Metabolic Energy Control

The metabolic energy control system of the human organism is designed to be fueled by either glucose (carbohydrates) or fatty acids (lipids).1, pp. 160  In a healthy individual, the fuel of choice is largely determined by diet composition and intake schedule.  Because food intake is a batch process for most people, the availability of food in the digestive system cycles daily through full, empty, full, and so forth.  Thus, for a diet in which the macronutrients (carbohydrates, proteins, and lipids) are consistent and in reasonable proportion, it is customary for the choice of fuel to switch back and forth seamlessly between glucose and fatty acids during the day in response to the alimentation cycles.

The messenger that tells the body which fuel to use is the blood insulin/glucagon ratio.  Immediately after eating, insulin is dominant (in response to glucose intake) and its analogous hormone glucagon is negligible.  The high insulin/glucagon ratio signals the use of glucose as fuel.  As hours go by, dietary glucose becomes spent and the need to conserve glucose by stopping its use as fuel comes into play.  The lowered insulin level makes way for glucagon to come to the fore and preserve blood glucose levels.  The drop in insulin/glucagon ratio signals conversion to use of fatty acids.

The insulin/glucagon ratio is the most important determinant of the relative contribution of the two major sources of fuel for the body’s energy needs.  When the ratio is large, glucose is the major fuel; when the ratio is small, it is fatty acids.  The insulin/glucagon ratio can vary almost a 100-fold depending on nutritional state and/or glucose availability.  It can be from as high as 30 after eating to as low as 0.3 after fasting.

In the well-fed state, glucose is the usual and ready source of metabolic energy for humans, with intermittent dependence on fatty acids for energy until the next supply of dietary glucose is forthcoming.  Despite the fact that glucose serves as the usual and ready source of energy for metabolic functions, fatty acids are a much more efficient fuel than glucose.  For example, palmitic acid (16 carbons) yields about 25 percent more energy than glucose (6 carbons) on a carbon-for-carbon basis.

Fatty acids are also a much more efficient form for storage of fuel.  Triglycerides, the storage form of fatty acids, require less space for storage than glycogen, the storage form of glucose.  In addition, triglycerides have an almost endless supply of adipose tissue storage depots throughout the human body whereas glycogen has a limited number of depots, the largest and most important of which is in the liver.

Biochemical Overview of Mechanism

Glucose as the energy source:  The glycolytic pathway is the biochemical entry point for conversion of glucose to chemical energy.  Glucose is metabolized by a series of ten reactions to form pyruvate, the end point of glycolysis.  Pyruvate is then oxidatively decarboxylated to form acetyl CoA in preparation for entry into the Krebs cycle (also known as the tricarboxylic acid or citric acid cycle).  In the eight reactions of the Krebs cycle, acetyl CoA is oxidized to CO2, H2O, and high energy phosphate bonds in the form of ATP.  The energy yield from one molecule of glucose by way of glycolysis and the Krebs cycle is approximately 32 molecules of ATP.

The switch to fatty acids:  A brief outline of the metabolic events that occur with conversion of the energy source from glucose to fatty acids is as follows: When blood glucose falls too low or below normal levels, the rate of glycolysis slows; This decreases the amount of pyruvate formed (the end point of glycolysis). The decrease in quantity of pyruvate results in a decrease in amount of acetyl CoA formed for entry into the Krebs cycle.  Because pyruvate is also a precursor of oxaloacetic acid, a decrease in the quantity of pyruvate also can result ultimately in a decrease in oxaloacetic acid (the entry point of acetyl CoA into the Krebs cycle) required for operation of the Krebs cycle.

The deficiencies of acetyl CoA and oxaloacetic acid slow the Krebs cycle.  The resulting reduction in energy production by the Krebs cycle creates the demand for more energy than is available from glucose alone.  This is met by mobilization of fat from storage depots and degradation of fatty acids.  The energy produced by b-oxidation of fatty acids replaces that normally provided by glucose.

The drop in acetyl CoA from pyruvate is more than made up by acetyl CoA from degradation of fatty acids (acetyl CoA is the end point of b-oxidation).  If the low-blood-glucose interval is relatively brief, as in the case of the normal individual described above, deficiency of oxaloacetic acid may not have time to occur.  In this event, acetyl CoA will continue to be processed by the Krebs cycle.

Fatty acids as the energy source: Part 1:  The catabolic pathway known as b-oxidation is the biochemical entry point for conversion of fatty acids to chemical energy.  Fatty acids are dismantled two carbons at a time starting at the carboxyl end of the fatty acid chain.  The first two carbons after the carboxyl carbon are labeled alpha and beta.  Thus, in b-oxidation, the beta carbon is oxidized to a carboxyl group and the original carboxyl and alpha carbons are split off from the carbon chain.  The original carboxyl and alpha carbons form an acetyl group, which becomes acetyl CoA, and the balance of the carbon chain becomes a two-carbon-shorter fatty acid.

b-oxidation reaction is repeated sequentially along the chain until the entire fatty acid has produced the appropriate number of acetyl CoA molecules.  The energy yield from formation of one molecule of acetyl CoA by b-oxidation is approximately 10 molecules of ATP.  However, b-oxidation is only half the story of fatty acid use as fuel for metabolic energy.  The acetyl CoA produced by b-oxidation has as much energy left in it as was liberated in its formation.  It produces the same energy through the Krebs cycle as does the acetyl CoA produced by glucose.

Fatty acids as the energy source: Part 2:  Prolonged insufficiency of glucose as the energy source can deplete the store of oxaloacetic acid in the Krebs cycle, as described above.  This moves the use of fatty acid as fuel into a second phase.

