https://doi.org/10.1371/journal.pone.0288440
https://pubmed.ncbi.nlm.nih.gov/37432920
Public interest in low-carbohydrate (LC) diets for type 1 diabetes (T1D) management has increased. This study compared the effects of a healthcare professional delivered LC diet compared to habitual diets higher in carbohydrates on clinical outcomes in adults with T1D. Twenty adults (18-70 yrs) with T1D (≥6 months duration) with suboptimal glycaemic control (HbA1c>7.0% or >53 mmol/mol) participated in a 16-week single arm within-participant, controlled intervention study involving a 4-week control period following their habitual diets (>150 g/day of carbohydrates) and a 12-week intervention period following a LC diet (25-75 g/day of carbohydrates) delivered remotely by a registered dietitian. Glycated haemoglobin (HbA1c -primary outcome), time in range (blood glucose: 3.5-10.0 mmol/L), frequency of hypoglycaemia (<3.5 mmol/L), total daily insulin, and quality of life were assessed before and after the control and intervention periods. Sixteen participants completed the study. During the intervention period, there were reductions in total dietary carbohydrate intake (214 to 63 g/day, P<0.001), HbA1c (7.7 to 7.1% or 61 to 54 mmol/mol, P = 0.003) and total daily insulin use (65 to 49 U/day, P<0.001), increased time spent in range (59 to 74%, P<0.001), and improved quality of life (P = 0.015), with no significant changes observed during the control period. Frequency of hypoglycaemia episodes did not differ across timepoints, and no episodes of ketoacidosis or other adverse events were reported during the intervention period. These preliminary findings suggest that a professionally supported LC diet may lead to improvements in markers of blood glucose control and quality of life with reduced exogenous insulin requirements and no evidence of increased hypoglycaemia or ketoacidosis risk in adults with T1D. Given the potential benefits of this intervention, larger, longer-term randomised controlled trials are warranted to confirm these findings. Trial Registration: https://www.anzctr.org.au/ACTRN12621000764831.aspx.
Turton JL
Brinkworth GD
Parker HM
Lim D
Lee K
Rush A
Johnson R
Rooney KB
------------------------------------------ Info ------------------------------------------
Open Access: True
https://doi.org/10.1016/j.mvr.2023.104585
https://pubmed.ncbi.nlm.nih.gov/37437687
Glucose constitutes the main source of energy for the central nervous system (CNS), its entry occurring at the blood-brain barrier (BBB) via the presence of glucose transporter 1 (GLUT1). However, under food intake restrictions, the CNS can utilize ketone bodies (KB) as an alternative source of energy. Notably, the relationship between the BBB and KBs and its effect on their glucose metabolism remains poorly understood. In this study, we investigated the effect of glucose deprivation on the brain endothelium in vitro, and supplementation with KBs using induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cell-like cells (iBMECs). Glucose-free environment significantly decreased cell metabolic activity and negatively impacted the barrier function. In addition, glucose deprivation did not increase GLUT1 expression but also resulted in a decrease in glucose uptake and glycolysis. Supplementation of glucose-deprived iBMECs monolayers with KB showed no improvement and even worsened upon treatment with acetoacetate. However, under a hypoglycemic condition in the presence of KBs, we noted a slight improvement of the barrier function, with no changes in glucose uptake. Notably, hypoglycemia and/or KB pre-treatment elicited a saturable beta-hydroxybutyrate diffusion across iBMECs monolayers, such diffusion occurred partially via an MCT1-dependent mechanism. Taken together, our study highlights the importance of glucose metabolism and the reliance of the brain endothelium on glucose and glycolysis for its function, such dependence is unlikely to be covered by KBs supplementation. In addition, KB diffusion at the BBB appeared induced by KB pre-treatment and appears to involve an MCT1-dependent mechanism.
