United States Department of Agriculture
 
Popular Diets: A Scientific Review 1/2

Obesity Research 9(2001):1s
by Marjorie R. Freedman, Janet King, and Eileen Kennedy
http://www.obesityresearch.org/cgi/reprint/9/suppl_1/33S.pdf

Janet King, Ph.D., R.D., is the Director at the U.S. Department of Agricultural Research Service, Western Human Nutrition Research Center, Presidio of San Francisco, CA and is currently the President of the American Society for Nutritional Sciences.

EXECUTIVE SUMMARY

Introduction

Weight loss is a major concern for the US population. Surveys consistently show that most adults are trying to lose or maintain weight (1). Nevertheless, the prevalence of overweight and obesity has increased steadily over the past 30 years. Currently, 50% of all adult Americans are considered overweight or obese (2,3). These numbers have serious public health implications. Excess weight is associated with increased mortality (4) and morbidity (5). It is associated with cardiovascular disease, type 2 diabetes, hypertension, stroke, gallbladder disease, osteoarthritis, sleep apnea and respiratory problems, and some types of cancer (6,7).

Most people who are trying to lose weight are not using the recommended combination of reducing caloric intake and increasing physical activity (1). Although over 70% of persons reported using each of the following strategies at least once in 4 years, increased exercise (82.2%), decreased fat intake (78.7%), reduced food amount (78.2%,) and reduced calories (73.2%), the duration of any one of these behaviors was brief. Even the most common behaviors were used only 20% of the time (8).

Obesity-related conditions are significantly improved with modest weight loss of 5% to 10%, even when many patients remain considerably overweight (6). The Institute of Medicine (9) defined successful long-term weight loss as a 5% reduction in initial body weight (IBW) that is maintained for at least 1 year. Yet data suggest that such losses are not consistent with patients’ goals and expectations. Foster (10) reported that in obese women (mean body mass index [BMI] of 36.3 6 4.3) goal weights targeted, on average, a 32% reduction in IBW, implying expectations that are unrealistic for even the best available treatments. Interestingly, the most important factors that influenced the selection of goal weights were appearance and physical comfort rather than change in medical condition or weight suggested by a doctor or health care professional. Is it any wonder that overweight individuals are willing to try any new diet that promises quick, dramatic results more in line with their desired goals and expectations than with what good science supports?

The proliferation of diet books is nothing short of phenomenal. A search of books on Amazon.com using the key words “weight loss” revealed 1214 matches. Of the top 50 best-selling diet books, 58% were published in 1999 or 2000 and 88% were published since 1997. Many of the top 20 best sellers at Amazon.com promote some form of carbohydrate (CHO) restriction (e.g., Dr. Atkins’ New Diet Revolution, The Carbohydrate Addict’s Diet, Protein Power, Lauri’s Low-Carb Cookbook). This dietary advice is counter to that promulgated by governmental agencies (US Department of Agriculture [USDA]/Department of Health and Human Services, National Institutes of Health) and nongovernmental organizations (American Dietetic Association, American Heart Association, American Diabetes Association, American Cancer Society, and Shape Up America!).

What is really known about popular diets? Is the information scientifically sound? Are popular diets effective for weight loss and/or weight maintenance? What is the effect, if any, on composition of weight loss (fat vs. lean body mass), micronutrient (vitamin and mineral) status, metabolic parameters (e.g., blood glucose, insulin sensitivity, blood pressure, lipid levels, uric acid, and ketone bodies)? Do they affect hunger and appetite, psychological well-being, and reduction of risk for chronic disease (e.g., coronary heart disease, diabetes, and osteoporosis)? What are the effects of these diets on insulin and leptin, long-term hormonal regulators of energy intake and expenditure?

The objective of this article is to review the scientific literature on various types of popular diets based on their macronutrient composition in an attempt to answer these questions (see Appendix for diet summaries).

Evidence-Based Guidelines

This article is limited to the effects of popular diets in overweight and obese adults; there are no good data on children and adolescents. Dietary claims are scrutinized, diets are analyzed, and information is compared with scientific data published in peer-reviewed journals. No published studies are excluded, despite inherent methodological problems (e.g., small or inadequate sample size, limited duration, lack of adequate controls and randomization, poor or minimal dietary collection and/or description of diets, and potential biases). However, the strength of the evidence supporting various conclusions made throughout the paper is based on the following grading system used by National Heart, Lung, and Blood Institute (NHLBI) (6) (Table 1).

Characterization of Diets

Diets are characterized below and in Tables 2 and 3. c High-fat (55% to 65%), low-CHO (,100 g of CHO per day), high-protein diets (e.g., Dr. Atkins’ New Diet Revolution, Protein Power, Life Without Bread). c Moderate-fat (20% to 30%), balanced nutrient reduction diets, high in CHO and moderate in protein (e.g., USDA Food Guide Pyramid, DASH diet, Weight Watchers). c Low-fat (11% to 19%), and very-low-fat (VLF) (,10%), very-high-CHO, moderate-protein diets (e.g., Dr. Dean Ornish’s Program for Reversing Heart Disease, Eat More, Weigh Less, The New Pritikin Program).

Summary of Findings

Weight Loss

Diets that reduce caloric intake result in weight loss. In the absence of physical activity, a diet that contains ;1400 to 1500 kcal/d, regardless of macronutrient composition, results in weight loss. Individuals consuming high-fat, low-CHO diets may lose weight because the intake of protein and fat is self-limiting and overall caloric intake is decreased (11,12). Low-fat and VLF diets contain a high proportion of complex CHOs, fruits, and vegetables. They are naturally high in fiber and low in caloric density. Individuals consuming these types of diets consume fewer calories and lose weight (13–17). Balanced nutrient reduction diets contain moderate amounts of fat, CHO, and protein. When overall caloric intake is reduced, these diets result in loss of body weight and body fat (6,18). Importantly, moderate-fat, balanced nutrient reduction diets produce weight loss even when they are consumed ad libitum.

In sum, all popular diets, as well as diets recommended by governmental and nongovernmental organizations, result in weight loss. However, it is important to note that weight loss is not the same as weight maintenance.

Evidence Statement: Caloric balance is the major determinant of weight loss. Diets that reduce caloric intake result in weight loss. In the absence of physical activity, the optimal diet for weight loss contains ;1400 to 1500 kcal/d, regardless of macronutrient composition. Evidence Category A.

Evidence Statement: Free-living overweight individuals who self-select high-fat, low-CHO diets consume fewer calories and lose weight. Evidence Category C.

Evidence Statement: Overweight individuals consuming high-fat, low-CHO, low-calorie diets under experimental conditions lose weight. Evidence Category C.

Evidence Statement: Overweight individuals consuming moderate-fat, balanced nutrient reduction diets lose weight because they consume fewer calories. These diets can produce weight loss when consumed ad libitum. Evidence Category A.

Evidence Statement: Overweight individuals consuming low-fat and VLF diets lose weight because they consume fewer calories. Evidence Category B.

Evidence Statement: Weight loss on VLF diets may be the result of lifestyle modification, which may include decreased fat and energy intake, increased energy expenditure, or both. Evidence Category B.

