By Harvard Gazette & The Nutrition Source
Finding yourself confused by the seemingly endless promotion of weight-loss strategies and diet plans? In this series, we take a look at some popular diets—and review the research behind them.
What is it?
The ketogenic or “keto” diet is a low-carbohydrate, fat-rich eating plan that has been used for centuries to treat specific medical conditions. In the 19th century, the ketogenic diet was commonly used to help control diabetes. In 1920 it was introduced as an effective treatment for epilepsy in children in whom medication was ineffective. The ketogenic diet has also been tested and used in closely monitored settings for cancer, diabetes, polycystic ovary syndrome, and Alzheimer’s disease.
However, this diet is gaining considerable attention as a potential weight-loss strategy due to the low-carb diet craze, which started in the 1970s with the Atkins diet (a very low-carbohydrate, high-protein diet, which was a commercial success and popularized low-carb diets to a new level). Today, other low-carb diets including the Paleo, South Beach, and Dukan diets are all high in protein but moderate in fat. In contrast, the ketogenic diet is distinctive for its exceptionally high-fat content, typically 70% to 80%, though with only a moderate intake of protein.
How It Works
The premise of the ketogenic diet for weight loss is that if you deprive the body of glucose—the main source of energy for all cells in the body, which is obtained by eating carbohydrate foods—an alternative fuel called ketones is produced from stored fat (thus, the term “keto”-genic). The brain demands the most glucose in a steady supply, about 120 grams daily, because it cannot store glucose. During fasting, or when very little carbohydrate is eaten, the body first pulls stored glucose from the liver and temporarily breaks down muscle to release glucose. If this continues for 3-4 days and stored glucose is fully depleted, blood levels of a hormone called insulin decrease, and the body begins to use fat as its primary fuel. The liver produces ketone bodies from fat, which can be used in the absence of glucose. 
When ketone bodies accumulate in the blood, this is called ketosis. Healthy individuals naturally experience mild ketosis during periods of fasting (e.g., sleeping overnight) and very strenuous exercise. Proponents of the ketogenic diet state that if the diet is carefully followed, blood levels of ketones should not reach a harmful level (known as “ketoacidosis”) as the brain will use ketones for fuel, and healthy individuals will typically produce enough insulin to prevent excessive ketones from forming.  How soon ketosis happens and the number of ketone bodies that accumulate in the blood is variable from person to person and depends on factors such as body fat percentage and resting metabolic rate. 
What is ketoacidosis?
Excessive ketone bodies can produce a dangerously toxic level of acid in the blood, called ketoacidosis. During ketoacidosis, the kidneys begin to excrete ketone bodies along with body water in the urine, causing some fluid-related weight loss. Ketoacidosis most often occurs in individuals with type 1 diabetes because they do not produce insulin, a hormone that prevents the overproduction of ketones. However in a few rare cases, ketoacidosis has been reported to occur in nondiabetic individuals following a prolonged very low carbohydrate diet. [4,5]
There is not one “standard” ketogenic diet with a specific ratio of macronutrients (carbohydrates, protein, fat). The ketogenic diet typically reduces total carbohydrate intake to less than 50 grams a day—less than the amount found in a medium plain bagel—and can be as low as 20 grams a day. Generally, popular ketogenic resources suggest an average of 70-80% fat from total daily calories, 5-10% carbohydrate, and 10-20% protein. For a 2000-calorie diet, this translates to about 165 grams fat, 40 grams carbohydrate, and 75 grams protein. The protein amount on the ketogenic diet is kept moderate in comparison with other low-carb high-protein diets, because eating too much protein can prevent ketosis. The amino acids in protein can be converted to glucose, so a ketogenic diet specifies enough protein to preserve lean body mass including muscle, but that will still cause ketosis.
Many versions of ketogenic diets exist, but all ban carb-rich foods. Some of these foods may be obvious: starches from both refined and whole grains like breads, cereals, pasta, rice, and cookies; potatoes, corn, and other starchy vegetables; and fruit juices. Some that may not be so obvious are beans, legumes, and most fruits. Most ketogenic plans allow foods high in saturated fat, such as fatty cuts of meat, processed meats, lard, and butter, as well as sources of unsaturated fats, such as nuts, seeds, avocados, plant oils, and oily fish. Depending on your source of information, ketogenic food lists may vary and even conflict.
The following is a summary of foods generally permitted on the diet:
Programs suggest following a ketogenic diet until the desired amount of weight is lost. When this is achieved, to prevent weight regain one may follow the diet for a few days a week or a few weeks each month, interchanged with other days allowing a higher carbohydrate intake.
The Research So Far
The ketogenic diet has been shown to produce beneficial metabolic changes in the short-term. Along with weight loss, health parameters associated with carrying excess weight have improved, such as insulin resistance, high blood pressure, and elevated cholesterol and triglycerides. [2,7] There is also growing interest in the use of low-carbohydrate diets, including the ketogenic diet, for type 2 diabetes. Several theories exist as to why the ketogenic diet promotes weight loss, though they have not been consistently shown in research: [2,8,9]
- A satiating effect with decreased food cravings due to the high-fat content of the diet.
- A decrease in appetite-stimulating hormones, such as insulin and ghrelin, when eating restricted amounts of carbohydrate.
- A direct hunger-reducing role of ketone bodies—the body’s main fuel source on the diet.
