Ketogenic Diets

   There has been a lot of hoopla recently among weight-loss cultists about ketogenic diets, e.g. Atkins or "low carbohydrate".  They are high animal-protein, high animal-fat diets, and force the body into a dangerous state called ketosis.  A criticism of these fad diets is given by Dr. John McDougall.  Unfortunately, McDougall promotes a high-carbohydrate diet, full of problems of its own, since grains are a relatively recent human invention, completely absent in our evolutionary past.  The Physicians' Committee for Responsible Medicine also has a web site devoted to the Atkins' diet.

  PURPOSE: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy.
  METHODS: A whole-blood selenium level was obtained on the symptomatic patient after noting the patient's poor appearance on physical examination. Children already treated and children beginning the KD were then evaluated prospectively for selenium status by measuring whole-blood or serum selenium as part of routine laboratory evaluation every 3 months.
  RESULTS: The index case had no detectable whole-blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy. Thirty-nine additional children had the selenium status evaluated. Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing). They were referred for cardiology evaluations, which were normal. Selenium supplementation improved levels in all children. Low levels were seen in some children after only a few months of treatment.
  CONCLUSIONS: The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated. Screening for selenium deficiency is suggested if the patient KD regimen does not meet >/=75% of the RDA or if the child is symptomatic. Nutrient supplementation should provide adequate trace elements for children treated with the KD. The KD requires close monitoring of the overall nutritional status.

PMID: 12681013

  Recommendations for increased consumption of protein are among the most common approaches of popular or fad diets. This review summarizes the effects of dietary protein on satiety, energy intake, thermogenesis, and weight loss, as well as its effect on a variety of health outcomes in adults.  In short-term studies, dietary protein modulates energy intake via the sensation of satiety and increases total energy expenditure by increasing the thermic effect of feeding. Whereas these effects did not contribute to weight and fat loss in those studies in which energy intake was fixed, one ad libitum study does suggest that a high-protein diet results in a greater decrease in energy intake, and therefore greater weight and fat loss.  In terms of safety, there is little long-term information on the health effects of high-protein diets.  From the available data, however, it is evident that the consumption of protein greater than two to three times the U.S. Recommended Daily Allowance contributes to urinary calcium loss and may, in the long term, predispose to bone loss. Caution with these diets is recommended in those individuals who may be predisposed to nephrolithiasis or kidney disease, and particularly in those with diabetes mellitus.

PMID: 12144197

  High-protein diets have recently been proposed as a "new" strategy for successful weight loss. However, variations of these diets have been popular since the 1960s. High-protein diets typically offer wide latitude in protein food choices, are restrictive in other food choices (mainly carbohydrates), and provide structured eating plans. They also often promote misconceptions about carbohydrates, insulin resistance, ketosis, and fat burning as mechanisms of action for weight loss. Although these diets may not be harmful for most healthy people for a short period of time, there are no long-term scientific studies to support their overall efficacy and safety. These diets are generally associated with higher intakes of total fat, saturated fat, and cholesterol because the protein is provided mainly by animal sources. In high-protein diets, weight loss is initially high due to fluid loss related to reduced carbohydrate intake, overall caloric restriction, and ketosis-induced appetite suppression. Beneficial effects on blood lipids and insulin resistance are due to the weight loss, not to the change in caloric composition. Promoters of high-protein diets promise successful results by encouraging high-protein food choices that are usually restricted in other diets, thus providing initial palatability, an attractive alternative to other weight-reduction diets that have not worked for a variety of reasons for most individuals. High-protein diets are not recommended because they restrict healthful foods that provide essential nutrients and do not provide the variety of foods needed to adequately meet nutritional needs. Individuals who follow these diets are therefore at risk for compromised vitamin and mineral intake, as well as potential cardiac, renal, bone, and liver abnormalities overall.