Body Composition

As body weight decreases, so does body fat and lean body mass. The optimal diet for weight loss is one that maximizes loss of body fat and minimizes loss of lean body mass. All low-calorie diets result in loss of body weight and body fat (6). Macronutrient composition does not seem to play a major role (19 –22). In the short-term, however, high-fat, low-CHO ketogenic diets cause a greater loss of body water than body fat (23). When these diets end, water weight is regained (24). Eventually, however, all reduced calorie diets result in loss of body fat if sustained long term (25). Physical activity, an important factor with respect to lean body mass, should be promoted to enhance the effects of diet on body composition.

Evidence Statement: All low-calorie diets result in loss of body weight and body fat. Macronutrient composition does not seem to play a major role. Evidence Category A

Evidence Statement: In the short term, low-CHO ketogenic diets cause a greater loss of body water than body fat. Water weight is regained when the diet ends. If the diet is maintained long term, it results in loss of body fat. Evidence Category C.

Nutritional Adequacy

Proper food choices are always important when considering the nutritional quality of a diet. When individuals consume foods from all food groups, it is more likely that their diet will be nutritionally adequate. The moderate-fat, balanced nutrient reduction diet is optimal for ensuring adequate nutritional intake. However, poor food choices may result in inadequate levels of nutrients (e.g., calcium, iron, zinc), regardless of overall macronutrient composition. High-fat, low-CHO diets are nutritionally inadequate. They are low in vitamins E, A, thiamin, B6, folate, calcium, magnesium, iron, potassium, and dietary fiber, and require supplementation. These diets are high in saturated fat and cholesterol. VLF diets are low in vitamins E, B12, and zinc because meat and fat intake is low.

Evidence Statement: With proper food choices, the moderate-fat, balanced nutrient reduction diet is nutritionally adequate. Evidence Category B.

Evidence Statement: High-fat, low-CHO diets are nutritionally inadequate, and require supplementation. Evidence Category C.

Evidence Statement: VLF diets are low in vitamins E, B12, and zinc. Evidence Category B.

Metabolic Parameters

Low-CHO diets result in ketosis, and may cause a significant increase in blood uric acid concentrations. Blood lipid levels (e.g., total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL] and triglycerides [TGs]) decrease as body weight decreases (6,26,27). However, the macronutrient and fatty acid composition of energy-restricted diets can exert substantial effects on blood lipids. There are significantly greater decreases in LDL cholesterol during active weight loss when diets are low in saturated fatty acids. Changes in HDL cholesterol depend on dietary fat content and duration of energy restriction (28). Moderate-fat, balanced nutrient reduction diets reduce LDL-cholesterol and normalize the ratio of HDL/TC.

Plasma TG levels also decrease with weight loss (6). Although they increase in response to short-term consumption of a VLF, high-CHO diet (29), the type of CHO consumed must be considered. High-fiber foods, including vegetables and legumes, do not lead to hypertriglyceridemia (30), and may easily be incorporated into moderate-fat, balanced nutrient reduction diets to help normalize plasma TG levels.

Energy restriction, independent of diet composition, improves glycemic control (21,22,31–33). As body weight decreases, so does blood insulin and plasma leptin levels (21,34).

Blood pressure decreases with weight loss, independent of diet composition (6,22,26). However, the DASH diet, high in fruits, vegetables, and low-fat dairy products effectively lowers blood pressure (35).

Evidence Statement: High-fat, low-CHO diets result in ketosis. Evidence Category B.

Evidence Statement: Metabolic profiles are improved with energy restriction and weight loss. Evidence Category A.

Evidence Statement: Low-CHO diets that result in weight loss may also result in decreased blood lipid levels, decreased blood glucose and insulin levels, and decreased blood pressure. Evidence Category C.

Evidence Statement: Low-fat and very low-fat diets reduce LDL-cholesterol, and may also decrease plasma TG levels, depending on diet composition. Evidence Category B.

Evidence Statement: Moderate-fat, balanced nutrient reduction diets reduce LDL-cholesterol, normalize the ratio of HDL/TC, and normalize plasma TGs. Evidence Category A.

Hunger and Compliance

Many factors influence hunger, appetite, and subsequent food intake. Macronutrient content of the diet is one, and it may not be the most important. Neurochemical factors (e.g., serotonin, endorphins, dopamine, hypothalamic neuropeptide transmitters), gastric signals (e.g., peptides, stomach distention), hedonistic qualities of food (e.g., taste, texture, smell), genetic, environmental (e.g., food availability, cost, cultural norms) and emotional factors (e.g., eating when bored, depressed, stressed, happy) must be considered. These parameters influence appetite primarily on a meal-tomeal basis. However, long-term body weight regulation seems to be controlled by hormonal signals from the endocrine pancreas and adipose tissue, i.e., insulin and leptin. Because insulin secretion and leptin production are influenced by the macronutrient content of the diet (36,37), effects of different diets on these long-term regulators of energy balance also need to be considered when investigating hunger and appetite.

All fat-restricted diets provide a high degree of satiety. Subjects who consume fat-restricted diets do not complain of hunger, but of having “too much food” (38,39). These diets, high in fiber and water content are low in caloric density. Subjects who consume these diets develop a distaste for fat (40), which may be useful in long-term adherence to reduced fat, low-calorie diets. However, it is not clear that restricting fat provides any advantage over restricting CHOs. Ogden (41) reports weight loss maintainers used healthy eating habits and adhered to calorie-controlled diets.

Long-term compliance to any diet means that short-term weight-loss has a chance to become long-term weight maintenance (42– 44). Dietary compliance is likely a function of psychological issues (e.g., frequency of dietary counseling, coping with emotional eating, group support) rather than macronutrient composition, per se (42,45). Being conscious of one’s behaviors, using social support, confronting problems directly, and using personally developed strategies may enhance long-term success (46). Ogden (41) notes that successful weight loss and maintenance may be predicted by an individuals’ belief system (e.g., that obesity is perceived as a problem that can be modified and if modifications bring changes in the short-term that are valued by the individual concerned).

Evidence Statement: Many factors influence hunger, appetite, and subsequent food intake. There does not seem to be an optimal diet for reducing hunger. Evidence Category B.

Evidence Statement: Long-term compliance is likely a function of psychological issues rather than macronutrient composition. Evidence Category B.

Summary and Recommendations

Caloric balance (calories in vs. calories out), rather than macronutrient composition is the major determinant of weight loss. However, what is not clear is the effect of macronutrient content on long-term weight maintenance and adherence. Furthermore, it is not known whether maintenance of weight loss and dietary adherence is related to psychological issues (and brain neurochemistry), physiological parameters (e.g., hormones involved in body weight regulation such as insulin and leptin), physical activity, energy density, or some other factor(s).

Controlled clinical trials of high-fat, low-CHO, and lowfat and VLF diets are needed to answer questions regarding long-term effectiveness (e.g., weight maintenance rather than weight loss) and potential long-term health benefits and/or detriments.

Prevention of weight gain and weight maintenance are important goals. Scientifically validated, yet understandable information is clearly needed by millions of overweight and obese Americans who often find weight loss attainable, but maintaining weight loss nearly impossible.

