HeConnection-Treatment-Prevention-Favorable Ketogenic Diet ArgumentsFavorable Ketogenic Diet Arguments

Health-e-Solutions comment: This lengthy article, Favorable Ketogenic Diet Arguments, gives much information about the health benefits and safety of ketogenic diets. The authors conclude that they are a safe, effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure, diminishing resistance to insulin with an improvement in blood levels of glucose and insulin and they also have neurological and antineoplastic benefits. We might add that the Health-e-Solutions lifestyle includes nutritional ketosis, which has proven to be safe and effective for our two boys with type 1 diabetes since 2008, having no side effects and helping keep their blood glucose levels without hypoglycemic episodes.

(Source)

Abstract

Many negative comments have been made about the use of ketogenic diets (KDs) and experts today believe that the best way to lose weight is by cutting back on calories, chiefly in the form of fat. The international consensus is that carbohydrates are the basis of the food pyramid for a healthy diet.

However, this review will clarify that low-carbohydrate diets are, from a practical and physiological point of view, a much more effective way of losing weight. It is also argued that such diets provide metabolic advantages, for example: they help to preserve muscle mass, reduce appetite, diminish metabolic efficiency, induce metabolic activation of thermogenesis and favor increased fat loss and even a greater reduction in calories. These diets are also healthier because they promote a non-atherogenic lipid profile, lower blood pressure and decrease insulin resistance with an improvement in blood levels of glucose and insulin. Low-carbohydrate diets should therefore be used to prevent and treat type 2 diabetes and cardiovascular problems.

Such diets also have neurological and antineoplastic benefits and diet-induced ketosis is not associated with metabolic acidosis, nor do such diets alter kidney, liver or heart functions.

The Evolution of The Human Diet

The fact that the nutritional change from a hunter-gatherer diet to a carbohydrate-based diet has affected populations negatively has been revealed by archaeological findings in ancient Egyptian mummies, since tooth decay, cardiovascular disease and obesity were very frequent in those times [8]. More recently, this problem has also been reflected historically by the change in eating habits of Inuit peoples in Alaska. Traditionally, their diet contained 3-5% carbohydrates (since it was based on fish, marine mammals, moose and caribou), obesity was virtually nonexistent and type 2 diabetes was rare. Since 1961, a growing tendency in type 2 diabetes and obesity problems has been observed due to a progressive substitution of the traditional protein and fat-based diet by a diet with higher carbohydrate content. This increase has been so dramatic that in 1978, carbohydrates represented 50% of the total calorie contribution in their diet [9]. Another historical fact worth considering when analyzing the nutritional habits of American society is their increased consumption of carbohydrates, either through eating more food in general or by replacing fats with carbohydrates. This leads to an increase in obesity and atherogenic markers such as triglycerides and VLDL [10].

Most hunter–gatherers, for example, are not obese when they live their traditional lifestyle based on a low carbohydrate diet. Many hunter-gatherers consumed a predominantly plant-based diet, which was supplemented with meat when available, and others such as the Inuits consumed a high fat-protein diet. When such people are exposed to high, refined carbohydrate intake, however, they develop truncal obesity and a much higher risk of diabetes, up to 50% in some populations. This high waist-hip ratio and carbohydrate intolerance is shared by all hunter–gatherer populations throughout the world: Canadian Inuits, Native Americans, Mexican Indians, Pima Indians, South American Indians, Middle-Eastern Nomads, African Pygmies, Australian Aborigines, Maoris, South Sea Islanders, etc. [11,12,13,14,15,16,17,18,19,20,21,22,23].

Thus, all these data might suggest that it could be wrong to consider carbohydrates as the basis of the human diet.

Biochemical Rationale

When a diet is based on an excess of carbohydrates, the body uses them as the main source of energy in place of fat. In contrast, the absence of carbohydrates in the diet accelerates the use of fat. This is because insulin blocks lipolysis (by blocking adipocyte lipase) and allows glucose to enter the fat cells. This glucose is turned into triglycerides inside the fat cell through its transformation into acyl-CoA and alpha-glycerophosphate (the acyl-CoA molecules combine to make fatty acids and three of these fatty acids are bound by diglycerol acyltransferase to glycerol, originating from the alpha-glycerophosphate, to form triglycerides). Moreover, the fatty acids originating from dietary fat require the action of the glucose and insulin in order to be transformed into triglycerides (inside the fat cells), since the insulin allows glucose to enter the fat cells and glucose is necessary for the formation of alpha-glycerophosphate, which is the main source of glycerol for the fatty acids originating from dietary fat to turn them into triglycerides [6]. The last step in the synthesis of the triglycerides is therefore the attachment of glycerol to the fatty acids, a reaction that is catalyzed by diglycerol acyltransferase (DGAT). If for some reason the last stage does not occur, this is due to a deficiency in glucose and insulin to guarantee the supply of glycerol or a failure in the DGAT; hence, it is logical to assume that there will be interruptions in the synthesis of triglycerides. It has been confirmed that mice with a homozygous deficiency of DGAT have less white fat mass and are resistant to the development of dietetic obesity [7]. Hence, low insulin levels in low-carbohydrate diets likely produce similar effects; this could be one explanation, for the greater success in weight loss of these diets.

The fact that low-carbohydrate diets with an equal number of calories are more effective than low-fat diets [26,27,28,29] can only be explained by the lower metabolic efficiency of low-fat diets. This may be because, from a physiological standpoint, there is a proven link between blood ketone levels and urinary ketones [30] and because acetone is a volatile ketone, part of which is lost through breathing [24]. Thus, energy would be lost through the elimination of urine and breathing ketones. Moreover, if we consider that Ketogenic diets do not induce hypoglycemia (low glucose levels) despite improvements in the glycemic profile [31,32,33,34], we may assume that gluconeogenesis plays a prominent role. There is a very significant loss of energy in this gluconeogenic process, since 100 grams of average quality protein are necessary to form only 57 grams of glucose [35], thus entailing an energy loss of 43%. Furthermore, during the formation of one mole of glucose from alanine, 6 moles of ATP are lost in the process [36]. This energy loss is significant because one glucose mole gives 38 of ATP [24] and a loss of 6 ATP entails an energy loss of 15.79% in the process of gluconeogenesis from alanine, an amino acid for which gluconeogenesis is metabolically easier than for other amino acids, which is why a global energy loss of around 43% is not surprising.

In addition to being less energy efficient, insulin is necessary for triglyceride formation and high-fat diets increase energy loss through metabolic activation of thermogenesis, since it has been shown that the expression of uncoupling proteins (UCP or thermogenin), which are responsible for thermogenesis, increases in high-fat diets, because monounsaturated fats [37], polyunsaturated fats [38] and saturated fats [39] are all used in their induction.

Low-carbohydrate diets also enhance body composition: body fat is reduced and muscle mass is increased [40]. The conservation of muscle mass associated with these types of diets must involve ketones because it has been shown that ketones can reduce protein catabolism in catabolic situations such as fasting [41].

Metabolic Effects

Weight loss

It should also be remembered that glucose is not the only substance to induce insulin release; this process is also stimulated by certain amino acids, such as arginine and lysine, and gastrointestinal hormones secreted with food consumption such as gastrin, secretin, cholecystokinin (CCK) and gastric inhibitory polypeptide, which are capable of producing a slight increase in insulin secretion. When amino acids are combined with glucose, however, they have a synergistic effect that can double the release of insulin that could produce the same concentration of glucose [24].

Another important aspect to consider is gastric capacity, which has a satiating effect on the central nervous system, and in which fat and proteins present advantages over carbohydrates because they remain in the stomach for a longer period of time and are therefore capable of prolonging the sensation of satiation for longer than carbohydrates [24]. Nevertheless,

…high-fiber carbohydrate meals also have high satiating power [42]. The carbohydrates used in KETOGENIC DIETs should therefore be from high-fiber carbohydrate sources such as vegetables.

Release in CCK, considered to be one of the most powerful appetite suppressants, is also stimulated by the consumption of fat and proteins but not carbohydrates [43]. β-hydroxybutyrate (the major circulating ketone body) has been shown to directly inhibit appetite [44].

The low glycemic nature of a KETOGENIC DIET may also prevent transient dips in blood glucose, something which can occur with higher carbohydrate diets. Thus, avoidance of hypoglycemic episodes may reduce appetite [45].

Furthermore, protein alone has a greater anorexic effect than carbohydrates that may be mediated by increased central nervous system leptin sensitivity [46] and decreased postprandial ghrelin concentrations [47]. Leptin is produced by adipose tissue and is a circulating signal that reduces appetite. Nevertheless, obese people have unusually high circulating concentrations of leptin. These people are said to be resistant to the effects of leptin. Ghrelin is a hormone produced by cells lining the stomach that stimulate appetite.

