Obesity and the Metabolic Syndrome: Role of Different Dietary

Special Article

Obesity and the metabolic syndrome: role of diﬀerent dietary macronutrient distribution patterns and speciﬁc nutritional components on weight loss and maintenance

Itziar Abete, Arne Astrup, J Alfredo Martínez, Inga Thorsdottir, and Maria A Zulet Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 Weight loss and subsequent body weight maintenance are difficult for obese individuals despite the wide variety of dietary regimens and approaches. A substantial body of scientific evidence has shown that by simply varying the macronutrient distribution and composition of dietary factors, weight losses of varying amounts, longer-term body weight maintenance periods, better appetite regulation, and changes in features of the metabolic syndrome can be achieved. At present, renewed efforts are underway to increase the protein content of weight-loss diets, simultaneously restrict fat consumption to no more than 30%, favor polyunsaturated fat, have carbohydrates account for between 40 and 50% of total energy intake, and promote the consumption of low-glycemic foods. The present article reviews the scientific evidence for the effects of several dietary manipulations and sustainable strategies for weight loss and body weight stability as well as for treating specific features of the metabolic syndrome. © 2010 International Life Sciences Institute

INTRODUCTION In diets designed to prevent and treat obesity by manipulating energy content, macronutrient distribution An excess amount of body fat not only leads to reduced was commonly set at 15% protein, <30% lipids, and quality of life and large healthcare-associated costs, it also 50–55% carbohydrates, with reductions in dietary fat and increases the risk of death.1 Indeed, obesity has been increases in fiber favored.Although this recommendation related to a number of cardiovascular and metabolic dis- seemed to be effective for decreasing energy density and orders such as hypertension, type 2 diabetes, hyperin- promoting weight loss in the short term, the low level of sulinemia, dyslipidemia, atherosclerosis, and even certain observed satiety it achieved decreased dietary adherence types of cancers.2,3 In addition to genetic predisposition, over longer periods.5,11 Monitoring of low-energy diets an inactive lifestyle and high caloric intake are the over- with these macronutrient proportions revealed that they riding causes of excessive weight gain.4,5 Thus, lifestyle were often not sustainable for long periods of time.12 changes affecting dietary habits and physical activity are Likewise, low-carbohydrate diets (low-CHO) have essential to promote weight loss.6–8 For decades, nutri- often been recommended as effective tools for weight loss tional intervention studies have been focused on reduc- over short-term periods, but their long-term effects have ing dietary fat with no positive results over long-term not been fully established.13 Moreover, the higher satu- periods.9,10 The carbohydrate content of diets was also rated fat intake of these diets may increase LDL- reduced in some populations, but obesity prevalence con- cholesterol levels14 and have other adverse effects.15 Other tinued to increase.11 clinical intervention programs have studied different

Aﬃliations: I Abete, J Alfredo Martínez, and MA Zulet are with the Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Navarra, Spain. A Astrup is with the Faculty of Life Sciences, Department of Human Nutrition, Centre for Advanced Food, Studies, University of Copenhagen, Frederiksberg, Denmark. I Thorsdottir is with the Unit for Nutrition Research Faculty of Food Science and Nutrition School of Health Sciences, University of Iceland and University Hospital IS-101, Reykjavik, Iceland. Correspondence: J Alfredo Martínez, Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain. E-mail: [email protected], Phone: +34 948425600 ext. 6424, Fax: +34 948425649. Key words: dietary compliance, metabolic syndrome, protein content, weight loss diets, weight management

doi:10.1111/j.1753-4887.2010.00280.x 214 Nutrition Reviews® Vol. 68(4):214–231 nutritional treatments in order to improve both weight ment of obesity due to its relation with energy balance.33 loss and weight maintenance or associated metabolic The regulation of appetite as well as feelings of hunger related disturbances.These treatments include the follow- and satiety is a determinant factor affecting adherence to ing: varying macronutrient composition,13,16–18 incorpo- a weight-loss program. Thus, nutritional programs have rating bioactive ingredients such as fiber19or flavonoids,20 modified the type of energy restriction to improve com- manipulating the glycemic index (GI)21,22 on the omega-3 pliance over long-term periods. Several decades ago most fatty acid profile,23 and manipulating the composition of dietary strategies were energy restricted, but a number of minerals such as calcium24 and selenium.25 Studies with currently available weight-loss diets are designed to be ad low-GI diets have shown a number of favorable effects libitum. Energy restriction has consistently been proven such as rapid weight loss, better management of glucose to produce weight loss and to have beneficial health and insulin levels, and reductions in triglyceride levels effects. However, most individuals are unable to sustain Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 and blood pressure.5,26,27 weight losses induced by reducing energy intake, poten- On the other hand, current evidence indicates that tially because of increased hunger levels9 and energy diets moderately high in protein and modestly restricted expenditure adaptations.40 Moreover, the dietary in carbohydrate and fat may have more beneficial effects monotony and lack of variability make compliance diffi- on body weight homeostasis and associated metabolic cult during extended periods. parameters.28–32 Likewise, the increase of dietary omega-3 Conversely, ad libitum programs with variety in the fatty acids (FAs) may be an important factor in weight macronutrient composition reduce the patient’s feeling of loss and weight maintenance approaches affecting satiety being restricted to a diet, which could improve their regulation.33 adherence and weight loss. Ad libitum low-fat diets, low- Nutritional intervention studies are presently CHO diets, and high-protein diets have all been proposed focused on decreasing hunger and promoting satiety in as tools for facilitating weight lowering and stability an effort to improve adherence and make weight loss and thereafter.22,41 Indeed, a few long-term trials have demon- weight maintenance easier.32–34 Thus, diets designed to strated better results in weight loss and weight mainte- achieve weight loss via a moderately high protein content, nance with ad libitum programs. Some studies based on low-GI carbohydrates, and specific omega-3 FAs may low-CHO intake strategies, lasting up to 12 months and have beneficial effects on satiety and compliance contrib- performed in obese subjects with no energy restriction, uting to weight loss and weight control, which may be an resulted in more weight loss than a conventional energy- alternative to conventional diets.35,36 restricted diet.42,43 The CARMEN trial also investigated The current article reviews the effects of different the long-term effect of ad libitum, low-fat, high-CHO weight-loss diets on body weight, metabolic markers, and diets containing simple or complex carbohydrates on body weight maintenance with a particular emphasis on body weight in comparison with a control diet group with moderate-protein diets (30–35% energy at the expense of normal macronutrient intake.After 6 months, they found carbohydrates), those with low-GI carbohydrates (within it was favorable to replace dietary fat with carbohydrates the 40% energy), and diets in which omega-3 FA intake is (simple or complex) for the purpose of body weight regu- high at the expense of saturated FAs (within 30% of total lation, since those patients following the low-fat high- fat). CHO (simple or complex) diets registered greater losses of weight and fat mass than patients in the control group.44,45 WEIGHT-LOWERING APPROACHES Thus, adherence to slimming programs and maintenance of achieved body weight reduction are challenging Ad libitum versus energy-restricted diets aspects of weight-loss strategies.46 Different nutritional intervention studies considering both energy-restricted The role of specific foods and nutrients in the prevention and ad libitum approaches have been reported to differ- and treatment of obesity, as well as in associated compli- entially affect thermogenesis, energy expenditure, satiety, cations, has become a major focus of concern in nutri- hormonal balance, and other factors that would not only tional research.37,38 Dietary strategies to reduce fat mass reduce energy intake, but improve compliance, weight have changed over time with variations seen in macronu- loss, and weight maintenance.11 trient composition, fiber content, and bioactive food ingredients; however, there is still an intense debate over Meal replacements which, if any, dietary regime might be the most beneficial for weight loss and long-term weight maintenance.39 The adoption of healthy dietary patterns to facilitate Control of food intake is one of the most important weight loss, cardiovascular disease risk reduction, and factors putatively involved in the success of dietary treat- weight management is often really difficult in an obe-