Despite controversy surrounding their use, high-fat, low- CHO diets are among the most popular types of diets today. The most famous is Dr. Atkins’ Diet Revolution (47) first published in 1972, and updated 20 years later as Dr. Atkins’ New Diet Revolution (48). Promoting a “lifetime nutritional philosophy,” Atkins claims that his diet has been embraced by an estimated 20-plus million people worldwide since the release of his first book (www.atkinscenter.com). His program was one of the first to popularize low-CHO, highprotein, ketogenic diets that individuals could use on their own, rather than in a medical setting (e.g., a protein-sparing modified fast). Other low-CHO diets with similar themes include Protein Power (49), The Carbohydrate Addict’s Diet (50), Dr. Bernstein’s Diabetes Solution (51), and Life Without Bread (52).

A. Underlying Philosophy, Claims, and Proposed Solutions

Proponents of high-fat, low-CHO diets dismiss the notion that caloric intake is important to either weight gain or weight loss. They claim that “most overweight individuals do not overeat” (48, p. 7; 50, p. 21), even as they suggest that high-CHO meals leave individuals less satisfied than meals that contain adequate fat, resulting in increased hunger and increased food intake (48, p. 55; 50, p. 43). They suggest that those who do overeat do so “because of a metabolic component driving them on, most often a truly addictive craving for CHOs” (48, p. 7; 52, p. 142). Because “carbohydrates are addictive,” the carbohydrate “addict” continues to eat carbohydrates, producing more and more insulin, which inhibits brain serotonin release. Reductions in this “satiety” neurotransmitter result in a decreased sense of satisfaction (50, pp. 26, 43; 51, p. 41). With respect to weight loss, Atkins (48) claims that on a low-CHO diet there are “metabolic advantages that will allow overweight individuals to eat as many or more calories as they were eating before starting the diet yet still lose pounds and inches” (p. 10).

Furthermore, proponents contend overproduction of insulin, driven by high CHO intake, is the cause of the metabolic imbalance that underlies obesity (48,50,53). Eating too much CHO results in increased blood glucose, increased blood insulin, and increased TGs (48, pp. 50–51). An already overweight person who continues to overeat CHOs develops hyperinsulinemia and insulin resistance, “resulting in insulin’s lack of effectiveness in converting glucose into energy, but enabling glucose (e.g., dietary CHO) to be stored as fat” (48, p. 52).

Advocates of low-CHO diets propose a simple solution to this “vicious cycle” of CHO addiction, CHO overeating, hyperinsulinemia, decreased glucose use and increased fat storage. It involves restricting CHOs severely enough to produce ketosis. The ketosis is a reliable indicator of fat mobilization. In this condition, the key benefit is that blood glucose and blood insulin levels are reduced, and appetite is suppressed. In short, authors contend that a high-fat, low- CHO, high-protein, ketogenic diet results in weight loss, body fat loss, preservation of lean body mass, and correction of serious medical complications of diabetes (51), heart disease, and high blood pressure (48, pp. 6, 63). The contention is that the high-fat, low-CHO diet supports longterm health, controls weight without hunger, and should be followed for the rest of one’s life (48, p. 27).

B. Scientific Evaluation of Claims

1. Caloric Intake, Body Weight, and Body Composition

c Is caloric intake relevant when looking at weight gain and weight loss?

c What is the effect of diet composition on weight loss, e.g., will consuming a high-fat, low-CHO diet, regardless of caloric intake, result in weight loss, body fat loss, and preservation of lean body mass?

Energy intake and energy expenditure are relevant when looking at weight gain and weight loss. Overweight and obesity results from an energy imbalance (e.g., excess caloric intake, decreased energy expenditure, or both) (54). Reduction of body weight and body fat can be achieved by creating an energy deficit (e.g., restricting energy intake, increasing energy expenditure, or a combination of the two) (6,18,54). Atkins (48) calls these basic thermodynamic principles “a millstone around the neck of dieters and a miserable and malign influence on their efforts to lose” (p. 6). Do followers of high-fat, low-CHO diets have a metabolic advantage that enables them to eat a greater number of calories, and still lose body weight and body fat?

No scientific evidence exists to suggest that low-CHO ketogenic diets have a metabolic advantage over more conventional diets for weight reduction (55). Studies consistently show that under conditions of negative energy balance, weight loss is a function of caloric intake, not diet composition (54). Table 4 indicates diet composition of individuals who self-select high-fat, low-CHO diets, and Tables 5a and 5b show weight change in obese individuals consuming high-fat, low-CHO diets. In all cases, individuals on high-fat, low-CHO diets lose weight because they consume fewer calories.

Evidence Statement: Free-living overweight individuals who self-select high-fat, low-CHO diets consume fewer calories and lose weight. Evidence Category C.

Evidence Statement: Overweight individuals consuming high-fat, low-CHO, low-calorie diets under experimental conditions lose weight. Evidence Category C.

Caloric Intake and Weight Change

Studies cited by Atkins (pp. 67–74) to support his contentions were of limited duration, conducted on a small number of people, lacked adequate controls, and used illdefined diets (24,58,61,63–65,67,68,71). Some of these, as well as other studies, actually refute the contention that low- CHO diets, in the absence of energy restriction, provide a metabolic advantage (11,12,21,22,45,56,57,59,60–64,66–68, 70,72). These studies are reviewed below.

Early Studies (Pre-1960)

Early studies on a limited number of obese men and women indicate individuals consuming low-CHO diets reduce overall caloric intake and lose weight (12,65,72,73). Pennington’s (73) was one of the earliest low-CHO diets, and contained less than 60 g CHO per day, an amount “calculated to not interfere with ketogenesis.”

The diet allows 24 ounces of meat with fat daily, and one ordinary portion of any of the following: white potatoes, sweet potatoes, boiled rice, half of a grapefruit, grapes, melon, banana, pear, raspberries, or blueberries; it allows no bread, flour, salt, sugar, or alcohol. The Pennington diet resulted in an unspecified amount of weight loss but critics were suspicious that the unpalatability, or high satiety value of the diet, resulted in food intake well below the minimum recommended 2870 kcal/d. However, Pennington concluded, “there is nothing remarkable in the observation that some obese must, of necessity, lose weight on an intake of 3000 kcal or more per day,” considering their normal intake to be up to 4500 kcal/d (72,73).

To substantiate weight loss could occur on 2870 kcal/d, regardless of diet composition, Werner (72) studied 6 obese subjects confined to a metabolic ward for 35 to 49 days. He fed them Pennington’s low-CHO, high-fat diet (2874 kcal, 52 g CHO, 242 g fat) or an isocaloric, high-CHO, lower-fat diet (2878 kcal, 287 g CHO, 146 g fat). Apart from transient changes in water balance, the rate of weight loss in obese subjects was the same on both diets, showing diet composition did not matter. Atkins (48) called Pennington’s study “exciting” (p. 67) yet he dismisses Werner’s study as too high in CHOs to promote ketosis (p. 70), despite the fact that Werner received the diet from Dr. Pennington. To support the concept of total caloric intake over diet composition, Yudkin and Carey (12), studied six adult overweight subjects and found that when they followed a low- CHO diet (,30 to 55 g/d) for 2 weeks, caloric intake was reduced 13% to 55% (180 to 1920 fewer daily calories). Caloric intake averaged 1383 per day. Although all subjects were allowed to consume an “unlimited” amount of fat, none consumed significantly more fat than before, and three showed a significant reduction of fat intake. Only one showed a slight increase in protein intake.