In the second phase, the Krebs cycle will slow to such an extent that the acetyl CoA from b-oxidation accumulates and cannot be converted adequately to CO2, H2O, and energy.  In this case, an oxidative pathway other than the Krebs cycle must be used for continued energy production.  This alternate pathway diverts acetyl CoA from the Krebs cycle via HMG CoA (b-hydroxy-b-methylglutaryl-butyrate CoA) to the pathway that leads to ketone body synthesis.  This pathway is called ketogenesis.

A rough sketch of the biochemistry of ketogenesis is as follows: Acetyl CoA condenses with itself to form acetoacetate; Acetoacetate is either reduced to b-hydroxybutyrate or decarboxylated to acetone (depending on body’s need at the moment); b-hydroxybutyrate is thought to be the ketone body responsible for energy production and acetone is considered a waste product to be excreted in the urine and breath.  Ketone bodies can restore activity of the Krebs cycle by entering the cycle at a point earlier than the blocked oxaloacetic acid step (e.g. the succinate step).  This may be a key mechanism by which ketone bodies are oxidized to provide metabolic energy.

What is acetoacetate’s true role in ketogenesis?  It has been described as being like an old maid waiting for a proposal; does it go to b-hydroxybutyrate? or acetone? or does it go back home to acetyl CoA?  What it does is follow the most immediate need of the body at the moment.  The synthesis of acetoacetate has been mentioned as one of biochemistry’s futile cycles (energy cost with no yield).  Apparently if acetoacetate is not used fairly quickly, the reaction reverses back to acetyl CoA.

Effect of Diet on Metabolic Energy Control

There are many biochemical pathways in the human organism that are not in constant use but are available for use when the need for them arises.  Like stand-by activities that figuratively march in time until their substrates are presented to them, the metabolic control switching mechanisms wait for orders.  The ease with which the body switches back and forth between glucose and fatty acids for energy depends on how often the switch is called into play.

In the case of routine operation, as described above, the switch is frequent and essentially effortless.  However, significant deviations from a nutritional pattern of moderate (controlled) carbohydrates, proper balance between omega-6 and omega-3 essential fatty acids, and adequate micronutrients can send confusing (inflammatory) signals to the switching mechanism.

The major disruptive force in the normal interconversion between fuel sources is the dietary indiscretion of excessive consumption of sugars and starches.   Diets that are low or lacking in sugars or starches do not appear to disrupt the switching mechanism but rather alter the relative contribution of each fuel to the organism’s metabolic energy production.

High-Carbohydrate Diet:  The sequence of events from normal weight through obesity to diabetes starts with a customary dietary pattern of high carbohydrate intake.  The usual chain of events is hypoglycemia (unstable blood glucose), hypoglycemia-hyperglycemia rollercoaster effect, insulin resistance, obesity, and ultimately type-2 diabetes.  Normal switching from glucose to fatty acid fuel is impeded by constant dietary replenishment with glucose that prevents the insulin/glucagon ratio from falling into a range that would signal a switch to fatty acids.  The glycolytic pathway is overwhelmed with an excess of dietary glucose; fatty acid oxidation is inhibited by high insulin/glucagon ratios.

This apparent disturbance of fuel selection at the cellular level is not a defect of the cell’s mechanism of energy production; rather it is the result of the cell’s energy production being dictated by its host’s diet.  The failure to switch from glucose to fatty acids is not a cause of obesity but a co-symptom with obesity as the consequence of an unhealthful diet.

The Controlled Carbohydrate Diet:  The overview of the metabolic fuel switching pattern discussed above describes that of nutritional plans that permit regular daily full-range excursions of the insulin/glucagon ratio.  It can be imagined that because the potential number of different dietary combinations of carbohydrates, proteins, and fats is large, so too is the number of individual fuel switching patterns that occur in response.

It is quite probable that in the range of controlled carbohydrate nutritional patterns, depending on the dietary contribution of glucose, the second step of fatty acid utilization (ketogenesis) for metabolic energy may seldom or never be invoked.

The Low- or No-Carbohydrate Diet:  A nutritional plan that contains little or no dietary carbohydrates is referred to as a ketogenic diet.  It provides little or no glucose for use as an energy source.  Any glucose that is gleaned from the diet or made anew from glycerol and/or nonessential amino acids is spared primarily to serve the blood glucose pool.  The major fuel for metabolic energy in ketogenic diets is fatty acids with the acetyl CA from b-oxidation diverted to HMG CoA.

The difficulty or ease of transition to a ketogenic diet can vary greatly depending on the nutritional plan that it is replacing.  The greatest difficulty occurs in people who have a long history of high-carbohydrate intake, disturbed insulin/glucagon ratios, and possible insulin resistance.   The only fuel these bodies have been offered is glucose; they do not have the familiarity of using fatty acids for energy.  It has been estimated that conversion to a metabolic energy control system normal for a ketogenic diet takes a minimum of two to three weeks.

The period of transition to a ketogenic diet, although difficult, is not dangerous.  It will relieve inflammation and ultimately support healing.  Once the new dietary pattern is established and the energy control system is stabilized, fuel use will be dictated by the insulin/glucagon ratio, with glucose serving only when in excess of needs for blood glucose and fatty acids serving at all other times.  A routine lack of glucose for fuel does not seem to impair the ease of switching between glucose and fatty acids as necessary.  However, it is at this point that the quality and quantity of fatty acids selected for use as fuel becomes critical (see Ketopia post The Importance of Dietary Animal Fat).

Ketone Bodies and Ketosis

Because the public has been so misinformed about the significance of ketone body production, it is important to explain more fully what ketone bodies are and how and why they are formed.

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 for human biochemistry are b-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.  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 breath a characteristic, sweetish odor.  If ketosis is maintained for prolonged periods, as can occur in untreated type-1 diabetes (insulin-dependent diabetes), the blood can become very acidic.  This life-threatening disorder is known as ketoacidosis.

