Cyclical Ketogenic Diets Review

4 Cycle Fat Loss Solution

This new and innovational approach to dieting created by Shaun Hadsall might be what people need. Shaun believes that when people do not provide their body with the right amount of nutriments, diet plan, exercises and vitamins, their weight escalates with time. The main idea is to force your body into using stored fat (instead of carbs and protein) as your primary source of energy via precision dieting. That is, the exact schedule and timing of your diet is as important as what foods your diet contains. 4 Cycle Fat Loss Solution is a 100% healthy and results-oriented plan to eat right, to drop off unwanted weight and to stay physically fit forever. With the 4 Cycle Fat Loss Solution, you learn about how your body works with high carb foods and why the information that you have been told about them is simply false. The methods taught in the program have been proven over many years and are backed by science. More here...

4 Cycle Fat Loss Solution Overview


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My 4 Cycle Fat Loss Solution Review

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14 Day Rapid Fat Loss Plan

This rapid fat loss program is a carb cycling system developed by Shaun Hadsall, who has been voted the most fit Health and Fitness Pro in America. Shaun has been working on the strategies for losing extra fat for more than 20 years in the industry of fitness. The experience he got from the fitness involvement over the years has helped him have ideas to create this organic weight loss program. There are 6 distinct sections in this well written guide to 14 Day Rapid Fat Loss. Each has a set of steps that explain what you must do to enjoy the highest benefit. Based on a patented macro patterning tactic he devised, the plan allows you to eat whatever you like as long as you alternate your eating in patterns. There are 3 kinds of days in the 14 day rapid fat loss plan: 1. Deplete Days, 2. Carb Baseline Days, 3. Cheat Days. More here...

14 Day Rapid Fat Loss Plan Overview

Contents: Ebooks
Author: Shaun Hadsall
Official Website:
Price: $17.00

Low Carbohydrate and Low Glycemic Index

There has been a dramatic increase in interest in use of diets low in carbohydrate content or having a low glycemic index (GI) to promote weight loss. (See Chapters 14 and 15 for discussion of these diets.) One 12-wk study in overweight adolescents showed significantly greater weight loss with a low-carbohydrate diet compared with a low-fat diet, with no adverse effects on lipid profiles in either group (86). In a small study of 14 adolescents, those on a low- to moderate-GI diet lost significantly more weight and showed less of an increase in insulin resistance over a 12-mo period than did the adolescents assigned to a low-fat diet (25-30 of energy from fat) (87). A low-GI diet may offer a more easily taught approach to dietary modification in the primary care setting than more traditional low-calorie low-fat diets (88).

The Natural History Of Type 2 Diabetes

Although the triple disturbance of insulin resistance, increased hepatic glucose production, and impaired insulin secretion critical to the development of type 2 diabetes has received a great deal of attention in research, the etiological sequence of events resulting in the diabetic state is also of compelling interest . Accelerated hepatic gluconeogenesis and glycogenolysis do not seem to exist in the state of impaired glucose tolerance, where insulin resistance and impaired insulin secretion predominate in fact, these two abnormalities precede the onset of hyperglycemia in the diabetic type 2 phenotype. Prediabetic individuals have severe insulin resistance, whereas insulin secretion tends to be normal or increased in the prediabetic or impaired glucose tolerant state, including first-phase insulin responses to intravenous challenges. Thus, the type 2 diabetic phenotype evolves from the individual with impaired glucose tolerance and insulin resistance. Although the genetic factors...

Weight concerns Overweight and obesity

She has been overweight all her life everyone in her family is heavy. She has tried Weight Watchers, the Atkins diet, and several others diets. Sometimes she loses weight, but she always regains it. She wonders whether there's a way for her to really lose weight, or whether it's hopeless at this point in her life. The Atkins Diet is a restricted-carbohydrate, high-protein, and restricted-fat diet. This diet takes advantage of the ketosis that develops during starvation the resulting anorexia reduces appetite. However, ketosis can also cause fatigue, constipation, and vomiting. Potential long-term side effects include heart disease, bone loss, and kidney damage. In addition, high-protein, low-carbohydrate diets tend to be low in calcium, fiber, and healthy phyto-chemicals. The proponents of this diet advise taking vitamin and mineral supplements to replace lost nutrients.