Studies by Kekwick and Pawan (24,71) are cited by Atkins to support his contention that diet composition, rather than caloric intake, is the key variable for weight loss. Yet, despite this contention, these studies support the notion that calories do count. Obese individuals confined to a metabolic ward were given diets with the same ratio of fat, protein and CHO, but different caloric values. Individuals lost more weight when they consumed lower calorie diets (e.g., 500 and 1000 kcal/d) compared with when they consumed higher calorie diets (e.g., 1500 and 2000 kcal/d). In another study, 14 obese patients were fed 1000-kcal diets containing either 90% protein (5 g of CHO), 90% fat (10 g of CHO), or 90% CHO (225 g of CHO). Food available in each of the diets was unspecified. Each subject consumed the high-fat, high-protein, or high-CHO diet for 5 to 9 days before being switched to another diet. Twenty-one days later, all patients had lost weight, regardless of the order they had consumed the different diets. However, patients consuming 90% fat lost the most weight over 5 to 9 days, whereas those eating 90% CHO lost little or none; some even gained back some weight lost earlier on the 90% fat or 90% protein diets. These results led Kekwick and Pawan to suggest, “obese patients must alter their metabolism in response to the contents of the diet.” In another study, they fed five obese individuals 2000 kcal balanced diets for 7 days, followed by a low-CHO, high-fat, high-protein diet providing 2600 kcal/d for 4 to 14 days. Although patients could maintain or gain weight on 2000 kcal/d, all, except one, lost weight on 2600 kcal/d. Weight loss was reported to be partly from body water (30% to 50%) and partly from body fat (50% to 70%). Unfortunately, none of these studies reported actual food intake, despite the author’s remarks, “the main hazard was that many of these patients had inadequate personalities. At worst they would cheat and lie, obtaining food from visitors, from trolleys touring the wards, and from neighboring patients.”

Convinced that fluid balance, not diet composition, was the cause of the weight loss reported by Kekwick and Pawan, Pilkington et al. (74) repeated their studies for longer periods of time (18 or 24 days). His results were comparable with Kekwick and Pawan’s during the first few days on each of the diets. However, there was a steady rate of weight loss with each of the 1000-kcal diets thereafter, regardless of whether the calories came from fat, protein, or CHO. Although he did not measure fluid balance, Pilkington (74) concluded that temporary differences in weight loss were due to such changes. He stated “if the periods of study are long enough to achieve a ‘steady state’ the rate of weight loss on a diet consisting mainly of fat does not differ significantly from the rate of weight loss on an isocaloric diet consisting mainly of CHO.” Oleson and Quaade’s (75) experiment, which lasted for 3 weeks, had a similar conclusion.

Studies from 1961 to 1979

Fletcher et al. (59) gave six obese women who were confined to a metabolic ward 800 kcal/d diets containing mostly CHO, protein, or fat. They received each diet for 14 days. The high-fat and high-protein diets each contained 36 g of CHO. Statistical analysis showed no significant difference in the rate of weight loss on the different diets. Kinsell et al. (19) maintained obese subjects on a fixed caloric intake and varied the macronutrient composition of the diet (e.g., fat intake varied from 12% to 80%, protein from 14% to 26%, and CHO from 3% to 61%). In any given subject, the rate of weight loss after the initial depletion of fluid was essentially constant throughout the entire study, irrespective of diet composition. Bortz (62) fed an 800-kcal liquid formula diet containing 80 g of protein, and either 54 g of fat (no CHO), or 120 g of CHO (no fat) to nine obese subjects who were confined to a metabolic ward. Each diet was given for 24 days, before switching to the other. No difference in rate of weight loss was noted, apart from that attributable to alterations in sodium and fluid balance. Krehl et al. (63) studied four healthy, normal weight male prison volunteers, and seven obese females (five were from 15 to 21 years old, and two were 36 and 53 years old) on a metabolic ward. The obese females were given 1200-kcal, 12-g CHO diets, comprised of fat and protein in different ratios (50/50; 60/40; 40/60; 70/30; 30/70). They received each diet for 1 month. They also had three ;1-hour periods of supervised physical activity daily. Although it is difficult to draw any conclusions from this small study, Krehl et al. (63) reported that all patients lost weight at a rate commensurate with caloric restriction and physical activity, regardless of diet composition.

In another short-term study, Worthington and Taylor (66) fed isocaloric diets (1182 kcal/d) for 2 weeks to 20 obese women who were confined to a state correctional institution. One diet was a low-CHO, ketogenic diet (17 g/d) with a 6:48:44 ratio of CHO to protein to fat calories. The other was a “balanced low-calorie diet” and contained 96 g of CHO and a 32:20:47 ratio of CHO to protein to fat. Although this diet was not meant to be ketogenic, two subjects tested positive for urinary ketones on Day 7 and four tested positive on Day 14. The 10 women on the low-CHO diet lost significantly more weight at the end of 14 days compared with the 10 women on the balanced diet (12.0 6 3.7 vs. 8.7 6 3.5, low-CHO vs. balanced). The difference in total weight loss was established primarily during the first week, when the average weight loss in the low-CHO group was 8.2 pounds, and that of the control group was 6 pounds. During the second week, weight loss was similar for the two groups.

In 1971, Young et al. (64), at Cornell University, looked at the effect of diet composition on weight loss and body composition. Eight moderately obese young male college students were fed isocaloric diets for 9 weeks (interrupted after 3 weeks for 1 week of spring vacation). Each diet contained 1800 kcal and 112 g of protein, but different amounts of CHO: either 104, 60, or 30 g/d. Physical activity was not controlled. Only those in the 30 g/d group tested positive for ketones throughout the 9-week study. As CHO in the diet decreased, weight and fat loss slightly, but not significantly, increased. Using underwater weighing to determine body composition, Young et al. reported that the weight lost by the lowest CHO group (30 g/d) was close to 100% fat. However, no difference between the groups with respect to nitrogen, sodium, or potassium balances was reported. Young et al. (64) concluded, “it would seem that of the low CHO diets used, the one at the 104-g level would be most suitable for long-term use.” Although their study lasted 9 weeks, Atkins extrapolated data to 30 weeks, implying even greater benefit (p. 73).

Rickman (56) monitored weight changes in 12 healthy volunteers (hospital employees) who were no more than 10% above ideal body weight (based on Metropolitan Life Insurance tables). Subjects were instructed to follow the Stillman diet, which allowed unlimited quantities of protein and fat, but no CHO. Average caloric intake was 1325 per day, with 50% of calories from fat (73 g), 48% from protein (160 g), and less than 1% from CHO (7 g). Subjects followed the diet for 3 to 17 days (average 7.6 days). During the first 3 to 5 days, each subject lost 1.3 to 2.2 kg. At the end, mean weight loss was 3.1 kg. In 8 of 10 subjects for whom there was follow-up within 7 days of the diet, average weight regain was 2 kg (range, 1 to 4.5 kg).

