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 ketogenic diet is usually initiated in combination with the patient's existing anticonvulsant regimen, though patients may be weaned off anticonvulsants if the diet is successful. There is some evidence of synergistic benefits when the diet is combined with the vagus nerve stimulator or with the drug zonisamide, and that the diet may be less successful in children receiving phenobarbital.[3]
Protein: When people first reduce carbohydrates in their diets, it doesn't seem as though the amount of protein they eat is as important to ketosis as it often becomes later on. For example, people on the Atkins diet often eat fairly large amounts of protein in the early stages and remain in ketosis. However, over time, some (perhaps most) people need to be more careful about the amount of protein they eat as (anecdotally) the bodies of many people seem to "get better" at converting protein into glucose (gluconeogenesis). At that point, each individual needs to experiment to see if too much protein is throwing them out of ketosis and adjust as necessary.
At the beginning of the year I was counting calories, I was losing weight but I was eating the same thing....every day....never deviating. I lasted 4 months. The lowest I ever hit was 325, starting from 347. I mean that is not bad, and I was losing weight, but I was so bored with my food. Since starting Keto, I am already down to 328 IN TWO WEEKS. I am shocked. I had to have my wife hide the scale, because I kept standing on it not believing what I was seeing. I am eating so well right now.
"I'm not obsessed with food anymore. Before keto, I was constantly hungry and thinking about food. If we got takeout, I would open all of the containers to see which one had the most in it and I would grab that one. It makes sense now because everything I was eating was full of sugar and carbs and I was in that vicious cycle. Growing up, if we had a bad day my dad would say, "Let’s go get some ice cream." He wasn’t trying to raise a food addict.
That’s what motivates most people to go keto. “It’s popular because in most cases it can produce very easy and effective weight loss — that’s the primary reason why people start it,” says Los Angeles–based Franziska Spritzler, RD, the founder of Low Carb Dietitian. There are some other researched benefits beyond weight loss, including possibly acting as a mood stabilizer in those with bipolar disorder (per a very small study in Neurocase) and lessening epileptic seizures (according to a study published in May 2016 in Epilepsy & Behavior).
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.

After increasing water intake and replacing electrolytes, it should relieve most all symptoms of Keto Flu. For an average person that is starting a ketogenic diet, eating 20-30g of net carbs a day, the entire adaptation process will take about 4-5 days. My advice is to cut your carbs to fewer than 15g to ensure that you are well on your way into ketosis within one week. If you are experiencing any more keto flu symptoms, double check your electrolyte intake and adjust.
Thanks for this article. It was really interesting. I have tried Atkins in the past, and I usually lose 10 pounds immediately and then start gaining it back PLUS MORE! Aaaargh. I tend to have high blood sugar and at age 41 am trying to do all I can to stay healthy and NOT get diabetes (I have five boys, the youngest of whom is only 6, who need their mama with all her limbs attached!). Anyhoo, I started the Trim Healthy Mama diet as soon as the book came out and lost 50 pounds in about 14 months. It was the first diet I ever did that gave me a lot of food freedom to eat carbs AND fats AND proteins. I am a HUNGRY mama, but I ate as much as my body wanted and had SOOOO much energy. A couple years into the diet, my middle son developed PANDAS and tic disorder, and we had to put him on GAPS diet and all kinds of nutritional therapy, so I found I didn’t have time to focus on my own health and diet at the same time as his, and his definitely took priority. So of course I gained over half the weight back over the past 3.5 years. But now my kiddo is doing so well and able to eat a lot of more normal foods, so I am back to eating THM style and riding my bike. I am already feeling better and hoping to lose this weight (4 pounds so far, but this is not a fast weight loss diet), bring the blood sugar down and get on with this wonderful, nutty life of mine! Thanks for all the great insight into why Atkins/keto does NOT work for this mama. God bless!
"Listening to podcasts while I run has completely changed my fitness routine. I thought I hated running, but what I hated was pop music. Keeping my mind engaged has helped me push passed physical barriers. Podcasts about keto, fitness, and nutrition is motivating to me to learn about my body while I’m actively working it. My favorite podcasts are Keto for Normies, The Keto Savage podcast, Seth Godin's podcast and Hiding in the Bathroom."
Those issues are part of what's known as the “keto flu,” Warren says. Other side effects of the keto diet, all of which are tied to carb withdrawal, can include lightheadedness, nausea, mental fog, cramps, and headaches, in addition to the diarrhea and tiredness. Luckily, the keto flu doesn't usually last more than a week—which is coincidentally about when people start to see the number on the scale go down, says Warren.
Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures and kidney stones.[3] The diet reduces levels of insulin-like growth factor 1, which is important for childhood growth. Like many anticonvulsant drugs, the ketogenic diet has an adverse effect on bone health. Many factors may be involved such as acidosis and suppressed growth hormone.[37] About 1 in 20 children on the ketogenic diet will develop kidney stones (compared with one in several thousand for the general population). A class of anticonvulsants known as carbonic anhydrase inhibitors (topiramate, zonisamide) are known to increase the risk of kidney stones, but the combination of these anticonvulsants and the ketogenic diet does not appear to elevate the risk above that of the diet alone.[38] The stones are treatable and do not justify discontinuation of the diet.[38] Johns Hopkins Hospital now gives oral potassium citrate supplements to all ketogenic diet patients, resulting in a sevenfold decrease in the incidence of kidney stones.[39] However, this empiric usage has not been tested in a prospective controlled trial.[9] Kidney stone formation (nephrolithiasis) is associated with the diet for four reasons:[38]
If you’re looking to get a jump start on your health and fitness goals this year, you may be thinking about trying the ketogenic diet. Maybe you’ve heard the phrase before — it’s a huge diet buzzword — but aren’t sure what it means. Here’s a primer: The ketogenic diet is an eating plan that drives your body into ketosis, a state where the body uses fat as a primary fuel source (instead of carbohydrates), says Stacey Mattinson, RDN, who is based in Austin, Texas.
Moreover, recent studies show that the Inuit have evolved a number of rare genetic adaptations that make them especially well suited to eat large amounts of omega-3 fat.[57][58][59] And earlier studies showed that the Inuit have a very high frequency—68% to 81% in certain arctic coastal populations—of an extremely rare autosomal recessive mutation of the CPT1A gene—a key regulator of mitochondrial long-chain fatty-acid oxidation[60][61]—which results in a rare metabolic disorder known as carnitine palmitoyltransferase 1A (CPT1A) deficiency and promotes hypoketotic hypoglycemia—low levels of ketones and low blood sugar.[62] The condition presents symptoms of a fatty acid and ketogenesis disorder.[62] However, it appears highly beneficial to the Inuit[60] as it shunts free fatty acids away from liver cells to brown fat, for thermogenesis.[63][64] Thus the mutation may help the Inuit stay warm by preferentially burning fatty acids for heat in brown fat cells.[64] In addition to promoting low ketone levels, this disorder also typically results in hepatic encephalopathy (enlarged liver) and high infant mortality.[65] Inuit have been observed to have enlarged livers with an increased capacity for gluconeogenesis, and have greater capacity for excreting urea to remove ammonia, a toxic byproduct of protein breakdown.[57][66][67][68] Ethnographic texts have documented the Inuit's customary habit of snacking frequently [69] and this may well be a direct consequence of their high prevalence of the CPT1A mutation[70] as fasting, even for several hours, can be deleterious for individuals with that allele, particularly during strenuous exercise.[57][70] The high frequency of the CPT1A mutation in the Inuit therefore suggests that it is an important adaptation to their low carbohydrate diet and their extreme environment.[57][60][70]
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).
Alcoholic ketoacidosis (AKA) presents infrequently, but can occur with acute alcohol intoxication, most often following a binge in alcoholics with acute or chronic liver or pancreatic disorders. Alcoholic ketoacidosis occurs more frequently following methanol or ethylene glycol intoxication than following intoxication with uncontaminated ethanol.[11]
Hi Ben – Great article. I had trouble at the end figuring out if you were now eating high fat (60-80% of calories), or if you went back to something closer to 50% fat calories and higher carbs and are using exogenous ketones to get int ketosis when needed. Are you doing any carbs at night or a refeed, or just having higher carbs on most days? Thanks
Because the ketogenic diet alters the body's metabolism, it is a first-line therapy in children with certain congenital metabolic diseases such as pyruvate dehydrogenase (E1) deficiency and glucose transporter 1 deficiency syndrome,[34] which prevent the body from using carbohydrates as fuel, leading to a dependency on ketone bodies. The ketogenic diet is beneficial in treating the seizures and some other symptoms in these diseases and is an absolute indication.[35] On the other hand, it is absolutely contraindicated in the treatment of other diseases such as pyruvate carboxylase deficiency, porphyria and other rare genetic disorders of fat metabolism.[9] A person with a disorder of fatty acid oxidation is unable to metabolise fatty acids, which replace carbohydrates as the major energy source on the diet. On the ketogenic diet, their body would consume its own protein stores for fuel, leading to ketoacidosis, and eventually coma and death.[36]
The ketogenic diet—also known as "keto"—has become the latest big thing in weight-loss plans, touted recently by celebs like Jenna Jameson, Mama June, and Halle Berry. The diet involves cutting way back on carbohydrates, to 50 grams a day or less, to help the body achieve a state of ketosis, in which it has to burn fat (rather than sugar) for energy.