Disorders Of The Intestines

Sprue, or malabsorption of nutrients from the small intestine, can be very serious. It usually involves impaired absorption of fats and vitamins that leads to vitamin deficiency and anemia (inadequate red blood cell count). Treatment of sprue usually consist s of a high carbohydrate, low protein, low fat diet with vitamin supplements. Emergency replenishment of vital nutrients, if necessary, can be accomplished by intravenous injection.

Sustained Weight Loss With Chronic Cannabinoid Stimulation

When mice are fed a palatable high-fat diet, they overeat and become obese. In one series of experiments, mice maintained on the palatable diet and chronically administered the CB1 antagonist (SR 141716) ate less food (104-106). What is particularly important is that the anorectic action of the antagonists lessened and then disappeared altogether over a week or two in spite of continued dosing, indicating apparent tolerance to the behavioral action (105). Nonetheless, there was a sustained and, in fact, increased reduction of body weight and body fat mass over the next several weeks despite the fact that food intake was normal, strongly implying that other actions of the CB1 antagonists were continuing to exert metabolic effects (104,105). At the end of the experiments, mice

Plasminogen Activator Inhibitor1

Plasma levels of PAI-1 are elevated with obesity and strongly correlated with visceral adiposity (120). It appears that secretion from AT is increased in obese individuals (121). Interestingly, mice that lack PAI-1 are completely protected against high-fat diet-induced obesity (122). Even ob ob mice, as a model of genetic morbid obesity, are protected (123). This suggests that PAI-1 effects are not limited to clotting but may have other systemic effects.

P Hydroxydehydrogenase1

To high fat diet-induced obesity (133,134). Interestingly, obese humans appear to have increased adipose tissue concentrations of the enzyme (131), possibly contributing to the development of central adiposity. Furthermore, healthy volunteers given an 11 HSD-1 inhibitor called carbenoxolone showed increased insulin sensitivity (135).

Plasma Coagulation Factor Tests

A high-fat diet may cause decreased prothrombin levels, whereas alcohol consumption may increase prothrombin levels. Many drugs can interfere with blood prothrombin levels. Medications that result in an increased level include chlorpromazine, methyldopa salicylates, barbiturates, and sulfonamides. Decreased levels are associated with anabolic steroids, digitalis, estrogens, and vitamin K.

Gestation Lactation And Maternal Environment

The majority of human beings are raised with their biological mothers. This means that they are exposed to the maternal environment throughout gestation and lactation, as well as through the rest of their formative years. Thus, outcome in humans is dependent not only on the biological effects of the perinatal maternal environment but also on a number of psychosocial and socioeconomic variables. Because these variables are not major factors in animal models, these models are best suited for investigating the effects of altering the metabolic perinatal environment on offspring outcome. Rodent models also have the advantage that lifelong patterns of food intake and body weight are generally established by the second week of life as long as dietary content is held constant thereafter (39,40). Whereas human studies can only suggest a relationship, it is clear that maternal obesity throughout gestation and lactation in rats leads to the development of obesity and metabolic syndrome in...

Postnatal Influences on Offspring

As would be expected, maternal diet is a primary determinant of milk composition. Cafeteria diets composed of highly palatable junk foods increase the long-chain and decrease the medium-chain fatty acid content of maternal milk and have an additive effect to the presence of maternal obesity in lowering the protein and raising the long-chain fatty acid content of milk (104). Diets high in polyunsaturated fatty acids have the effect of lowering pup body weight and adiposity and leptin levels (58). Feeding dams a high-fat diet also accelerates the onset of independent feeding in neonates by 1 to 2 days (116) in association with increased weight gain (117) and the development of hypertension and abnormal glucose homeostasis as adults (118). Furthermore, feeding successive generations of dams a high-fat diet leads to progressive increases the level of obesity of their offspring (119). This feed-forward effect may have important relevance to the increasing incidence of obesity in the...

Perinatal Environment And Brain Development

Once obesity develops, it effectively becomes a permanent condition, particularly in genetically predisposed individuals (219-223). This appears to be due to a neural set point that resides in the network of metabolic sensing neurons involved in energy ho-meostasis and is determined by a host of factors including genetic predisposition, diet composition, sex, and environmental conditions (220,221,224-231). Regardless of the starting point, the brain and periphery interact to preserve adipose stores when food supply is limited. Thus, during prolonged periods of caloric restriction, rats and humans maintain a reduced level of energy expenditure (219,222,223,232). When allowed ad libitum access to food, they increase their intake and maintain a reduced level of energy expenditure until they regain their previous level of obesity (220-223). This protective mechanism undoubtedly underlies the high recidivism rate in the treatment of human obesity (233,234). Thus, the best treatment for...