PMID: 11591629

  Forty young healthy ambulatory volunteers were given a very-low-energy diet (2.34 MJ, 560 kcal) containing 70 g of proteins of good biological value, 36 g carbohydrates, 2 g potassium, 0.5 g sodium, polyvitamins and 21 water. The nitrogen balance reached equilibrium on the 8th day. No risk factors were found. These results were compared with 4000 cases collected over 12 years. The latter were given a protein diet with neither salt nor carbohydrates. The addition of salts and carbohydrates resulted only in an increase of the subjects' comfort. The analysis of deaths occurring in the U.S.A. after protein diets lead to the conclusion that these very probably linked to the duration of the protein diet, the poor biological value of proteins provided, the insufficiency in potassium intake. The conditions for a safe use of a very-low-energy diet, are a large intake of proteins of good biological value, a large intake of potassium and probably small intake of carbohydrates and sodium.

PMID: 7228470

  The effects of starvation, an 800-kcal mixed diet and an 800-kcal ketogenic (low carbohydrate-high fat) diet on the composition of weight lost were determined in each of six obese subjects during three 10-day periods.The energy-nitrogen balance method was used to quantify the three measurable components of weight loss; protein, fat, and water. On the 800-kcal ketogenic diet, subjects lost (mean +/- SE) 466.6 +/-51.3 g/day; on the isocaloric mixed diet, which provided carbohydrate and fat in conventional proportions, they lost 277.9+/- 32.1 g/day. Composition of weight lost (percentage) during the ketogenic diet was WATER 61.2, fat 35.0, protein 3.8. During the mixed diet, composition of loss was water 37.1, fat 59.5, protein 3.4.

PMID: 956398

  The effect of a high energy, low carbohydrate (ketogenic) diet on serum levels of lipids and lipoproteins was studied in two normal individuals. A marked rise in serum levels of cholesterol and phospholipid occurred during the diet, but serum triglyceride levels remained within the normal range. High density lipoprotein cholesterol level did not change, and the rise in serum level of cholesterol levels with its distribution in lipoproteins, these observed changes pose a potential atherogenic risk. Serum lipid and lipoprotein levels reverted to normal on discontinuation of the diet. A modest weight loss observed during the diet was regained within 24 hours of the diet's cessation.

PMID: 7231313

  The "Atkins dietary revolution" is a ketogenic diet consisting almost exclusively of food from animal origin. A similar diet was introduced as the "Banting diet" more than a century ago by the English physician Harvey. This carbohydrate-free diet is high in fat, cholesterol and purines. The measurable ketosis is a precondition for the effect of this kind of diet. However, the predictable hyperlipacidemia and ketosis are recognized health risks. Additionally, hypercholesterolemia is to be expected in a greater part of the adherents to such a diet. Even children under ketogenic diet develop hypercholesterolemia within a short time. A similar high-fat diet, known as the Sippy diet for ulcer therapy, was found earlier to cause an increased incidence in coronary heart disease. On the basis of the known facts the Atkins diet seems to be potentially hazardous to health, unless a controlled study is performed. However, considering the risks it seems very problematic to perform such a study.

PMID: 711091

  Very fat people die earlier than people of normal weight because hypertension, diabetes and coronary disease are more frequent among the markedly obese. Most obese subjects, however, are only slightly overweight and their mortality is not elevated. Reasons for dieting are more often psychological than somatic. 2. Reducing diets are ineffective because the obese rarely follow them. Total fasting and intestinal bypass may provide better results, but are more dangerous. 3. Atkins' diet eliminates carbohydrates from food without restricting protein and fat intake. Deprived of carbohydrates, the body uses fat for fuel. A small part of metabolized fat is eliminated in the urine as ketone bodies, and this is why such diets are called "ketogenic". They have been known at least since 1863. 4. Caloric loss due to ketonuria does not exceed 100 Cal/day in the non-diabetic. It is maximal during total fasting and cannot be increased by a ketogenic diet. 5. In the short run, such diets produce rapid weight loss due to polyuria. On the other hand, refeeding carbohydrates causes water retention and weight gain. 6. The diet decreases appetite: patients eat less without feeling severe hunger and without measuring their food intake. 7. Orthostatic hypotension, fatigue, and nausea are frequent, despite what Dr. ATKINS claims. 8. The diet increases plasma cholesterol and uric acid. It may be dangerous in diabetes (anorexia, acidosis) and in heart or kidney failure (hypokalemia). 9. The diet, though far from good, is better than the book. ATKINS' theories are at best half-truths, and the results he claims lack credibility. The obese subject's disappointment with traditional reducing diets and the book's hard-sell style account for ATKINS' success.