The lower metabolic efficiency and anorexic effect of protein may contribute to weight loss. In fact protein intake is inversely associated with abdominal obesity in multi-ethnic populations [48].

Bearing in mind all these physiological concepts, a logical hypothesis might be that carbohydrates alone and in large quantities could induce obesity; when consumed together with fat, carbohydrates allow fat to build up; when consumed together with proteins, carbohydrates multiply their obesity-inducing effect; and finally, carbohydrates have a lower satiating effect than lipids and proteins. Therefore, the best combination for many people to lose weight would be a diet containing fat and proteins, as this would achieve blood levels of insulin that would allow a metabolic change to take place to combat fat accumulation and favor the use of accumulated fat. Glycolytic metabolism would therefore make way for lipolytic or oxidative metabolism. The activation of this lipolytic metabolic route triggers the appearance of ketones in the blood, which is a natural response to fasting, prolonged exercise and high fat content diets [49]. For this reason, from a physiological standpoint, weight loss strategies that are based on the reduction of fat intake and the maintenance of carbohydrate intake as a main source of energy may be incorrect and would only be effective through simple calorie restriction and not through metabolic change.

Metabolic change is achieved when the content of carbohydrates in the diet is low enough to cause Ketosis (hence the name “ketogenic” or “low-carbohydrate” diets). The question is what level of ketosis is necessary to define a ketogenic diet (KD)? This will depend on the purpose of such diet [We argue that it also depends on the glycemic load of the carbohydrates, which is why they recommend high-fiber carbs from vegetables].

When used for weight loss, a carbohydrate intake of less than 0.2-0.4 grams per kilogram of weight per day must be achieved and you can eat limitless amounts of fat and protein. However, KETOGENIC DIETs used to treat intractable pediatric epilepsy are the most restrictive for obtaining stronger ketosis, since although they are very low in carbohydrates (less than approximately 10g/day), they are also low in proteins and very high in fat: the lipid to non-lipid (protein+carbohydrates) ratio is about 4:1 [50,51,52,53].

The cardiovascular system and glucose metabolism

Compared with low-fat diets, low-carbohydrate diets foster an improvement in blood glucose levels, insulin and insulin resistance [34]. Moreover, insulin resistance is believed to play a central role in the pathogenesis of cardiovascular dysmetabolic syndrome, which is characterized by a constellation of hypertension, dyslipidemia, glucose intolerance and hyperuricemia [54]. Insulin resistance promotes dyslipidemia (high triglycerides, total cholesterol and lower high-density lipoprotein) [55] regardless of obesity [56] and carotid intima-medial thickness (which is an early indicator of atherosclerosis), regardless of blood pressure, weight and whether or not the individual is a smoker or diabetic [57].

Insulin levels are the main cause of hypertension associated with obesity [58]. This is due to the fact that hyperinsulinemia causes antinatriuresis, antikaliuresis, and antiuricosuria [59]. It is therefore not surprising that insulin resistance is associated with hypertension [60]. Another benefit is that there is an inverse association between higher dietary protein intake and blood pressure [61,62], which may be linked to liquid loss through increased urea production/elimination as urea comes from protein metabolism and kidneys need to eliminate urea with a large quantity of water [63].

The nervous system

Ketosis has been shown to protect against cerebral damage produced by hypoxia [64] and toxic substances such as free radical MPP deriving from meperidine [65], which produces an instant neurological form of Parkinsonism [66].

The KETOGENIC DIET is an effective and well-tolerated medical therapy for intractable epilepsy. Although ketosis is believed to produce the anticonvulsant effects of KETOGENIC DIETs, the mechanisms involved are still unknown [67].

Anti-tumor activity

KETOGENIC DIETs have shown to be efficient in reducing tumor size. Specifically, it has been confirmed that in astrocytomas they can reduce tumor mass by 80% through the inhibition of angiogenesis [68]. Another factor that may be involved in this tumor inhibition is the reduced availability of glucose to the tumor [69].

Anti- inflammatory activity

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine secreted by several types of immune defense cells including lymphocytes, eosinophils, neutrophils and monocyte/macrophages [70]. It is also secreted along with ACTH by the pituitary gland in response to stressors such as endotoxinemia [71]. New functions have been reported recently for MIF in several processes, such as cell proliferation, angiogenesis, atherosclerosis and wound healing [72,73]. Ketone bodies reportedly counteract certain inflammatory processes [74,75] by blocking the ketonase activity of MIF[76] .

Results of Clinical Trials

The effectiveness of ketogenic diets in weight loss

In addition to the fact that an equal number of calories are ingested, KETOGENIC DIETs are more effective for achieving fat loss than conventional high-carbohydrate/low-fat diets. Low-carbohydrate diets have even proved to be more effective than conventional diets for more selective fat loss and conserving muscle mass [26,77]. Benoit et al. reported that when a 1000 kcal KETOGENIC DIET (10 g of carbohydrates/day) was consumed for 10 days, seven male subjects lost an average of 600 g/day, of which 97% was fat [77]. Young et al. [26] compared three diets, each consisting of 1800 kcal, but containing different proportions of carbohydrates (104 grams, 60 grams and 30 grams, respectively) and observed a negative correlation between the proportion of carbohydrates in the diet and weight loss and a positive correlation with lean weight loss. Thus, the lowest carbohydrate diet proved to be most effective way of losing weight and conserving muscle mass. Willi et al. [78] also concluded that the use of a low-carbohydrate diet in adolescents with morbid obesity was effective for weight loss and conserving muscle mass. Sondike et al. [28] found that the use of a low-carbohydrate diet in adolescents without calorie restrictions in fats and proteins was a more effective way of losing weight than a low-fat diet and significantly improved triglyceride and cholesterol levels. The aforementioned authors also affirmed that in adolescents on a low-carbohydrate diet with no calorie restriction in terms of fats and proteins, despite consuming an average of 700 Kcal more per day than the group on the low-fat diet, weight loss was more than double and the improvement in the level of triglycerides was more pronounced [79]. These findings were also confirmed by Greene et al. [27], who showed that with an equal number of calories and even increasing the number of calories by 300 or more, low-carbohydrate diets foster greater weight loss than low-fat diets. Samaha et al. performed a six-month study and found that severely obese subjects with a high prevalence of diabetes or metabolic syndrome lost more weight over the course of six months on a carbohydrate-restricted diet than on a calorie-fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost [80]. Yancy et al. [81] also conducted a six month study and concluded that a low-carbohydrate diet program achieved better participant adherence and greater weight loss than a low-fat diet program. All these studies have one important limitation: the study period in each case was never longer than 6 months. However, Foster et al. and Stern et al. [82,83] compared low carbohydrate diets to traditional diets (low calorie-high carbohydrate diets in clinical trials) for weight loss over the course of one year. In both clinical trials, low carbohydrate diets produced greater weight loss than the conventional diet for the first six months, but the differences were not significant at 1 year. In both diets, adherence was poor but, the participants on the low-carbohydrate diet displayed more favorable overall outcomes at 1 year than those on a conventional diet. Dansinger et al. [84], in another one-year clinical trial, compared the effectiveness of 4 popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss and reported that overall dietary adherence rates were low, although increased adherence was associated with greater weight loss for each diet group. All 4 diets resulted in modest statistically significant weight loss at 1 year, with no statistically significant differences between diets. Brinkworth et al. [85] performed a clinical intervention study on two groups of subjects randomly assigned to either a standard protein or high-protein diet. These authors also reported poor long-term dietary adherence behavior for both dietary patterns at month 17. Taking into account all these long-term studies, the real problem associated with long-term diets is poor adherence. People get bored following the same food patterns. Therefore strong willpower is needed to achieve better adherence.

Another advantage of low-carbohydrate diets is the full feeling they provide and the suppression of hunger, unlike high-carbohydrate diets since carbohydrates do not satisfy the appetite and may even increase it [86].