Potential Explanations For The Antiobesity Effect Of A Vegetarian Diet

Vegetarian diets tend to contain significantly more carbohydrates, particularly complex carbohydrates. A high carbohydrate meal may actually speed up the resting metabolic rate, while a high fat meal seems to have little effect on metabolism. There is some evidence that overfeeding with carbohydrates but not with fat provokes an insulin-mediated ther-mogenesis that acts to retard weight gain.34 Toth and Poehlman35 found that young male vegetarians had an 11 higher resting metabolic rate than non-vegetarians in spite of similar energy intakes. The major dietary difference between the two groups was an increased ingestion of carbohydrate and a reduction in fat intake by the vegetarians. Campbell36 has proposed that excess protein intake may be responsible for excess weight. Vegetarian diets tend to provide a much lower protein intake than diets that include meat products. The China study, involving dietary records on thousands of Chinese, indicated that protein intake paralleled body...

Diabetes And Carbohydrates

Although carbohydrates, like monounsaturates, do not have significant effects on cholesterol, they can have significant effects on lipoprotein metabolism. This is because high-carbohydrate diets stimulate the synthesis of very low-density lipoprotein (VLDL) and triglycerides and subsequently can raise serum triglyceride levels. This usually effects HDL in a reciprocal fashion, with decreased levels of HDL. Removal of fats from the diet and replacement with carbohydrates reduces LDL levels despite the lowering effects of HDL. A significant volume of information does support the effectiveness of a high-fiber, low-fat, and low-carbohydrate diet in the prevention and treatment of diabetes. Thus, choosing carbohydrates from the lower end of the glycemic scale seems advisable. Highfiber diets are associated with improved ability to handle blood sugar. Dietary fibers can slow the rate of food progression through the intestine, thus attenuating postprandial glucose excursions. This is in...

Diabetes And Protein

In cases of insulin deficiency, gluconeogenesis can be stimulated when protein intake does not exceed 20 of the total daily consumption. There is no increased risk of diabetic nephropathy although long-term consumption of greater than this amount has not been studied, the ADA recommends avoiding such excess protein intake. The safety and long-term efficacy of low-carbohydrate, high-protein diets remains unknown and has not been widely studied, although these diets can produce short-term weight loss and improve glycemic control.

Molecular Mechanisms Of Energy Expenditure Variability

The study of obesity in human individuals is inherently difficult. This is because of factors related to the disease itself, including heterogeneity, age-dependent penetrance, uncontrollable gene-environment interactions, and gene-gene interactions. Ultimately, proof that a putative mechanism of energy expenditure actually has a role in maintaining caloric homeostasis must come through genetic studies in animal models and then through the discovery of genetic variability for these mechanisms in humans. It is likely that further gene discoveries in animal models will add to this knowledge and continue to identify novel pathways that are important in nutrient partitioning and energy balance in humans. Evidence that these mechanisms actually promote or limit the development of obesity by stimulating or decreasing energy expenditure or nutrient partitioning must be demonstrated. Some of the significant advances in our understanding of the regulation of energy balance have stemmed from...

Diacylglycerol Transferase

Triglyceride synthesis has been implicated to occur through the acyl CoA diacylglycerol transferases (DGATs), enzymes that catalyze the final reaction in the glycerol phosphate pathway. DGAT enzymes are highly expressed in tissues associated with triglyceride synthesis. In humans, an abundant expression of DGAT enzymes has been observed in adipose tissue and liver (142,143). Dgat1- - mice are leaner than wildtype mice and have smaller adipocytes (120,144). When fed a high-fat diet, Dgat1- -mice are resistant to obesity and are protected from diet-induced hepatic steatosis (120). These effects are likely caused in part by increased energy expenditure. Moreover, Dgat- - mice demonstrate an increase in spontaneous physical activity (145), increased expression of UCP-1 (144,146), and increased leptin sensitivity (144). An intact leptin pathway appears to be required for the effects of DGAT deficiency on energy metabolism. Although DGAT1 deficiency reverses obesity and insulin resistance...

The aGlucosidase Inhibitors

A-Glucosidase inhibitors are modestly effective in treating diabetes with hemoglobin A1-C reductions of 0.5-1 and can be particularly effective in patients who consume high-carbohydrate diets. Adverse effects of a-glucosidase inhibitors are gastrointestinal and include abdominal bloating, pain, diarrhea, and flatulence, occurring in up to 70 of patients. Although these adverse effects tend to dissipate in 4-6 weeks, they are to be a major reason for discontinuation of medications.