The investigators found that this was because ketone metabolism resulted in greater “free energy per ATP molecule” (G). ATP is adenosine triphosphate and is the "energy currency" of biology. The “free energy” (∆G) of ATP represents how much potential energy is stored in each ATP molecule, and this value can shift slightly depending on the conditions inside the cell. The more negative the value of the ‘free energy’ of ATP, the more potential to do work the ATP molecule has. 
It has recently been proposed that the ARC is required for the coordination of homeostatic circadian systems including temperature and activity. Authors tested this hypothesis by injecting saporin toxin conjugated to leptin into the ARC of rats. Wiater et al. showed that the leptin-sensitive network is required for entrainment of activity by photic cues and entrainment of temperature by food but is not required for entrainment of activity by food or temperature by photic cues (Wiater et al., 2013).
"I was on Reddit one day when I saw a weight loss transformation of a guy who had lost 140 pounds in a year using the keto diet. I started reading the keto subReddit and began researching the science behind it. After years of using upcoming events as excuses not to diet, I chose to start keto in January when the holidays were over and there weren’t any weddings or parties for the next few months. 
Ketosis is an energy state that your body uses to provide an alternative fuel when glucose availability is low.  It happens to all humans when fasting or when carbohydrate intake is lowered.  The process of creating ketones is a normal metabolic alternative designed to keep us alive if we go without food for long periods of time. Eating a diet low in carb and higher in fat enhances this process without the gnawing hunger of fasting.
This is why epilepsy patients have to get prescribed diets from profession nutritionists. Without getting into true ketosis, dieters risk ingesting an enormous amount of fat—and potentially a lot of saturated fat, if you’re eating animal meat—without any of the fat-burning effects of ketosis. "The fat is the thing that's problematic for a lot of people on keto," Fung says. "They basically give a pass for any types of fat and a lot of the recipes encourage saturated fats like butter." Dieters who are careful to focus on healthy, unsaturated fats like those in avocados may not have issues, but again Fung notes that you end up with a fairly monotonous diet that way, and thus a lot of people end up eating more saturated fats. "To me as a nutritionist, that's pretty scary."
Despite what health science has beaten into us over the last fifty or so years, humans thrive on high-fat, low-carb diets. Millions of people around the world have discovered that a ketogenic lifestyle is the key to weight loss, disease prevention and intervention, and a more vibrant life. Gone are the days of constant hunger and low energy. This book leads you on a path to better health, a slimmer waistline, elimination of cravings, and endless energy.

It is possible that you don’t have as much fat to lose as you think. There are several ways to measure body fat, which will give you an accurate gauge of how much you need to lose. A DEXA Scan is an x-ray that measures bone mineral density and body fat percentage. While it’s most accurate, it’s also expensive. You can also use skinfold calipers at a gym or your doctor’s office to get a body fat percentage estimate. This information gives you a good indication of your body fat stores and how much you have to lose healthfully. The silver lining in this case — the more fat you have, the more you have to lose.
To understand exogenous ketones, you should know that there are three types of ketones: beta-hydroxybutyrate (BHB), acetoacetate (ACA) and acetone, and all three are the normal by-products of fat breakdown by your body. In much the same way as glucose, ketones can be used by your tissues, especially your brain, diaphragm and heart and are actually a far more efficient fuel source than glucose.

“The Bulletproof Diet uses ketosis as a tool, but tweaks it for even better performance,” goes a blog post on the Bulletproof website. “It is a cyclical ketogenic diet, which means you eat keto for 5 to 6 days a week and then do a weekly protein fast, which lowers inflammation and kickstarts fat-burning. This is much better for your body and spurs weight loss even more.”

Ketone esters (BHB-BD) decreases muscle protein breakdown30. Exercise triggers the breakdown of some muscle proteins in order to top up metabolic processes inside the cell. This results in a rise in ‘branched chain amino acid’ levels inside the muscle after exercise. Taking a ketone ester drink before exercise decreased the exercise-induced rise in muscle branched chain amino acid levels. This could help to protect muscle during exercise. 