Nutrition Reviews® Vol. 68(4):214–231 215 sogenic environment in which palatable, inexpensive, and major macronutrient influence on weight loss. Neverthe- high-fat foods are easily available. Thus, alternative less, compliance with dietary goals (whether high protein dietary strategies are being studied to facilitate adherence or low fat) was associated with improved weight loss.54,55 to healthy dietary habits. To this end, a number of investigations have suggested that meal-replacement products Low-fat diets. An alternative to calorie restriction is to may represent an important strategy for combating the decrease the fat content of the diet. In this context, a worldwide epidemic of obesity due to their simplicity and multicenter intervention trial investigated whether a convenience.11,47–49 Meal replacements may simplify the hypoenergetic low-fat diet was superior to a hypoener- weight-loss regimens by replacing one or two meals a day getic moderate high-fat diet for the treatment of obesity. with a product of defined nutrient and calorie content. After a 10-week weight-loss period, the low-fat diet pro- Compared with the simple provision of food plans, a duced similar mean weight loss to the high-fat diet, but it Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 weight-loss program based on meal replacements for one resulted in more subjects losing >10% of their initial body or two meals per day has been shown to improve com- weight and fewer dropouts.56 However, the long-term pliance with a calorie-restricted diet as well as weight effects of fat-restricted diets on weight loss have not been management in overweight and obese individuals.47,48,50 established. In a literature review by Summerbell et al.12 The composition of the meal replacement is also of inter- the authors investigated low-fat diets for obesity and con- est. In this sense, moderate- or high-protein meal replace- cluded that fat-restricted diets are no better than calorie- ments may increase feelings of satiety and may favor the restricted diets for achieving stable weight loss in reduction of energy intake in subsequent meals.51 overweight or obese people. Accordingly, one nutritional intervention study showed Another recent nutritional intervention trial com- that a relatively high-protein meal (25% proteins; 45% pared the effects of three ad libitum diets on weight main- carbohydrates; 30% fats) was more satiating and had a tenance after an initial weight loss of Ն8%. The diets had higher thermogenic effect than a lower protein meal (10% different dietary contents, including carbohydrates and proteins; 60% carbohydrates; 30% fats).52 Several health types of fat (monounsaturated fatty acid [MUFA] diet with professionals currently recommend the use of meal- 35–45% fat and >20% MUFA content; low-fat diet with replacement products, and these products are used 20–30% fat; or control diet with 35% fat), but the protein increasingly in weight-loss studies Meal-replacement content was similar (10–20%). After 6 months, dietary products may prove very useful for facilitating compli- composition had no major effect on preventing weight ance with weight-reduction programs and weight man- regain; however, both the MUFA diet and the low-fat diet agement, at least in the short term. resulted in less body fat regain than the control diet.57 Overall, the evidence supports that low-fat diets are Macronutrient distribution an optimal choice for the prevention of weight gain and obesity. A reduction in the percentage of energy con- Low-calorie diets can achieve acute weight loss, but often sumed as fat is positively associated with weight loss. the slimming result is not maintained long term.53 A Indeed, a 10% reduction in dietary fat is predicted to number of nutritional approaches and diets with different produce a 4–5 kg weight loss in an individual with a BMI proportions of lipids,proteins,and carbohydrates are cur- of 30 kg/m2.58 However, future research needs to focus on rently being investigated. There is intense controversy improving and maintaining adherence to the treatments about the types of diets and macronutrient distributions used to promote weight loss and maintenance. that are most effective for treating overweight or obesity. Many trials investigating the macronutrient composition Low-carbohydrate diets. Low-CHO/high-fat diets have of diets have been carried out for years to improve both the been compared with low-fat energy-restricted diets. This weight loss and the weight maintenance process. One nutritional strategy becomes an alternative to a low-fat recent nutritional intervention study compared the effect diet for producing weight loss in short periods of time. of four weight-loss diets with different compositions of fat, Several reports indicate low-CHO diets can be favored for protein, and carbohydrates.54 The investigators assessed their proven effectiveness in producing rapid weight the change in body weight after 2 years, comparing diets losses and beneficial metabolic changes.13,59 However, the with low fat versus high fat, average protein versus high lack of long-term studies and reports of some undesirable protein, and the highest and lowest carbohydrate content. effects, such as increased levels of ketone bodies, high At 6 months, participants had lost 7% of their initial body losses of body water, headache, constipation, and, espe- weight with no group differences; however, all groups cially, difficulties maintaining weight loss after the diet, began to regain weight after 12 months. After 2 years, make it difficult to recommend these diets as a healthy differences in weight loss were not apparent among the option for weight loss. Nevertheless, a recent intervention dietary groups. The authors also concluded there was no study evaluated the effect of a low-CHO high-fat diet for