Studies using low-CHO, liquid formula diets conducted in Germany had small sample sizes, short duration (1 month), and poor design (61,67,68). Kasper et al. (61) compared the weight loss of 16 obese subjects on low-CHO diets (56g/d) with 4 obese subjects on isocaloric (1707 kcal), high-CHO diets (156 g/d). The average duration on the low-CHO diet was 16 days (range, 6 to 30 days); mean weight loss was 0.3 kg/d. The average duration on the high-CHO diet was 10 days (range, 6 to 14 days); mean weight loss was 0.05 kg/d. The small sample size, difference in study duration, and fact that 3 of the 4 subjects on the high-CHO diet also received the low-CHO diet (before or after?) prevents adequate interpretation. Seventeen subjects (some of whom had received other diets) were fed a high-fat formula diet containing 2150 kcal and 112 g of CHO per day. The average length of time on this diet was 18 days (range, 6 to 40 days) and the mean weight loss was 0.32 kg/d, an amount comparable with the low-CHO, lower calorie (1707) diet. Body composition was not measured during any of these studies.

A similar, but better controlled study was conducted by Lewis et al. (60). They compared the responses to two cholesterol-free, isocaloric (10 kcal/kg per day; ;1115 kcal), liquid formula diets of differing composition (70% CHO, 20% protein, 10% fat vs. 70% fat, 20% protein, 10% CHO) in 10 obese men who were confined to a metabolic ward. Diets were administered for 14 days in random order and each diet was preceded by a 7-day control, weight-maintenance diet (30 kcal/kg per day, 40% CHO, 20% protein, 40% fat). Although the low- CHO diet was clearly ketogenic, Lewis et al. (60) concluded that both low-calorie diets effected similar losses of nonaqueous body weight. Their conclusions regarding body composition changes were not based on actual body composition measurements. Instead, they were based on the significant rebound in body weight and the significant urinary sodium retention observed when the weight maintenance diet followed the ketogenic diet, along with the significant increase in serum albumin concentration noted during the period in which the low-CHO diet was ingested. These changes were not seen when the maintenance diet followed the high-CHO diet.

However, to support that low-CHO diets result in loss of body fat, Atkins cites Benoit et al. (58), who compared the effects of 10 days of fasting with a 1000-calorie, 10 g of CHO ketogenic diet in seven active-duty Naval personnel (mean weight, 115.6 kg). Over the 10-day period, the mean weight loss for the fasting and ketogenic groups were 9.6 kg and 6.6 kg, respectively. The ketogenic diet resembled fasting in terms of ketosis, acidosis, and mild anorexia (which the authors speculated may influence caloric restriction by the patient). However, the ketogenic diet resulted in greater fat loss (97% vs. 35%) and decreased loss of lean body mass (3% vs. 65%) relative to fasting. Although all patients on both diets were in negative N balance, potassium balance seemed unaffected by the ketogenic diet, an impossibility according to Grande (76), who seriously questioned the scientific validity of Benoit’s entire study.

Atkins cites Rabast et al. (67,68) to support his contention that low-CHO diets result in greater weight loss than high- CHO diets. Rabast et al. (66,68) fed 45 obese German men and women 1000-calorie, isonitrogenous, low-CHO (25 g/d) or high-CHO (170 g/d) formula diets. The duration of the treatment period differed between the two groups. On the low-CHO diet, it averaged 38 6 19 days (range, 15 to 78 days). On the high-CHO diet, it averaged 32 6 13 days (range, 18 to 59 days). Due to significant drop out in both groups, data were analyzed only up to Day 30. Results indicate by Day 15, the 25 subjects following the low-CHO diet lost significantly more weight than the 20 subjects following the high-CHO diet (6.81 6 0.30 kg vs. 5.49 6 0.37 kg). There was no significant difference in weight loss between the groups at Day 20 or 25. By Day 30, the weight loss between the two groups again reached statistical significance (11.77 6 0.77 kg vs. 9.81 6 0.43 kg, low-CHO vs. high-CHO, respectively), even though by day 30, almost 40% of subjects in each group had dropped out (no reasons given). Body composition data were not presented, and the authors did not report any increased water or electrolyte excretions during either of the diets. In another article, Rabast et al. (67) presented the exact same data found in the article just described (68). In addition, it included new data from 28 additional subjects who received low-CHO (48 g/d, n 5 13) or high-CHO (355 g/d, n 5 15) liquid formula diets containing 1900 kcal/d for 25 days. In this study, all subjects lost weight, regardless of caloric intake or diet composition.

The Rabast study that Atkins cites (p. 74) in support of his position actually refutes it. This study confirms weight loss on low-calorie diets, independent of CHO content after Day 10 on 1900 kcal, and after Day 15 on 1000 kcal. Atkins cites the difference of 4.2 kg (9.24 pounds) in total weight loss between the 1000-calorie low-CHO and 1000-calorie high-CHO groups as proof that the low-CHO diet works better. The problem with this is that these data (e.g., the 4.2-kg weight difference) represent the final weight loss between the two groups at the end of the study (59 to 78 days). However, we have no idea how many subjects actually completed the study. We do know that of 45 persons who started the study, only 28 remained by Day 30.

Studies after 1980

Larosa (57) studied 24 obese free-living men and women for 12 weeks. For the first 2 weeks, they followed their current diet. For the next 4 weeks, they were instructed to follow Stage I of the study diet, taken from the book, Dr. Atkins’ Diet Revolution (47). Stage I is devoid of CHOs but places no caloric limits on protein or fat. Based on urinary ketone measurement all but 3 were confirmed as restricting CHOs. After 4 weeks on Stage I, patients advanced to Stage II, which allows 5 to 8 g of CHO per day for an additional 4 weeks, bringing the total time on the low-CHO diet to 8 weeks. The final 2 weeks (off the diet) allowed ad libitum intake. No prescription for changes in exercise was given and subjects were asked not to alter their exercise habits from prestudy levels.

Results indicated that all but 2 of 24 subjects lost weight the first 2 weeks of the study while eating ad libitum. After 8 weeks on the low-CHO diet, all subjects (except for 1 male) lost weight. Mean weight loss was 4.1 6 0.64 kg from the ad libitum period, and 7.7 6 0.73 kg from the pre-diet period (10 weeks before). Almost half of the total weight loss occurred in the first 2 weeks on the low-CHO diet. When subjects resumed ad libitum food intake at the end of the 8-week diet period, some weight was gained back (11.5 6 0.45 kg). However, data from 21 subjects showed an overall significant loss of body weight (6.8 6 0.91 kg) over the course of the 12-week study. One year later, weight data were available from 62% of subjects. Although almost all had gained back some of the weight they had previously lost while on the low-CHO diet, only 2 subjects weighed more than they had at the start of the study, whereas 13 weighed less (mean weight loss 5.9 6 1.7 kg). Body composition was not determined.

Results of this uncontrolled study support that low- CHO diets lead to weight loss. Closer examination reveals weight loss results from caloric restriction. Diet analysis (assessed using food intake records) revealed a 500-kcal decrease in total caloric intake from the start of the study to the end of Stage II, 8 weeks later, when the average intake was 1461 kcal/d. Just as Yudkin and Carey (12) reported 20 years earlier, when protein and fat were permitted in unlimited quantities, subjects did not greatly increase their intake of these nutrients. In fact, fat intake decreased (5 g) and protein intake only slightly increased (11 g). The greatest caloric effect was the near total elimination of CHO (165 g).

