Biologically Occurring Ketone Bodies.

Ketosis, Ketone Bodies, And Ketoacidosis – An Excerpt From Modern Nutritional Diseases, 2nd Edition

The following text is excerpted from Lipids (Chapter 8) of Modern Nutritional Diseases, 2nd Edition. Ketone Bodies and Ketosis: Ketones are organic chemicals in which an interior carbon in a molecule forms a double bond with an oxygen molecule. Acetone, a familiar chemical, is the smallest ketone possible. It is composed of three carbons, with the double bond to oxygen on the middle carbon. Biological ketone bodies include acetone, larger ketones, and biochemicals that can become ketones. The most important of the ketone bodies are hydroxybutyrate and acetoacetate, both of which are formed from condensation of two acetyl CoA molecules. Acetone is formed from a nonenzymatic decarboxylation of acetoacetate. Ketone bodies are fuel molecules that can be used for energy by all organs of the body except the liver. The production of ketone bodies is a normal, natural, and important biochemical pathway in animal biochemistry (17, p. 577). Small quantities of ketone bodies are always present in the blood, with the quantity increasing as hours without food increase. During fasting or carbohydrate deprivation, larger amounts of ketone bodies are produced to provide the energy that is normally provided by glucose. Excessive levels of circulating ketone bodies can result in ketosis, a condition in which the quantity of circulating ketone bodies is greater than the quantity the organs and tissues of the body need for energy. People who go on extremely low-carbohydrate diets to lose a large excess of body fat usually go into a mild ketosis that moderates as weight is lost. There is no scientific evidence that a low-carbohydrate diet is capable of producing sufficient ketone bodies to be harmful. Excess ketone bodies are excreted by the kidneys and lungs. Exhaled acetone gives the brea Continue reading >>

Metabolic Intervention With Glp-1 Or Its Biologically Active Analogues To Improve The Function Of The Ischemic And Reperfused Brain

CROSS REFERENCE TO A RELATED APPLICATION This application is a continuation-in-part of provisional application No. 60/103,498 filed Oct. 8, 1998. FIELD OF THE INVENTION This invention relates to an/effective treatment to improve the function of the ischemic and reperfused brain. BACKGROUND OF THE INVENTION Strokes, or cerebrovascular accidents, are the result of an acute obstruction of cerebral blood flow to a region of the brain. There are approximately 500,000 cases each year in the United States, of which 30% are fatal, and hence stroke is the third leading cause of death in the United States. Approximately 80% of strokes are “ischemic” and result from an acute occlusion of a cerebral artery (usually a clot or thrombus), with resultant reduction in blood flow. The remainder are “hemorrhagic”, which are due to rupture of a cerebral artery with hemorrhage into brain tissue and consequent obstruction of blood flow due to local tissue compression, creating ischemia. Stroke commonly affects individuals older than 65 years, and the most powerful risk factor is hypertension. However, there are additional strong risk factors, of which the most important is diabetes mellitus, which confers a two to three-fold increased risk and is associated with increased mortality and morbidity after stroke. Moreover, there is strong evidence that hyperglycemia per se, whether associated with diabetes or not, correlates with increased stroke-related mortality and morbidity, although the causal relationship and underlying mechanisms remain controversial. Until recently, there was no approved therapy for acute stroke, which was treated by general medical support only, followed by rehabilitation from the observed damage. In 1996, the FDA approved the use of tissue plasminogen activator Continue reading >>