Ketone bodies that are excreted in the urine and the breath carry with them the calories they contain.  These are calories that were counted in the diet but were made unavailable to the body by being excreted before being used.  In effect, the body actually receives fewer calories than the amount calculated.  Thus, for individuals with normal pancreatic function, a ketogenic (low-carbohydrate) diet containing a given number of calories will result in greater weight loss than a nonketogenic diet (high-carbohydrate) containing the same number of calories.  This difference in apparent caloric content between low-carbohydrate and high-carbohydrate diet plans has given rise to the observation that ketogenic diets have a metabolic advantage over nonketogenic diets with regard to weight loss.  The difference is also relevant to the argument about whether a calorie is a calorie.

Dietetic versus Diabetic Ketosis

The nutrition community has fostered the popular misconception that ketone-body production, per se, is an undesirable metabolic circumstance.  It has warned that the formation of ketone bodies is a dangerous consequence of low-carbohydrate diets in an effort to discredit any recommendations that deviate from official dietary recommendations.  As a result, the public has come to view formation of ketone bodies as a symptom of a pathological condition rather than a normal move by the body to satisfy its demands for energy when glucose supplies are short.  This unfortunate misunderstanding stems from allegations that brief periods of dietary ketosis from diets low in carbohydrates have the same medical significance as diabetic ketosis.  These allegations are grossly in error.

Diabetic Ketosis:  There is no question that the ketosis of type-1 diabetes is undesirable and dangerous.  In type-1 diabetes, the ability of the pancreas to make insulin is either diminished or absent.  The mechanism by which ketone bodies are formed in type-1 diabetes is similar to that which occurs with a low-carbohydrate diet.  In the absence of insulin, fatty acids are mobilized and degraded, excess acetyl CoA is produced, and the excess is directed to HMG CoA and ketone bodies and potentially to ketoacidosis.

Dietary Ketosis:  Dietary ketosis is an entirely different condition because it usually occurs in people with sound pancreatic function with an ample supply of insulin.  If glucose is not supplied by the diet, blood glucose levels drop.  As a result of low blood glucose, insulin drops to a low level and its counterpart hormone, glucagon, assumes control.  To spare glucose by providing a substitute energy source, glucagon stimulates the degradation of fatty acids and the conversion of surplus acetyl CoA to ketone bodies.  It is only when glucose sources are severely restricted that excess ketone bodies are produced and the acetone odor in the breath becomes noticeable.

In summary:  Diabetic ketosis is the body’s demanding call for insulin.  It is a warning signal that insulin levels have been permitted to fall too low and blood sugar levels are too high and out of control.  On the contrary, dietary ketosis is the body’s demanding call for glucose.  It is a warning signal that the glucose supply is insufficient and, as a result, the body is burning fatty acids mobilized from fat storage sites for energy.

  1. Adapted from Ottoboni A, Ottoboni F. The Modern Nutritional Diseases and How to Prevent Them, Second Edition.  Fernley, NV: Vincente Books, 2013.

39 Responses to “Metabolic Energy Control”

  1. Good summary. One point I would add is the feedback control on ketone body metabolism. One of the major ones is the effect on insulin. Ketone bodies stimulate insulin secretion which feeds back and turns off lipolysis leading to reduced ketone bodies. This feedback control keeps ketone bodies at an appropriate level. In type 1 diabetes, you lose this control so ketone bodies continue to be produced.

    Also, I don’t understand your comment on acetoacetate. Acetoacetate/beta-hydroxybutyrate ratio is largely determined by the redox potential of the cell (beta-hydroxybutyrate dehydrogenase (NAD)). Equilibrium favors beta-hydroxybutyrate but acetoacetate is the immediate substrate for oxidation. (Acetoacetate + succinyl-CoA –> acetoacetylCoA + succinate; acetoacetyl-CoA –> 2 acetyl-CoA).

  2. Alice and Fred Ottoboni

    Many thanks, Dr. Feinman. Your comments are very constructive. They emphasize the complexity of the overall process and clarify the intricate series of biochemical steps that show the pathway of acetoacetate (formed from condensation of two molecules of acetyl CoA) to the ultimate regeneration of two molecules of acetyl CoA. We are grateful for your important contribution.

  3. I find I feel so much better in ketosis; all body functions seem to work better. I had become insulin resistant, and far too close to becoming T2 diabetic; it took ketosis to get my BG coming back under 100, along with finally being able to lose weight. I don’t think everyone needs to be on a ketotic diet, but it is a lifesaver for those who spent too many years on starvation diets and/or eating loads of overly processed sugar-laden foods so typical in the west.

    • Alice and Fred Ottoboni

      We are so happy for you, Digby. You are doing the right thing for your body.

      You mention insulin resistance. Here is some important information on the subject: Few people realize that magnesium deficiency is directly involved in insulin resistance and type-2 diabetes. The reason is that the body’s cells require magnesium to allow entry of glucose being carried by insulin in the bloodstream. With magnesium deficiency, cells cannot accept glucose, blood glucose rises, and insulin production also increases. This is the mechanism of insulin resistance that eventually turns into type-2 diabetes. When dietary magnesium is adequate, the risk of type-2 diabetes in substantially reduced.

      • I have been taking magnesium for other reason, but good to know about the glucose-insulin connection. Thanks!

  4. michael goroncy

    I say Yo! Alice and Fred
    Thank you for an informative post.
    Having CHD…CABG at 38, Iam ‘armed to the teeth’ with supplements and what I consider appropriate nutrition.

    On the topic of magnesium, it is my understanding:
    (1) magnesium should not be taken together with zinc..they compete for the same pathway.
    (2) What is the best form of magnesium? Currently I am taking 1/3 teaspoon of both glycinate and citrate……Any thoughts.