Alford et al. (45) manipulated CHO content of lowcalorie diets (1200 kcal/d) to determine possible effects on body weight and body fat reduction over 10 weeks. At least 11 women in each diet group consumed either a low-, medium-, or high-CHO diet. The low-CHO diet was 15% to 25% CHO (75 g/d) (30% protein, 45% fat), the moderate-CHO diet was 45% CHO (10% protein, 35% fat), and the high-CHO diet was 75% CHO (15% protein, 10% fat). The women were free-living, but attended weekly classes on nutrition and behavior modification. All were sedentary and agreed to remain so for the duration of the study. Weight loss occurred in all groups, but there was no significant difference in weight loss among the groups. Percent body fat loss, based on underwater weighing was similar among the groups. Alford et al. (45) concluded, “there is no statistically significant effect derived in an overweight adult female population from manipulation of percentage of CHO in a 1200-kcal diet. Weight loss is the result of reduction in caloric intake in proportion to caloric requirements.”

Baron et al. (70) conducted a three-month randomized controlled trial to determine acceptability of different sets of dietary advice (e.g., low-CHO vs. low-fat) among freeliving subjects. Participants included 135 men and women ranging from barely overweight to frankly obese, recruited with the help of six diet clubs in Oxford, England. Within each participating diet club, subjects were randomly given a low-CHO diet (,50 g/d) or a low-fat/high-fiber diet (,30 g fat/d). All diets contained 1000 kcal/d. Each subject planned his/her own menus, with the assistance of group leaders and study investigators, and received appropriate dietary instruction. Moderate weight loss occurred in both groups during the 3-month period, although at 1 year, much of this was regained. Body weight changes at 3 months indicated that those following the low-CHO diet, especially women, lost more weight than those following the low-fat/high- CHO diet (5.0 vs. 3.7 kg, low-CHO vs. high-CHO). However, further analysis consistently showed club membership (e.g., nature of participants in each club, or effectiveness of leaders) to be a better predictor of weight loss than composition of diet.

Golay et al. (21,22) studied the effect of varying levels of CHO intake (15%, 25%, and 45%) on weight loss in obese subjects. In one study, 68 outpatients followed for 12 weeks received a low-calorie (1200 kcal), 25% CHO (75 g), or 45% CHO diet (21). Protein content of the diets was comparable (;30%); fat made up the difference. After 12 weeks, the mean weight loss was similar between the two groups (10.2 6 0.7 kg vs. 8.6 6 0.8 kg; 25% vs. 45% CHO, respectively). Loss of adipose tissue was similar. Despite a high protein intake (1.4 g/kg IBW) there was a loss of lean body mass in both groups. The waist-to-hip ratio diminished significantly and identically in both groups. In another study (22), 43 obese inpatients followed for 6 weeks received a low-calorie diet (1000 kcal), and participated in a structured, multidisciplinary program that included physical activity (2 h/d), nutritional education, and behavioral modification. The natural food diet contained either 15% CHO (37.5 g), or 45% CHO. Protein content of the diets was comparable (;30%); fat made up the difference. After 6 weeks, there was no significant difference in weight loss in response to either diet (8.9 6 0.6 kg vs. 7.5 6 0.5 kg; 15% vs. 45% CHO, respectively).

Significant and comparable decreases in total body fat and waist-to-hip ratios were seen in both groups. Both studies show that energy intake, not diet composition determines weight loss and fat loss in response to low-energy diets over a short time period. Wing et al. (69) confined 21 severely obese women to a metabolic ward for 31 days. They were randomly assigned to ketogenic (10 g of CHO) or nonketogenic liquid formula diets containing ;600 kcal/d for 28 days. Weight losses were comparable between the two diets (mean, 8.1 kg). Because the objective was to determine whether ketogenic weight reducing diets have adverse effects on cognitive performance, no data on body composition were obtained. One might argue that because low-CHO diets result in decreased caloric intake, these diets offer an advantage. If subjects lose weight on these diets, or even gain some weight back when the diet ends (57), these diets might still be of long-term benefit. Astrup and Ro¨ssner (77) concludes that a greater initial weight loss improves long-term maintenance, so long as the weight loss is followed by 1 to 2 years of an integrated weight maintenance program consisting of dietary change, behavior modification, and increased physical activity.

Body Composition Changes

During the early days of a ketogenic diet, weight loss is partly due to water loss (25,55,78). In contrast, during the early days on a mixed diet, weight loss is primarily due to loss of body fat (23). After several weeks, subjects who stay on a ketogenic diet regain water equilibrium (25). Because they restrict calories, low-CHO diets result in loss of body fat if the diets are maintained for a longer period of time. A 4.5% reduction in body fat was reported in individuals consuming low-CHO diets for 10 weeks (45). Golay et al. (21,22) reported significant body fat reduction (16.8% to 21.6%) in obese subjects consuming 15%, 25%, or 45% CHO isocaloric diets for 6 and 12 weeks. Losses of protein and fat are about the same during a ketogenic diet as during an isocaloric, nonketogenic diet (21,22,25). Total energy (calories) 1152 1627 1990 1972 2000–2200

Evidence Statement: In the short-term, low-CHO ketogenic diets cause a greater loss of body water than body fat. Water weight is regained when the diet ends. If the diet is maintained long-term, it results in loss of body fat. Evidence Category C. In conclusion, calories count, and low-CHO diets fail to confer a metabolic advantage with respect to body weight or body composition.

2. Nutritional Analysis

What is the nutritional profile of high-fat, low-CHO diets?

Do these diets provide adequate levels of nutrients, based on current dietary recommendations?

Tables 6 and 7 are nutritional analyses of 1-day menus of popular diets (presented in Tables 8 and 9), and a diet based on the USDA Food Guide Pyramid. Menus came from books (48, pp. 338–340; 49, pp. 147–164; 50, pp. 209–217) and a representative diet based on the Food Guide Pyramid. Diets are compared with current Recommended Dietary Allowances (RDAs) and Dietary Reference Intakes (DRIs). All food records were analyzed using the USDA 1994 to 1998 Continuing Survey Nutrient Database.

Analyses reveal high-fat, low-CHO diets are also low in calories (e.g., 1152 to 1627 kcal/d). The Atkins’ Maintenance Diet, to be followed after weight loss, provides 1990 kcal/d. Low-CHO diets are high in fat, especially saturated fat, and cholesterol. They are also high in protein (mainly animal), and provide lower than recommended intakes of vitamin E, vitamin A, thiamin, vitamin B6, folate, calcium, magnesium, iron, potassium and dietary fiber.

Evidence Statement: High-fat, low-CHO diets are nutritionally inadequate, and require supplementation. Evidence Category C.