216 Nutrition Reviews® Vol. 68(4):214–231 1 year. The reported results showed that a low-CHO diet loss when high in protein (25% of calories; -9.4 kg) than was effective for weight loss, did not induce deleterious when normal in protein (12% of calories; -5.9 kg) after 6 metabolic effects, and did not increase risk for cardiovas- months of treatment. Moreover, after 1 year of follow up, cular disease.13 Another nutritional study showed that a the protein diet reduced visceral fat to a greater degree low-CHO ketogenic diet produced greater weight loss than found from the loss of fat.31 than a low-GI diet and led to greater improvements in A number of studies have suggested that protein is glycemic control independent of weight reduction.59 the most important macronutrient mediating satiety and However, most dietary studies have a relatively low dura- leads to increased weight loss with retention of lean body tion (less than 1 year) and focus on weight reduction mass.32,61 Thus, the satiating effect of moderate-protein efficacy. Considerably less information is available diets could be a key factor in body weight loss programs regarding the potential clinical impact of very-low-CHO and in body weight stability. Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 diets after weight has been stabilized. Indeed, results pre- sented in one recent study suggest that during weight Moderate-protein-content (30%) diets. The popularity of maintenance, following a high-fat low-CHO diet (Atkins moderately high-protein diets with an emphasis on some diet) was associated with higher total cholesterol and degree of carbohydrate restriction is increasing. Con- LDL-cholesterol, and the high saturated fat intake was trolled energy intake in combination with a moderately inversely correlated with endothelial function.60 It has elevated protein intake may represent an effective and also been suggested that very-low-CHO diets are not practical weight-loss strategy.28 compatible with a healthy and palatable diet.11 Potentially beneficial effects associated with On the other hand, a diet with moderate protein moderate-protein diets have been reported (Figure 1) content (30%) at the expense of carbohydrates (40%) since protein has been observed to increase satiety to a achieves a higher satiating effect than conventional greater extent than carbohydrate and fat, which may energy-restricted diets and induces spontaneous weight facilitate a reduction in energy consumption under ad loss.11 In this context, Skov et al.31 showed that diets with libitum dietary conditions.31 It has also been shown62 that a fat content of 30% of calories produced greater weight dietary protein has the highest and most prolonged

Hypocaloric diet

(energy restricted or ad libitum)

30% P; 40% CHO; 30% L

Protein Low-GI CHO ω3-FAs

↑satiety levels Appetite regulation Improve adherence ↑ satiety levels ↓ blood pressure Enhance weight and fat mass loss ↓ blood pressure Improve insulin regulation ↑ lean mass retention Improve insulin regulation ↓ TG ↓ blood pressure ↓ TC, LDL-c ↑ HDL-c Improve insulin regulation ↓ oxidative stress markers ↓ inflammatory markers ↓ TG ↓ inflammatory markers ↑ Leptin sensitivity Protect energy expenditure Energy expenditure protection reduction

METABOLIC SYNDROME

Figure 1 Metabolic changes that could be achieved with an energy-restricted or ad libitum diet combining moderate protein content with low glycemic index carbohydrates and high omega-3 fatty acids intake.