    • Alice and Fred Ottoboni

      You are very wise, Michael, to learn all you can about your body. Simply provide it with what it needs and it will heal itself!

      Adequate dietary magnesium is required for good health. Yet a large fraction of the public is deficient in magnesium. Magnesium deficiency is associated type-2 diabetes, heart disease, stroke, obesity, Alzheimer’s disease and other inflammatory diseases. Because excess dietary calcium works against magnesium, it takes some studying to get both your calcium and magnesium right. Zinc requirements are an additional variable. The best source of this information is a low cost, paperback book, “The Miracle of Magnesium” by Carolyn Dean, MD. It is available at her website, Magnesium is very important, and we wish you well.

  5. michael goroncy

    Thank you for your reply and link (Dean/Magnesium)
    Must plead not guilty to “Wise”….If I was, I wouldn’t be smoking 30 fags a day and drinking ½ litre of cask red wine daily.

    I have been an extreme bio-hacker for many years ( mainly to counter tobacco and alcohol), this is beyond stupidity. I make the excuse that it’s a predisposition to bad habits and poor coping skills with the downside of personal frustrations. Obviously I am no orphan in this scenario.

    I was a member of the “Heart org”….which was futile because of the overwhelming number of stupid cardiologists. EG: they totally ignore Hyperglycaemia as a major player in heart disease. I get the impression with many Health professionals that ‘Good health is bad for business’..but that’s politics.

    The current rave with ‘Resistant Starch’ looks fascinating and have been a ‘fly on the wall’ watching it unfold.

    Some of my bio-hacking for over the past 20 years has included:
    (1) Self administered chelation …edta.
    (2) Injecting 22,000 units of Vit C
    (3) Injecting IV Hydrogen Peroxide 1% of 35% food grade….11 times
    (4) Taking ‘Sodium Thiosulfate’ crystals 6…sublingually daily to diminish the effects of carbon dioxide, cyanide and other toxins due to my smoking.

    I cannot endorse any of the above. Simply don’t know how effective or deleterious.

    • Alice and Fred Ottoboni

      We are sure, as you know, that our only advice can be , “Stop smoking.” You also know that lectures do no good – you are the only one who can stop your own smoking habit.

      However, since you appear to be a reader, we were wondering if ever you read any of the books by Roger J. Williams (You Are Extra-Ordinary, Biochemical Individuality, Nutrition Against Disease – available used at Amazon). He had an active career in nutritional research and was really an inspiring person to work for (he discovered vitamin B5 – also known as pantothenic acid and coenzyme A).

      Dr Williams’ research gave ample evidence that people varied in their nutritional needs and that the cure of illnesses was filling these individual needs. He was well known in medical circles and helped many people with nutritional problems (no radical stuff – just proper food).

      We wish you well in your search.

      • michael goroncy

        “Thankyouverymuch” Fred and Alice.
        No one knows better than a smoker how deleterious this habit is…go figure!
        I have ordered one book by Roger Williams and also your own book ‘Modern Nutritional Diseases and How To Prevent Them ‘ although they could be beyond my biology intelligence.

        After a MI and CABG (25 years ago) and living with ischaemia (currently running on one coronary artery) all four of my past cardiologists told me they had never seen a reversal in blocked arteries.

        Would like to see you do a post on your diet and supplements.

        BTW: I can’t believe you are in your 90’s…bless you both.

        • Alice and Fred Ottoboni

          Michael, thank you for you kind words. Your perseverance bodes well for you; remember always that the body strives constantly to repair itself. All it needs is the proper fuel for its optimal operation. It is never too late. It may not reverse damage, but it can stop progression.

          Biochemistry tells us that man’s proper fuel, as dictated by his evolution, is as follows: low, very low, or no carbohydrates with appropriate protein and sufficient fat to provide energy; proper ratio of omega-6 to omega-3 fatty acids; and adequate micronutrients. Individual needs fall within these general requirements.

          We hope you find help in our book – your comments tell us that that you will have no trouble with scientific terminology. One point we should mention is that the email address given in the book has been changed. It is now

          In closing, as you are reading this, delay your next cigarette until you finish reading. Then another delay until you start the next task. And then another delay.. ad infinitum. Good luck to you.

  6. Leah Trim

    I started a ketogenic diet two weeks ago last Monday. I refuse to weigh, preferring to go by how my clothing fits and indeed, all ready it’s a bit more loose. But, while weight loss was and is still my primary goal, I feel like keto is going to be pretty much a way of life, be aide I have found some major unforeseen benefits. First, I am cooking more, so it’s more economical. Fast food at lunch or after work is a thing of the past…so many carbs, as a rule! Second, the processed foods in my diet have been dramatically reduced. Third, I am getting a lot more water, which I know is good for me. Fourth, no sugar, refined or otherwise. I am now seeing how much carbs and sugar drove my appetite, leading me to stick so many useless and damaging carbs and sugars in my mouth. I don’t worry about portion control, it’s verysimple to know what I can and cannot have (when in doubt, read the label), and NEVER go hungry. But I tell people, if you are going to do this, you have to see it as a pretty much permanent diet change; you cannot jump on and off and back on, it’s too much work and time to get back into keto if you blow it. This is by far the best diet I ha ever found.

  7. Alice and Fred Ottoboni

    Thank you very much, Leah, for taking the time to write about your experience with a ketogenic diet. We can remember how good it felt when we started about 20 years ago. We feel the same pleasure today plus we are in much better health than we were then. And you are so right about perseverance! Because you are new to the diet, we would like to offer a few tips.