Assessing Weight History

Assessing previous weight-loss attempts is also important. some patients comment with frustration that diets never work for me. Often, though, when discussed in greater detail, previous efforts are revealed that produced an expected degree of weight loss (38 ) that was not maintained because of difficulties in sustaining the chosen weight-loss strategy. Acknowledging and exploring these previous weight-loss attempts can provide a useful platform for discussing the amount of weight that is commonly lost with a diet and exercise program and to explore strategies that were or were not successful previously as a prelude to a discussion of potential future approaches to treatment. it is common to hear a person say that he or she tried Weight Watchers or the Atkins diet and had some success, but then encountered difficulties. This kind of discussion allows the clinician to provide empathy and support around what are extremely common, almost expected, periods of relapse. In addition, the...

Special Concerns For Athletes On Vegetarian Diets

A near-vegetarian diet is often needed to take advantage of high carbohydrate plant foods such as cereals, pasta, grains, dried fruits, and legumes. In one study of 347 marathon runners, more than 75 reported higher intake of fruits, vegetables, and whole grains, and lower intake of red meat and eggs when compared with pre-running dietary habits.37 (See Figure 12.2.) Nonetheless, in most studies, intake of carbohydrate by endurance athletes falls below recommended levels, although there are some noteworthy exceptions (e.g., Tarahumara Indian ultramarathon runners, and triathletes).137-41 The Tarahumara Indians, a Ute-Aztecan tribe inhabiting the rugged Sierra Madre Occidental Mountains in the north-central state of Chihuahua, Mexico, are extraordinary endurance runners who consume a simple, near-vegetarian diet composed primarily of corn and beans (75-80 of total energy intake is carbohydrate).38

Angela P Makris phd rd and Gary D Foster phd

Efficacy of Low-Carbohydrate Diets on Weight Loss Efficacy of Low-Carbohydrate Diets on Fasting Lipids Efficacy of Low-Carbohyrate Diets on Imflammatory Biomarkers Efficacy of Low-Carbohydrate Diets on Lipoprotein Subfractions Efficacy of Low-Carbohydrate Diets on Blood Pressure Efficacy of Low-Carbohydrate Diets on Insulin Sensitivity Traditionally, the gold standard for obesity treatment has been the combination of a low-fat, low-calorie diet with regular physical activity and behavior therapy. This combination has been shown to be safe and effective however, the best dietary approach to weight loss continues to be a matter of debate among professionals and the public alike. Preliminary short-term findings suggesting that low-carbohydrate diets are effective in reducing body weight and do not appear to increase the risk of cardiovascular disease have generated interest in the low-carbohydrate approach and have spawned further research. This chapter reviews the most recent findings...

Diseasespecific Guidelines

Despite the public health significance of type 2 diabetes, little is known about the dietary risk factors in the development of the disease.91 Although genetic predisposition is a determinant of insulin resistance, diet and lifestyle are thought to play a role in the development of the syndrome. Animal studies suggest that a high-fat, high-refined carbohydrate, low fiber diet (typical Western diet) induces insulin resistance and precedes other aspects of the syndrome including obesity. Epidemiological studies of groups such as the Pima Indians have shown decreased prevalence with high-carbohydrate native diets, and increased with Westernized high-fat diets. Risk of diabetes has also been associated with low fiber intake and large glycemic response of foods.92 Although the evidence is not strong, vegetarians may have lower rates of type 2 diabetes.96 There have been a number of large cohort studies that show an inverse association between incidence of diabetes and intakes of cereal...

Efficacy Of Lowcarbohydrate Diets On Weight Loss

Five randomized studies conducted over 6 to 12 mo have compared the effects of a low-carbohydrate diet and a calorie-controlled, low-fat diet on weight and body composition in obese adults (8-13). (Note that the Samaha and Stern papers refer to the same study but report 6-mo and 12-mo data, respectively.) With the exception of one study that prescribed nutritional supplements including vitamins, minerals, essential oils, and chromium picolinate to the low-carbohydrate group but not the low-fat group (12), diet prescriptions in these studies were comparable (e.g., a low-carbohydrate diet containing Participants who consumed a low-carbohydrate diet lost significantly more weight than those who consumed a low-fat diet during the first 6 mo of treatment in four of the five studies (8-12). Despite differences at 6 mo, there were no differences in weight loss at 1 yr (8,11,13) (Table 1). Two studies (8,13) observed weight regain in both groups after 6 mo, with a greater regain in the...