Ketone Bodies To Protect Tissues From Damage By Ionizing Radiation

Described herein is the surprising discovery that ketone bodies protect cell and tissues from ionizing radiation. Based on this finding, methods of protecting animal tissue and cells from damage caused by radiation exposure are disclosed which include, contacting the tissue with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage. Ketone esters can be used to minimize, reduce and/or prevent tissue damage following intentional and accidental radiation exposure, as well as increasing the therapeutic efficacy of radiation therapies by protecting non-target tissue from incidental radiation damage. We claim: 1. A method of protecting animal tissue from damage caused by radiation exposure, comprising contacting the tissue of a subject in need thereof with a therapeutically effective amount of an agent including at least one ketone ester, thereby protecting the tissue from radiation damage, wherein the agent is: 11. A method of enhancing the therapeutic window for radiotherapy in a subject, comprising contacting tissue of the subject with a therapeutically effective amount of an agent including at least one ketone ester prior to the radiotherapy, thereby protecting the tissue from radiation damage, wherein the agent is: 13. The method of claim 1, wherein the radiation exposure comprises tissue-incorporated radionuclides from ingestion of contaminated food or water, non-medical or unintentional exposure to ionizing radiation from a nuclear weapon, non-medical or unintentional exposure to a radioactive spill, cosmic radiation, and/or space flight-associated radiation expose. RELATED APPLICATIONS This application is a 371 filing of International Application No. PCT/US2013/068545, filed Nov. 5, 201 Continue reading >>

Ketogenic Diet Does Not “beat Chemo For Almost All Cancers”

One of the difficult things about science-based medicine is determining what is and isn’t quackery. While it is quite obvious that modalities such as homeopathy, acupuncture, reflexology, craniosacral therapy, Hulda Clark’s “zapper,” the Gerson therapy and Gonzalez protocol for cancer, and reiki (not to mention every other “energy healing” therapy) are the rankest quackery, there are lots of treatments that are harder to classify. Much of the time, these treatments that seemingly fall into a “gray area” are treatments that have shown promise in animals but have never been tested rigorously in humans or are based on scientific principles that sound reasonable but, again, have never been tested rigorously in humans. (Are you sensing a pattern here yet?) Often these therapies are promoted by true believers whose enthusiasm greatly outstrips the evidence base for their preferred treatment. Lately, I’ve been seeing just such a therapy being promoted around the usual social media sources, such as Facebook, Twitter, and the like. I’ve been meaning to write about it for a bit, but, as is so often the case with my Dug the Dog nature—squirrel!—other topics caught my attention. I’m referring to a diet called the ketogenic diet, and an article that’s been making the rounds since last week entitled “Ketogenic diet beats chemo for almost all cancers, says Dr. Thomas Seyfried.” Of course, when I see a claim such as that, my first reaction is, “Show me the evidence.” My second reaction is, “Who is this guy?” Well, Dr. Seyfried is a professor of biology at Boston College, who’s pretty well published. He’s also working in a field that has gained new respectability over the last five to ten years, namely cancer metabolism, mainly thanks to a red Continue reading >>

Tutorial Series On Lipids

Tutorials and lectures on lipids Index Set of Powerpoint files covering Lipid Chemistry and Lipid Metabolomics Lipids defined Lipid Definition Categories of lipids Fatty Acyls [FA] Glycerolipids [GL] Glycerophospholipids [GP] Sphingolipids [SP] Sterol lipids [ST] Prenol lipids [PR] Saccharolipids [SL] Polyketides [PK] Biological functions References References and resources See Also Author Recommendations and tools Tutorial Series on Lipid Chemistry and Lipid Metabolomics Presented as a set of Powerpoint files A: Lipid Chemistry Lipid chemistry and classification B: Lipid Metabolomics Lipid Definition A lipid is generally considered to be any molecule that is insoluble in water and soluble in organic solvents. Biological lipids usually refer to a broad grouping of naturally occurring molecules which includes fatty acids, waxes, eicosanoids, monoglycerides, diglycerides, triglycerides, phospholipids, sphingolipids, sterols, terpenes, prenols, fat-soluble vitamins (such as vitamins A, D, E and K) and others [1,2,3], in contrast to the other major groupings of biological molecules, namely the nucleic acids, amino acids, and carbohydrates (sugars). The main biological functions of lipids include their central role in energy storage, as structural components of cell membranes, and as important signaling molecules.Lipids may be broadly defined as hydrophobic or amphipathic small molecules that originate entirely or in part by carbanion-based condensations of thioesters and/or by carbocation-based condensations of isoprene units [4]. Lipid biochemical "building blocks" Using this approach, lipids have been divided into eight categories: fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids and polyketides (derived from condensation of ketoacyl subunit Continue reading >>