Iqra P
Yash M
Kinzie S
Dhavalkumar P
Jacob AA
------------------------------------------ Info ------------------------------------------
Open Access: False
------------------------------------------ Open Access ------------------------------------------
ABSTRACT
Cancer cells harness a mechanism known as ketolysis to generate energy, a process that involves the enzymes SCOT and ACAT1, instrumental in the creation of a crucial molecule named acetyl-CoA. This molecule plays a vital role in cellular energy production. Interestingly, cancer cells are capable of alternative methods for generating acetyl-CoA, such as the incorporation of external acetate by an enzyme called acetyl-COA synthetase. Although restraining the function of SCOT and ACAT1 may decelerate cancerous growth, inhibiting acetyl-CoA synthetase which feeds the lipogenic pathways could potentially impede the tumor cells’ ability to produce necessary new membranes for their survival
Introduction
The human body requires two primary nutrient sources for proper functioning: glucose and ketone bodies. During periods of food scarcity, the body secretes hormones such as glucagon, epinephrine, and cortisol, initiating the breakdown of stored nutrients within various organs. Glucagon aids in releasing energy from stored reserves in the liver and muscles by converting it into accessible glucose, whereas insulin and insulin-like growth factor (IGF) assist in glucose uptake for energy utilization. Once glucose is available in the body, it undergoes glycolysis, a process that transforms glucose into pyruvate while releasing energy. Subsequently, the process of mitochondrial oxidative metabolism, which is a more efficient energy extractor from glucose, commences. This event occurs in the citric acid Krebs cycle, where an enzyme named pyruvate dehydrogenase changes pyruvate into acetyl-CoA. The body can also utilize ketone bodies when more energy is required or when glucose supply is inadequate. Hormonal action initiates the breakdown of stored fats that are subsequently converted into acetyl-CoA and, later, into ketone bodies within the liver. These ketone bodies serve as an energy source for tissues that are responsive to anabolic hormones, chiefly insulin and IGF. We would like to point out that we have made the effort to make our PUBMED article more accessible, for non-biochemists, unlike the article in Reference J. Clin. Med. 2023, 12(4), 1589 https:// doi.org/10.3390/jcm12041589 from which this simplified version is taken. During periods of fasting, the body taps into stored nutrients, ensuring an energy supply to active tissues that require either glucose or ketone bodies.
...
Conclusions
Tumor cells face a challenge in utilizing an energy source known as glycolysis due to certain alterations in a protein in the cell. This compels them to depend heavily on glucose and lactic acid production. For growth and division, tumor cells require fatty acids, but this process hinders them from utilizing acetyl-CoA, an essential component for energy production. Consequently, tumor cells lean on ketones for energy generation. However, this also aids tumor growth, creating a dilemma in discerning whether ketones are beneficial or detrimental in cancer research. Researchers speculate that a specific enzyme known as SCOT serves as a crucial target for cancer treatment. They aim to tackle each phase of the ketolytic process to gradually starve the tumor without damaging other tissues. By targeting the downstream pathway of SCOT-ACAT1 with compounds like Lipoic acid, Hydroxycitrate, Allicine, Docosahexanoic acid, and Bergamotin, researchers can diminish the lipogenic supply. Upstream of SCOTACAT1, researchers intend to inhibit the ketone transporters MCT2-4 using compounds like epigallocatechin, syrosingopine, while curtailing ketogenesis with octreotide. For SCOT, researchers are exploring the optimal hydroxamic acid derivative to employ as a treatment, without causing harm to other tissues. Additionally, researchers aim to limit the ketone supply to the SCOT ketolytic pathway to conserve the signaling action over the HCA2 receptors, vital for tumor growth. They recommend testing these compounds on animal models to look out for possible toxic interactions and advise against a high-fat keto diet. Researchers posit that using a combination of low toxicity compounds to target each phase of the ketolytic supply to ketone dependent tumor cells will gradually impede their metabolic advantage and immortality. This will render them noticeable to the immune system and guide them towards an apoptotic demise. Author Contributions Following discussions with G.T. and E.B. on fasting, cancer and on the “Keto paradox”, they convinced M.I. that it was necessary to explain the ketone dependency of tumors, and to write this review. All authors have read and agreed to the published version of the manuscript.
About Community
r/ketoscience Rules
Wikis & Guide
WIKIS
Video on how to use this Subreddit - please send to people that should be here!