Low-CHO diets are often referred to as high-protein or high-fat diets because of the high percentage of calories from protein (25% to 30%) and fat (55% to 60%). Because overall caloric intake decreases on low-CHO diets, and consumption of protein and fat is self-limiting (11), the absolute amount of protein and fat is not as high as these percentages imply. However, the absolute amount of these nutrients are higher in low-CHO as compared with the typical American diet (105 g vs. 82.5 g of protein and 94 g vs. 85 g of fat, low-CHO vs. American diet, respectively) (Table 3). When low-CHO diets are compared with moderate-fat, balanced nutrient reduction diets, they provide twice as much protein and 2.4 times more fat at the same caloric level.

3. Metabolic and Adverse Effects

What are the metabolic effects of high-fat, low-CHO diets?

Will these diets correct the complications of diabetes, heart disease, and high blood pressure?

cWhat effects, if any, do these diets have on bone health, cancer risk, and renal function?

c Are there any adverse effects when consuming these diets?

A number of different metabolic effects have been reported for high-fat, low-CHO diets. The most common is ketosis, as measured by increased urinary ketones (24,57,58,60,63,69,79). Ketogenic diets usually have less than 20% calories from CHOs (80). Because many of these are also low calorie, average CHO intake is 50 to 100 g/d. All popular low-CHO diets recommend ,100 g of CHO per day. Ketogenic diets may cause a significant increase in blood uric acid concentration (57,60,63,67,78).

Other metabolic effects range from decreased blood glucose and insulin levels, to altered blood lipid levels (Table 10). Many of these effects (e.g., decreased LDL and HDL cholesterol) may be the consequence of weight loss, rather than diet composition, especially considering that the absolute amount of fat consumed on the low- CHO diet may be similar to that consumed before the diet (Table 3).

Evidence Statement: High-fat, low-CHO diets result in ketosis. Evidence Category B.

Evidence Statement: Low-CHO diets that result in weight loss may also result in decreased blood lipid levels, decreased blood glucose and insulin levels, and decreased blood pressure. Evidence Category C. Possible effects of such high saturated fat diets on endothelial dysfunction need to be assessed. It has been proposed that a single high-fat meal transiently impairs conduit vessel endothelial function (81). However, this hypothesis has been recently challenged (82).

If excess weight causes complications of diabetes, heart disease, and high blood pressure, then individuals who lose weight on low-CHO diets, and maintain weight loss, may see health benefits. However, no data support long-term adherence to such diets, and high-fat, low-CHO diets contradict all governmental and nongovernmental dietary recommendations with respect to reducing risk, or treating such conditions.

Bone Health, Cancer Risk, and Renal Function

The potential effect of low-CHO diets on bone health is an important consideration. In a study of diet and osteoporosis, Wachman and Bernstein (83) hypothesized the role of the skeleton in acid-base homeostasis in adults, observing a reservoir of alkaline salts of calcium as key to the regulation of pH and plasma bicarbonate concentrations (see also 84 – 86). New (87), after reviewing other studies showing that acidification increases the activity of osteoclasts and inhibits that of osteoblasts, concluded that a diet high in meat but low in fruits and vegetables could lead to bone loss. Barzel and Massey (88) concluded that excessive dietary protein from foods with high potential renal acid load leads to calciuria, which adversely affects bone, unless buffered by the consumption of alkali-rich foods (e.g., fruits and vegetables). Recently, New et al. (89) found that potassium, magnesium, fiber, b-carotene and vitamin C, and a high intake of fruit was important to bone health. Low-CHO diets, often providing inadequate amounts of these nutrients (and foods) may pose long-term risks to the skeleton.

The effect of high protein intake on renal function during weight loss induced by high- (25%) vs. low-protein (12%), moderate-fat (30%) diets in overweight subjects over 6 months was assessed by Skov et al. (90). Protein intake in the low-protein group decreased from 91 to 70 g/d, and increased from 91 to 108 g/d in the high protein group. Results indicate moderate changes in dietary protein intake caused adaptive alterations in renal size and function without indications of adverse effects. However, CHO content of diet was not restricted (e.g., 45% or 58%) so this study did not directly speak to the issue of a high-protein, high-fat, and low-CHO diet. For further information on metabolic consequences of high-protein intake see Metges and Barth (91).

Finally, low-CHO diets are often low in fruits, vegetables, and dietary fiber. This raises the specter of increased cancer risk if such diets are consumed long-term (92–95). However, because no long-term consumption data exist, it is currently impossible to assess cancer risk in individuals consuming low-CHO diets.

Adverse Effects

Few clinically significant adverse effects have been reported in subjects consuming high-fat, low-CHO diets. Some reported side effects include bad taste in mouth (57), constipation (70), diarrhea (49,56,72), dizziness (66), halitosis (57), headache (66), insomnia (49), nausea (56,66,74), thirst (57), and tiredness, weakness, or fatigue (49,56,57,64,74).

Only one study assessed cognitive effects of low-CHO diets (69). Performance on attention tasks did not differ as a function of diet. Performance on the trail making task, a neuropsychological test that requires higher order mental processing and flexibility, was adversely affected by the ketogenic diet. Worsening of performance was observed primarily between baseline and Week 1 of the diet.

4. Hunger and Appetite: Compliance, CHO Cravings, and Addiction

Do low-CHO ketogenic diets decrease hunger? c What data support compliance to a low-CHO diet? c Are CHOs addictive?

Dietary adherence is one of the most difficult challenges faced by obese dieters (54). The stronger the feeling of hunger, the greater the urge to break the diet. If diet com- position affects feelings of hunger, it may influence the ability of patients to adhere to the weight-loss regimen. Atkins claims the low-CHO diet is a revolution because no hunger is experienced (48, pp. 112–113). Individuals are allowed to eat as much protein and fat as they desire as long as they avoid CHOs. Atkins believes this combination of nutrients has a high satiety value and results in individuals eating less (and losing weight). In studies lasting up to 16 weeks, data indicate subjects consuming low-CHO diets decrease food intake and lose weight (Tables 5a,b). Young et al. (64) found each of the low-CHO levels (30 g to 104 g/d) effective in controlling hunger, and that hunger was not a problem after the first week. Cedarquist et al. (65) wrote “subjects had a feeling of well-being and satisfaction. Hunger between meals was not a problem.” Krehl et al. (63) reported the highest level of satiation on a 12-g CHO diet with a 70:30 ratio of fat to protein compared with diets having 60:40, 50:50; 40:60; or 30:70 ratios. (Note: this 70:30 ratio is close to the Atkins’ ongoing weight loss phase, which has a ratio of fat to protein of 60:30.). Not all studies support these findings. Baron et al. (70) found that low-CHO dieters complained of hunger with the same frequency as low-fat dieters. Worthington (66) reported no difference in acceptability, appetite, or satiety after 2 weeks on either low-CHO or balanced diets, and ketosis did not suppress appetite. Rosen et al. (96,97) found no support for the idea that a minimal-CHO, protein-supplemented fast (800 kcal; 58% protein, and 42% fat) decreases appetite and elevates mood in comparison with an isocaloric CHO-containing diet that minimized ketosis. Thus, the effect of low-CHO diets on hunger and satiety remains controversial.