PMID: 897645

  Consumption of protein-rich, carbohydrate-restricted reducing diets has been associated anecdotally with an increased appetite for carbohydrate. We have tested the effect of such a diet on carbohydrate intake by rats. Rats were given either a calorie-restricted ketogenic diet containing protein and fat or a control diet containing carbohydrate along with the protein and fat. When allowed to choose from a pair of isocaloric, isonitrogenous diets containing 25 or 75% dextrin, ketotic rats ate significantly more carbohydrate and total food than control animals during the first 30 minutes of feeding, apparently requiring more of the carbohydrate to obtain an increase in brain tryptophan similar to controls. Ketotic rats ate a significantly higher proportion of total calories as carbohydrate. Similar results were obtained when sucrose replaced dextrin. When ketotic and control rats chose between two diets differing in proportions of fat or protein, no differences were observed between the groups in total food intake nor in the amounts or proportions of fat or protein eaten. We also compared the effects of a small, isocaloric premeal containing only carbohydrate (1.4 g dextrose) or mixed nutrients on subsequent carbohydrate consumption in otherwise untreated rats allowed to choose from 25 and 75% dextrin diets. Rats eating the carbohydrate premeal subsequently ate as much total food as the mixed-nutrient controls, but significantly less carbohydrate. These observations suggest that carbohydrate intake is influenced by prior nutrient consumption and that prolonged deprivation of carbohydrate can lead to overconsumption of this nutrient when it is reintroduced into the diet.

PMID: 6822892

  The ketogenic diet (KD) is designed to simulate the biochemical effects of fasting by maintaining a state of ketosis. The complex interplay of endocrine and metabolic factors requires that a continuous ingestion of a diet high in lipid calories is necessary to achieve such a state and yet maintain body weight. The resulting condition provides for much of the cerebral energy requirements in the form of ketone bodies. We review energy metabolism with special emphasis on fatty acid oxidation to provide the readers with a foundation that facilitates identification of patients who will especially benefit from this diet, as well as to assist clinicians in screening candidates who may experience a catastrophic outcome if fasted and placed on this diet. The review includes a discussion of the role of carnitine in mitochondrial fatty acid metabolism, and the criteria for carnitine supplementation. Only limited information is available regarding the interaction of the diet with the commonly used antiepileptic drugs.

   BACKGROUND: The effects of a prolonged low-carbohydrate diet rich in n-3 fatty acids on blood lipid profiles have not been addressed in the scientific literature. OBJECTIVE: This study examined the effects of an eight-week ketogenic diet rich in n-3 fatty acids on fasting serum lipoproteins and postprandial triacylglycerol (TG) responses. DESIGN: Ten men consumed a low-carbohydrate diet rich in monounsaturated fat (MUFA) and supplemented with n-3 fatty acids for eight weeks. Fasting blood samples were collected before and after one week of habitual diet and on two consecutive days after 2, 4, 6 and 8 weeks of the intervention diet. Postprandial TG responses to a fat-rich test meal were measured prior to and after the intervention diet. RESULTS: Compared to the habitual diet, subjects consumed significantly (p < or = 0.05) greater quantities of protein, fat, MUFA and n-3 fatty acids and significantly less total energy, carbohydrate and dietary fiber. Body weight significantly declined over the experimental period (-4.2+/-2.7 kg). Compared to baseline, fasting total cholesterol, LDL cholesterol and HDL cholesterol were not significantly different after the intervention diet (+1.5%, +9.7% and +10.0%, respectively). Fasting TG were significantly reduced after the intervention diet (-55%). There was a significant reduction in peak postprandial TG (-42%) and TG area under the curve (-48%) after the intervention diet. CONCLUSIONS: A hypocaloric low-carbohydrate diet rich in MUFA and supplemented with n-3 fatty acids significantly reduced postabsorptive and postprandial TG in men that were not hypertriglyceridemic as a group before the diet. This may be viewed as a clinically significant positive adaptation in terms of cardiovascular risk status. However, transient increases in total cholesterol and LDL cholesterol were also evident and should be examined further in regard to which particular subfractions are elevated.