Cardiovascular benefits

Contrary to past opinions, KETOGENIC DIETs also lead to improvements in cardiovascular health. When analyzing the nutritional habits of American society, carbohydrate consumption has risen, resulting in an increase in obesity and atherogenic markers such as triglycerides and VLD [10]. For Dasthi et al. [32], the use of a KETOGENIC DIET with obese patients over a period of 12 weeks, in addition to being effective and safe for weight loss, also modified cardiovascular risk factors favorably in these patients. Specifically, there is a significant decrease in fasting and postprandial (in response to high-fat meals) blood triglyceride levels [87] and both blood levels are considered independently as risk factors for cardiovascular disease [88,89]. Furthermore, the phenomenon of carbohydrate-induced hypertriglyceridemia is long established [10,90,91,92]. The serum triglyceride levels decreased more and high-density lipoprotein cholesterol level increased more with the low-carbohydrate diet than with the low-fat diet: at 6 months [81] and at 12 months [82]. Bearing in mind that the atherogenic lipoprotein phenotype is characterized by an increase in liver production of VLDL, low levels of HDL and a predominance of small LDL particles [93], it is surprising that low-fat and high-carbohydrate diets favor this atherogenic profile in patients who previously did not have this problem [94]. Low-carbohydrate high-fat diets, on the other hand, improve all aspects of atherogenic dyslipidemia, decreasing fasting and postprandial triglyceride levels and increasing HDL and LDL particle size. These diets prompt an increase in larger LDL particles, a drop in smaller LDL particles and a decrease in the cholesterol/HDL ratio [87,95,96], which lowers glucose levels and favors weight loss [87,96]. KETOGENIC DIETs based around proteins also have cardiovascular benefits, such as decreasing total cholesterol, LDL and triglyceride levels and increasing HDL levels [32]. When comparing low-carbohydrate/high-protein diets and low-carbohydrate/high-fat diets, it seems that the difference between both diets in relation to blood lipid levels lies in the LDL, which are significantly lower in high-protein diets [97]. Low-carbohydrate diets clearly have short-term cardiovascular benefits, but such benefits can also be observed over longer periods of time: 6 months, since improvements in blood pressure and blood levels of total cholesterol, LDL, HDL and triglycerides are noted in the 6 month period [98,99]; 12 months, since the low-carbohydrate diet was associated with a greater improvement in certain risk factors for coronary heart disease (higher HDL and lower triglyceride levels) [82,83].

In relation to cardiovascular health, these diets have also proven to be effective for hypertension [100,101].

Low-carbohydrate/high-protein diets are more effective than high-carbohydrate diets for decreasing blood pressure (both diastolic and systolic) [100].

Benefits in the prevention and treatment of type 2 diabetes

Low-carbohydrate diets also have beneficial effects in the prevention and treatment of type 2 diabetes, since they improve the glycemic profile [32,102,103,104], insulin sensitivity, hemoglobin A1c [102,103,104] and reduce plasma triglyceride and cholesterol levels. KETOGENIC DIETs may also result in spontaneous reductions in energy intake [106]. These diets should therefore be recommended in the prevention of not just cardiovascular problems but also type 2 diabetes [99]. Volek et al. [34] observed that in comparison with a low-fat diet, a low-carbohydrate diet improved blood glucose levels, insulin and insulin resistance, and was also more effective for weight loss in obese and overweight women. Nobels et al. [31] and Brehm et al. [61], also reported that a low-carbohydrate diet, besides reducing weight and blood pressure, corrected glucose metabolism, as revealed by a decrease in glucose and insulin circulating in the blood. Furthermore, Bisschop et al. [33] compared the effects of three diets (A: 85% carbohydrates and 0% fat; B: 4% carbohydrates and 41% fat; C: 83% fat and 2% carbohydrates) and observed that diet C was able to turn a glycolytic metabolism into a lipolytic metabolism, with fat becoming the main source of energy. In type 2 diabetes, insulin resistance gives rise to an inability to decrease glucose blood levels due to an impaired capacity to use glucose for energy and to store glucose as glycogen. According to the results obtained in the study, a high-fat low-carbohydrate diet does not suppress the removal of glucose from the blood as a result of the body’s ability to increase the storage of glucose as glycogen and avoid hypoglycemia with improved gluconeogenesis. Bisschop et al. [33] also emphasize that although a lipolytic metabolism is present in low-carbohydrate high-fat diets and in fasting, important differences exist between them because the low-carbohydrate high-fat diets do not cause insulin resistance and cause glucose to be stored as glycogen, whereas fastingr causes insulin resistance and does not increase glucose storage.

Yancy et al. [105] examined the safety and effectiveness of a KETOGENIC DIET for improving glycemic control in patients with type 2 diabetes. After 16 weeks, the 19 men and women completing the study displayed significant improvements in glycemic control (HbA1c decreased 15%) and triglyceride levels, significant weight loss of 7%, and improvements in fasting serum glucose. Diabetes medications were discontinued or reduced in 13 of the participants. Results indicated that type 2 diabetics may benefit from a KETOGENIC DIET, since body weight and triglycerides were reduced and improved glycemic control enabled participants to use less medication.

Over the course of one year, comparing a low-carbohydrate diet and a low-fat/ low-calorie/ high-carbohydrate diet, the low-carbohydrate was associated with a greater improvement in glycemic control [83].

As regards insulin resistance, polycystic ovary syndrome, an endocrine disorder characterized by insulin resistance, central obesity, and abnormal blood lipid levels, is common in women of reproductive age. Westman et al. [106] and Mavropoulos et al. [107] studied the effects of a KETOGENIC DIET on polycystic ovary syndrome. After 24 weeks, the KETOGENIC DIET led to significant improvement in weight, percent free testosterone [99,100], LH/FSH ratio, and fasting insulin in women with obesity and polycystic ovary syndrome over a 24 week period [100]. These results indicated that a KETOGENIC DIET may be beneficial for women with polycystic ovary syndrome.

Neurological benefits

The development of Alzheimer’s disease and the accumulation of amyloid-β have been linked to dietary factors. Engelhart et al. [108] found that a high intake of cholesterol, saturated fat, trans and total fat, and a low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with an increased risk of dementia or its subtypes. Nevertheless, diets rich in saturated fat have been repeatedly associated with dementia in epidemiological studies [107,108,109,110,111,112], although they have been difficult to reproduce [113]. Moreover, several experiments in mouse models seem to confirm the link between lipid rich diets and Alzheimer’s disease. Using transgenic mouse models of Alzheimer’s disease, several groups have reported that high-fat diets or diets with added cholesterol increased levels and deposition of the amyloid-β peptide [114,115,116,117,118]. However, these studies did not examine the effects of lipid rich diets in combination with low carbohydrate intake. Van der Auwera et al. [119] showed that a diet high in saturated fats and low in carbohydrates can actually reduce levels of amyloid-β peptide in a mouse model of Alzheimer’s disease. They concluded that dietary strategies aimed at reducing amyloid-β peptide levels should take into account interactions of dietary components and metabolic outcomes, paying particular attention to carbohydrate levels, total calories and the presence of ketone bodies.

Ketogenic diets for intractable seizures

The KETOGENIC DIET is an effective and well-tolerated medical therapy for intractable childhood epilepsy [52,53,120,121,122,123,124,125], adolescent epilepsy [126] and very probably adult epilepsy [127].

It has been shown that the state of ketosis induced by the consumption of a KETOGENIC DIET that is high in fat and low in carbohydrates has a protective effect against epileptic attacks in children since it allows better control of these attacks [128] and can be potentially more effective than new anticonvulsant drugs in cases of intractable epilepsy [120], working synergistically or complementarily to anticonvulsant drugs such as valproic acid and phenytoin, respectively, elevating seizure thresholds and reducing seizure severity [129]. Specifically, in a study of 58 patients with histories of approximately 20 seizures per day, refractory to over 6 drugs, a KETOGENIC DIET was effective in two thirds of the cases. In one third, it produced the cessation of seizures and in another third a significant reduction in frequency [130]. Kossof et al. [53] examined 20 children (aged 3 to 18) who were having between 4 and 470 seizures a week and who did not respond to drug therapy. The children were put on a diet that included fewer carbohydrates than the standard Atkins diet, for six months. Of the 16 who completed the study, 13 (65%) displayed a greater than 50 percent improvement in seizures, seven (35%) achieved a greater than 90 percent improvement and four were seizure-free. The overall side effects were low, with one child developing a complication that did not warrant stopping the diet, despite a brief period of hospitalization. Finally, the authors concluded that a modified Atkins diet is an effective and well-tolerated therapy for intractable pediatric epilepsy.

Severe myoclonic epilepsy in infants or Dravet syndrome is one of the most malignant epileptic syndromes. Caraballo et al. [131] studied the severity and intractability of seizures in patients with Dravet syndrome, and reported a significant reduction in the number of seizures in 10 of the 13 children who remained on the diet, showing that the KETOGENIC DIET is an interesting therapeutic alternative. Even when seizure reduction was not dramatic, the patient’s quality of life improved, and the number of antiepileptic drugs administered to all the children was reduced to one or two. These authors stated that children with Dravet syndrome should be offered the KETOGENIC DIET immediately after three adequate trials of antiepileptic drugs have failed.