    Make sure you get enough animal fat. Your body needs energy, so if you do not give it glucose, you must provide adequate fat (see Ketopia The Importance of Dietary Animal Fat). Otherwise you will tire more easily and not realize why.
    Make sure you are getting enough magnesium. Magnesium deficiency (and so many people are) can cause constipation and other problems.
    We suggest that people on a ketogenic diet up their vitamin C (ascorbic acid) level 2000-3000 mg/day is a good level. Vit. C is essential for good immune health (see Ascorbic Acid and the Immune System). Because the cells of our bodies cannot distinguish between vitamin C and glucose, the more C that is available, the more C that is taken up by our cells.

    Many happy, healthy years to you

  8. Ilaine

    Michael Goroncy, hope you are still reading, if so, if you really want to stop smoking, please try e-cigarettes. My husband and I both switched 2 1/2 years ago and zero tobacco since then. Please consider unflavored, I have no idea what the flavors are made of, and they don’t make the nicotine work better. Not saying this method is risk free, nobody can say for sure, but it’s way better than cigarettes . No tar, no ash, no smoke, no fire, not butts, no stench.

  9. michael goroncy

    Thanks Ilain
    Electronic fags are the only thing I haven’t tried. On your recommendation, I will get the kit.
    Even if they don’t do the the cost, it is worth a try.
    BTW: can you tell me what type and model you use?


    • Ilaine

      Michael, since you use the word “fag” for cigarettes I wonder if you are in the UK? I don’t know what is available there. My husband and I use 21st Century, which we buy at the Rite Aid around the corner. They also have a website where you can shop. We like 21st Century because this is the only brand we have found so far with unflavored juice. We are looking for unflavored liquid to put into reuseable systems, which would be better for the environment. 21st Century has a rechargeable battery but the nicotine cartridges are disposable, not refillable. If you prefer the tobacco taste there are many brands. Sorry to the site administrators if this is off topic, but smoking cessation is key to better health., so thank you for your kind indulgence. Happy I found this site.

      • Sorry to the site administrators if this is off topic, but smoking cessation is key to better health., so thank you for your kind indulgence.

        I’m not a huge fan of e-cigarettes…but I don’t think a blanket prohibition against mentioning something like this is in anyone’s best interest. I’d prefer that we a have authentic conversations here instead of tip-toeing around an ever-burgeoning list of forbidden topics.
        Of course I’ll intervene if it seems like there’s any sort of abuse, but it seems like that’s a long way off from the context of this conversation… Feel free to carry on!


  10. Please explain how, in a ketogenic state, the excess ketone bodies, leftover from cellular consumption, excretion and exhalation, get stored by the body?

    • Alice and Fred

      Hi PY, Good Question. No ketone bodies are stored in the body. Any not used for energy are eliminated in urine and breath as acetone or converted back to acetyl CoA and converted to carbon dioxide and water in the Krebs cycle.

  11. Alice and Fred

    Michael O’Neill, We are very pleased with your decision and your philosophy – and Goroncy seems very happy too. If it helps him – GREAT. We just assumed that because it was an obvious ad it was a no -no

    • ilaine

      Hi, sorry, not an ad. I am a for-real low carber, post on other sites like cureality, heartlifetalk, freetheanimal, hyperlipid, under the same name but mostly lurk. Type 2 diabetic, bankruptcy lawyer, wife, mother of two, butterfly gardener. Not necessarily in that order.

      • Alice and Fred Ottoboni

        Our profound apologies to Michael O’Neill, Michael Goroncy, and ilaine:

        We are very concerned about the uproar caused by our ignorance of blog rules and regulations. So our first apology goes to Michael O’Neill for our questioming whether the original comment by Ilaine (see above) recommending that Michael G. try e-cigarettes was inappropriate because it sounded to us like an advertisement for e-cigarettes. We thought Michael’s explanation for printing Ilaine’s recommendation (see above) was very responsible. We thought our response to Michael O’Neill saying we were pleased at his decision ended the matter.

        Second, we want to apologize to Michael Goroncy for his feeling that the problem was his fault because he “swayed off topic” to the subject of smoking. No, Michael, the fault is not yours but ours for misunderstanding the intent of Ilaine’s original comment. We hope you have excellent results from the information that Ilaine is transmitting to you. We hope, too, that other readers may find benefit.

        Finally, we apologize to Ilaine for not understanding her motivation in contacting Michael G. about e-cigarettes. Ilaine, we did not know that you are a for-real low-carber, type-2 diabetic, bankruptcy lawyer, wife, mother of two, and that Ilaine is your real name. All of that information might have made us realize that you intention was only to help Michael G., but all we knew is what you wrote: You and your husband have been smokers; you switched two-1/2 years ago to e-cigarettes with good results; and you urge Michael to try them if he really wants to stop smoking.

        We hope you will accept that there was no callous intention in our action. We hope also that you accept our apology and regain your happiness at finding Ketopia.

  12. michael goroncy

    Mad World with Mad Minds
    It’s my fault…I strayed off topic which created confusion.
    I respect that this is a speciality site ‘Ketone’s’ and people like to know the ‘facts’ as currently known.

    After reading the last posts, I have concluded that we are all ‘Mad’ in a innocent sense, and why problems arise in everything to do with communication.

    In my mind…..although, I drink and smoke like a witch. And try and cheat death by being armed to the teeth with supplements and medication, the current posts need cleansing.

    (1) ilaine, was not trolling. She was sharing information to help.
    (2) How anyone could interpret this any other way, is beyond my small brain.
    (3) Which brings us to how strange the mind works.

  13. Thanks for answering my inquiry. Continuing on the hypothetical that in a healthy ketonic state, does that mean a ketogenic diet, excess caloric content (over and beyond the body’s energy requirement) will not produce weight gain?
    This inability to store excess ketones, is that an evolutionary disadvantage for surviving thru the lean times?
    And if true, that would explain the purpose of insulin as a evolutionary tool for ancestral humans to convert and store the excess energy from carbohydrates feasted during the fruitful seasons for famines around the corner.