Calories or Carbohydrates

The focus of the low-carbohydrate approach is on carbohydrate rather than the number of calories consumed. Given that individuals following this approach track the grams of carbohydrate from only a limited number of foods, it is appealing to many dieters because it reduces the burden of accounting for all foods consumed however, it may also reduce awareness of total calories consumed because the emphasis is placed on altering one's metabolic state rather than altering one's energy balance. Rather than attribute differences in weight loss between low- and high- carbohydrate diets to differences in energy intake, some suggest that low-carbohydrate diets confer a metabolic advantage (i.e., differences in the metabolism of nutrients, increased energy expenditure, etc.) that results in greater weight loss (6,14). Comparing the effects of isocaloric low-carbohydrate and low-fat diets on body weight would test the hypothesis that metabolic factors rather than calories account for the...

Efficacy Of Lowcarbohydrate Diets On Fasting Lipids

A principal concern about low-carbohydrate approaches is that the high-fat content of the diet may adversely affect serum lipids and increase the risk for cardiovascular disease. As discussed in a review by Volek et al. (31), preliminary findings challenge this argument. In studies that compared low-carbohydrate and low-fat diets over the course of 6 to 12 mo, there were no differences in total cholesterol or low-density lipoprotein (LDL) cholesterol concentrations between groups (8-12,21). One study reported that the low-carbohydrate diet was less effective than the low-fat diet in reducing total cholesterol and LDL cholesterol at 1 yr (13). Only one study reported a small, transient increase in total cholesterol and LDL cholesterol during the third month of a 1-yr treatment (8). Furthermore, compared with the conventional group, those in the low-carbohydrate group experienced greater improvements in high-density lipoprotein (HDL) cholesterol (8,12) and triglycerides (8-10,12). Only...

Efficacy Of Lowcarbohydrate Diets On Insulin Sensitivity And Glycemic Control

A limited number of studies have compared the effects of low- and high-carbohydrate diets on insulin sensitivity. Differences in methodology preclude a pooled analysis of measures of glucose and insulin (32) however, there is some evidence to suggest that low-carbohydrate diets are effective in improving insulin sensitivity and glycemic control (10,11,48). Samaha et al. (10) measured fasting glucose and mean glycosylated hemoglobin levels in nondiabetic and diabetic participants and insulin sensitivity (measured by the quantitative insulin sensitivity check QUICK ) in nondiabetic participants. Compared with the low-fat group, greater decreases in fasting glucose were observed in the low-carbohydrate group and a trend toward greater decreases in mean glycosylated hemoglobin levels was observed in diabetic participants consuming a low-carbohydrate diet after 6 mo. After adjustment for the amount of weight lost at 6 mo, the low-carbohydrate diet was no longer a significant predictor of...

Low Fat Diets Are Best for Preventing Weight Regain

Most successful weight-loss maintainers eat a low-fat, high-carbohydrate diet that is low in total calories. Even though there is great controversy in the literature over the best diet composition for maintaining a healthy body weight, the overwhelming majority of the NWCR participants report eating a diet with less than 30 fat and that is high in carbohydrate to keep their weight off. It is important to note that we did not see all NWCR participants eating a low-fat, high-carbohydrate diet to lose weight, suggesting that there can be more variety in weight-loss diets than in weight-loss maintenance diets.

Treatment Of Fractures

Treatment of fractures requires restoration of the parts to their normal positions (reduction of a fracture) and immobilization (fixation) of the parts for about 6 to 8 weeks until a union between the bony parts takes place. Reduction of the fracture may be either closed or opened. In a closed reduction, the bone segments are manipulated back into position without surgically exposing the bone. Usually, arch bars and wires are used for fixation. In an opened reduction, the fractured bone segments are surgically exposed, which allows the fracture to be reduced exactly because of unobstructed, direct vision. In opened reductions, fixation generally is accomplished by drilling holes on either side of the fracture and using wire or metal plates to hold the segments in close approximation. Careful postoperative care is needed. Patient instruction in proper diet is essential because often the teeth are immobilized in the closed position, called intermaxillary fixation (the jaws being wired...

Blood Urea Nitrogen BUN

Dietary habits and age can affect BUN levels. Low-protein, high-carbohydrate diets can decrease blood urea nitrogen, and a high-protein diet will increase BUN. Inefficient concentration of the urine can cause increased BUN levels in the elderly. Drugs that may cause increased BUN levels are cephalosporins, cisplatin, aspirin, tetracyclines, and thiazide diuretics. Streptomycin may cause a decreased BUN.