Carbohydrate neoplastic effects versus ketogenic diet antineoplastic effects

Many scientists believe that the healthiest diets contain 55-70% carbohydrates and that KETOGENIC DIETs may be potentially cancerous since many epidemiological studies have linked a high intake of animal products with the genesis of cancer. However, when collecting and analyzing data, these studies fail to take into account the possible effects of dietary carbohydrates and glucose metabolism abnormalities, which are important confounding variables. Factors related to the carbohydrate and glucose metabolism, such as the energetic contribution of carbohydrates, glycemic index and glycemic load, fasting glycemia and insulinemia, as well as glucose and insulin levels after oral glucose load, are associated with the risk of developing many types of cancer. Therefore, these factors should be borne in mind when collecting and interpreting epidemiologic information. Moreover, many studies have reported tumor-inhibitory effects in KETOGENIC DIETs [132].

A direct link has been identified between the risk of endometrial cancer and the glycemic index [133] or glycemic load [133,134]. Augustin et al. [135] found a connection between carbohydrate intake and the risk of gastric cancer. Augustin et al [136] also found a direct link between glycemic index and glycemic load and the risk of ovarian cancer and, consequently, a possible role of hyperinsulinemia/insulin resistance in the development of ovarian cancer. Borugian et al. [137] reported that increased non-fiber (“effective”) carbohydrate and total carbohydrate consumption are both associated with the increased risk of colorectal cancer in both sexes. In women, relative risk is higher for the right colon, whereas in men the relative risk is higher for the rectum. Franceschi et al. [138] found a positive link between the glycemic index and glycemic load and colorectal cancer. It has been suggested that this association is caused by insulin resistance; insulin resistance therefore leads to colorectal cancer [139,140] through the lesion-promoting effect of elevated levels of insulin, glucose or triglycerides [139]. The most important carbohydrates associated with the risk of colorectal cancer are bread, cereal dishes, potatoes, cakes and desserts, and refined sugar intake. In contrast, fish, raw and cooked vegetables and fruit displayed a negative association with the risk. Consumption of eggs and meat (white, red or processed meats) appeared to be non-influential [141]. In relation to the risk of developing breast cancer, Holmes et al. [142] discovered no evidence linking meat or fish intake during mid-life and later with the risk of breast cancer. Nevertheless, carbohydrates provided by starch were the most frequently found component contributing to the positive association with breast cancer. Starch food sources included food such as white bread, pasta, rice, crackers and cookies were particularly linked [143]; this is due to the proven association between the glycemic index or glycemic load and the risk of breast cancer, possibly due to the role of hyperinsulinemia/insulin resistance in breast cancer development [144]. Franceschi et al. [143] found that high intakes of polyunsaturated and unsaturated fatty acids were associated with a lower risk of breast cancer and that saturated fatty acids, protein and fiber were not significantly associated with breast-cancer risks. Romieu et al. [145] also found a positive connection between carbohydrate intake and breast cancer risk but not with fat intake.

KETOGENIC DIETs have shown to be efficient in reducing the size of tumors and avoiding the loss of muscle mass associated with disease in humans [146,69] and mice [147].

Adverse Effects

A higher intake of total and saturated fat is widely believed to contribute to the development of coronary heart disease. This belief is largely based on ecological studies relating dietary intake of saturated fat and the incidence of coronary heart disease.

The principle of carbohydrate restriction says that by keeping insulin low, the metabolism is biased towards lipid oxidation rather than storage or the effects of fatty acids on peripheral tissues.

Most studies that have reported deleterious effects of saturated fat have been carried out in the presence of high carbohydrate, which begs the question as to whether such effects carry over into hypocaloric conditions or those where insulin is better controlled [148,149,150,151]. In the Seven Countries Study [152], intake of saturated fat as a percentage of calories was strongly correlated with coronary death rates across 16 defined populations in seven countries (r=0.84). Interestingly, the correlation between the percentage of energy from total fat and coronary heart disease incidence was much weaker (r=0.39). Indeed, the regions with the highest (Finland) and lowest (Crete) coronary heart disease rate had the same amount of total fat intake, about 40% of energy, which was the highest among the 16 populations. In a more recent analysis of the Seven Countries Study [153], Kromhout et al. found a strong positive correlation between 25-year death rates from coronary heart disease and intakes of four major long-chain saturated fatty acids and trans fatty acids.

Data from international comparisons as well as migration studies, although they provide evidence for the importance of diet and environmental factors in the cause of coronary heart disease, are inadequate for testing specific hypotheses regarding the role of individual dietary components due to the confounding effect of other aspects of diet, physical activity, smoking, obesity and economic development. Prospective cohort studies of individuals, in which diet is assessed prior to the occurrence of disease, are typically considered to be the strongest non-randomized design. Despite the long-standing interest in the diet-heart hypothesis, the number of cohort studies that have directly addressed associations between dietary fat intake and risk of coronary heart disease is surprisingly low and the results are not consistent. A significant positive association between saturated fat intake and the risk of coronary heart disease was found in two studies [154,155] but not in others [156,157,158,159,160,161,162]. A significant inverse association between polyunsaturated fat intake and coronary heart disease was found in only one study [160], but not in others [156,159,161,162]. The interpretation of these findings is complicated by the small study size, inadequate dietary assessment, incomplete adjustment for intake of total energy, failure to account for trans isomers of unsaturated fats and lack of control for intakes of other types of fat and other components of diet.

As for the serious concerns regarding the possible negative effects of KETOGENIC DIETs on the heart, kidney and liver functions and situations of acidosis, it must be emphasized that low-carbohydrate diets do not produce harmful alterations in kidney [69,156,157,158] or liver functions [79,163,164]. This is because high-protein diets are not associated with harmful alterations of kidney functions in patients with normal kidney functions [166,167] and also because ketosis, which is linked to the use of KETOGENIC DIETs, is not associated with acidosis and does not alter heart function [68]. This is demonstrated by Inuit peoples, who can live on a diet based almost exclusively on fat; they do not suffer acidosis as a result of ketones, and therefore do not suffer from Ketoacidosis. This is due to the physiological situations in which the body is capable of adapting to the change from a carbohydrate-based diet to a very low-carbohydrate diet, in such a way that even the brain cells that obtain almost all their energy from glucose are able to adapt and obtain between 50% and 75% of their energy from fat [24], specifically ketone bodies, a brain metabolic change that also occurs with fasting [168]. This would explain why ketoacidosis appears fundamentally in pathological situations such as diabetes mellitus and starvation [24], in other words situations in which there is no insulin or this is ineffective. This does not occur with KETOGENIC DIETs since, as explained previously, the amino acids and gastrointestinal hormones produced with food ingestion are able to stimulate the release of low doses of insulin which, in accordance with the findings of the authors cited, are sufficient to avoid pathological situations deriving from the total absence of the insulin effect and are necessary to avoid fat accumulation, thus promoting fat loss and improving insulin sensitivity. Nevertheless, the KETOGENIC DIET may produce a state of ketoacidosis, as in the case reported by Chen et al. [169] in a 40-year-old obese white woman. She had morbid obesity, known to be a pathological situation that can be associated with many metabolic problems. This may be the explanation in the case reported because it is the only case of ketoacidosis reported in the entire bibliography consulted in relation to KETOGENIC DIETs and weight loss.

In connection with acidosis, since ketosis from KETOGENIC DIETs is not linked to acidosis, it would clearly not affect the activities that can increase acidosis such as physical activity. Indeed, some studies indicate that the use of KETOGENIC DIETs does not imply a limitation in physical activity, the only exception being reduced performance in anaerobic activities such as weight lifting or sprints, and should therefore be borne in mind by certain sports competitors [170]. Some authors go even further, showing that KETOGENIC DIETs increase performance in aerobic physical activities such as cycling, due to the fact that the organism is better prepared to use fat as a source of energy [171] since a metabolic adaptation occurs in which fat becomes the main source of energy without affecting blood glucose levels [172], thus a glycolytic metabolism becomes a lipolytic metabolism.

Another drawback that has been attributed to high-protein diets is that they have a negative effect on the calcium metabolism and are therefore damaging in relation to bone density. There are conflicting studies that state that the consumption of high levels of protein does not affect bone density negatively [173,174], that the consumption of low levels of protein has a negative impact on older people’s bone density [173] and that an increase in animal protein intake to 1.55 grams per kilogram of body weight per day has a beneficial effect on the bone mass of older people [175]. Moreover, no link has been found between the consumption of proteins/phosphorus and calcium absorption efficiency [176], and also the negative effect on bone mass can be avoided when proteins levels are very high, by consuming 20 mg of calcium per gram of protein consumed [177].

Nevertheless, KETOGENIC DIETs have side effects and most of them have been reported in KETOGENIC DIETs used to treat intractable pediatric epilepsy. This is very likely due to the fact that these KETOGENIC DIETs are the most restrictive since they are very low in carbohydrates (less than about 10g/day), low in proteins and very high in fat. The lipid to non-lipid (protein+carbohydrates) ratio is about 4:1 [50,51,52,53] for strong ketosis.