Nutrition Reviews® Vol. 68(4):214–231 217 thermic effect of separate macronutrients (20–30%), fol- order to improve weight loss and long-term weight lowed by carbohydrate (5–15%) and fat (0–3%). Indeed, maintenance. higher-protein diets are not only associated with increased thermogenesis, they also influence satiety and Other nutritional factors enhance energy expenditure.34 Finally, for the maintenance of fat-free mass, in some individuals, a moderately Glycemic index. The glycemic index (GI) of foods is con- high-protein diet may provide a stimulatory effect on sidered an important dietary factor that can influence muscle protein anabolism, favoring the retention of lean body weight control.5 Although there are different con- muscle mass while improving the metabolic profile.34 clusions for the efficacy of low-GI diets in body weight Several intervention studies have been conducted loss, appetite suppression, and reduction of metabolic with diets relatively high in protein and the results rate, it is also known that many starchy foods, refined Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 showed positive effects and better results pertaining to grain products, and potatoes produce high glycemic weight loss and weight maintenance than normal-protein responses that elicit a sequence of hormonal changes that diets. Thus, with identical fat intake, a diet with a higher alter fuel partitioning and cause overeating.69 Studies in protein intake exchanged with carbohydrate, compared animal models have shown that diets based on high-GI to an adequate protein intake, increases 24-h satiety, ther- starches promote weight gain, visceral adiposity, and mogenesis, sleeping energy expenditure, protein balance, higher activities of lipogenic enzymes than do counter- and fat oxidation.63 Another recent multicenter weight- part diets based on low-GI foods.70–72 On the contrary, loss trial compared changes in body weight and compo- diets based on low-GI foods may enhance weight control sition after short-term weight loss (4 months), which was because they promote satiety, minimize postprandial followed by a weight maintenance follow-up period (8 insulin secretion, and maintain insulin sensitivity.17,73–75 months) using a moderate-protein diet (30% of energy Several intervention studies have been performed in from protein, 40% carbohydrates, and 30% fat) or a con- humans in which energy-restricted diets based on low-GI ventional high-CHO diet (15% protein, 55% carbohy- foods produced greater weight loss than comparable diets drates, and 30% fat); the results showed that the 30% based on high-GI foods.21,69,76 protein diet was more effective for fat mass loss and body Data from clinical trials suggest that low-GI diets, composition improvement during the initial period of based on high amounts of fruits, vegetables, legumes, and weight loss and during long-term maintenance.64 In addi- whole grains, are better than conventional diets for tion to the beneficial effects of the moderate-protein diet weight loss,26,77 even though some smaller trials may have for changes in body composition, more participants com- been underpowered to detect the weight loss produced by pleted the study in the moderate-protein group (64%) the low-GI diet.78 Low-GI diets are also characterized by than in the high-CHO group (45%). These findings dem- high fiber content79 and have been shown to delay hunger onstrate there was greater compliance with a moderate- and decrease subsequent energy intake compared with protein diet for long-term weight management than with high-GI diets.80 A recent dietary intervention trial showed the high-CHO diets often advocated for weight loss.65 that the patients who followed a low-GI diet during an Reduction of fat mass and maintenance of lean mass 8-week energy-restricted period registered higher weight are critical factors for long-term health status and the loss (7% of the initial body weight) than those included in prevention of weight regain.64 Evidence is accumulating a conventional diet (5% of the initial body weight) and that the recommended daily allowance for protein is the reduction in body weight was directly associated with inadequate to maintain muscle mass in adults during fiber intake.21 Moreover, in studies comparing ad libitum energy restriction for weight loss.66 The current recom- low-GI diets to conventional energy-restricted low-fat mendation for protein represents the minimum protein diets, participants fared as well or better on the low-GI needs for healthy young adults with adequate energy diet, even though they could eat as much as they intakes.67,68 During weight lowering, energy restriction desired.45,80 Thus, studies evaluating the effect of eating a increases the amount of protein required to maintain high- or low-GI meal showed that voluntary energy muscle mass.66 Thus, moderate-protein diets (30–35%) intake after a high-GI meal was greater than after a could be one of the most indicated strategies for weight low-GI meal.81 loss and weight management, with the caveat that they In addition to the higher satiety effect, benefits should not be used by subjects with renal diseases. related to body composition, and improved insulin regu- Energy deficit is the key factor for weight loss, but the lation, it has been shown that low-GI diets also produce macronutrient composition influences changes in body favorable metabolic changes. In one study, patients fol- composition and long-term compliance. In this context, lowing a low-GI diet lost less lean mass and showed a more studies are needed to establish higher protein rec- reduced decrease in resting metabolic rate, which could ommendations during periods of energy restriction in help improve weight loss as well as weight management.21

218 Nutrition Reviews® Vol. 68(4):214–231 Indeed, the amount of weight regained 1 year after the as fat) on weight management during a 6-month con- end of the weight-loss program was lower in the low-GI- trolled dietary intervention after an initial weight loss of diet group. These findings are in accordance with previ- 8%. Protein constituted 10–20% of energy in all three ous studies, which also suggested that a low-GI-based diet diets. At the end of the study the researchers found that may improve weight loss and weight management, mini- dietary composition had no major effects on preventing mizing negative metabolic adaptations during a period of weight regain. Both the low-fat and the high-MUFA diets energy restriction.26,27 However, controversy remains produced less body fat regain than did the control diet. about the use of low-GI diets, since evidence from inter- The high-MUFA diet was more beneficial for decreasing vention studies using a low-GI approach for weight loss fasting insulin levels and improving insulin resistance as have produced inconsistent results, especially in longer- well as the LDL-cholesterol/HDL-cholesterol ratio. term studies. In intervention studies involving patients Intake of fish and fish oil is considered an impor- Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 with type 2 diabetes, consumption of a low-GI diet tant part of a healthy diet, since they are rich sources of resulted in lower hemoglobin A1c concentrations in omega-3 FAs. Regular consumption of fish or fish oils is shorter-term studies. However, as reported in a recent known to have pleiotropic effects, including effects review of the topic, other evidence exists that adds to the against inflammation, platelet aggregation, hypertension, controversy regarding the effectiveness of consuming and hyperlipidemia.87–89 These beneficial effects may be low-GI diets for glycemic control and weight reduction.82 mediated through several distinct mechanisms, includ- Moreover, there are limitations to how well the use of GI ing alterations in cell membrane composition and func- tables can predict the GI composition of a diet, leaving the tion, gene expression modulation, or eicosanoid applicability of the GI in the context of mixed meals and production.90 In addition to these beneficial effects, it diets debatable.9,83 was suggested that the inclusion of fish in dietary strategies could improve weight reduction. In this sense, one Fatty acids. In much of the current dietary advice “good” study showed that the substitution of fish oil for visible fats such as MUFAs and omega-3 FAs are emphasized, fats in a control diet (52% carbohydrates, 16% protein, while saturated and trans fats are restricted. Olive oil, 32% fat) reduced body fat mass and stimulated lipid oxi- almonds, avocados, and nuts, for example, are considered dation in healthy adults.91 Also, a recent nutritional important sources of MUFAs. Several studies have evalu- intervention program showed that the patients who par- ated the effects of these fats on weight loss and weight ticipated in a weight-reduction regimen (–30% energy management. Recently, Sloth et al.84 compared three dif- restriction) with fish consumption (150 g of cod, 5 days/ ferent weight-maintenance diets (a moderate-fat 35–45% week) for 8 weeks showed greater weight loss in com- of energy from fat diet with high MUFA content; a low- parison with the control group.92 However, the most fat diet with 20–30% energy from fat, or a control diet important effects of omega-3 FAs provided as dietary with 35% energy from fat) on appetite, glucose, and fat fish have been described as improvements in cardi- metabolism for 6 months after a weight-loss period. ometabolic changes,23 inflammation,93 and oxidative These authors did not find differences in appetite, energy stress.94 In addition, omega-3 FAs from fish consump- intake, or body weight after the weight-maintenance tion have been considered as nutritional factors that period, but the MUFA and low-fat diets were equally may influence appetite and satiety perception,33,95 two effective at managing glucose metabolism, while the very important factors during an energy-restriction or control diet was associated with decreased insulin sensi- weight-maintenance program. A nutritional interven- tivity.Another recent study compared the effectiveness of tion study showed that omega-3 FAs provided as dietary energy-restricted high-MUFA and high-CHO diets on fish were able to modulate postprandial satiety in over- anthropometric and metabolic parameters specifically in weight and obese volunteers during weight loss.33 diabetic individuals for 1 year; the results suggested that One observational study suggested that diet-derived high-MUFA diets can be healthy alternatives to conven- omega-3 FAs lower leptin levels independent of body tional lower-fat diets.85 Keogh et al.86 studied the effects of fat.96 High leptin levels have been related with features of a low-CHO diet with a high monounsaturated fat content the metabolic syndrome as well as with the presence of (50% fat; 20% protein; 30% carbohydrates) in relation to a leptin resistance in obesity.97 Since leptin is involved in relative high-protein, moderate-fat (30% protein; 30% fat; the regulation of energy expenditure and energy intake, a 40% carbohydrates) diet. However, limited subject com- decrease in plasma leptin levels may involve an improve- pliance with the dietary patterns did not allow a long- ment in the control of its functions, favoring greater term assessment of both diets. Due et al.57 compared the dietary intake control as well as better weight mainte- effect of a diet providing a moderate amount of fat (35– nance. Conversely, other authors suggest the process of 45% of energy) and >20% of fat as MUFAs with a low-fat weight loss may produce a state of leptin insufficiency, diet (20–30% of energy) and a control diet (30% of energy which may produce deleterious effects on energy metabo-