Prenatal Influences on Offspring

It is not surprising that major alterations in the metabolic milieu in which a fetus grows can markedly affect its development. Cross-fostering studies in which pups are placed with surrogate dams shortly after birth suggest that prenatal factors account for 61 to 96 of the variance in body weight gain in male and 35 to 92 in female offspring (68). Offspring of dams fed a high-fat diet during gestation became more obese than those whose dams were fed a low-fat diet, even if the high-fat offspring were fostered with dams on a low-fat diet throughout lactation (49,69). As suggested by human epidemio-logical studies, malnutrition during gestation can also result in obese offspring. To model these studies, Jones and colleagues (70,71) restricted the caloric intake of dams by up to 50 during the first two trimesters of pregnancy. Male (but not female) offspring of these calorically restricted dams became hyperphagic, gained more weight beginning at weaning (71), and became obese as adults...

Physiological Activities

A puzzling observation made a decade ago was that glitazones, which were developed for the treatment of insulin resistance, are PPARg-selective ligands. The link between the promotion of adipocyte differentiation and lipid storage by PPARg and the antidiabetic effects of these compounds is not fully understood. One hypothesis is fat redistribution from muscle to adipose tissue more particularly to subcutaneous fat, which is itself more sensitive to insulin than visceral fat (Gurnell et al., 2003 Wajchenberg, 2000). Alternately, some data support the hypothesis that adiponectin, an adipokine with insulin-sensitizing property and a PPARg target gene, might be a crucial component connecting PPARg activation in the adipose tissue and the metabolic response of the peripheral organs (Gurnell et al., 2003). Other possibilities are the inhibition of hepatic neoglucogenesis or induction of a futile cycle, as mentioned above. Unexpectedly, PPARy+' heterozygous mice, rather than being prone to...

Acetyl CoA Carboxylase

ACC1 is expressed mainly in lipogenic tissue such as liver and adipose, and ACC2 in the heart and skeletal muscle (148). In humans both isoforms have central roles in fatty acid biosynthesis and oxidation (149). Although mice lacking ACC1 die young, the ACC2-null mice have a normal life span and, compared with wild-type animals, demonstrate continuous oxidation of fatty acid and therefore have substantial reductions in fat stores and body weight (150,151). When fed a high-fat high-carbohydrate diet, the ACC2- - mice demonstrate a resistance to obesity and the development of diabetes (150). Primary adipocyte cells cultured from the ACC2-null mice fed either a normal or high-fat high-carbohydrate diet suggested that higher levels of fatty acid oxidation and lipolysis are major factors contributing to leaner ACC2- - mice (152). These findings indicate that pharmaceutical targets that inhibit ACC2 may prove to be important for the treatment of obesity and diabetes (149). An...


Syndecan-3, a neuronal heparan sulfate proteoglycan (HSPG), was recently identified as a modulator of feeding behavior by acting as a coreceptor for the melanocortin receptors in the hypothalamus (240). Syndecan-3 expression is regulated by nutritional status ablation of the gene leads to reduced food intake and resistance to high-fat diet-induced obesity (241). The finding was quite unexpected, but provides a novel mechanism for regulating body weight. Syndecan-3 is a member of a family of four type I transmembrane HSPGs that act as coreceptors for diverse cell surface receptors (242). As coreceptors, the syndecans modulate a variety of cellular and physiological processes. Syndecan function is regulated by transcriptional, post-transcriptional, and post-translational processes. Syndecans are also regulated by cleavage of their extracelluar domain in a process commonly referred to as shedding (243). Release of the extracellular domain can inactivate the signaling modulated by the...


Elevated triglyceride levels increase the individual's risk of atherosclerosis, ASHD, and peripheral vascular disease. Other clinical conditions associated with increased triglycerides include all types of hyperlipidemia, poorly controlled diabetes, pancreatitis, kidney syndromes, and toxemia. Individuals with a history of myocardial infarction may show increased triglycerides for up to one year postinfarction. A high-carbohydrate diet may contribute to high triglyceride levels.

