By Daniel Gwartney, MD
Anyone who calls the gym their second home, those who strive for optimal health, or anyone who has struggled with weight loss, undoubtedly has heard of, and possibly tried a ketogenic diet. For the majority, this would have been a lemming-like pursuit of the popular Atkins diet. Contrary to perceived image, the Atkins diet was not exclusively ketogenic, though it did incorporate an initial phase with a very-low carbohydrate diet (VLCD) designed to induce ketogenesis. With the marketing success achieved by the Atkins group, other plans were launched that followed similar plans. Some were more extreme, touting a ketogenic lifestyle as opposed to periodic or short-term phases.
Along the way, something happened to the ketogenic programs, as they were usurped by the glamour of protein. The stigma against dietary fat caused many to shy away from the fat, calorie-rich foods in preference for lean cuts of meat, egg whites and protein powders. Fitness conscious people were easily swayed by their bias toward the lean mass retention powers of protein. Health experts compounded the problem by railing against perceived risks associated with high fat content diets.1 These pressures caused many to alter the macronutrient profile of the ketogenic diet far from its origins, ablating much of the fat-loss power of these diets.
Origins of Ketogenic Diets
It is important to understand the origins of ketogenic diets, and how deviating from the established guidelines might affect the metabolic goal of inducing ketogenesis and accelerating fat loss by increasing the rate and ratio of fatty acid oxidation (burning fat for calories, as opposed to storing as body fat). Ketosis was long thought to be a pathologic state, seen only in people suffering from starvation or uncontrolled type 1 diabetes mellitus. Ketosis, the elevated presence of ketone bodies in the blood and urine, signifies that there is insufficient glucose (blood sugar) to meet the metabolic demand. During starvation, the body’s tissue stores of glucose (glycogen) are depleted; in uncontrolled type 1 diabetes, the absence of insulin prevents sugar from entering the cell, resulting in a condition called hyperosmotic ketoacidosis. This causes the cells to utilize fatty acids as the primary source of fuel for ATP (energy) production. Fatty acids can be derived from stored fat in muscle cells, breakdown of stored fat from adipocytes (fat cells), and fatty acids circulating in the blood following a meal.
Ketones are a byproduct of fatty acid oxidation. Additionally, cellular proteins can be broken down and the amino acids released are subjected to a variety of enzymes to generate either metabolites that can be converted into glucose (sugar) or ketone bodies; these are referred to as glucogenic or ketogenic amino acids. Some amino acids can be diverted into either route, depending upon the needs of the cell and type of tissue.
Fatty acid oxidation and ketone production occur at all times. The body typically generates the cellular energy needed to maintain body temperature and basic functions by oxidizing (burning) sugars, fatty acids and (minimially) amino acids in people eating adequate calories and a balanced macronutrient ratio (carbs/protein/fat). The ratio burned for calories is weighted such that most energy comes from fatty acids at rest, with the majority of the remainder coming from sugar. However, during exercise, the increased energy demand is met primarily by sugar. This is especially true in high-intensity (greater than 60% of VO2 max) activity; low- and moderate-intensity exercise demands can be largely met by increasing the rate of fatty acid and glucose oxidation equally.2
How the Diets Work
Ketogenic diets work by depleting the body’s stores of glycogen over the first several days, quicker if the person is active. This is accomplished by restricting the dietary carbohydrate intake to very low amounts, typically less than 20 grams per day. As the body senses and responds to the change in diet, the level and activity of relevant enzymes adapt in the cells. This is necessary to increase the uptake of free fatty acids by metabolically active tissue, breakdown of stored fat in active tissue, breakdown and release of stored fat from adipocytes (fat cells); carrier molecules and co-enzymes ramp-up to deliver fatty acids to the interior of the mitochondria (the “furnace” of the cell) and dispose of waste products and damaging oxidants. The switch to a fat-burning state increases certain metabolites and waste products that impair burning glucose for energy as well.