Foods and Carb Counts - pdf file
Our goal is to compile a huge amount of information that is organized and concise in explaining the science behind a ketogenic diet. This means studies, biochemistry, self-experiments, questions, and anything else science related is encouraged here. We want to create a complete and informative library of the topics that explain and are relevant to keto, while avoiding dogma and seeking truth through science. We love studies of ketogenic diets(0-50 grams max carbs/day) and their results in the factors of obesity, Type 2 Diabetes, Type 1 Diabetes, chronic disease/disease of civilization/metabolic syndrome, PCOS, Infertility, Insulin Resistance, Alzheimer's, psychiatry, gout, heart disease, cancer, longevity, fat loss, depression, autoimmune diseases. We generally condemn grains, sugars, and seed oils, and to a lesser extent starches, and a much less extent fiber - but we are generally skeptical about what is 'known' to be true. Adopt this mindset and realize that the truth is always going to be more complex than we think.
All Wiki links
- Fiber - optional, not beneficial, possibly harmful
- Protein - GlucoNeoGenesis
- Omega 6 Polyunsaturated Toxic Processed Seed Oils
- Saturated Fat
- Sugar
- Cholesterol - Debunked Boogeyman
- LDL cholesterol levels and Dave Feldman's LMHR profile
- Cancer - Metabolic Disease Reversed w/ Keto
- Diabetes - Reversible intolerance to carbohydrates(WIP)
- Type 1 Diabetes - Autoimmune helped with VLCKD(WIP)
- Learn how to critically read science articles
- Human evolution - Role of Meat Eating
- Ketone Bodies (WIP)
- Ketoscience Short Guide to doing keto stressfree
- Recommended Medical Tests - Lipids, Blood, Urine
- What is KetoAcidosis?
- Lactic Acidosis
What is ketosis?
Ketosis is a metabolic state in which an animal is producing ketone bodies in the liver and filling them with energy from FFA. Ketone bodies can be used by tissues as a more efficient form of energy than glucose. Humans are able to enter this state if they consume between 0 and 50 grams of carbohydrates(sugar, starch, fructose) a day for several days, but most people target 20 grams to stay safe, while others target as close to zero.
Keto Science is about posting and discussing:
- the state of ketosis
- diet, macronutrients, fats, carbs, protein
- biochemistry
- evolution
- epidemiology
- metabolic syndrome (MetS)
- Type 2 Diabetes, Type 1 Diabetes
- Alzheimer's (Type 3 Diabetes)
- Obesity (overfat)
- Heart Disease (CVD, Afib)
- RCTs
- Nutritionists and Doctors
- sugar
- grains
- role of fiber in the diet
- cancer(fermentation illness)
- animal science
- autism, adhd, pregnancy, migraine
- mythbusting
- in depth scientific questions
- hormones - endocrinology
Myths
Myth 1: The Healthiest Diet Is a Low-Fat, High-Carb Diet With Lots of Grains
BOTTOM LINE:Numerous studies have been done on the low-fat, high-carb diet. It has virtually no effect on body weight or disease risk over the long term.
Myth 2: Salt Should Be Restricted in Order to Lower Blood Pressure and Reduce Heart Attacks and Strokes
BOTTOM LINE:Despite modestly lowering blood pressure, reducing salt/sodium does not reduce the risk of heart attacks, strokes or death.
Myth 3: It Is Best to Eat Many, Small Meals Throughout the Day to "Stoke the Metabolic Flame"
BOTTOM LINE:It is not true that eating many, smaller meals leads to an increase in the amount of calories burned throughout the day. Frequent meals may even increase the accumulation of unhealthy belly and liver fat.
Myth 4: Egg Yolks Should Be Avoided Because They Are High in Cholesterol, Which Drives Heart Disease
BOTTOM LINE:Despite eggs being high in cholesterol, they do not raise blood cholesterol or increase heart disease risk for the majority of people.
Myth 5: Whole Wheat Is a Health Food and an Essential Part of a "Balanced" Diet"
BOTTOM LINE:The wheat most people are eating today is unhealthy. It is less nutritious and may increase cholesterol levels and inflammatory markers.