Barry E Levin md

Epidemiological studies suggest that maternal undernutrition, obesity, and diabetes during gestation and lactation can all produce obesity in offspring. Animal models provide a means of assessing the independent consequences of altering the pre- versus postnatal environments on a variety of metabolic, physiologic, and neuroendocrine functions that lead to the development of offspring obesity, diabetes, hypertension, and hyperlipidemia. During the gestational period, maternal malnutrition, obesity, type 1 and type 2 diabetes, and psychological, immunological, and pharmacological stressors can all promote offspring obesity. Normal postnatal nutrition can sometimes reduce the adverse impact of some of these prenatal factors but may also exacerbate the development of obesity and diabetes in offspring of dams that were malnourished during gestation. The genetic background of the individual is also an important determinant of outcome when the perinatal environment is perturbed. Individuals...

Weight Reduction

Carbohydrate restriction leads to ketosis, with fat from adipose tissue being the major source of energy. Ketosis can suppress appetite and have a diuretic effect. The low-carbohydrate diets are usually associated with quick weight loss in the first 1-2 weeks. A study comparing low-carbohydrate diets (< 30 g day) with a low-fat, calorie-restricted diet in 132 severely obese patients with a mean BMI of 43 and a high prevalence of diabetes and the metabolic syndrome showed that after 6 months, the 43 patients still on the low-carbohydrate diet lost a mean of 5.8 kg, compared with 1.9 kg lost by the 36 patients still on the low-fat, low-calorie diet. At least for the first 6 months of a high-fat, low-carbohydrate diet, there seem to be no adverse effects on risk factors for atherosclerosis, although carotid intimal thickening can occur if high-saturated fat alternatives to carbohydrates are chosen. Ketosis can cause bad breath and prolonged ketosis may increase the risk of osteoporosis...

Uncoupling Protein

UCP-3 is abundantly expressed in skeletal muscle, an important tissue for thermogen-esis (53). Phenotypes of mice in which UCP-3 genes have been inactivated do not indicate that these homologs have a function in regulating either body temperature or body weight (134-137). In one study in which UCP-3 was overexpressed in skeletal muscle of transgenic mice, mice showed a resistance to diet-induced obesity and an improvement in insulin sensitivity (138). As the amount of UCP-3 in the muscle of the transgenic mice was at a level that had been shown previously, by the same group of investigators, to be toxic to the mitochondria of mammalian cells, it is possible that the mitochondria of the transgenic mice were leaky owing to toxicity from the high levels of UCP-3 (139). Consequently, the effects of the UCP-3 transgene expression were not indicative of normal physiological function. A recent study, in which UCP-3 was induced in human muscle by a high-fat diet and then the rate of recovery...

Fatty Acid Synthase

Fatty acid synthase is a large multienzyme complex in the cytoplasm that is rapidly induced in the liver after a meal by high carbohydrate and the concomitant rise in insulin levels. It contains an acyl carrier protein (ACP) that requires the vitamin pantothenic acid. Although malonyl CoA ls the substrate used by fatty acid synthase, only the carbons from the acetyl CoA portion are actually incorporated into the fatty acid produced. Therefore, the fatty acid is derived entirely from acetyl CoA.


Unlike low-fat diets, the FDA has not established a clear definition for low-carbohydrate diets however, diets prescribing less than 100 g of carbohydrate or approx 10 to 20 , 25 to 35 , and 55 to 65 of total energy from carbohydrate, protein, and fat, respectively, are generally considered low-carbohydrate (7). The focus of existing low-carbohydrate diets is replacement of foods containing refined carbohydrates (i.e., white bread, rice, pasta, desserts, chips, and sweetened soft drinks) with controlled amounts of nutrient-dense carbohydrate-containing foods (i.e., nonstarchy vegetables, fruits, and whole-grain products). The hypothesis underlying this approach is that high intake of refined carbohydrates results in hyperinsulinemia and insulin resistance, which ultimately leads to weight gain therefore, lower intakes of carbohydrate and a shift toward consumption of foods that contain nutrients that do not cause a dramatic spike in insulin levels is metabolically advantageous....


Sharman and Volek compared the effects of short-term (6-wk) consumption of hypocaloric low-carbohydrate and low-fat diets on C-reactive protein (CRP), CAMs, and proinflammatory cytokines (i.e., IL-6, TNF-a, and P-selectin) in 15 overweight but otherwise healthy men (36). Consumption of both low-carbohydrate and low-fat diets resulted in weight loss (-6.5 3.0 kg and -3.7 3.3 kg, respectively). Improvements in inflammatory biomarkers were also observed following both diets (i.e., reductions in IL-6, TNF-a, CRP, and sICAM-1). These data were analyzed further to represent the delta change in inflammatory biomarkers per 1 kg reduction in body weight. There were no significant differences between the diets for IL-6, TNF-a, CRP, and sICAM-1 however, there was a significantly lower response for P-selectin in the low-fat group. Compared with individuals consuming a low-fat diet, greater reductions in CRP have been reported in individuals consuming a low-carbohydrate diet after adjusting for...