PMID: 10872901

  OBJECTIVE: To determine whether ketogenic weight reducing diets have adverse effects on cognitive performance. SUBJECTS: 21 overweight women (mean BMI = 41 kg/m2). DESIGN: Randomized double-blinded study. METHOD: Subjects were randomized to ketogenic or nonketogenic liquid formula very low energy diets, that were comparable in energy and in protein content. Subjects remained on the diet for 28 days and were reevaluated periodically with brief measures of cognitive performance assessing attention and mental flexibility. RESULTS: Weight losses were comparable on the two diets (Mean = 8.1 kg). Performance on attention tasks did not differ as a function of the diet. However, performance on the trail making task, a neuropsychological test that requires higher order mental processing and flexibility, was adversely affected by the ketogenic diet. The worsening in performance was observed primarily between baseline and week one of the ketogenic diet. CONCLUSIONS: Further research is needed to confirm this finding and to determine whether ketogenic diets negatively affect other complex mental tasks, such as problem solving.

PMID: 8589783

  PURPOSE: The ketogenic diet has been successfully used in treatment of pediatric epilepsy for >70 years. Few serious complications caused by the diet have been reported. We report complications that have been experienced by children receiving the ketogenic diet. METHODS: In a 22-month period, we treated 52 children with the classic ketogenic diet and monitored them in a prospective manner. RESULTS: Five children (10%) experienced serious adverse events (AE) after initiation of the diet. Four patients (80%) were treated with valproate (VPA) in addition to the diet, as compared with 25 (53%) of the other 47 children. Two patients developed severe hypoproteinemia within 4 weeks of initiation of the diet, and 1 of them also developed lipemia and hemolytic anemia. A third child developed Fanconi's renal tubular acidosis within 1 month of diet initiation. Two other children manifested marked increases in liver function tests, 1 during the initiation phase and the other 13 months later. CONCLUSIONS: Clinicians who wish to use the ketogenic diet must be aware of the potential of serious AE and possible interactions of the diet with VPA.

PMID: 9670903

  Ketosis was induced in four lactating dairy cows at an average of 36 d postpartum and 24 d after initiation of a protocol for inducing ketosis. Liver and adipose biopsies were taken at five stages; once prepartal, once early postpartal, once during an induction protocol, once during ketosis, and once during recovery after treatment of ketosis. At each stage, in vitro estimates were made of capacities of liver slices for gluconeogenesis, fatty acid oxidation, and ketogenesis and of capacities of adipose tissue slices for lipogenesis and lipolysis. There were no significant differences for any metabolic capacity between prepartal and early postpartal stages; however, a significant decrease in hepatic metabolic activity was associated with ketosis. Gluconeogenic rates from all substrates tested were decreased significantly during ketosis, and similar decreases were measured for oxidation of gluconeogenic substrates and fatty acids. Treatment of ketosis resulted in complete recovery from impairments of metabolism in liver. Results suggest that a prolonged energy deficit, plus a major influx of ketone precursors, is accompanied by eventual hepatic impairment, that clinical ketosis is associated with this impairment, and that the impairment is reversed by effective treatment of ketosis.