Myth 6: Saturated Fat Raises LDL Cholesterol in the Blood, Increasing Risk of Heart Attacks
BOTTOM LINE:Several recent studies have shown that saturated fat consumption does not increase the risk of death from heart disease or stroke.
Myth 7: Coffee Is Unhealthy and Should Be Avoided
BOTTOM LINE:Despite being perceived as unhealthy, coffee is actually loaded with antioxidants. Numerous studies show that coffee drinkers live longer and have a lower risk of many serious diseases.
Myth 8: Eating Fat Makes You Fat... So If You Want to Lose Weight, You Need to Eat Less Fat
BOTTOM LINE:The fattening effects of dietary fat depend entirely on the context. A diet that is high in fat but low in carbs leads to more weight loss than a low-fat diet.
Myth 9: A High-Protein Diet Increases Strain on the Kidneys and Raises Your Risk of Kidney Disease
BOTTOM LINE:Eating a lot of protein has no adverse effects on kidney function in otherwise healthy people and improves numerous risk factors.
Myth 10: Full-Fat Dairy Products Are High in Saturated Fat and Calories... Raising the Risk of Heart Disease and Obesity
BOTTOM LINE:Despite being high in saturated fat and calories, studies show that full-fat dairy is linked to a reduced risk of obesity. In countries where cows are grass-fed, full-fat dairy is linked to reduced heart disease.
Myth 11: All Calories Are Created Equal, It Doesn't Matter Which Types of Foods They Are Coming From
BOTTOM LINE:Not all calories are created equal, because different foods and macronutrients go through different metabolic pathways. They have varying effects on hunger, hormones and health.
Myth 12: Low-Fat Foods Are Healthy Because They Are Lower in Calories and Saturated Fat
BOTTOM LINE:Processed low-fat foods tend to be very high in sugar, which is very unhealthy compared to the fat that is naturally present in foods.
Myth 13: Red Meat Consumption Raises the Risk of All Sorts of Diseases... Including Heart Disease, Type 2 Diabetes and Cancer
BOTTOM LINE:It is a myth that eating unprocessed red meat raises the risk of heart disease and diabetes. The cancer link is also exaggerated, the largest studies find only a weak effect in men and no effect in women.
Myth 14: The Only People Who Should Go Gluten-Free Are Patients With Celiac Disease, About 1% of the Population
BOTTOM LINE:Studies have shown that many people can benefit from a gluten-free diet, not just patients with celiac disease.
Myth 15: Losing Weight Is All About Willpower and Eating Less, Exercising More
BOTTOM LINE:It is a myth that weight gain is caused by some sort of moral failure. Genetics, hormones and all sorts of external factors have a huge effect.
Myth 16: Saturated Fats and Trans Fats Are Similar... They're the "Bad" Fats That We Need to Avoid
BOTTOM LINE:Many mainstream health organizations lump trans fats and saturated fats together, which makes no sense. Trans fats are harmful, saturated fats are not.
Myth 17: Protein Leaches Calcium From the Bones and Raises the Risk of Osteoporosis
BOTTOM LINE:Numerous studies have shown that eating more (not less) protein is linked to a reduced risk of osteoporosis and fractures.
Myth 18: Low-Carb Diets Are Dangerous and Increase Your Risk of Heart Disease
BOTTOM LINE:Despite having been demonized in the past, many new studies have shown that low-carb diets are much healthier than the low-fat diet still recommended by the mainstream.
Myth 19: Sugar Is Mainly Harmful Because It Supplies "Empty" Calories"
Although sugar is fine in small amounts (especially for those who are physically active and metabolically healthy), it can be a complete disaster when consumed in excess.
Myth 20: Refined Seed and Vegetable Oils Like Soybean and Corn Oils Lower Cholesterol and Are Super Healthy
The truth is that several studies have shown that these oils increase the risk of death, from both heart disease and cancer.
Even though these oils have been shown to cause heart disease and kill people, the mainstream health organizations are still telling us to eat them.
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