Acetyl-CoA can be metabolized through the TCA in any cell, but it can also undergo a different process in liver cells: ketogenesis, which produces ketone bodies.[27] Ketone bodies are also produced in mitochondria, and usually occur in response to low blood glucose levels.[28] When glucose levels are low, oxaloacetate is diverted away from the TCA cycle and is instead used to produce glucose de novo (gluconeogenesis). But when oxaloacetate is unavailable to condense with acetyl-CoA, acetyl-CoA cannot enter the cycle, and so the body has evolved an alternative way to harvest energy from it.

The findings of a stable (Chearskul et al., 2008) or slightly increased response (Sumithran et al., 2013) of post-prandial FFA after KD can be viewed in the nutrient-static context. Elevated circulating FFA may actually reduce food intake and glucose production through actions on specific hypothalamic neurons (Obici et al., 2003). It has been suggested that this effect could be mediated by the increase of cellular concentration of long-chain FAs-CoA in the arcuate nuclei of the hypothalamus (Obici et al., 2003).
My dad was diabetic even though he was a competitive cyclist and ate "healthy". I grew up in a Weight Watchers household where everything was sugar-free and fat-free. Back then, if you had diabetes, you switched your white bread, rice, and pasta to whole wheat and you were fine. My dad died of pancreatic cancer when I was 19 years old. They say there’s no cause for this cancer, but I think the stress from his diabetes on his pancreas had a lot to do with it.
Ketone esters: These are the raw ketones (in this case, beta-hydroxybutryate) that are not bound to any other compound. These exogenous ketones can be utilized quicker and potentially have a better effect at raising blood ketone levels as your body doesn’t have to cleave the BHB from any other compound. The downside? They typically have a foul taste and can cause an upset stomach.
The Johns Hopkins Hospital protocol for initiating the ketogenic diet has been widely adopted.[42] It involves a consultation with the patient and their caregivers and, later, a short hospital admission.[18] Because of the risk of complications during ketogenic diet initiation, most centres begin the diet under close medical supervision in the hospital.[9]
One of the most extraordinary claims in Dr. Atkins' New Diet Revolution was the metabolic advantage hypothesis, which theorizes that the inefficiencies in the fat-burning process caused an energy advantage (in layman’s terms, it was hypothesized that using fat for fuel causes you to burn more calories). Unfortunately, a 2006 study in the American Journal of Clinical Nutrition said that calorie per calorie, you’ll lose the same amount of weight on both a ketogenic diet and a reduced calorie, controlled carb (but not ketogenic) diet. Amazing what you can get people to believe when you sell some books.
This is in part because patients need to be in deep ketosis to see an impact on epilepsy, likely deeper than the average dieter, but without a nutritionist guiding you it’s still hard to get down into ketosis. It’s not exactly clear why ketosis seems to improve epilepsy, but it seems to have something to do with the brain’s use of ketone bodies in place of glucose, which only happens when you’re nearly in starvation mode. (It's important to note here that "starvation mode" is not in reference to how hungry you feel.)
This was a great article! Thanks so much for clarifying about the KETO diet. I am a thin woman who cannot really gain weight, even though I eat a pretty well rounded diet. My fiancé mentioned the KETO diet because he wants to lose weight. He also would like us to eat dinner together and eat the same things. The latter was mentioned before the KETO diet came into conversation. I already had misgivings about the KETO diet because I feel like my body needs carbs. I do not eat much meat at all and most of my protein comes from beans and other plant foods. Now, I KNOW that the KETO diet is not for me. I am already concerned with losing muscle mass due to aging and changing biologically through peri-menopause and not exercising as much as I should. I LOVE sweet potatoes and other foods you mentioned and could not see giving them up. Anyway, thanks for the information about your experience!