Nutrition Reviews® Vol. 68(4):214–231 219 lism that may hinder weight loss maintenance. In this or enriched with different components have shown a sense, the administration of a low dose of leptin was variety of results regarding weight loss as well as weight found to be effective for reversing the energy expenditure maintenance. decrease to pre-weight-loss levels, which could be a valid Dietary calcium appears to play a pivotal role in the strategy for preventing weight regain.98 regulation of energy metabolism and obesity risk.102–104 Overall, Mori et al.99 have shown that weight loss in Zemel et al.105 observed that those patients in the highest combination with a daily serving of fish had additive quartile of adiposity were negatively associated with effects on blood pressure reduction, improved heart rate, calcium and dairy product intake. A more recent nutri- serum lipids, and glucose and insulin metabolism, leading tional intervention trial also demonstrated that higher to greater benefits than those achieved with a weight-loss low-fat dairy intake among overweight type-2 diabetic intervention alone. Later, they also found that dietary fish patients on isocaloric-restricted regimens enhances the Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 enhanced the effects of weight loss on serum leptin lev- weight-loss process.106 The proposed mechanisms are pri- els.97 In agreement with this finding, a clinical trial that marily mediated by circulating calcitriol.107 The increased evaluated the effects of fish consumption during a period calcitriol produced in response to low-calcium diets of energy restriction found a specific leptin and insulin stimulates adipocyte Ca2+ influx and, consequently, pro- decrease that was independent of body fat mass reduc- motes adiposity, while higher calcium diets inhibit tion.23 This study also suggested an improvement in the lipogenesis, stimulate lipolysis, lipid oxidation and ther- control of leptin and insulin functions, which could mogenesis, and inhibit diet-induced obesity in mice.107 involve better body weight regulation after a nutritional Moreover, a published meta-analysis concluded that intervention. dietary calcium has the potential to increase fecal fat The health benefits of consuming fatty fish, fish oils, excretion, which could be relevant for preventing weight or foods rich in omega-3 FAs by persons with cardiovas- (re)gain.108 However, some investigators did not find cular disease have led to recommendations to increase dietary calcium enrichment to have beneficial effects fish consumption.100,101 However, little fish is consumed in during a weight-loss process.109,110 Thus, the effect of many Western societies and an increase in the consump- calcium on weight loss continues to be unclear, indicating tion of omega-3 FAs would involve major dietary that more long-term studies are required in this field. changes. In this sense, supplements as well as enriched Other dietary micronutrients that have been used in foods may be considered. Thus, fatty fish, fish oils, the treatment of obesity and some metabolic disorders omega-3 FA-rich foods, and omega-3 FA supplements are potassium and magnesium. Both minerals are main could be included in weight loss and weight maintenance components of the DASH diet, which has been designed programs as well as be incorporated into the dietary as an anti-hypertensive treatment.111 This diet basically habits of healthy subjects. consists of high fruit, vegetable, and low-fat dairy content and is designed to be lower in total fat, saturated fat, and cholesterol and abundant in nutrients such as magne- Micronutrients or other dietary components. Modest sium, calcium, and protein. Some data suggest that higher weight loss is possible for most subjects; however, very potassium and magnesium intake could favor decreases few achieve stable management of the body weight lost. in blood pressure.111 Thus, high levels of potassium, mag- Most studies of individuals who participated in a weight- nesium, and calcium seem to have a beneficial effect on lowering program show that the subjects regain their the weight loss process as well as on metabolic diseases. initial body weight, indicating that individuals did not Indeed, some nutritional intervention studies have found change their eating behavior adequately. the DASH diet to be more effective for weight loss and A large number of new interventions are being metabolic variables than other conventional diets,112,113 designed in order to improve weight lowering and long- but the responsible mechanism remains to be elucidated. term weight maintenance. Because of this trend, the Long-term weight maintenance is a key factor in the micronutrient composition of weight-loss diets is cur- effective treatment of obesity. In this regard, interest in rently considered an important factor to consider in addi- natural herbal supplements is growing rapidly. Human tion to the more traditional emphasis on macronutrient studies have shown that caffeine and green tea catechins distribution. Indeed, several putative bioactive food may improve weight loss as well as weight maintenance ingredients, such as minerals and other dietary or herbal through their effects on thermogenesis and fat components could affect satiety, thermogenesis, energy oxidation.114–116 One recent study investigated the role of balance, and other factors that would improve adherence a green tea-caffeine mixture on weight maintenance after to slimming programs, reduce energy intake, and favor a period of body weight loss and found weight stability to weight loss and weight maintenance. Thus, a number of be improved in comparison with patients that did not eat nutritional intervention studies with diets supplemented the mixture.117