Another problem possibly associated with epilepsy KETOGENIC DIETs is that Hopkins protocol has a fasting phase and fluid restriction [178,179]. In fact, Kim et al. [180] concluded in their study that initial fasting and fluid restriction are not essential for the KETOGENIC DIET and that the tolerability of this treatment may be improved. Ballaban et al. [50] found that only 10% (5 patients) of children (total: 52) in their study experienced serious adverse effects events after initiation of the diet: two patients developed severe hypoproteinemia within 4 weeks of starting the diet, and 1 of them also developed lipemia and hemolytic anemia; 1 child developed Fanconi’s renal tubular acidosis within 1 month of starting the diet and two other children manifested marked increases in liver function tests, one during the initiation phase and the other 13 months later. Bergvist et al. [51] found an association between selenium deficiency in KETOGENIC DIETs and cardiomyopathy. Selenium deficiency was found in 20% of the patients evaluated and only one of them had cardiomyopathy, with normal cardiac physical examination and ECG, but abnormal echocardiogram. They found that selenium supplementation improved levels in all children. Kang et al. [52] found dehydration as the most common early-onset complication (46.5% patients), especially in patients who started the KETOGENIC DIET with initial fasting. Gastrointestinal disturbances, such as nausea/vomiting, diarrhea and constipation, were the second most common early-onset complication noted (38.8% patients), sometimes associated with gastritis and fat intolerance. Other early-onset complications detected in patients, in order of frequency, were hypertriglyceridemia (27.1% of patients), transient hyperuricemia (26.4%), hypercholesterolemia (14.7%), various infectious diseases (9.3%), symptomatic hypoglycemia (7%), hypoproteinemia (5.4%), hypomagnesemia (4.7%), repetitive hyponatremia (4.7%), low concentrations of high-density lipoprotein (3.9%), lipoid pneumonia due to aspiration (2.3% ), hepatitis (2.3%), acute pancreatitis (0.77%), and persistent metabolic acidosis (0.77%). Late-onset complications also included osteopenia (14.7%), kidney stones (3.1%), cardiomyopathy (0.77%), secondary hypocarnitinemia (1.6%), and iron-deficiency anemia (1.6%). They concluded that most KETOGENIC DIET complications are transient and can be easily remedied with various conservative treatments. As regards KETOGENIC DIETs and kidney stones, the high risk of both uric acid and calcium stone formation is due to the conjunction of hypercalciuria, acid urine and low urinary citrate excretion with low fluid intake [181]. Fluid intake should therefore be optimum in KETOGENIC DIETs to prevent kidney stone formation.

Summary

In the opinion of most physicians and nutrition experts, carbohydrates should be a major component of daily energy intake for a healthy lifestyle. For that reason, this paper presents a one-sided review of the literature (the other is already well-known), giving scientific arguments in favor of ketogenic diets and proving that these diets are safe and may be very useful for weight loss, glucose intolerance, type 2 diabetes, neurological disorders or epilepsy and cancer.

Conclusions

Low-carbohydrate diets are a safe, effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure, diminishing resistance to insulin with an improvement in blood levels of glucose and insulin and they also have neurological and antineoplastic benefits.

Further research is needed on the safety and effectiveness of this diet, and for that reason a low-carbohydrate diet under medical supervision would be the most suitable option.

Health-e-Solutions comment: The Health-e-Solutions lifestyle is ketogenic, which causes the body to become fat-adapted, and able to get nearly all of its energy requirements from non-carbohydrates sources. Nevertheless, the Health-e-Solutions lifestyle is not a true low-carb diet. Instead, the emphasis is on very low-glycemic foods that have plenty of high-fiber carbohydrate, but not the kind that cause hyperglycemia, hyperinsulinemia and the other accompanying problems associated with higher-glycemic foods. The Health-e-Solutions lifestyle is in line with what these authors stated above: “High-fiber carbohydrate meals also have high satiating power. The carbohydrates used in KETOGENIC DIETs should therefore be from high-fiber carbohydrate sources such as vegetables.”

HeS Right Carbs-Favorable Ketogenic Diet ArgumentsOur Recipe e-Books provide alternatives to the usual high-carb, high insulin-demand, low nutrition foods that are standard fare for the typical western diet. Our Home Study Course teaches you how to implement the Health-e-Solutions lifestyle in a practical and livable way. Our support services can make the difference between success and failure during your transformation. And our advanced resources will take you deeper into practical application and underlying research. We think it can form the foundation for a natural, way to better control all types of diabetes.