As the above run-on sentence suggests, it is more than a simple flick of the switch to adapt to a ketogenic diet. The upside is that rapid weight loss is experienced, and insulin sensitivity can rise as active tissue depletes unhealthy stores of fat.3 The downside is that it is stressful to the cell, increases oxidative damage and results in low circulating glucose concentration, which might impact mood and cognitive function during the transitional period. In fact, it is the first week or two that is most challenging to people in regard to adhering to the prescribed diet. Once the metabolism has adapted, and social pressures have been defeated, a ketogenic diet can be maintained by most.
This switching process can be sabotaged if even a small amount of carbohydrates is ingested. The primary factor is the insulin response to carbohydrates, but also glucose availability to cells. Insulin not only shuttles glucose into cells, but it also suppresses the delivery of fatty acids to the mitochondria for calorie burning while promoting fat storage and water retention.4 If glucose is in circulation, and the person is active, GLUT4 transporters will grab glucose into muscle cells even in the relative absence of insulin.5 This is the reason exercise is such a vital component of treatment for type 1 diabetics.
Ketogenic Diets Sabotaged
So, how have ketogenic diets been sabotaged? Originally, ketogenic diets were developed to decrease the frequency and severity of epileptic seizures, a brain condition.6,7 These diets, which prioritized ketosis above all else, were vastly different from the VLCD diets practiced today, purported to be “ketogenic.” The macronutrient ratio of the ketogenic diets provided to infants and teens was 4:1.8 Note there are only two factors accounted for, not three as might be expected to account for carbohydrates, proteins, and fats. The 4:1 ratio of the epileptic ketogenic diets is 4 grams of fat per 1 gram of protein and carbohydrate. Note, that is 1 gram of (protein and carbohydrate), not 1 gram of protein and 1 gram of carbohydrate, which would be written as 4:1:1. Also, note that the ratio is by weight (gram to gram), not by calorie. This is very relevant, as fat has nine calories per gram, whereas protein and carbohydrate have four calories per gram. If you wrote the ratio by calorie, it would be 9:1 – fat to (protein and carbohydrate).
This ratio would seem an anathema to both athletes and dieters in this modern world. In fairness, the ketogenic diet did “loosen” to a 3:1 ratio during infancy and adolescence to allow for the increased growth during those phases of development. Still, it is hard to imagine serious trainers consuming the allotted 10 grams of carbohydrate per day, and 1 gram per kilogram of bodyweight per day of protein. Yet, these are the parameters found to be necessary to induce consistent ketosis in this vulnerable population of epileptic children. Interestingly, medium-chain triglycerides were found to be much more efficient at achieving ketosis, and allowed for a lower fat calorie intake with similar results.9 To improve the palatability of the foods, and compliance by the patients, a modified Atkins diet was tested and found to be nearly as effective as the classical ketogenic diet.10 The carbohydrate restriction was pronounced at 10 grams per day, and it needed to produce at least a moderate ketone presence in the urine to provide benefit.
Ketogenic Diets and Training
People who work out generally are not worried about seizures but increasing or maintaining lean muscle mass. So how have the modern diets been compromised? In the quest for lean mass, which requires protein, lifters typically ingest up to 1 gram per pound of bodyweight daily. To maintain the ketogenic ratio, a considerable amount of fat would have to be consumed, with the burden of the calories contained. Instead, the VLCD diets, which are intended to be ketogenic, typically end up providing very little response. This is due to the metabolic impact of a large protein load in the diet.
First, meals containing protein, especially a quickly absorbed protein such as whey, are insulinogenic.11 In other words, even though they may not contain much or any carbohydrates, the pancreas still releases insulin to aid in directing the nutrients to insulin-sensitive tissue. This will suppress the release of stored fat, and the burning of fatty acids in the mitochondria. If there is not any accompanying carbohydrate, another hormone will also be released from the pancreas called glucagon. Glucagon stimulates gluconeogenesis – the production of glucose from certain amino acids. If the purpose of the carbohydrate-depleted diet is to deplete body stores of glucose and glycogen, this is counterproductive.