KBs can cross the BBB but not in a homogenous manner. For example, past experiments have demonstrated that BHB utilization is different in various brain areas (Hawkins and Biebuyck, 1979). Areas without BBB, hypothalamic regions and the lower cortical layers have a higher BHB metabolism compared to the lower one of the basal ganglia (Hawkins and Biebuyck, 1979). Also the metabolic meaning of the three KBs is different: while the main KB produced in the liver is AcAc, the primary circulating ketone is BHB. The third one, acetone, is produced by spontaneous decarboxylation of AcAc, and it is the cause of the classic “fruity breath.” Acetone does not have any metabolic functions, but it can be used as a clinical diagnostic marker. BHB acid is not, strictly speaking, a KB because the ketone moiety has been reduced to a hydroxyl group. Under normal conditions the production of free AcAc is negligible and this compound, transported via the blood stream, is easily metabolized by various tissues including skeletal muscles and the heart. In conditions of overproduction, AcAc accumulates above normal levels and a part is converted to the other two KBs. The presence of KBs in the blood and their elimination via urine causes ketonemia and ketonuria. Apart from being the fundamental energy supply for CNS, glucose is necessary for the replenishment of the quota of oxaloacetate, since this intermediate of the tricarboxylic acid cycle (TCA) is labile at body temperature and cannot be accumulated in the mitochondrial matrix. Hence it is necessary to refurnish the TCA with oxaloacetate via the anaplerotic cycle that derives it from glucose through ATP dependent carboxylation of pyruvic acid by pyruvate carboxylase (Jitrapakdee et al., 2006). This pathway is the only way to create oxaloacetate in mammals. Once produced by the liver, KBs are used by tissues as a source of energy (Fukao et al., 2004; Veech, 2004; McCue, 2010): initially BHB is converted back to AcAc that is subsequently transformed into Acetoacetyl-CoA that undergoes a reaction producing two molecules of Acetyl-CoA to be used in the Krebs cycle (Figure ​(Figure22).
A high proportion of energy from ketone oxidation is transferred to the electron transport chain at the start (as NADH+), in comparison to the energy from fat, where a high proportion is transferred ‘downstream’ (as FADH). This means that, even though there is a high amount of ‘potential energy’ in a fat molecule, less of this can be transferred to ATP.   
Almost all commercially produced mayo has sugar added (WHY!?) among other crap ingredients. Good mayo is just oil, egg, acid (vinegar or lemon juice) and salt, so perfectly in line with the dietary guidelines for keto or paleo etc. It only takes 30 seconds to make you own and I haven’t gone back since I learned that, but check out Primal Kitchen if you want to buy a better quality version. Mayo represent.
I started Keto 6 months ago and my physical and mental health has never been better. I used to suffer pretty bad mood swings.They are now gone. Bloating has completely gone. Low energy has gone. I have lost lots of weight and people tell me I look younger. My skin glows and my hair shines. I genuinely feel amazing and this is most certainly not a fad diet. This is for life. I wouldn’t dream of going back to eating rice and pasta. There are so many interesting alternative to carbs and some great recipes now online that food and cooking has become really exciting and experimental. I make great Keto ice cream. The first 2 weeks were awful yes, it’s called Keto flu. It’s your body adjusting to being a fat burner as opposed to a sugar burner. Then WOW did I feel good. It’s completely changed my life and my relationship with other people. My kids have told me they love the new “calmer” me and are much happier. I would urge anyone to really try this lifestyle choice and give it at least 6 months, experiment with recipes. Caulirice fried in butter with some chicken stock and garlic is a delicious alternative to rice. Have your bacon and eggs for breakfast with some almond bread smothered in salty butter and a cup of coffee with cream. Have fun learning about Keto cookery. You will be amazed at some of the wonderful recipes out there. Crabs were definitely detrimental to my health in a big way, particularly my mental health. For the first time in my life I feel happy. I’m 50 yrs old.
The high fat content in the diet, especially if you’re eating saturated fats, can raise your cholesterol levels and contribute to developing cardiovascular disease. Without the fiber from whole grains and fruits, you’re also likely to get constipated and have other digestive issues. Plus you need fiber to maintain a health gut microbiome, which tends to come from the kind of whole grains that you can’t eat on the diet, and though it is possible to get enough fiber from vegetables on the keto diet you have to carefully monitor your eating to ensure that. Neither Giancoli nor Fung any of the other dietitians and nutritionists who evaluated keto for a recent US News & World Report diets ranking would recommend it. Many of them said they had serious concerns about long-term safety of doing keto. Though you may very well lose weight, most people on most diets gain the weight back (and sometimes even more) when they go off the diet, which many dieters do because radical shifts in what you eat are hard to maintain for long periods of time.
Low-carb has become the new low-fat. During the early Atkins era, snacks included cucumbers, beef jerky, and pork rinds. Now there’s a wealth of low-carb snacking options; there are junk-foody low-carb recipes all over Pinterest; a low-carb aisle at the grocery store. There are low-carb replacement foods and ingredients for low-carb replacement foods. It’s Snackwell’s 2.0.