Compliance

Although compliance was not directly assessed, some data indirectly apply to this issue. Kekwick and Pawan (24) fed patients low-calorie diets containing either 90% calories from fat, protein, or CHOs. They noted, “Many of these patients had inadequate personalities. At worst they would cheat and lie, obtaining food from visitors, from trolleys touring the wards, and from neighboring patients. (Some required almost complete isolation). A few found the diet so trying they could not eat the whole of their meals. When this happened, the rejected part was weighed, and the equivalent calories and foodstuffs were added to a meal later in the day.

A considerable number of failures in discipline were discarded.” Rabast et al. (67,68), who studied subjects on a metabolic ward receiving low-calorie, low-CHO liquid formula diets, reported that after 30 days, “conditions for comparative investigations were no longer met because the two groups were declining rapidly.” No explanation for dropouts was given.

Most studies on low-CHO diets (or of subjects receiving advice to consume low-CHO diets) were of short duration and had small sample sizes (Tables 5a,b). Of studies published over the last 44 years, those that lasted 9 weeks or longer included a total of 76 subjects (21,45,57,64,65).

Are CHOs Addictive?

Some authors state that “CHOs are addictive” (50,51). Furthermore, they speculate that hyperinsulinemia prevents a rise in brain serotonin, leading the CHO craver to feel hungry and eat more CHOs. This vicious cycle of hunger, CHO craving, CHO consumption, and hyperinsulinemia is proposed to be the underlying cause of obesity (50,51). Some confuse the matter further by stating, “certain people have a natural, overwhelming desire for CHO that doesn’t correlate to hunger. These people in all likelihood have a genetic predisposition toward CHO craving . . . which can be reduced for some by embarking on a low-CHO diet” (51, p. 118). The latter suggests that a change in dietary composition will override a purported genetic defect. Research has not substantiated any of these contentions.

Wurtman (98) characterized self-selected, obese, “CHO cravers” by their powerful and frequent cravings for and consumption of foods rich in CHO over those high in protein, especially during the afternoon snacking period. This snacking among obese CHO-cravers represents a variable that contributes to excess caloric intake (and weight), and became the basis for The Carbohydrate Addict’s Diet (50). This diet limits daily food intake to two “Complementary” high-fiber, low-fat, low-CHO meals (how is that pos- sible?) and one “Reward Meal” of unlimited quantity or quality, consumed within 60 consecutive minutes. No snacks are allowed. The authors claim that eating “Complementary Meals” fools the body into producing less insulin, relative to what it would have produced if CHOs were consumed at each meal. The claim that insulin output will be low no matter what is consumed at the “Reward Meal” so long as it is limited to 1 hour (50, p. 96) is unsubstantiated (and if true, potentially dangerous). This diet works simply because eliminating snacks and after-dinner eating results in decreased caloric intake.

If CHO cravings were due to decreased serotonin, then drugs that increase serotonergic output should alleviate cravings and result in decreased food intake. Early studies with the serotonergic drug fenfluramine showed effectiveness in decreasing CHO intake (99). However, the effect was not limited to CHO; it resulted in decreased intake of protein as well (100). Toornlivet et al. (101,102) demonstrated that obese CHO cravers and non-CHO cravers responded similarly to treatment with fenfluramine with respect to eating behavior and weight loss. Although the evidence may be interpreted to provide support for the existence of a self-medication effect among a large segment of obese individuals, the mechanism by which CHO mediates this effect has not yet been identified. Furthermore, a more likely interpretation is that some people simply have an unusually large appetite (i.e., they are cravers). Drewnowski (103) has pointed out that the so-called “sweet-tooth” characterizing CHO cravers is just as much a “fat-tooth” because the foods typically selected are high in both CHO (often sugar) and fat. Thus, the effect of low- CHO diets on hunger, appetite, and satiety need further study.

4a. Role of Insulin in Obesity

Is overproduction of insulin, driven by high CHO intake, the cause of the metabolic imbalance that underlies obesity?

If so, can obese, hyperinsulinemic individuals lose more weight on low-CHO diets as compared with high-CHO diets?

Does leptin interact with insulin in regulation of appetite and body weight?

Dietary CHO, as well as dietary protein, increases insulin secretion. The hyperinsulinemia of obesity may be the result of dietary factors, genetic factors (e.g., “thrifty genotype”) or secondary adaptation to insulin resistance (31). Increased appetite and consequent overconsumption may drive increased insulin, but as body weight increases, and insulin resistance develops, this too will drive increased insulin secretion.

The relationship between insulin resistance and weight gain yield conflicting results (104). Swinburn et al. (105) and Schwartz et al. (106) indicated that insulin resistance and hyperinsulinemia predicted decreased weight gain over 3 years in glucose-tolerant adult Pima Indians. In contrast, Sigal et al. (107) reported hyperinsulinemia predicts increased weight gain. However, this study was questioned on the basis of subject sampling and methodology (33). Even if hyperinsulinemia is the cause of the metabolic imbalance, is there evidence to show that low-CHO diets are better for weight loss than high-CHO diets?

Energy restriction, independent of diet composition (e.g., 15% to 73% CHO) improves glycemic control (21,31–33). The ability to lose weight on a calorically restricted diet over a short-time period does not vary in obese healthy women as a function of insulin resistance or hyperinsulinemia (104). Although diet composition may play a role in absolute reduction in blood insulin levels, weight loss seems to be independent of such changes. For example, Golay et al. (21) reported subjects consuming isocaloric diets (1000 kcal) containing 15% CHO had significantly lower insulin levels as compared with those consuming 45% CHO, yet there was no difference in weight loss between the two groups. In another study, isocaloric diets (1200 kcal) containing 25% and 45% CHO resulted in similar reductions in blood insulin levels as well as similar average weight losses (22).

Grey and Kipnis (31) studied 10 obese patients who were fed hypocaloric (1500 kcal/d) liquid-formula diets containing either 72% or 0% CHO for 4 weeks before switching to the other diet. A significant reduction in basal plasma insulin levels was noted when subjects ingested the hypocaloric formula devoid of CHO. Refeeding the hypocaloric, high- CHO formula resulted in a marked increase in the basal plasma insulin. However, patients lost 0.75 to 2.0 kg/wk irrespective of caloric distribution.

The effect of protein vs. CHO on blood insulin levels and subsequent weight loss was assessed by Baba et al. (32), who studied 13 male obese hyperinsulinemic subjects for 4 weeks. They were fed a hypoenergetic diet (comprised of 80% of the person’s resting energy expenditure) containing either 25% CHO and 45% protein, or 58% CHO, and 12% protein. Both diets contained 30% calories from fat. Despite the significant, but not different degrees of reductions in blood insulin levels that occurred on both diets, the insulin levels were reduced to within the normal range only in the high-protein group. Although individuals in both groups lost weight, the mean weight loss was significantly higher on the high-protein as compared with the high-CHO diet, a consequence, perhaps, of the higher protein, lower CHO content of the diet.

The optimal macronutrient composition of a weight-reducing regimen in obese hyperinsulinemic patients is the subject of research, but beyond the scope of this article (for more information see Reaven et al. (108)).
 
Atkins Facts:
 
> What the Experts Think of Atkins
> Faulty Science
> Short-Term Side Effects
> All Long-Term Studies on Atkins a Wash
> Long-Term Side Effects
> The Safer Alternative
> References 1-1160

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