  14. Alice and Fred

    Hi PY. Lots of good thoughts, but as you say, pretty hypothetical.

    First, about overeating on a ketogenic diet. Are you concerned about this? The fear of overeating is not a practical concern with a ketogenic diet. The diet provides satiety, which discourages overeating. More often, ketogenic diets are fat (Calorie)-deficient.

    If one takes in more Calories than required on a ketogenic diet, what happens? Excess dietary proteins are broken down to constituent amino acids. The essential amino acids each have their own individual catabolic pathway that generally requires energy to achieve, so no storage required there. The nonessential amino acids, depending on structure, are converted to a biochemical component of glycolysis or the Krebs cycle. Any contribution to energy production is negligible in the overall energy balance.

    In ketogenesis, dietary fats are used for practically all of the energy needs of the body. If they are insufficient to supply all the energy needed, the body will mobilize body fat to supply the difference (weight loss). If dietary fats are in excess of energy needs, the body has ingenious way to use the excess energy (this energy is not stored – no weight gain).

    We are not expert in paleobiology-pathology – so about evolutionary advantage- disadvantage, all we know is that the ability of excess carbohydrates to be stored as body fat (fatty acids in triglyceride form) is the biological mechanism that provides for surviving food shortages. Ketone bodies are just by-products of fatty acid breakdown.

    About the purpose of insulin – it is not to convert and store energy from carbohydrates. That is just a tool insulin uses to do the job it is primarily designed for. Evolution made blood the circulating fluid in mammals that delivers nutrients to all parts of the body and carries away waste products. In formulating the composition of blood, it required blood to contain a certain quantity of glucose. Insulin and glucagon are responsible for keeping blood glucose within prescribed limits. Insulin acts to get rid of excess glucose (e.g. store it as fat) when dietary glucose is too high, and glucagon acts to conserves glucose when it dietary glucose becomes too low.

    Hope this helps.

  15. Over 3 years ago my doctor prescribed me statin due to increasing level of LDL in my annual checkup, though all my other metabolic indicators (weight, BMI, heart rate, & fasting glucose level) were exceptional. For most of my life, I had adhered to the perfect pyramidal SAD (complex carb, lean protein and low fat). Blame the bad genes, said my doctor. In the six months under statin, it lowered my LDL by 50%.
    Yet I thought that blaming my genes seem too facile. I decided to bone up on the science of nutrition and then read Protein Power by Drs. Eades. The chapter on how our body processed macro-nutrients was revealing. It was the first time I learned about the tandem insulin/glucagon.
    As an experiment I ditched statin, inverted the SAD pyramid and ate low-carb for 4 months; followed by a cholesterol test which showed a jump in LDL, along w/ a big jump HDL and a huge drop in triglyceride. I have been on low carb ever since. Though my purpose to eat low carb is not to shed weigh, I lost 4 off my 129 pound body. Your observation that ketogenic diets are often caloric deficient is certainly applicable in my case. Fatty protein, like miso- braised pork belly, is indeed satiating, lasting for hours and hours.
    I took biology and chemistry eons ago. To grasp the technical details in your book, I had to re-read multiple times. The more I understand the metabolic processes, the more confident I am and see the fallacies when confronted by scary headlines or the latest epidemiological studies blaming saturated fat or red meat for obesity or cancer. Your blog and explanation are invaluable to keep me doing (eating) the right thing. Thanks!

    • Alice and Fred

      Many thanks, PY, for a great comment. You have gladdened our hearts. In our Amazon biography, we cautioned our readers:

      “Remember always that ‘Your Body is the Temple of Your Mind.’ All of your study, all of your work, all of your hopes, all of your dreams are for naught if your mind is not able to function properly because of ill health. So read, study, and learn what nutritional science tells you. You will never regret the time and effort expended.”

      We admire you for your energy and motivation to help yourself. You will benefit more and more as the years go by. You will never regret it. You could not have selected more knowledgeable nutritional scientists to start your journey than the Drs. Eades. They were our first twenty year ago and still are the scientists we consider as nutrition and health authorities.

      We are so glad, too, that you stopped statins. Cholesterol does not cause heart disease. It is only a symptom, like heart disease, of an improper diet. Statin drugs not only inhibit cholesterol synthesis but also synthesis of a very important enzyme called coenzyme Q10 (CoQ). Statins can cause a deficiency of CoQ, which, in turn, can cause congestive heart failure.

      Your drop in triglyceride level is very interesting. It says that you are very diligent in following a low-carbohydrate diet. This is because triglycerides in fasting blood can only come from carbohydrates. Our bodies cannot make fatty acids (triglycerides) from dietary fat (cannot make fat from fat). Other animals can, but in humans the biochemical pathway from dietary fatty acids to synthesis of new fatty acids is blocked.

      Keep up the good work, PY. The low-carbohydrate-ketogenic diet is basic to achieving optimal good health. Loss of extra body weight is just a nice added bonus. We hope your experience encourages other readers to study, learn, and benefit from the wealth of good nutritional science that is available to them.

      Bless you.