References

  1. Eaton SB, Konner M: Paleolithic Nutrition: a consideration of its nature and current implications. N Engl J Med1985, 312: 283-289.
  2. Miller J, Colagiuri S: The carnivore connection: dietary carbohydrate in the evolution of NIDDM. Diabetologia 1994; 37:1280-6.
  3. Speth JD, Spielmann KA: Energy source, protein metabolism, and hunter-gatherer subsistence strategies. J Anthropol Archaeol 1983; 2:1-31.
  4. Cordain L, Brand-Miller J, Eaton SB, Mann N, Holt SH, Speth JD: Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherers. Am J Clin Nutr 2000, 71:682-92.
  5. Cordain L: The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. J Am Neutraceut Assoc 2002, 5:15-24.
  6. Cordain L, Eaton SB, Miller JB, Mann N, Hill K: The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr 2002, 56(Suppl 1):S42-52.
  7. Eaton SB, Konner M, Shostak M: Stone agers in the fast lane: Chronic degenerative diseases in evolutionary perspective. Am J Med 1988, 84: 739-749.
  8. Leek FF. In: David AR, ed. Science in Egyptology. 1st ed. Dental health and disease in ancient Egypt with special reference to the Manchester mummies. Manchester, United Kingdom: Manchester University Press; 1986: 35-42.
  9. Murphy NJ, Schraer CD, Thiele MC, et al: Dietary Changes and Obesity Associated with Glucose Intolerance in Alaska Natives. J Am Diet Assoc 1995, 95: 676-682.
  10. Parks EJ, Hellerstein MK: Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 2000, 71: 412-433.
  11. O’Keefe JH, Cordain L: Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin Proc 2004, 79:101-8.
  12. Dowse GK, Spark RA, Mavo B, Hodge AM: Extraordinary prevalence of non-insulin-dependent diabetes mellitus and bimodal plasma glucose distribution in the Wanigela people of Papua New Guinea. Med J Aust 1994, 160:767-74.
  13. Cockram Clive S: Diabetes mellitus: perspective from the Asia-Pacific region. Diabetes Res Clin Pract 2000,50(Suppl 2):S3-7.
  14. McKeigue PM, Shah B, Marmot MG: Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991, 337:382-6.
  15. O’Dea K, Patel M, Kubisch D, Hopper J, Traianedes K. Obesity: diabetes and hyperlipidaemia in a Central Australia Aboriginal community with a long history of acculturation. Diabetes Care 1993, 16:1004-10.
  16. Roosevelt AC, Lima de Costa M, Lopes Machado C, Michab M, Mercier N, Valladas H, et al.: Paleo-Indian cave dwellers in the Amazon: the peopling of the Americas. Science 1996, 272:373-84.
  17. Milton K: Protein and carbohydrate resources of the Maku Indians of northwestern Amazonia. Am Anthropol 1984, 86:7-27.
  18. Martorell R: Diabetes and Mexicans: why the two are linked. Prev Chronic Dis 2005, 2:A04.
  19. Dabelea D, Knowler WC, Pettitt DJ: Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians. J Matern Fetal Med 2000;9:83-8.
  20. Szathmary EJE: Non-insulin dependent diabetes mellitus among aboriginal North Americans. Annu Rev Anthropol 1994, 23:457-82.
  21. Robinson EJ, Gebre Y, Pickering JL, Petawabano B, Superville B, Lavallée C: Effect of bush living on aboriginal Canadians of the Eastern James Bay region with non-insulin-dependent diabetes mellitus. Chronic Dis Can 1995, 16:144-8.
  22. Ebbesson SO, Schraer CD, Risica PM, Adler AI, Ebbesson L, Mayer AM, et al.: Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations: the Alaska-Siberia Project. Diabetes Care 1998;21:563-9.
  23. Dowse GK, Zimmet PZ, Finch CF, Collins VR: Decline in incidence in epidemic glucose intolerance in Nauruans: implications for the “thrifty genotype”. Am J Epidemiol 1991, 133:1093-104.
  24. Guyton AC, Hall JE. Fisiología Médica. 9th ed. Madrid, Spain: Interamericana McGraw-Hill; 1996: 927-952, 1063-1077.
  25. Smith S, Cases S, Jensen DR, et al: Obesity resistance and multiples mechanisms of triglyceride synthesis in mice lacking Ggta. Nat Genet 2000, 25: 87-90.
  26. Young CM, Scanlan SS, Im HS, Lutwak L: Effect on body composition and other parameters in obese young men of carbohydrate level of reduction diet. Am J Clin Nutr 1971, 24: 290-296.
  27. Greene PJ, Devecis J, Willett WC: Effects of low-fat vs ultra-low-carbohydrate weight-loss diets: A 12-week pilot feeding study. Abstract presented at Nutrition Week 2004, February 9-12, 2004, in Las Vegas, Nevada.
  28. Sondike SB, Copperman N, Jacobson MS: Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr 2003, 142: 253-258.
  29. Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D’Alessio DA: The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets. J Clin Endocrinol Metab 2005, 90: 1475-1482.
  30. Coleman MD, Nickols-Richardson SM: Urinary ketones reflect serum ketone concentration but do not relate to weight loss in overweight premenopausal women Following a low-carbohydrate/high-protein diet. J Am Diet Assoc 2005, 105: 608-611.
  31. Nobels F, van Gaal L, de Leeuw I: Weight reduction with a high protein, low carbohydrate, calorie restricted diet: Effects on blood pressure, glucose and insulin levels. The Netherlands Journal of Medicine 1989, 35: 295-302.
  32. Dashti HM, Bo-Abbas YY, Asfar SK, et al: Ketogenic diet modifies the risk factors of heart disease in obese patients. Nutrition 2003, 19: 901-02.
  33. Bisschop PH, de Metz J, Ackermans MT, et al. ,: Dietary fat content alters insulin-mediated glucose metabolism in healthy men. Am J Clin Nutr 2001, 73: 554-559.
  34. Volek JS, Sharman MJ, Gomez AL: Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J Am Coll Nutr 2004, 23: 177-184.
  35. Fine EJ, Feinman RD. Thermodynamics of weight loss diets. Nutr J 2004, 1: 15.
  36. Voet D, Voet JG, Pratt W: Fundamentals of biochemistry. 3rd ed. New York: John Wiley & Sons; 2004: 457-459.
  37. Rodriguez VM, Portillo MP, Pico C, Macarulla MT, Palou A: Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle. Am J Clin Nutr 2002, 75:213-220.
  38. Sadurskis A, Dicker A, Cannon B, Nedergaard J: Polyunsaturated fatty acids recruit brown adipose tissue: increased UCP content and NST capacity. Am. J. Physiol 1995, 269:E351-360.
  39. Portillo MP, Serra F, Simon E, del Barrio AS, Palou A: Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats. Int J Obes Relat Metab Disord 1998, 22: 974-979.
  40. Volek JS, Sharman MJ, Love DM, et al: Body composition and hormonal responses to a carbohydrate restricted diet. Metabolism 2002, 51: 864-870.
  41. Sherwin RS, Handler RG, Felig R: Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest. 1975, 55: 1382-1389.
  42. Holt SH, Delargy HJ, Lawton CL, Blundell JE: The effects of high-carbohydrate vs high-fat breakfasts on feelings of fullness and alertness, and subsequent food intake. Int J Food Sci Nutr 1999, 50:13-28
  43. Fernández López JA, Remesar X, Alemany M: Tratado de Nutrición. 1st ed. Madrid, Spain: Díaz de Santos; 1999: 265-275.
  44. Arase K, Fisler JS, Shargill NS, York DA, Bray GA: Intracerebroventricular infusions of 3-OHB and insulin in a rat model of dietary obesity. Am J Physiol 1988, 255:R 974-981.
  45. Melanson KJ, Westerterp-Plantenga MS, Saris WH, Smith FJ, Campfield LA: Blood glucose patterns and appetite in time-blinded humans: carbohydrate versus fat. Am J Physiol 1999, 277:R 337-345.
  46. Weigle DS, Breen PA, Matthys CC, et al: A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr 2005, 82: 41-48.
  47. Blom WA, Lluch A, Stafleu A, et al: Effect of a high-protein breakfast on the postprandial ghrelin response Am J Clin Nutr 2006, 83: 211-220.
  48. Merchant AT, Anand SS, Vuksan V, et al: Protein intake is inversely associated with abdominal obesity in a multi-ethnic population. J Nutr 2005, 135: 1196-1201.
  49. Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, et al: Medical aspects of ketone body metabolism. Clin Invest Med 1995, 18:193-216.
  50. Ballaban-Gil K, Callahan C, O’Dell C, Pappo M, Moshé S, Shinnar S: Complications of the ketogenic diet. Epilepsia 1998, 39:744-748.
  51. Bergqvist CAG, Chee CM, Lutchka L, Rychik J, Stallings VA: Selenium deficiency associated with cardiomyopathy: a complication of the ketogenic diet. Epilepsia 2003, 44: 618-620.
  52. Kang HC, Kim JY, Kim DW, Kim HD: Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. Epilepsia 2005, 46:272-279.
  53. Kossoff EH, McGrogan JR, Bluml RM, Pillas DJ, Rubenstein JE, Vining EP: A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsy 2006, 47:421-424.
  54. DeFronzo RA: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerosis. Neth J Med 1997, 50: 191-197.
  55. Kalra A, Nair S, Rai L: Association of obesity and insulin resistance with dyslipidemia in Indian women with polycystic ovarian syndrome. Indian J Med Sci 2006, 60:447-53.
  56. Mather KJ, Kwan F, Corenblum B: Hyperinsulinemia in polycystic ovary syndrome correlates with increased cardiovascular risk independent of obesity. Fertil Steril 2000, 73: 150-156.
  57. De Pergola G, Ciccone M, Pannacciulli N, Modugno M, Sciaraffia M, Minenna A, Rizzon P, Giorgino R: Lower insulin sensitivity as an independent risk factor for carotid wall thickening in normotensive, non-diabetic, non-smoking normal weight and obese premenopausal women. Int J Obes Relat Metab Disord. 2000, 24:825-9.
  58. Lucas CP, Estigarribia JA, Darga LL, Reaven GM: Insulin and Blood Pressure in Obesity. Hypertension 1985, 7: 702-706.
  59. Muscelli E, Natali A, Bianchi S, et al: Effect of insulin on renal sodium and uric acid handling in essential hypertension. Am J Hypertens 1996, 9: 746-752.