- Increased calorie expenditure due to the metabolic effects of converting fat and protein to glucose.
- Promotion of fat loss versus lean body mass, partly due to decreased insulin levels.
The following is a summary of research findings:
Following a very high-fat diet may be challenging to maintain. Possible symptoms of extreme carbohydrate restriction that may last days to weeks include hunger, fatigue, low mood, irritability, constipation, headaches, and brain “fog.” Though these uncomfortable feelings may subside, staying satisfied with the limited variety of foods available and being restricted from otherwise enjoyable foods like a crunchy apple or creamy sweet potato may present new challenges.
Some negative side effects of a long-term ketogenic diet have been suggested, including increased risk of kidney stones and osteoporosis, and increased blood levels of uric acid (a risk factor for gout). Possible nutrient deficiencies may arise if a variety of recommended foods on the ketogenic diet are not included. It is important to not solely focus on eating high-fat foods, but to include a daily variety of the allowed meats, fish, vegetables, fruits, nuts, and seeds to ensure adequate intakes of fiber, B vitamins, and minerals (iron, magnesium, zinc)—nutrients typically found in foods like whole grains that are restricted from the diet. Because whole food groups are excluded, assistance from a registered dietitian may be beneficial in creating a ketogenic diet that minimizes nutrient deficiencies.
- What are the long-term (one year or longer) effects of, and are there any safety issues related to, the ketogenic diet?
- Do the diet’s health benefits extend to higher risk individuals with multiple health conditions and the elderly? For which disease conditions do the benefits of the diet outweigh the risks?
- As fat is the primary energy source, is there a long-term impact on health from consuming different types of fats (saturated vs. unsaturated) included in a ketogenic diet?
- Is the high fat, moderate protein intake on a ketogenic diet safe for disease conditions that interfere with normal protein and fat metabolism, such as kidney and liver diseases?
- Is a ketogenic diet too restrictive for periods of rapid growth or requiring increased nutrients, such as during pregnancy, while breastfeeding, or during childhood/adolescent years?
Available research on the ketogenic diet for weight loss is still limited. Most of the studies so far have had a small number of participants, were short-term (12 weeks or less), and did not include control groups. A ketogenic diet has been shown to provide short-term benefits in some people including weight loss and improvements in total cholesterol, blood sugar, and blood pressure. However, these effects after one year when compared with the effects of conventional weight loss diets are not significantly different. 
Eliminating several food groups and the potential for unpleasant symptoms may make compliance difficult. An emphasis on foods high in saturated fat also counters recommendations from the Dietary Guidelines for Americans and the American Heart Association and may have adverse effects on blood LDL cholesterol. However, it is possible to modify the diet to emphasize foods low in saturated fat such as olive oil, avocado, nuts, seeds, and fatty fish.
A ketogenic diet may be an option for some people who have had difficulty losing weight with other methods. The exact ratio of fat, carbohydrate, and protein that is needed to achieve health benefits will vary among individuals due to their genetic makeup and body composition. Therefore, if one chooses to start a ketogenic diet, it is recommended to consult with one’s physician and a dietitian to closely monitor any biochemical changes after starting the regimen, and to create a meal plan that is tailored to one’s existing health conditions and to prevent nutritional deficiencies or other health complications. A dietitian may also provide guidance on reintroducing carbohydrates once weight loss is achieved.
A modified carbohydrate diet following the Healthy Eating Plate model may produce adequate health benefits and weight reduction in the general population. 
- Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013 Aug;67(8):789.
- Paoli A. Ketogenic diet for obesity: friend or foe?. Int J Environ Res Public Health. 2014 Feb 19;11(2):2092-107.
- Gupta L, Khandelwal D, Kalra S, Gupta P, Dutta D, Aggarwal S. Ketogenic diet in endocrine disorders: Current perspectives. J Postgrad Med. 2017 Oct;63(4):242.
- von Geijer L, Ekelund M. Ketoacidosis associated with low-carbohydrate diet in a non-diabetic lactating woman: a case report. J Med Case Rep. 2015 Dec;9(1):224.
- Shah P, Isley WL. Correspondance: Ketoacidosis during a low-carbohydrate diet. N Engl J Med. 2006 Jan 5;354(1):97-8.
- Marcason W. Question of the month: What do “net carb”, “low carb”, and “impact carb” really mean on food labels?. J Am Diet Assoc. 2004 Jan 1;104(1):135.
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- Abbasi J. Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes. JAMA. 2018 Jan 16;319(3):215-7.
- Gibson AA, Seimon RV, Lee CM, Ayre J, Franklin J, Markovic TP, Caterson ID, Sainsbury A. Do ketogenic diets really suppress appetite? A systematic review and meta‐analysis. Obes Rev. 2015 Jan 1;16(1):64-76.
- Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013 Oct;110(7):1178-87.
- Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr. 2013 Jul;67(7):759.
- Paoli A, Bianco A, Grimaldi KA, Lodi A, Bosco G. Long term successful weight loss with a combination biphasic ketogenic mediterranean diet and mediterranean diet maintenance protocol. Nutrients. 2013 Dec 18;5(12):5205-17.
- Hu T, Mills KT, Yao L, Demanelis K, Eloustaz M, Yancy Jr WS, Kelly TN, He J, Bazzano LA. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. 2012 Oct 1;176(suppl_7):S44-54.
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(Reprinted with permission from The Harvard Gazette.)