  16. The Protein Power’s chapter on metabolic processes tore up my eating paradigm. The sciences contradicted the my conventional beliefs touted by epidemiological studies, government, popular media and nutritionists. Mortal men such as Collin Campbell (China Study author), Dean Ornish, and Dr. Willett are idolized due their espousing. For layman such as myself, ignorant of metabolic processes, it would take a huge leap of faith to alter their eating paradigm. And even if they do switch, recidivism is likely, as obstacles, discomfort and dissenting off-hand comment from others would turn them back to their previous habits of eating.
    The ‘food as medicine’ model, means the amount/dosage of carb in low-carb is critical. Like meds, the dosage for optimum result is a narrow band for an individual. Outside of that narrow dosage band, results could vary widely. When taking new meds, external tools, such as cholesterol assay, are used to verify and adjust to find the proper dosage. An educated low-carber would experiment by differing the consumed amount of carb to find the desired outcome instead of simply ditching low-carbing, as a less-knowing newbie would. Thus, the term low-carb is too generic. One’s low-carb intake could still be too high for a metabolically different low carber. An improvement would be a carb intake parameter for categories of dieters, based on their metabolic conditions, age, gender and etc. Imagine how difficult this is for a layman to switch, navigate, sustain and stay with a new paradigm, haunted by self-doubts and pounded by conventions. So often, when I tell friends about my low-carbing and that carbs from wholesome whole-grain bread is identical to carbs from Wonder white bread, they respond by rolling their eyes in disbelief or w/ oh, that Atkin thing…
    I can’t blame them. For most of my life, I firmly believed that my SAD eating was healthful, supported by evidences and credentialized authorities. Back then, a 3 egg omelet had only one-yolk and fried w/ poly veg oil. Nowadays, it’s a 4 egg omelet w/ 4 yolks and one white, fried in coconut oil or Kerrygold.
    Oh, the latter is much much tastier!

  17. michael goroncy

    I have travelled a similar path as PY.
    (1) Read Eades 15yrs ago and tweaked my nutrition..protein shakes etc.
    (2) Became suspicious of wheat about 10 years ago and eliminated it. And within 5 months, my weight dropped to 80kg ( from 100kg, which I had been for over about 40 yr s) and remains so today….the only change I made was the elimination of wheat.
    (3) Also, my lipids had a remarkable improvement…..Trigs from 2.4 mmol to 0.5 mmol (currently 0.7)
    (4) Ldl/Hdl ratio=1.3…..Chol/Hdl ratio=2.5. Although I have been on a ‘hat-full’ of medications, these numbers were not even close, until I put the cross on wheat.
    (5) Although I am ‘low carb/high fat’ my journey towards ‘Ketosis’ is in the distance, due to my craving for starch, namely ‘spuds’. And to make it worse, I have just found ‘Oat sourdough’bread, the ingredients being oat flour & sourdough, organic oat bran, filtered water, olive oil and sea salt…’bugger’, it’s delish. And does not raise my blood sugars.
    I would be happy if my Carb craving diminished and to go Ketogenic.

  18. Over the forty plus years, we have been bombarded w/ studies, much epidemiological, promulgating SAD as healthful and saturated fat as harmful. As you have laid out so clearly in your writings, the underlying science on how the body process macro-nutrients contradict their basic premise. And many who analyzed their pro-SAD studies, found the underlying data also fail to support their hypothesis. Many a highly qualified professionals, such as Keys, Ornish, Willett, & Campbell, so very smart and ethical, conducted these researches and went on to achieve accolades, honors and positions based on their findings. If we, as lay persons, see the fallacies and are casting doubts on the SAD paradigm, why aren’t the nutrition authorities spearheading the effort to tear it down? Perpetuated by an alliance of government, commerce, medicine, and media who derive much financial benefits, SAD ideology is an industrial complex. Is it just simple self-interests blinding their objectivity and adherence to scientific method? You had been researchers for many decades. Please speculate how such experts got blinded?

    • Alice and Fred

      Py, yours is a very thoughtful comment,. What happened politically has been well described in books by Gary Taubes (Good Calories, Bad Calories) and Nina Teicholz (The Big Fat Surprise). Others like Atkins, Eades, Sears, Ravnskov, and McCully have described the scientific aspects of this issue.

      We do not have the knowledge to answer your question of how such experts got blinded. However, the American historian, Barbara Tuchman, may have an explanation. In her book “The March of Folly,” she says that governmental behavior that is antithetical to the best interests of its citizens is common in history. She calls it “Folly” and has written that if such government activities persist for long periods, they are very costly and historically end in national catastrophe.

  19. Lorraine

    I linked here from Dr. Eades blog and am enjoying your posts immensely. Unlike some of the other posters, I didn’t go searching for the answers to my weight gain, I thought it par for the course, i.e. getting older, perimenopause, genetics, etc. However, a keto lifestyle found me about 10 months ago when I happened to see a video about a young woman who lost 88 lbs in one year and I thought to myself, “Wow, that’s a lot, how did she do that?” Her answer was a keto diet and some exercise. I did a little research and thought that a diet full of fat where I could eat steak and hamburgers (sans bun) was a diet I could stick to. I started Sept 5, 2013, all in, no gradual introduction. I lost 14 lbs the first week, which I now know to be water weight, and 57 lbs to date. During the first 4 months, weight just melted off, but the rate has slowed down considerably in the past 6 months. I’m still chugging along, with about 15 – 20 lbs to go, depending on muscle gain. Even if that takes a while to come off, I’m extremely happy with where I am now, having gone from a size 20 to a size 12, and FAR healthier with more energy.

    Some people may think that losing water weight is no big deal, but it was an eye-opener for me. I struggled with hormonal water retention since my first pregnancy in my early 20s (when I ended up with pre-eclampsia near the end of my pregnancy), and it just got worse as I hit my 30s with PMS, then even worse with perimenopause. It was what led me to lots of walking, since walking increases circulation with helped relieve the swelling. I was ecstatic when I saw that it wasn’t coming back!

    Although I didn’t have any defined health problems before, other than being fat, all of my numbers have improved consistently over the past 10 months. My cholesterol, LDL, triglycerides, and TSH have gone down while my HDL has gone up. Blood pressure was normal and has remained so. Because I am far more active now (because I can be), my resting heart rate is at the elite athlete level and I can do things like hike for hours without maxing out my target heart range. I can even run a 5k, when I had never been a runner in my life, not even as a kid.