220 Nutrition Reviews® Vol. 68(4):214–231 Overall, more and longer nutritional intervention reduction does not promote weight loss in comparison strategies should be developed to investigate the efficacy with a conventional diet; however, it does induce positive of more micronutrient supplements or natural effects on insulin resistance, independently from changes micronutrient-enriched foods for improving weight loss in body weight,23,132 and it reduces triglyceride concentra- and facilitating weight maintenance. tions in a dose-dependent way89 as well as circulating inflammatory cytokines.90,133 Metabolic syndrome treatment Low-fat diets, on the other hand, may effectively reduce plasma LDL-cholesterol levels; however, if they Metabolic syndrome (MetS) is defined by a group of risk promote higher carbohydrate consumption (intake of factors such as visceral obesity, insulin resistance, elevated sugar and highly refined starches), this could have adverse blood pressure, and dyslipidemia, associated with subse- effects on the metabolic risk profile.134,135 Indeed, there are Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 quent development of type 2 diabetes and cardiovascular reported negative effects of high-CHO diets on triglycer- disease.118 Despite the complexity of its origins, there is ide levels as well as on insulin resistance.136 In the same general agreement that the rising prevalence of MetS is way, very-low-CHO diets may induce rapid weight losses largely due to the increasing incidence of obesity.119 and some beneficial metabolic changes, such as insulin Abdominal obesity or visceral fat are closely associated level reduction over short-term periods. However, these with insulin resistance and a low-grade pro-inflammatory diets in which saturated and trans fats as well as high-fat state,120 which are considered primary factors in the meats and products are not controlled could produce development of MetS.121 adverse metabolic effects, especially in susceptible There is general agreement that lifestyle changes patients with MetS.11 A recent study assessed the effect of focused on weight reduction should comprise the first- a very-low-CHO diet on endothelial function and line approach to treating patients with MetS.122 Currently, reported that the cardiovascular risk was increased in the however, there is no single diet recommended for these first days following a very-low-CHO diet.137 patients. General recommendations include a total fat Diets prescribing an increased dietary protein intake of 25–35% of daily caloric consumption with an intake have also been evaluated for use in the treatment emphasis on unsaturated fat, saturated fat <7% of total of MetS.138 In conjunction with facilitating weight loss, calories, trans fatty acid intake <1% of total calories and diets in which carbohydrates are replaced by protein <200 mg of dietary cholesterol, an intake of carbohy- usually result in improvements in body composition drates oscillating from 50% to 60% of total calories, and and in plasma lipids and lipoproteins. High-protein low- 15% of total calories as protein.123,124 However, some CHO diets have been found to have positive effects on authors have emphasized that dietary treatment should reducing risk factors for heart disease, including reduc- be different depending on the presence of MetS compo- ing serum triacylglycerol, increasing HDL cholesterol, nents. For example, dietary treatment could be individu- increasing LDL particle size, and reducing blood pres- alized on the basis of the specific metabolic disorders sure. These diets appear to be particularly useful for developed in each patient.26,36 individuals exhibiting the atherogenic dyslipidemia of Nutritional factors currently proposed for the treat- MetS.139 Several studies have shown that increasing ment of obesity, cardiovascular diseases, and MetS are all dietary protein content (30%) and decreasing carbohy- those previously mentioned, i.e., high-protein low-CHO drates (40%) may favor the reduction of fat mass, par- diets, low-GI carbohydrates, and regular fish consump- ticularly abdominal fat mass.140 Decreasing the dietary tion in order to assure an adequate omega-3 FA intake. intake of carbohydrates and replacing it with either fat Diets with low-GI and high-fiber content induce greater or protein has been shown to reduce triacylglycerides weight loss than conventional diets, decrease fasting and increase HDL cholesterol even under weight-stable glucose and insulin levels, reduce total and LDL choles- conditions.141,142 However, substitution with protein may terol, and improve blood pressure.5,123 Several trials have be even more beneficial than fat for eliciting lipid already shown the benefits of dietary consumption of changes141–143 and improving insulin action.16,143 omega-3 FAs in MetS and obesity patients.90,92,125,126 Fish McAuley et al.142 provide evidence that the primary intake and omega-3 FAs have been recommended as an means of lowering triacylglycerides is reducing carbo- integral component of the treatment of patients with hydrate intake; they further suggest that increasing MetS, since its consumption has been related with several dietary fat as an approach to lowering dietary carbohy- metabolic benefits, including blood pressure drates may not be as efficacious as increasing protein. reduction,97,125–128 decreased plasma levels of triglycer- Following extensive research, consensus was achieved ides,129 improved HDL-cholesterol levels,130and reduced that reducing dietary carbohydrates is the critical inflammation.131 Moreover, several studies have con- approach to treating or managing the manifestations of firmed that omega-3 FA consumption during energy MetS.144