“Instead of engaging in the next popular diet that would last only a few weeks to months (for most people that includes a ketogenic diet), try to embrace change that is sustainable over the long term. A balanced, unprocessed diet, rich in very colorful fruits and vegetables, lean meats, fish, whole grains, nuts, seeds, olive oil, and lots of water seems to have the best evidence for a long, healthier, vibrant life."
C8 is the rarest MCT found in coconut oil, comprising about 6% of coconut oil. It has potent anti-microbial properties (way more potent than lauric acid) to help you maintain a healthy gut, and it is the fastest MCT to metabolize in the brain. (hence the name Brain Octane). Your liver does not need to process C8, and it only takes the steps for your body to turn it into ATP cellular energy (sugar takes 26 steps). You would need 18 tablespoons of coconut oil to get just one tablespoon of Brain Octane.

Great article! As someone who just started a “ketogenic diet” two weeks ago, I am opting to hold off on using ketone supplements for the following reason. You state how “Keto-adaptation occurs when you have shifted your metabolism to relying on fat-based sources, instead of glucose (sugar) sources, as your primary source of fuel.” If the goal is to “switch” our body’s energy supply to ketones and one uses supplemental ketones, how do they really ever know if their body has successfully accomplished this goal if they are using supplemental ketones? Aren’t they getting a false sense of ketosis if their blood or breath tests show them above 0.5 millimolar through the use of the supplements? I understand that it may take me longer to reach ketosis naturally but I guess I see it was worth it to truly reap all of the benefits that you outline in your article.
If you’re following the keto diet, you will need protein, but you should limit your intake to about 20 percent of your total daily calories. (1) This is important because when you consume more protein than you need, your body converts the excess protein into carbs through a process called gluconeogenesis. This process pushes your body out of ketosis.
Medium-chain triglycerides, or MCTs, are a type of fat that gets digested quickly and can help ketogenic dieters boost fat intake and stay in ketosis. Studies suggest that supplementing with MCT oil can help promote weight loss and boost feelings of fullness. Hence, MCT oil can be a great weight loss tool for those following a keto diet. Read - Weight loss and crash diets: Beware, yo-yo dieting can give you belly fat - use these 6 tips to lose weight

Almost all commercially produced mayo has sugar added (WHY!?) among other crap ingredients. Good mayo is just oil, egg, acid (vinegar or lemon juice) and salt, so perfectly in line with the dietary guidelines for keto or paleo etc. It only takes 30 seconds to make you own and I haven’t gone back since I learned that, but check out Primal Kitchen if you want to buy a better quality version. Mayo represent.
For patients who benefit, half achieve a seizure reduction within five days (if the diet starts with an initial fast of one to two days), three-quarters achieve a reduction within two weeks, and 90% achieve a reduction within 23 days. If the diet does not begin with a fast, the time for half of the patients to achieve an improvement is longer (two weeks) but the long-term seizure reduction rates are unaffected.[43] Parents are encouraged to persist with the diet for at least three months before any final consideration is made regarding efficacy.[9]
Another product of elevated levels of free FA is polyunsaturated FA (PUFA). The potential ability of PUFA to block seizure activity in the brain is speculated to be associated with KD. Some mechanisms are thought to be a direct inhibition of voltage-gated sodium and calcium channels, modulation of a lipid-sensitive potassium channel, the activity of the sodium pump to limit neuronal excitability, or the induction of expression and activity of proteins in the mitochondria, thereby inducing a neuroprotective effect by partially inhibiting the production of reactive oxygen species (ROS) (Bough and Rho, 2007; Paoli et al., 2014).
“The argument is that after decades of abusing your body with carbohydrates and thus creating insulin resistance, your body is not going to magically heal itself from a measly 30 days on a low-carb eating plan,” she explains. “If you need things to celebrate while you wait for the scale to start ticking down, look toward your other accomplishments—body composition, pictures, and measurements after three months.”
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Now, I’m in low carb recovery, I need to re-lose some of what I’ve gained in the carb rebound, and to do it I’m just counting calories. I’m only 5’4, so I have a goal of 1620 per day, with the understanding that I am not going to hit that goal every day, because sometimes I will eat out or eat a donut that’s brought in at the office. I finally got tired of saying “I can’t have that” or lying and saying I didn’t even want it. Now, if I want to eat something, I eat it. I can adjust my other decisions for the day if necessary to accommodate a treat, or not, it just depends on how I feel. Some days I feel motivated to lose weight, and some days I feel motivated to eat ice cream, and the one desire does not have to destroy the other. I finally feel like I can enjoy the goodness of all of the food groups again, and I am steadily losing an average of 1 lb per week – no longer miserable.

Forget the word “diet”. I’m eating low carb/keto for about two months now. Before, I was always hungry, always thought about food. My stomach never felt good. I had awful heartburn all the time, so I took Prilosec every other day! Now the inflammation is gone because I lost all the “water weight”. Yay!! The side effects are amazing. I feel better than I have in years. No more heartburn! This isn’t a diet. It’s a new way of life for me, and I’ll never go back.

Interesting article and I applaud you challenging any way of eating as so many of us are like sheep these days. However, for me, it’s really all about sugar. For example, the significant results of lowering sugar intake on type two diabetics should not be ignored. Look up Dr David Unwin’s success in the UK where many of his patients are in remission and, off their medication. I started a low sugar way of eating (diet is not a good word for anyone) Two years ago. I lost 20 kgs and have kept it off. I’ve looked at the science, I’ve looked at the manipulative history and current strategies of food manufacturers, but moreover, I look at my own results. Like you, I want my own ‘truth.’ We need to take individual responsibility in all areas of our lives to do that, instead of jumping on the next wagon of craze.
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