    I sure wish I could convince my family about the benefits of such a lifestyle. My parents did the Dr. Ornish thing when Dad had a heart attack at age 55. He is, of course, taking a statin, as is one of my sisters. their doctor believes that everyone over 45 should be taking it (!!). They eat very low fat, very low everything really, and use some icky fake margarine that’s supposed to be good for your heart. Mom replaces the fat in baked goods with prunes or applesauce (sugar!). Despite giving them the information about how that’s not good for your heart, they are convinced that I’m wrong and that I’ll gain back the weight or have a heart attack because of all the fat. Just the other day Mom said that Grandma lived to be 89 even though she had a can of bacon grease sitting by the stove. Of course, I pointed out that it was healthy. She then mentioned pies and the like, but sugar was a luxury until recent years (especially during the Depression), and was rationed during WWII. Remembering Grandma’s cooking, I don’t think she made a lot of treats, and certainly didn’t keep junk food in the house.

    My husband is mostly on board, he kind of has to be since I do all the cooking, but still eats bread and stuff when we eat out. He does enjoy the new variety of food that we eat, as do I. He has also gone off of the statin his doctor put him on and says he feels a lot better. He does a lot of resistance training and also joins me in other activities such as hiking and country dancing. Our adult kids acknowledge the truth, but don’t want to give up their sugar and carbs despite my demonstration of all the great alternatives.

    My brother and his family also eat low-carb, my sister-in-law has also lost a lot of weight and their son is an elite athlete, a wrestler, so is very familiar with how to gain and lose weight. They are my biggest supporters. My sisters, not so much. They are all convinced that I will gain back the weight, since that’s what they all did on their various diets over the years. They all have myriad health problems too, even though two of them are thinner than I am. Even before my lifestyle change, I was the healthiest of the 4 of us.

    I will be proving them wrong since I intend for this to be my lifestyle for the rest of my life. I look forward to meeting my weight goal, only because it will be nice not to have to track carbs after a while. It will also be nice to settle on a clothing size, instead of needing a new size every couple of months.

    I am thoroughly enjoying a new way of cooking and baking and am forever grateful to the low-carb food bloggers that post so many great recipes. I am also grateful to all of the researchers and scientists such as yourselves who share so much information freely, I find the biochemistry of it all fascinating. I only wish I had searched it out years ago.

    P.S. I do take extra magnesium, 800mg/day, plus other supplements recommended by Dr. McCleary in his book The Brain Trust Program, as does my husband. We both feel much more alert, even with a lack of sleep (I finally got my sleep issues straightened out, i.e. stop eating at least 4 hours before bed), and the menopause cocktail has stopped my hot flashes.

    • Alice and Fred Ottoboni

      Thank you for taking time to tell your story, Lorraine. There are many people relatively new to ketogenic dieting who are discouraged by naysayers. You will be a source of encouragement for them.

      Keep up the good work, Lorraine, it gets better day by day. You are very fortunate to have a cooperative husband. Your diet will help him, too.

  20. Thank you for this informative post, as well as the interesting an elucidative comments. I am a Liberal Arts major, so the scientific details are not my forté. But I get the general idea. I am doing a Ketogenic diet for health reasons that extend far beyond weight control. I was diagnosed with Chronic Fatigue Syndrome back in the mid-1990s, and I have been ill most of of my adult life. Looking back, I can see that it began with the adoption of a vegan diet at the age of 16. I chose to eschew animal foods for ethical reasons, as so many young people do, but it was a physiological disaster for me. It changed my macronutrient ratios significantly in favor of carbohydrates and deprived me of nutrients only found in animal foods. The result was severe hypoglycemia and all the dangerous hormonal affects that has on the body when experienced over many years. It has been a long, long journey to where I am now, but I am hopeful that – over time – a Ketogenic diet will heal my body. I am already experiencing the benefits of blood sugar stability. My biggest challenge at the moment has to do with my digestive system. It has been such a long time since I have consumed concentrated animal protein, that my body seems to have lost the ability to digest it. i know I am benefiting from the Ketotic effects of the diet, but I do not feel as good as I would like – and know that I can – due to the digestive problems. I will persevere on this path because the only direction to go is forward

  21. This is a very informative website with detailed and well written feedback from your audiences. I changed to an LCHF lifestyle over 2 and half years ago. I have never felt better I am 50 this year and weigh the same as I did at 21, I have not had even a “sniffle” in this time …. this past year has been the most stressful period ever but eating right and exercising has made all the difference. I have proved beyond a doubt that my endurance and recovery on a bicycle has quadrupled. Many will say this is anecdotal , there is no reason to stop my self experiment. All I have looked at is my Trig to HDL ratio of 0.224 so I am happy.

  22. Many thanks, Sean, for taking the time to write about your experience with an LCHF diet. It is very important for people to hear about the health benefits that other people have had by restricting carbs. A few of us, by ourselves, may just be anecdotal cases, but add up the great number of anecdotal cases that exist and they become proof that the LCHF diet is based on valid science.

    It is well known that there are all sorts of people recommending all sorts of diets. It is very confusing. But remember that good nutrition does not recommend ANY specific diet that all people should eat, but it does recommend what foods people should NOT eat. Very simply, people should not eat excess sugar and starch, vegetable seed fats and oils, and amounts of omega-6 fats in excess of the amount of omega-3 fats. That’s the prescription for good health.

    We wish you many happy bicycling miles

  23. What supplements and dosages do you take daily, including your dosage of aspirin? Do you take any other supplements several times a week? I have your book, but I’d really like to know what you are doing to maintain your health.
    You are both incredibly inspiring role models for health and vitality. Thank you so much for your excellent website and articles


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