Ketone Bodies

Sort Ketone Bodies -->Represent 3 molecules that are formed when excess acetyl CoA cannot enter the TCA Cycle -->Represents 3 major molecules: 1)Acetoacetate 2)β-Hydroxybutyrate 3)Acetone -->Normal people produces ketones at a low rate -->Are only formed in the **LIVER**(by liver mitochondria) Reactions that lead to the formation of ketone bodies (***See pwrpt***) 1)2 Acetyl CoA molecules condense to form ***Acetoacetyl-CoA -->Is catalyzed by THIOLASE -->Represent the oppostie of thiolysis step in the oxidation of fatty acids -->Represent the parent compound of the 3 ketone bodies (2)Acetoacetyl CoA then reacts with another mol. of acetyl CoA to form **HMG-CoA* (3-hydroxy-3-methylglutaryl CoA) & *CoA** -->Reaction is catalyzed by **HMG-CoA Synthetase** -->HMG-CoA has 2 fates (can either progress to form ketone bodies OR can enter the pathway of CHOLESTEROL synthesis) -->Represent the **RATE-LIMITING STEP** in the synthesis of ketone bodies (3)HMG-CoA is cleaved to form **Acetoacetate**(First major ketone; represent ~20% of ketones) & another mol. of acetyl CoA -->Catalyzed by **HMG-CoA Lyase** (4) Acetoacetae can lead to the formation of β-hydroxybutyrate (~78% of ketone bodies) & Acetone (~2% of ketone bodies) via 2 separte reactions Interrelationships of the ketone bodies from Acetoacetate (1)Formation of β-hydroxybutyrate -->Acetoacetate will be reduced to form β-hyroxybutyrate in the mitochondrial matrix of the liver cell -->Is a REVERSIBLE RXN. -->Requires 1 mol of NADH (***Dependent on the NADH/NAD ratio inside the mitochondria) -->Catalyzed by β-hydroxybutyrate dehydrogenase (2)Formation of Acetone -->A slower, **spontaneous** decarboxylation to acetone -->In **DIABETIC KETOACIDOSIS, acetone imparts a characteristic smell to the patient's breath Features of Continue reading >>

Can Ketones Help Rescue Brain Fuel Supply In Later Life? Implications For Cognitive Health During Aging And The Treatment Of Alzheimer’s Disease

1Research Center on Aging, Sherbrooke, QC, Canada 2Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada 3Department of Pharmacology and Physiology, Université de Sherbrooke, Sherbrooke, QC, Canada We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic i Continue reading >>

Metabolism And Ketosis

Dr. Eades, If the body tends to resort to gluconeogenesis for glucose during a short-term carbohydrate deficit, are those who inconsistently reduce carb intake only messing things up by not effecting full blown ketosis? If the body will still prefer glucose as main energy source unless forced otherwise for at least a few days, is it absolutely necessary to completely transform metabolism for minimal muscle loss? Also, if alcohol is broken down into ketones and acetaldehyde, technically couldn’t you continue to drink during your diet or would the resulting gluconeogenesis inhibition from alcohol lead to blood glucose problems on top of the ketotic metabolism? Would your liver ever just be overwhelmed by all that action? I’m still in high school so hypothetical, of course haha… Sorry, lots of questions but I’m always so curious. Thank you so much for taking the time to inform the public. You’re my hero! P.S. Random question…what’s the difference between beta and gamma hydroxybutyric acids? It’s crazy how simple orientation can be the difference between a ketone and date rape drug…biochem is so cool! P.P.S. You should definitely post the details of that inner mitochondrial membrane transport. I’m curious how much energy expenditure we’re talkin there.. Keep doin your thing! Your Fan, Trey No, I don’t think people are messing up if they don’t get into full-blown ketosis. For short term low-carb dieting, the body turns to glycogen. Gluconeogenesis kicks in fairly quickly, though, and uses dietary protein – assuming there is plenty – before turning to muscle tissue for glucose substrate. And you have the Cori cycle kicking in and all sorts of things to spare muscle, so I wouldn’t worry about it. And you can continue to drink while low-carbing. Continue reading >>