PMID: 3084603

  These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.

PMID: 3708579

  The rate of tumor growth in vivo in adult rats (250- to 350-g total body weight) is stimulated during an acute fast. No tumor growth stimulation is observed in fasted immature rats (less than about 200-g total body weight). The different tumor growth responses in rats of these two age groups appear to depend on the increased availability to the tumor of nutrients from host fat stores in adult rats. Immature rats, which lack significant fat stores, show neither hyperlipemia nor ketosis during fasting. These experiments were performed to determine the relationship between blood fat store-derived nutrient concentrations and the onset of stimulated tumor growth in fasted adult rats. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fast. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Mobilization of host fat stores leading to increased blood concentrations of free fatty acids, glycerol, ketone bodies, and triglycerides started about 7 h after food was removed and reached its maximum after about 15 h. Increased rates of tumor growth and incorporation of thymidine into tumor DNA correlated closely with the higher circulating nutrient concentrations. Both the nutrient concentrations and tumor growth were decreased by refeeding. These findings suggest that the availability of nutrients derived from host fat stores may be rate limiting for tumor growth in vivo.

PMID: 3802090

  Despite its clinical use as a therapy for refractory epilepsy for more than 75 years, the ketogenic diet (KD) remains a therapy in search of an explanation. The mechanism of action of the KD is unclear and the optimal indications for its clinical use are incompletely defined. Animal models could help to elucidate these questions. Surprisingly, there have been very few animal studies of the KD, and those that have been performed are difficult to compare because of wide discrepancies in experimental methods. Earlier models concentrated on the effect of the KD on acute seizure threshold in normal (i.e. nonepileptic) animals. Recent studies are beginning to examine the longer term effects of the KD and its role in epileptogenesis. Some features of clinical experience have been replicated in animal models, including the role of ketosis, elevation of seizure threshold by both classic ketogenic and medium chain triglyceride diets, better effectiveness at younger ages, and rapid reversal of the seizure protective effect when the diet is discontinued. These parallels raise hope that pertinent clinical questions can be addressed in the more controlled setting of the research laboratory. As in the clinical arena, there has been a recent resurgence of interest in pursuing basic questions related to the ketogenic diet, using techniques of modern neuroscience. Experimental approaches such as brain slice neurophysiology, genetic models, dissection of metabolic pathways, and neurohistological techniques hold much promise in the effort to understand this intriguing alternative to standard anticonvulsants.

  Vitamin D and mineral metabolism status was examined in five children maintained chronically on combined ketogenic diet-anticonvulsant drug therapy (KG), and the results compared to those obtained in 18 patients treated with anticonvulsant drugs alone (AD) and 15 normal controls. KG patients exhibited biochemical findings of vitamin D deficiency osteomalacia: decreased serum 25-hydroxyvitamin D (25OHD) and calcium concentrations, elevated serum alkaline phosphatase and parathyroid hormone concentrations, decreased urinary calcium and increased urinary hydroxyproline excretion, and decreased bone mass. Although the KG and AD groups demonstrated similar reductions in serum 25OHD concentration, the KG patients exhibited a significantly greater reduction in bone mass. In response to vitamin D supplementation (5000 IU/day), mean bone mass in the KG group increased by 8.1 +/- 0.9% (P less than 0.001) over a 12-month period. These results suggest that ketogenic diet and anticonvulsant drug therapy have additive deleterious effects on bone mass and that these effects are partially reversible by vitamin D treatment.

PMID: 115548

  A symmetrical, bilateral optic neuropathy is reported in 2 patients being treated with ketogenic diets for seizure control. Laboratory tests suggested a thiamine deficiency, and both patients recovered normal visual function after several weeks of treatment with thiamine. The risk of optic nerve dysfunction occurring during the treatment with a ketogenic diet can be minimised if routine vitamin B supplements are given and periodic evaluation of optic nerve function undertaken.