The researchers observed that the mice in the group that received ketone supplements experienced greater weight loss than the animals in the third group that received similar caloric intake. Latest findings on ketones could have vital implications for an alternative to low-carb and high-fat keto diets to help you lose weight and reduce body fat, including that stubborn belly fat. Read - Keto diet for weight loss: Is the low-carb ketogenic eating plan safe for you?
I was Keto for 6 months and did not lose a pound ! Couldn’t figure out WHY – I was doing 36hr fast, staying in my macros etc… So after 6 months of NO progress I switched it up , and lost 11 pounds in 1 month. AND that was with adding in more carbs, grains, fruit etc.. I think Keto works for some and those that are very large will initially drop as they would on any diet plan cutting out the junk. It wasn’t for me .

These findings are in line with another meta-analysis on 13 randomized controlled trials lasting at least six months comparing low-fat and low-carbohydrate diets. They noted that at six months, subjects who consumed less than 60 grams of carbohydrates per day had an average greater weight-loss of 8.8 lbs. compared to subjects on low-fat diets. [20] At one year, the difference had fallen to only 2.3 lbs. [20]
As a matter of fact, in animal models intracerebroventricular injections of long-chain FA reduced hypothalamic expression of NPY. NPY is an important orexogenic neuropeptide that is a downstream target of leptin and insulin in the hypothalamus. In some forms of hyperphagic obesity, characterized by elevated plasma leptin and insulin levels, the lack of action of insulin on NPY expression could explain the pathological condition. Central administration of oleic acid, fatty-acid synthase, or CPT-1 inhibitors prevents the rise in hypothalamic NPY mRNA induced by fasting (Obici et al., 2003). But glucose level is also involved in KD's food control mechanisms. According to glucostatic theory (Mayer, 1955) data indicates that ketosis did not influence FA glucose but instead stimulated the elevation of post-prandial glucose (Sumithran and Proietto, 2013) in non-diabetic subjects, while in diabetics there was a reduction of fasting glucose (Westman et al., 2008). It is important to note that carbohydrate availability may increase cellular levels of long-chain FA-CoA through an increase of malonyl-CoA, which inhibits oxidation of FAs.

Ketosis is a metabolic state where most of the body's energy supply comes from ketone bodies in the blood, in contrast to a state of glycolysis where blood glucose provides most of the energy. Ketosis is characterized by serum blood concentrations of ketone bodies over 0.5 millimolar with low and stable levels of insulin and blood glucose. However, with ketone supplementation (as you’ll learn about later in this article) ketosis can actually be induced even when there are high levels of blood glucose.
The ketogenic diet—also known as "keto"—has become the latest big thing in weight-loss plans, touted recently by celebs like Jenna Jameson, Mama June, and Halle Berry. The diet involves cutting way back on carbohydrates, to 50 grams a day or less, to help the body achieve a state of ketosis, in which it has to burn fat (rather than sugar) for energy.
Because tumor cells are inefficient in processing ketone bodies for energy, the ketogenic diet has also been suggested as a treatment for cancer.[58][59] A 2018 review looked at the evidence from preclinical and clinical studies of ketogenic diets in cancer therapy. The clinical studies in humans are typically very small, with some providing weak evidence for anti-tumour effect, particularly for glioblastoma, but in other cancers and studies, no anti-tumour effect was seen. Taken together, results from preclinical studies, albeit sometimes contradictory, tend to support an anti-tumor effect rather than a pro-tumor effect of the KD for most solid cancers.[60]
"One of the most amazing things that can happen is finding someone who sees everything you are and won't let you be anything less. They see the potential of you. They see endless possibilities. And through their eyes, you start to see yourself the same way. As someone who matters. As someone who can make a difference in this world.  If you're lucky enough to find this person, never let them go" . . . . . From the day we met, he's never seen me for my weight. He saw me for me. It's so much fun to go through life with this guy. He's always KNOWN the real me... and now he gets to SEE the real me. #throwbackthursday . . . . . . . . #tbt #transformation #ketojourney #fitnessjourney #weightlossjourney #fitnesstransformation #ketotransformation #weightlosstransformation #weightloss #losingweight #bodytransformation #love #mrandmrs #couplepreneurs #husbandandwife #powercouple #ketocouple #ketogeniclifestyle #fatfueled #ketogenic #ketolife #ketomom #ketofamily #ketoworks