  60. Rocchini AP: Proceedings of the Council for High Blood Pressure Research, 1990: Insulin resistance and blood pressure regulation in obese and non-obese subjects: Special lecture. Hypertension 1991, 17: 837-842.
  61. Stamler J, Elliott P, Kesteloot H, et al: Inverse relation of dietary protein markers with blood pressure: Findings for 10,020 men and women in the INTERSALT Study. INTERSALT Cooperative Research Group. International Study of Salt and Blood Pressure. Circulation 1996, 94: 1629-1634.
  62. Liu L, Ikeda K, Yamori Y, WHO-CARDIAC Study Group: inverse relationship between urinary markers of animal protein intake and blood pressure in Chinese: Results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. Int J Epidemiol 2002, 31: 227-233.
  63. Lehninger AL: Principios de Bioquímica. Barcelona, Spain: Ediciones Omega; 1991: 531-557.
  64. Dardzinski BJ, Smith SL, Towfighi J, Williams GD, Vannucci RC, Smith MB: Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment. Pediatr Res 2000, 48: 248-255.
  65. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL: -beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci USA 2000, 97: 5440-5444.
  66. Langston JW, Langston EB, Irwin I: MPTP-induced parkinsonism in human and non-human primates-clinical and experimental aspects. Acta Neurol Scand Suppl 1984, 100: 49-54.
  67. Schwartzkroin PA: Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet. Epilepsy Res 1999, 37: 171-180.
  68. Mukherjee P, El Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN: Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br J Cancer 2002, 86: 1615-1621.
  69. Nebeling LC, Miraldi F, Shurin SB, Lerner E: Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995, 14: 202-208.
  70. Lolis E, Bucala R: Macrophage migration inhibitory factor. Expert Opin on Ther Tar 2003, 7: 153-164.
  71. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracey KJ, Voelter W, Manogue KR, Cerami A, Bucala R: MIF is a pituitary-derived cytokine that potentiates endotoxinaemia. Nature 1993, 365: 756-759.
  72. Nishihira J: Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth. J Interferon Cytok Res 2000, 20: 751-762.
  73. Burger-Kentischer A, Goebel H, Seiler R, Fraedrich G, Schaefer HE, Dimmeler S, Kleemann R, Bernhagen J, Ihling C: Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 2002, 105: 1561-1566.
  74. Sato N, Shimizu H, Shirmomura Y, Suwa K, Mori M, Kobayashi I: Mechanism of inhibitory action of ketone bodies on the production of reactive oxygen intermediates (ROIS) by polymorphonuclear leukocytes. Life Sci 1992, 51: 113-118.
  75. Sjogren F, Groth O, Anderson C: Acetone has anti-inflammatory effects on experimental contact reactions. Contact Dermatitis 1999, 41: 22-29.
  76. Garai J, Lorand T, Molnar V. Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor. Life Sci. 2005, 77: 1375-80.
  77. Benoit FL, Martin RL, Watten RH: Changes in body composition during weight reduction in obesity: Balance studies comparing effects of fasting and a ketogenic diet. Ann Intern Med 1965, 63: 604-612.
  78. Willi SM, Oexmann MJ, Wright NM, Collop NA, Lyndon L: The effects of a high-protein, low-fat, ketogenic diet on adolescents with morbid obesity: body composition, Blood chemistries, and sleep abnormalities. Pediatrics 1998, 101: 61-67.
  79. Sondike SB, Copperman NM, Jacobson MS: Low carbohydrate dieting increases weight loss but not cardiovascular risk in obese adolescents: A randomized controlled trial. J Adolesc Health 2000, 26: 91.
  80. Samaha FF, Iqbal N, Seshadri P, et al.: A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003, 348: 2074-2081.
  81. Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004, 140: 769-777.
  82. Foster GD, Wyatt HR, Hill JO, et al. : A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003, 348: 2082-2890.
  83. Stern L, Iqbal N, Seshadri P, et al.: The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: One-year follow-up of a randomized trial. Ann Intern Med 2004, 140:778-785.
  84. Dansinger ML, Geeason JA, Griffith JL, Selker HP, Schaefer EJ: Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction. JAMA 2005, 293:43-53.
  85. Brinkworth GD, Noakes M, Keogh JB, Luscombe ND, Wittert GA, Clifton PM: Long-term effects of a high-protein, low-carbohydrate diet on weight control and cardiovascular risk markers in obese hyperinsulinemic subjects. Int J Obes Relat Metab Disord 2004, 28: 661-670.
  86. Yudkin J, Carey M: The treatment of obesity by the “high-fat” diet: the Inevitability of Calories. The Lancet 1960, 2: 939-941.
  87. Volek JS, Gómez AL, Kraemer WJ: Fasting lipoprotein and postprandial triacylglycerol responses to a low-carbohydrate diet supplemented with N-3 fatty acids. J Am Col Nutr 2000, 19: 383-391.
  88. Patsch JR, Miesenböck G, Hopferwieser T, et al.: Relation of triglyceride metabolism and coronary artery disease: studies in the postprandial state. Arterioscler Thromb. 1992, 12: 1336-1345.
  89. Austin MA, Hokanson JE, Edwards KL: Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998, 81: 7B-12B.
  90. Hellerstein MK: Carbohydrate-induced hypertriglyceridemia: modifying factors and implications for cardiovascular risk. Curr Opin Lipidol 2002, 13: 33-40.
  91. Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J: Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest 1996, 97: 2081-2091.
  92. Hudgins LC: Effect of high-carbohydrate feeding on triglyceride and saturated fatty acid synthesis. Proc Soc Exp Biol Med 2000, 225: 178-183.
  93. Austin MA, King MC, Vranizan KM, Krauss RM: Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 1990, 82: 495-506.
  94. Dreon DM, Fernstrom HA, Williams PT, Krauss RM: A very-low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins. Am J Clin Nutr 1999, 69: 411-418.
  95. Campos H, Dreon DM, Krauss RM: Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low-density lipoprotein subclasses. J Lipid Res 1995, 36: 462-472.
  96. Sharman MJ, Gomez AL, Kraemer WJ, Volek JS: Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. J Nutr 2004, 134: 880-885.
  97. McAuley KA, Hopkins CM, Smith KJ, et al.: Comparison of high-fat and high-protein diets with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia 2005, 48: 8-16.
  98. Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE: Effect of 6-month adherence to a very low carbohydrate diet program. Am J Med 2002, 113: 30-36.
  99. Brehm BJ, Daniels SR, D’Alessio DA: A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003, 88: 1617-1623.
  100. Sargrad KR, Homko C, Mozzoli M, Boden G. Effect of high protein vs high carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c, and blood pressure in patients with type 2 diabetes mellitus. J Am Diet Assoc 2005, 105:573-80.
  101. Meckling KA, Gauthier M, Grubb R, Sanford J: Effects of a hypocaloric, low-carbohydrate diet on weight loss, blood lipids, blood pressure, glucose tolerance, and body composition in free-living overweight women. Can J Physiol Pharmacol 2002, 80:1095-105.
  102. Gannon MC, Nuttall FQ: Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 2004, 53: 2375-2382.
  103. Boden G, Sargrad K, Homko C, et al.: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med 2005, 142: 403-411.
  104. Nuttall FQ, Gannon MC: The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 diabetes mellitus. Metabolism 2006, 55:243-51.
  105. Yancy WS, Foy M, Chalecki AM, et al.: A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab 2005, 2:34.
  106. Westman EC, Yancy WS, Hepburn J, et al.: A pilot study of a low-carbohydrate, ketogenic diet for obesity-related polycystic ovary syndrome. J Gen Intern Med 2004, 19(1S):111.
  107. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC: The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study. Nutr Metab 2005, 2:35.
  108. Engelhart MJ, Geerlings MI, Ruitenberg A, et al.: Diet and risk of dementia: Does fat matter? The Rotterdam Study. Neurology 2002, 59: 1915-1921.
  109. Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM: Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997, 42: 776-782.
  110. Grant WB: Dietary links to Alzheimer’s disease: 1999 update. J Alzheimers Dis 1999, 1: 197-201.
  111. Morris MC, Evans DA, Bienias JL, et al.: Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 2003, 60: 194-200.
  112. Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS: Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology 2004, 62: 1573-1579.
  113. Engelhart MJ, Geerlings MI, Ruitenberg A, et al.: Diet and risk of dementia: Does fat matter?: the Rotterdam Study. Neurology 2002, 59: 1915-1921.
  114. Refolo LM, Malester B, LaFrancois J, et al.: Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model.
  115. Ho L, Qin W, Pompl PN, et al: Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. Faseb J 2004, 18: 902-904.
  116. Levin-Allerhand JA, Lominska CE, Smith JD: Increased amyloid- levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet. J Nutr Health Aging 2002, 6: 315-319.
  117. Shie FS, Jin LW, Cook DG, Leverenz JB, LeBoeuf RC: Diet-induced hypercholesterolemia enhances brain A beta accumulation in transgenic mice. Neuroreport 2002, 13: 455- 459.
  118. George AJ, Holsinger RM, McLean CA, et al.: APP intracellular domain is increased and soluble Abeta is reduced with diet-induced hypercholesterolemia in a transgenic mouse model of Alzheimer disease. Neurobiol Dis 2004, 16:124-132.
