ± 11.4 kg, corresponding to 15.5% total body weight loss with concomitant deprescription of 96 medications, while starting only 8 medications. In patients who discontinued GLP-1 receptor agonists, weight loss continued or was maintained. Annualized cost savings from the TOWARD approach were approximately -$1700 per patient, as compared to an annualized cost burden of roughly +$13000 per patient for a GLP-1 receptor agonist.

Full Paper https://doi.org/10.3389/fnut.2025.1548609