Nutrition Reviews® Vol. 68(4):214–231 221 Diets with a high-MUFA content can positively affect effects on almost all components of MetS as well as other insulin levels, as shown by several authors,57,84,95 and have conditions associated with it, including inflammation, consequently been suggested for the treatment of obesity insulin resistance, and endothelial dysfunction.119,157,158 and MetS. Diets containing foods with antioxidant prop- The PREDIMED study evaluated the effect of the tradi- erties have also been studied to investigate the potential tional Mediterranean diet on the features of MetS and on association between obesity and oxidative stress.145 cardiovascular disease (CVD) prevention. The Mediter- Several studies have found different effects on weight loss ranean diet employed in the study was based on high and cardiometabolic changes when antioxidant-enriched intake of cereals, vegetables, fruits, and olive oil, moderate foods such as legumes, fruits, and vegetables are con- intake of fish and alcohol, mostly wine, and low intake of sumed during a weight-reduction period.146–148 Inclusion dairy products, meats, and sweets. The results of this trial of legumes in a weight-lowering program has been shown showed that among older participants at high risk for Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 to increase the intake of isoflavones, saponins, a variety developing CVD, those who consumed a non-energy- of micronutrients, and phytochemicals.149 Flavonoids restricted, traditional, Mediterranean-style diet supple- occurring normally in the diet exhibit a variety of benefi- mented with one daily serving of mixed nuts for 1 year, cial effects on health. In addition to reducing total and showed an overall reduction in the prevalence of MetS LDL cholesterol, as well as triglyceride levels, intake of compared with participants given advice on following a these plant products by obese subjects has been related low-fat diet.159 These positive findings are supported by with higher plasma antioxidant status and greater reduc- those of a prospective cohort study conducted in 13,380 tions in oxidative stress.145 Spanish university graduates who were followed up for a The anti-inflammatory properties of flavonoids have median of 4.4 years; the results indicated that adherence also been studied.20 Recent investigations have shown to a Mediterranean diet is associated with reduced risk of that some flavonoids are modulators of proinflammatory diabetes.160 gene expression, leading to attenuation of the inflammatory response.150,151 Thus, the utility of flavonoids as thera- peutic agents in the treatment of inflammatory diseases is CONCLUSION also under consideration.20 Likewise, antioxidant minerals are dietary factors of interest for the nutritional man- As shown in this review, there are many dietary strategies agement of MetS.19 Particular attention is paid to the focused on macronutrient distribution or micronutrient development of selenium-enriched food and nutritional and food-enriched manipulation for the treatment of products,152 since this element acts as a cofactor of obesity and features of MetS features (Table 1). However, enzymes, which protect against oxidative stress and are the real challenge is to find the appropriate approach for also involved in the regulation of the inflammatory maintaining body weight loss and preventing subsequent response.153 Moreover, selenium-enriched diets have been relapse, while simultaneously reducing cardiovascular associated with lower body mass index. In this context, risk factors. vitamin C is also considered of nutritional value. In addi- The ideal diet should be personalized to each tion to its antioxidant properties, which may induce patient and should include those dietary factors that improvements in oxidative stress,154 an observational imbue healthy and satiating dietary habits that are ben- study examined the relationship between plasma vitamin eficial not only for effective weight loss, but are also C and adiposity, showing that plasma vitamin C was good for body-weight maintenance as well as for reduc- inversely related to BMI, percentage of body fat, and waist ing cardiovascular risk. Thus, a currently available diet circumference in both women and men. However, in a may be one that has a moderate protein content (30%), nutritional intervention trial, supplementation of the diet high monounsaturated and omega-3 FAs, low-GI carbo- with vitamin C did not improve weight loss in compari- hydrates (40%), and includes adequate quantities of son with the placebo group.155 Thus,the effects of ascorbic fiber, isoflavones, calcium, and antioxidant minerals. acid during weight loss remain inconclusive. Since adherence to healthy dietary patterns can be dif- Overall, the ideal diet should combine all the dietary ficult, meal replacement and dietary supplements should factors thought to influence cardiometabolic risk. A diet be considered as effective strategies for weight loss, reflecting a lower content of refined carbohydrates, a high weight maintenance, and treatment of MetS. Several content of fiber and low-GI carbohydrates, antioxidants factors such as genetics, physical activity, psychopatho- and phytochemicals from vegetables, fruits, and legumes, logical conditions, obesity type, gender, age, or yo-yo a moderate fat content (mostly unsaturated and omega-3 cycles may influence the outcome of any dietary inter- FAs), and a moderate-to-high content of vegetable and vention.161 They should be taken into account as much fish proteins,156 should be appropriate for the treatment of as possible when dietary advice is prescribed for body MetS patients. These dietary patterns may exert positive weight management.