Strain Differences

A second issue is the choice of an appropriate strain for mutagenesis according to the category of phenotypes and parameters that have to be assessed (12,22,31). In phenotype-driven screens, inbred strains with a genetic predisposition might not be appropriate where this genetic predisposition represses the phenotype of interest. This could be possible, for example, for wild-type C57BL 6, which displays a genetic susceptibility to arteriosclerosis (32) or non-insulin-dependent diabetes mellitus and hypertension (33) when fed a high-fat diet. In addition, the C3H mouse strain should be used with care in behavioral studies, since these mice carry the rd (retinal degeneration) gene and are blind after about 6 weeks.


In addition to elevated fasting cholesterol, LDL cholesterol concentrations and inflammatory markers, increased large very-low-density lipoprotein (VLDL) particle concentration, increased chylomicron concentration, small particle size diameter, and elevated postprandial lipemia are associated with increased risk for cardiovascular disease. Lipids and lipoprotein subfractions (i.e., chylomicrons and VLDL, LDL, and HDL subfractions) were evaluated in one study in which 78 obese individuals were randomly assigned to a low-carbohydrate (< 30g d) or low-fat (< 30 energy from fat) diet for 6 mo (37). Forty percent of these participants had diabetes and 77 of those who did not have diabetes had metabolic syndrome. After 6 mo, participants in the low-carbohydrate group lost more weight than those in the low-fat group (-8.5 9.3 kg vs -3.5 4.9 kg). At 6 mo more participants in the low-carbohydrate group had detectable chylomicron concentrations. In addition, greater decreases in large VLDL...

Brown Adipose Tissue

To test this hypothesis, several lines of transgenic mice with selective ablation of the brown adipose tissue have been generated. In these mice, the regulatory elements of the brown adipose tissue-specific UCP protein gene were used to drive expression of DTA transgene resulting in specific ablation of brown adipose tissue. These mutants are characterized by reduced energy expenditure (lower body temperature but not locomotor activity), marked obesity, increased food intake, hyperglycemia, hyperlipidemia, and increased susceptibility to a high-fat diet induced obesity (151,158-160). These abnormalities are associated with insulin resistance and non-insulin-dependent diabetes mel-litus (NIDDM) with both receptor and postreceptor components (161,162). Interestingly, in this model, increased body wt, hyperlipidemia, late hyperphagia, and glucose homeo-stasis are leptin-resistant, while hypothalamic NPY and the hypothalamic-pituitary-adrenal axis remain under leptin control (151,163)....

Lipoprotein Lipase

Generation of transgenic mice that overexpress human lipoprotein lipase in skeletal muscle allowed the examination of whether high-fat feeding-induced obesity would be prevented by diverting lipoprotein-derived triglyceride fatty acids away from storage in adipose tissue to oxidation in muscle. These mice have markedly increased lipoprotein-lipase activity in skeletal muscles with lower plasma triglycerides and carcass lipid content. The targeted overexpression of lipoprotein lipase in skeletal muscle clearly prevents a high-fat diet-induced lipid accumulation. These findings point out the possibility of preventing or treating obesity in humans by increasing lipoprotein-lipase activity in muscle by gene or drug delivery (176).

Diabetes And Fats

Fat intake should clearly be individualized with monounsaturated fat and carbohydrates providing 60-70 of total energy intake. For example, low-saturated fat diets (supplying < 10 of energy), along with high-carbohydrate intake, increased postprandial glucose levels, insulin, triglycerides, and decreased HDL when compared with isocaloric high-monounsaturated fat diets. However, high-monounsaturated fat diets have not been shown to lower hemoglobin A1-C values or have a beneficial effect on fasting plasma glucose. Thus, these high-monounsaturated fat diets may result in weight gain and increased energy intake in an uncontrolled setting.

Low Carb Diets Explained

Low Carb Diets Explained

You can burn stored body fat for energy and shed excess weight by reducing the carbohydrate intake in your diet. Learn All About The Real Benefits of Low Carb Diets And Discover What They Can Really Do To Improve The Quality Of Your Life Today.

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