Secondly, a large amino acid influx induces a state of insulin resistance in the liver.12 This means that the liver does not respond to the signal of insulin, and thus does not shut down gluconeogenesis. So, even though the meal may contain enough energy (calories), the liver does not slow down gluconeogenesis. This is similar to the insulin resistance and elevated blood glucose experienced by type 2 diabetics.
A high-protein content diet, especially one rich in leucine (as is practiced by gym-goers and athletes), further compounds the fat-loss effect in two ways. Based upon the findings in a rat study, it appears that a high-protein, carbohydrate-free diet reduces the fat breakdown response to signaling hormones and chemicals in fat cells.13 This means that the body resists fat loss in the presence of such a diet. And as much as amino acids, particularly leucine, are anabolic to muscle, the same effect is seen in adipocytes (fat cells). Leucine promotes growth not just as a structural component to cellular proteins, but also as a signaling molecule. Leucine activates an anabolic pathway called mTOR, which is also present in fat cells.14 Researchers have even explored leucine-poor diets as a means of promoting fat loss. Obviously, this would be unacceptable to trainers.
Effects on Physique
It is difficult to say whether a ketogenic diet is appropriate, long term. Certainly, glycogen depletion followed by carb-loading remains popular. VLCD diets are still practiced by a number of lifters and trainers of all calibers, though long term it seems to have affected some negatively in regard to their physique. As it is easy to follow the progress of physique competitors throughout the year on social media, when an accomplished athlete shows up looking flat and depleted, it is readily evident. However, others have come in razor-sharp. It appears that the diet may be useful, but not for prolonged periods.
These VLCD diets often are not ketogenic, however, despite the near absence of carbohydrates. For the athlete, especially one competing in a weight-based sport, it is possible a ketogenic diet may have some benefit. However, one should realize that it takes about two weeks to adapt physiologically to the ketogenic diet, and during this period, performance may be impaired.15
There is nothing wrong with following a VLCD diet – it is effective for weight loss. However, do not assume that a low or absent carbohydrate diet is necessarily ketogenic. A large influx of protein in one meal or over the course of the day may slam the door on ketogenesis and rob your body of the weight-loss benefits that arise from the elevated ketones. Be aware that you need to monitor your status to determine whether you have achieved and maintained ketosis with your specific diet.
1. Astrup A, Meinert Larsen T, et al. Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet 2004;364:897-9.
2. van Loon LJ, Greenhaff PL, et al. The effects of increasing exercise intensity on muscle fuel utilisation in humans. J Physiol 2001;536:295-304.
3. Erlanson-Albertsson C, Mei J. The effect of low carbohydrate on energy metabolism. Int J Obes 2005;29 Suppl 2:S26-30.
4. Alberti KG, Johnston DG, et al. Hormonal regulation of ketone-body metabolism in man. Biochem Soc Symp 1978;43:163-82.
5. Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev 2013;93:993-1017.
6. Wilder RM. The effects of ketonemia on the course of epilepsy. May Clin Proc 1921;2:307-308.
7. Peterman MG. The ketogenic diet in epilepsy. JAMA 1925;84:1979-1983.
8. Neal EG, Chaffe H, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008;7:500-6.
9. Liu YM, Wang HS. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed J 2013;36:9-15.
10. Kossoff EH, McGrogan JR, et al. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia 2006;47:421-4.
11. Schmid R, Schusdziarra V, et al. Role of amino acids in stimulation of postprandial insulin, glucagon, and pancreatic polypeptide in humans. Pancreas 1989;4:305-14.
12. Li H, Lee J, et al. Suppression of mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids. Am J Physiol Endocrinol Metab 2013 Dec 3. [E-pub, ahead of print]
13. Martins-Afférri MP, Festuccia WT, et al. Response to intra- and extracellular lipolytic agents and hormone-sensitive lipase translocation are impaired in adipocytes from rats adapted to a high-protein, carbohydrate-free diet. J Nutr 2004;134:2919-23.
14. Lynch CJ, Patson BJ, et al. Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue. Am J Physiol Endocrinol Metab 2002;283:E503-13.
15. Paoli A, Grimaldi K, et al. Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr 2012;9:34.