PMID: 435431

  With the conventional method of fasting or aggressive dieting to reduce excess body fat, hunger, weakness, ketogenesis and ketosis are the sequential events that follow. It is not fully understood why, under conditions of negative calorie balance where complete energy release from storage fat is critical, ketosis should arise with a concomitant wastage of energy. Here, I wish to propose a theory that relates the formation of ketone bodies under such conditions to a deficiency in dietary pantothenic acid. Supplementation of this vitamin would facilitate complete catabolism of fatty acids and thus the formation of ketone bodies could be circumvented. As a result, a sufficient amount of energy would be released from storage fat to relieve dieters of the sensation of hunger and weakness which otherwise would be difficult to endure. Hence, using this method for weight reduction together with a careful observation of calorie intake, I have great success in treating overweight-to-obese patients to lose weight.

PMID: 8583972

  The ketogenic diet is an effective alternative therapy used to control intractable seizures. It was originally described in 1921 as a way to duplicate and prolong the beneficial effects that fasting appeared to have on seizure control. It involves consuming a calorie-restricted diet in which the fat:carbohydrate + protein ratio ranges from 2:1 to 5:1. Recent prospective studies in children demonstrate that about 50% of children will continue on the diet for at least a year, with 40-50% of those starting the diet having a >50% reduction in seizures after 12 months. When the diet is discontinued it is usually due to lack of efficacy. The diet is a radical medical therapy and nutritional well-being is a constant concern. Renal stones have occurred in 5-8% of children on the diet; lipids are elevated, but the significance of this is not known. The mechanism of action of the diet remains unknown, and it is difficult to assess which biochemical parameters should be monitored as adjustments are made to the diet.

  With the introduction of Internet communications, parental interest has increased in the use of the ketogenic diet for epilepsy. It was decided to audit current practice in the use of the ketogenic diet in the UK. All paediatric dietitians who were members of the Paediatric Group of the British Dietetic Association were surveyed by a postal questionnaire. There was a 51% response rate. Twenty-two hospitals (17%) used the ketogenic diet with 101 patients being treated. Fifty-nine percent used the traditional 4:1 (four parts fat : one part carbohydrate, one part protein) classical ketogenic diet and 41% used the medium chain triglyceride diet (60% MCT fat). The age of patients ranged from 1 to over 11 years. There were wide variations in its application, with 66% of hospitals initiating the diet in hospital and 33% at home. The dietary energy administered varied from 60 to 90 kcal/kg/day, and there was no consistent policy on vitamin and mineral supplementation. Twenty-five patients continued to follow the diet after 12 months. Therefore, the ketogenic diet is commonly used for the treatment of intractable epilepsy in the UK. Further research work is needed on its nutritional safety and application.

PMID: 10845737

  Ketogenic diet therapy has been found to be an effective means of treating afebrile seizures that are refractory to antiepileptic medication alone. Controversies exist regarding its use. Potential harmful side effects include Staphylococcus aureus infections, retarded growth, hypoglycemia, hyperlipidemia, urolithiasis, and optic neuropathy. Pediatric nurses with knowledge about ketogenic diet therapy and current research regarding its use, will be better able to determine the appropriateness of this form of therapy for children with seizures that cannot be controlled by medication alone.

PMID: 9355582

  There has been renewed interest in the ketogenic diet in the treatment of medically refractory seizure disorders in childhood. This article reports the results of a retrospective chart review of 52 patients who were treated with the ketogenic diet. The vast majority (49 of 52) were treated with the classic 4:1 diet. Seizure control improved in 67.3% of patients with complete abolition of seizures in six. Adverse reactions were uncommon and included the development of renal stones, gall bladder stones, and hypoproteinemia in one patient each. Routine biochemical screening during the diet did not identify or prevent adverse events. The authors' experiences with the diet emphasize the need for close ongoing medical and dietary supervision.

PMID: 10465141