Sglt2 Inhibitors May Predispose To Ketoacidosis

SGLT2 Inhibitors May Predispose to Ketoacidosis Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Division of Diabetes, Endocrinology, and Nutrition (S.I.T.), Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201 Address all correspondence and requests for reprints to: Simeon I. Taylor, MD, PhD, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Mail Stop 1453, 9000 Rockville Pike, Bethesda, MD 20892. Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: Diabetes, Endocrinology, and Obesity Branch (S.I.T., J.E.B., K.I.R.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Search for other works by this author on: The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Simeon I. Taylor, Jenny E. Blau, Kristina I. Rother; SGLT2 Inhibitors May Predispose to Ketoacidosis, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 8, 1 August 2015, Pages 28492852, Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of di Continue reading >>

Energy Intake, Metabolic Homeostasis, And Human Health

Abstract The energy substances (mainly carbohydrates and fats) are the basis and guarantee of life activity, especially the oxidative phosphorylation for energy supply. However, excessive absorption and accumulation of these substances can lead to metabolic diseases such as obesity, hyperlipidemia, diabetes, and cancers. A large amount of studies demonstrate that G protein-coupled receptors (GPCRs) play a key role in identification and absorption of energy substances, and the signaling network of nerves, immune, and endocrine regulates their storage and utilization. The gastrointestinal mucus layer not only identifies these substances through identification in diet components but also transfers immune, metabolic, and endocrine signals of hormones, cytokines, and chemokines by promoting interactions between receptors and ligands. These signaling molecules are transferred to corresponding organs, tissues, and cells by the circulatory system, and cell activity is regulated by amplifying of cell signals that constitute the wireless communication network among cells in the body. Absorption, accumulation, and utilization of energy substances in the body obey the law of energy conservation. Energy is stored in the form of fat, and meets the demand of body via two coupled mechanisms: catabolism and oxidative phosphorylation. Under normal physiological conditions, fat consumption involves ketone body metabolism through the circulatory system and glucose consumption requires blood lactic acid cycle. Accumulation of excessive energy leads to the abnormal activation of mammalian target of rapamycin (mTOR), thus promoting the excretion of glucose or glycogen in the form of blood glucose and urine glucose. Alternatively, the body cancels the intercellular contact inhibition and promo Continue reading >>

Problems

Summary The fatty acid components of triacylglycerols furnish a large fraction of the oxidative energy in animals. Triacylglycerols ingested in the diet are emulsified in the small intestine by bile salts, hydrolyzed by intestinal lipases, absorbed by intestinal epithelial cells and reconverted into triacylglycerols, then formed into chylomicrons by combination with specific apolipoproteins. Chylomicrons deliver triacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue of vertebrate animals are mobilized by the action of hormones through a hormone-sensitive triacylglycerol lipase. The fatty a,cids released by this enzyme bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. Once inside cells, free fatty acids are activated at the outer mitochondrial membrane by esterification with coenzyme A to form fatty acyl-CoA thioesters. These are converted into fatty acylcarnitine esters, which are carried by a specific transporter across the inner mitochondrial membrane into the matrix, where fatty acyl-CoA esters are formed again. All subsequent steps in the oxidation of fatty acids take place in the form of their coenzyme A thioesters, within the mitochondrial matrix. In the first stage of fatty acid β oxidation, four reactions are required to remove each acetyl-CoA unit from the carboxyl end of saturated fatty acylCoAs: (1) dehydrogenation of the α and β carbons (C-2 and C-3) by FAD-linked acyl-CoA dehydrogenases, (2) hydration of the resulting trans-Δ2 double bond by enoyl-CoA hydratase, (3) dehydrogenation of the resulting L-β-hydroxyacyl-CoA by NADlinked β-hydroxyacyl-CoA dehydrogenase, and (4) CoA-requiring Continue reading >>

Ketone Bodies

Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy.[3] In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids).[1] They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting)[1]. When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted Continue reading >>