  119. Van der Auwera I, Stefaan W, Van Leuven F, Henderson ST: A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab 2005, 2: 28.
  120. Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM: The efficacy of the ketogenic diet. A prospective evaluation of intervention in 150 children. Pediatrics 1998, 102: 1358-1363.
  121. Freeman JM: What every pediatrician should know about the ketogenic diet. Contemporary Pediatrics 2003, 20:113-127.
  122. Vining EPG, Freeman JM: A multi-center study of the efficacy of the ketogenic diet. Archives of Neurology 1998, 55:1433-1437.
  123. Kossoff EH, Krauss GL, McGrogan JR, et al.: Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology 2003, 61: 1789-1791.
  124. Kossoff EH: More fat and fewer seizures: dietary therapy for epilepsy. Lancet Neurol 2004, 3: 415-420.
  125. Bergqvist AG, Schall JI, Gallagher PR, Cnaan A, Stallings VA: Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 2005, 46: 1810-1819.
  126. Mady MA, Kossoff EH, McGregor AL, et al.: The Ketogenic Diet: adolescents can do it, too. Epilepsia 2003, 44: 847-851.
  127. Sirven J, Whedon B, Caplan D, et al.: The ketogenic diet for intractable epilepsy in adults: preliminary results. Epilepsia 1999, 40: 1721-1726.
  128. Cunnane SC: Metabolic and health implications of moderate ketosis and the ketogenic diet. Prostaglandins Leukot Essent Fatty Acids 2004, 70: 243-251.
  129. Bough KJ, Eagles DA: Comparison of the anticonvulsant efficacies and neurotoxic effects of valproic acid, phenytoin, and the ketogenic diet. Epilepsia 2001, 42:1345-1353.
  130. Kinsman SL, Vining EP, Quaskey SA, Mellits D, Freeman JM: Efficacy of the ketogenic diet for intractable seizure disorders: review of 58 cases. Epilepsia 1992, 33: 1132-1136.
  131. Caraballo RH, Cersósimo, Sakr D, Cresta A, Escobal N, Fejerman N: Ketogenic diet in patients with Dravet syndrome. Epilepsia 2005, 46:1539-1544.
  132. Pérez-Guisado J: Carbohydrates, glucose metabolism and cancer. Endocrinología y Nutrición 2006, 53: 252-255.
  133. Augustin LS, Gallus S, Bosetti C, et al.: Glycemic index and glycemic load in endometrial cancer. Int J Cancer 2003, 105: 404-407.
  134. Folsom AR, Demissie Z, Harnack L: Glycemic index, glycemic load, and incidence of endometrial cancer: the Iowa Women’s Health Study Nutr Cancer 2003, 46: 119-124.
  135. Augustin LS, Gallus S, Negri E, La Vecchia C: Glycemic index, glycemic load and risk of gastric cancer. Ann Oncol 2004, 15: 581-584.
  136. Augustin LS, Polesel J, Bosetti C, et al.: Dietary glycemic index, glycemic load and ovarian cancer risk: a case-control study in Italy. Ann Oncol 2003, 14: 78-84.
  137. Borugian MJ, Sheps SB, Whittemore AS, Wu AH, Potter JD, Gallagher RP: Carbohydrates and colorectal cancer risk among Chinese in North America. Cancer. Epidemiol Biomarkers Prev 2002, 11:187-193.
  138. Franceschi S, Dal Maso L, Augustin L, et al.: Dietary glycemic load and colorectal cancer risk. Ann Oncol 2001, 12: 173-178.
  139. Bruce WR, Wolever TM, Giacca A: Mechanisms linking diet and colorectal cancer: The possible role of insulin resistance. Nutr Cancer 2000, 37: 19-26.
  140. Colangelo LA, Gapstur SM, Gann PH: Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 2001, 11: 385-391.
  141. Franceschi S, Favero A, La Vecchia C, et al.: Food groups and risk of colorectal cancer in Italy. Int J Cancer 1997, 72: 56-61.
  142. Holmes MD, Colditz GA, Hunter DJ, et al.: Meat, fish and egg intake and risk of breast cancer. Int J Cancer 2003, 104: 221-227.
  143. Franceschi S, Favero A, Decarli A, et al.: Intake of macronutrients and risk of breast cancer. The Lancet 1996, 347: 1351-1356.
  144. Augustin LS, Dal Maso L, La Vecchia C, et al.: Dietary glycemic index and glycemic load, and breast cancer risk: a case-control study. Ann Oncol 2001, 12: 1533-1538.
  145. Romieu I, Lazcano-Ponce e, Sánchez-Zamorano LM, Willet W, Hernandez-Avila M: Carbohydrates and the risk of breast cancer among Mexican Women, Cancer Epidemiol Biomarkers Prev 2004, 13: 1283-1289.
  146. Nebeling LC, Lerner E: Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer. J Am Diet Assoc 1995, 95: 693-697.
  147. Beck SA, Tisdale MJ: Nitrogen excretion in cancer cachexia and its modification by a high fat diet in mice. Cancer Res 1989, 49: 3800-3804.
  148. Van der Auwera I, Wera S, Van Leuven F, Henderson ST: A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab 2005, 2: 28
  149. Feinman R: When is a high fat diet not a high fat diet? Nutr Metab 2005, 2:27
  150. Mozaffarian D, Rimm EB, Herrington DM: Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr 2004, 80: 1175-1184.
  151. Volek JS, Forsythe CE: The case for not restricting saturated fat on a low carbohydrate diet. Nutr Metab 2005, 2:21.
  152. Keys A: Seven Countries. A multivariate analysis of death and coronary heart disease. Cambridge, MA: Harvard University Press, 1980.
  153. Kromhout D, Menotti A, Bloemberg B, et al.: Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study. Prev Med 1995, 24: 308-315.
  154. McGee DL, Reed DM, Yano K, Kagan A, Tillotson J: Ten-year incidence of coronary heart disease in the Honolulu Heart Program: Relationship to nutrient intake. Am J Epidemiol 1985, 119: 667-676.
  155. Kushi LH, Lew RA, Stare FJ, et al.: Diet and 20-year mortality from coronary heart disease: the Ireland-Boston Diet-Heart study. N Engl J Med 1985, 312: 811-818.
  156. Kromhout D, De Lezenne Coulander C: Diet, prevalence and 10-year mortality from coronary heart disease in 871 middle-aged men: the Zutphen Study. Am J Epidemiol 1984, 119: 733-741.
  157. Garcia-Palmieri MR, Sorlie P, Tillotson J, Costas Jr R, Cordero E, Rodriguez M: Relationship of dietary intake to subsequent coronary heart disease incidence: the Puerto Rico Heart Health Program. Am J Clin Nutr 1980, 33: 1818-1827.
  158. Gordon T, Kagan A, Garcia-Palmieri M, et al.: Diet and its relation to coronary heart disease and death in three populations. Circulation 1981, 63: 500-515.
  159. Morris JN, Marr JW, Clayton DG: Diet and Heart: a postscript. BMJ 1977, 2: 1307-1314.
  160. Shekelle RB, Shryock AM, Paul O, et al.: Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. N Engl J Med 1981, 304: 65-70.
  161. Pietinen P, Ascherio A, Korhonen P, et al.: Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol 1997, 145: 876-887.
  162. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer MJ, Willett WC: Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ 1996, 313: 84-90.
  163. Phinney SD, Bistrian BR, Wolfe RR, Blackburn GL: The human metabolic response to chronic ketosis without caloric restriction: physical and biochemical adaptation. Metabolism 1983, 32: 757-768.
  164. Fagan TC, Oexmann MJ: Effects of high protein, high carbohydrate, and high fat diets on laboratory parameters. J Am Coll Nutr 1987, 6: 333-343.
  165. Martin WF, Armstrong LE, Rodriguez NR: Dietary protein intake and renal function. Nutr Metab 2005, 2:25.
  166. Skov AR, Toubro S, Bulow J, Krabbe K, Parving HH, Astrup A: Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects. Int J Obes 1999, 23: 1170-1177.
  167. Knight EL, Stampfer MJ, Hankinson SE, Spiegelman D, Curhanet GC: The Impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med 2003, 138: 460-467.
  168. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr: Brain Metabolism during fasting. J Clin Invest 1967, 46: 1589-1595.
  169. Chen TY, Smith W, Rosenstock JL, Lessnau KETOGENIC DIET: A life-threatening complication of Atkins diet. Lancet 2006, 367: 958.
  170. Phinney SD: Ketogenic diets and physical performance. Nutr Metabol 2004; 1:1-7.
  171. Lambert EV, Speechly DP, Dennis SC, Noakes TD: Enhanced endurance in trained cyclists during moderate intensity exercise following 2 weeks adaptation to a high fat diet. Eur J Appl Physiol Occup Physiol 1994, 69: 287-293.
  172. Phinney SD, Horton ES, Sims EA, Hanson JS, Danforth E Jr, LaGrange BM: Capacity for moderate exercise in obese subjects after adaptation to a hypocaloric, ketogenic diet. J Clin Invest 1980, 66: 1152-1161.
  173. Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DP: Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 2000, 15: 2504-2512.
  174. Kerstetter JE, O’Brien KO, Caseria DM, Wall DE, Insogna KL: The Impact of Dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab 2005, 90: 26-31.
  175. Dawson-Hughes B, Harris SS, Rasmussen H, Song L, Dallal GE: Effect of dietary protein supplements on calcium excretion in healthy older men and women. J Clin Endocrinol Metab 2004, 89: 1169-1173.
  176. Heaney RP: Dietary protein and phosphorous do not affect calcium absorption. Am J Clin Nutr 2000, 72: 758-761.
  177. Heaney RP: Excess dietary protein may not adversely affect bone. J Nutr 1998, 128: 1054-1057.
  178. Millichap G: Ketogenic diet in epilepsy. to fast or not to fast. AAP Grand Rounds 2005, 13: 54-55.
  179. Freeman JM, Vining EPG: Seizures rapidly decrease after fasting: preliminary studies of the ketogenic diet. Arch Pediatrics & Adolescent Medicine 1999, 153: 946-949.
  180. Kim DW, Kang HC, Park JC, Kim HD: Benefits of the non-fasting ketogenic diet compared with the initial fasting ketogenic diet. Pediatrics 2004, 114: 1627-1630.
  181. Furth SL, Casey JC, Pyzik PL, et al.: Risk factors for urolithiasis in children on the ketogenic diet. Pediatric Nephrology 2000,15: 787-790.