Msud And Carnitine

Over the past 30 years, carnitine has become a vital component of the treatment plan for many inborn errors of amino acid, organic acid and fat metabolism. Despite the increased use by metabolic specialists and the approval of L-carnitine by the FDA for the treatment of inborn errors of metabolism, the lack of randomised controlled trials comparing carnitine supplementation with different doses, frequency and duration versus placebo in any of the inborn errors has continued to raise concerns regarding its efficacy.In order to make an informed decision regarding the use of carnitine therapy, for you or your child, it is important you understand more about this molecule. Carnitine’s main role in the body is transport.It is the vehicle that carries fat into the cellular furnace, the the mitochondria, and the vehicle that removes accumulat- ing”ashes”of poorly burnt fats and amino acids from the mitochondria and carries them out of the body via the urine.These”ashes” attached to carnitine are known as carnitine esters, bound carnitine or acylcarnitines. Without carnitine,fat cannot be transported into the mitochondria to generate energy. Patients with a genetic metabolic disorder often develop carnitine deficiency due to the massive accumulation of unme- tabolized chemicals(ashes) which are only removed attached to carnitine molecule. If they are not given carnitine supplementation, these “ashes” deplete the store of body carnitine and can cause life threatening complete mitochondrial failure with the inability to produce energy from all fuels. In these disorders, supplemental carnitine can directly remove the accumulating unburnt metabolic”ashes” and restore mitochondrial function. L carnitine is a natural occurring substance similar to vitamins and miner Continue reading >>

Carnitor Oral Single Dose 1g

Indicated for the treatment of primary and secondary carnitine deficiency in adults and children over 12 years of age. For oral administration only. The Oral Solution can be drunk directly or diluted further in water or fruit juices. Adults and children over 12 years of age It is advisable to monitor therapy by measuring free and acyl carnitine levels in both plasma and urine. The management of inborn errors of metabolism The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide. An oral dosage of up to 200mg/kg/day in divided doses (2 to 4) is recommended for chronic use in some disorders, with lower doses sufficing in other conditions. If clinical and biochemical symptoms do not improve, the dose may be increased on a short-term basis. Higher doses of up to 400mg/kg/day may be necessary in acute metabolic decompensation or the i.v. route may be required. Haemodialysis - maintenance therapy If significant clinical benefit has been gained by a first course of intravenous Carnitor then maintenance therapy can be considered using 1g per day of Carnitor orally. On the day of the dialysis oral Carnitor has to be administered at the end of the session. While improving glucose utilisation, the administration of levocarnitine to diabetic patients receiving either insulin or hypoglycaemic oral treatment may result in hypoglycaemia. Plasma glucose levels in these subjects must be monitored regularly in order to adjust the hypoglycaemic treatment immediately, if required. The safety and efficacy of oral levocarnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral levocarnitine in Continue reading >>

Implications Of The Circadian Nature Of Ketones.

Ketosis. Happens during starvation and also by restricting carbohydrates (and protein, to a lesser degree)… might be important for epilepsy and bipolar disorder, too. Ketostix measure urinary acetoacetate (AcAc) and reflect the degree of ketosis in the blood probably about 2-4 hours ago. Blood ketone meters measure beta-hydroxybutyrate (bHB) right now. bHB fluctuates to a greater degree, eg, it plummets after a meal whereas AcAc takes longer to decline. AcAc/bHB is usually around 1, but increases after a meal (Mori et al., 1990): Conversely, when glucose levels decline and fatty acid oxidation increases, liver redox potential drops which reduces AcAc/bHB. Galvin et al., 1968 Ketogenic diet-induced ketosis: 90% fat diet for 9 days. Ketones ~0.3-9.4 mM. Starvation-exercise ketosis: 36 h fast, then 2.5 h walk. 0.7-6.9 mM. Exercise-induced ketosis: same as above, sans starvation. 0.2-1.7 mM Whether it is Jane Plain’s pee, or Jimmy & Freda’s blood, ketosis register strongest at night. Why? It’s not measurement error. From Cameron (2012): Urinary acidity increases in the evening, which should favor false negatives on the ketostix. Urine is more dilute in the evenings which also favors lower ketone readings… but this doesn’t happen; confirmed by blood testing. It occurs in dairy cows, too (Nielsen et al., 2003): And in rats fed a ketogenic diet: bHB is elevated after they’ve been eating all night; similar to humans who have been eating keto all day (closed squares, solid line) (De Gasquet 1977): PM ketones are likely higher because of the convergence of a few “normal” biological events. 1) Adipose-derived FFAs are not as robust of a delivery mechanism as keto-buffet in stimulating ketogenesis. 2) Exercise is a known ketogenic stimulus. Daily activity is a wea Continue reading >>