222 Nutrition Reviews® Vol. 68(4):214–231 urto eiw®Vl 68(4):214–231 Vol. Reviews® Nutrition Table 1 Changes on weight loss as well as biochemical and metabolic variables in some selected nutritional intervention studies differing in macronutrient distribution or dietary factors composition. Reference Study data Diets Weight loss and Glucose and Inflammation and/or blood pressure lipid metabolism oxidative stress markers Abete et al. n = 32 healthy obese Higher-GI (15%P; 30%L; -5.3%, ↓SBP, ↓DBP ↑insulin, ↑HOMA, ↓TC, Not reported (2008)21 men and women 55%CHO) -7.7%, ↓SBP, ↓DBP ↓LDL-c, ↑TG, ↓HDL-c 8 weeks Lower-GI (15%P; 30%L; ↓Insulin, ↓TC, ↓LDL-c, ↓TG, 55%CHO) ↓HDL-c Abete et al. n = 19 healthy obese Control (15%P; 30%L; -5.5%, ↓SBP, ↓DBP =insulin, =HOMA, ↓TC, ↓LDL-c, Not reported (2009)162 men 55%CHO) -8.3%, ↓SBP, ↓DBP =TG, ↓HDL-c 8 weeks Moderate-P (30%P; 30%L; ↓insulin, ↓HOMA, ↓TC, 40%CHO) ↓LDL-c, ↓TG, ↓HDL-c Abete et al. n = 32 healthy obese Control (15%P; 30%L; -5.3%, ↓SBP, ↓DBP ↑Insulin, =HOMA, =TC, =LDL-c, =leptin (2008)23 men and women 55%CHO) -5.5%, ↓SBP, ↓DBP =TG, =HDL-c ↓leptin 8 weeks Fatty fish (15%P; 30%L; ↓Insulin, ↓HOMA, ↓TC, 55%CHO) + 3 fatty fish ↓LDL-c, ↓TG, ↑HDL-c meals/week. Agus et al. n = 10 moderately Low-GI (43%CHO; 27%P; -3.6 kg ↓Insulin, REE decreased to a ↓leptin (2000)26 overweight young 30%L) -3.2 kg lesser extent men High-GI (67%CHO; 15%P; Low-GI diet increased hunger Two 9-day periods 18%L) levels separated by a washout period of 2–6 weeks Backes et al. n = 23 overweight Low-CHO (40% CHO) -5.0 kg; ↓DBP ↓Glucose, ↓TG Not reported (2008)16 insulin-resistant women 3 months Brehm et al. n = 50 healthy obese Low-CHO (ad libitum) -9.7Ϯ0.7 kg No differences between diets Not reported (2005)163 women Low-fat (15%P; 30%L; -6.1Ϯ0.9 kg on glucose, insulin, and 4 months 55%CHO) HOMA. Both diets: ↓TC, ↓LDL-c, and ↓ TG ↑ HDL-c with low-CHO Brinkworth n = 118 men and LC (4%CHO; 35%P; 61%L) -14.5 kg; ↓SBP; ↓DBP Both diets: ↓glucose, ↓insulin, ↓CRP independently of diet et al. women with LF (46%CHO; 24%P; 30%L) -11.5 k; ↓SBP; ↓DBP ↓HOMA-IR composition (2009)14 abdominal obesity LC: ↓TG, ↑LDL-c, ↑HDL-c, and at least one ↑Apo-B additional metabolic syndrome risk factor

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Table 1 Continued Reference Study data Diets Weight loss and Glucose and Inﬂammation and/or blood pressure lipid metabolism oxidative stress markers Buscemi et al. n = 20 healthy obese Atkin (30%P; 65%L; 5%CHO) -7.6 kg;↓SBP; ↓DBP Both diets: ↓insulin, ↓HOMA, Both diets =IL-6, =TNF-a, (2009)137 women Mediterranean (20%P; 25%L; -4.9 kg ↓TC, ↓LDL-c, =HDL-c, =TG =adiponectin, 2 months 55%CHO) =8-iso-PGF2a, Claessens et al. n = 48 healthy obese High-CHO (ad libitum) +1.1 kg Both diets: =insulin, =HOMA, Both diets ↓adiponectin, (2009)37 6-week weight loss + >55%CHO; 30%L -1.1 kg; ↓SBP; ↓DBP ↑TC, ↑LDL-c and ↑HDL-c ↑leptin 12-week High-P (ad libitum) >25%P; Only high-P: ↓TG maintenance 30%L Clifton et al. n = 79 healthy HP (34%P; 20%L; 46%CHO) -4.6 kg ↓Glucose, ↓insulin, ↓LDL-c, Both diets: ↓CRP, (2008)10 overweight / HC (64%CHO; 20%L; 17%P) -4.4 kg ↓TG, ↑HDL-c with no ↓homocysteine obese women <10% of saturated fat in both diﬀerences between diets 64 weeks (12-week diets weight loss + 52-week follow-up) Crujeiras et al. n = 32 healthy obese Control (15%P; 30%L; -5.3%; ↓SBP; ↓DBP ↑Insulin, ↑HOMA, ↓TC, =ox-LDL,=MDA, 145 (2007) men/women 55%CHO) -7.7%; ↓SBP; ↓DBP ↓LDL-c, ↑TG, ↓HDL-c =8-iso-PGF2a 8 weeks Legume (15%P; 30%L; ↓Insulin, ↓HOMA, ↓TC, ↓ox-LDL, ↓MDA, 55%CHO) ↓LDL-c, ↓TG, ↓HDL-c ↓8-iso-PGF2a, ↑AOP (4 legume meals/week) Dumesnil et al. n = 12 healthy obese Low-fat-high-CHO-high-P -2.3 kg; ↓Insulin, =TC, =LDL-c, ↓TG, Not reported (2001)134 men two 6-day (30%P; 30%L; 40%CHO) ad Higher satiety level =HDL-c experimental libitum No change in body weight =insulin, =TC, =LDL-c, ↑TG, periods with a AHA (15%P; 30%L; 55%CHO) Low-satiety level ↓HDL-c 2-week washout ad libitum period Das et al. n = 34 healthy High-glycemic load (20%P; -8.0% Both diets: ↓insulin, ↓TC, Not reported (2007)46 overweight adults 20%L; 60%CHO) -7.8% ↓LDL-c, ↓TG, and ↑HDL-c urto eiw®Vl 68(4):214–231 Vol. Reviews® Nutrition 12 months Low-glycemic load (30%P; 30%L; 40%CHO) Foster et al. n = 63 obese men Low-CHO high-P high-L (ad -7.3%; =SBP;↓DBP ↑HDL-c; ↓TG Not reported (2003)42 and women libitum) -4.5%; =SBP;↓DBP Both diets: ↓insulin; =TC; 1 year High-CHO (60%CHO; 25%L; =LDL-c Poor adherence in 15%P)

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Gardner et al. n = 77 Atkins -4.7 kg, ↓SBP; ↓DBP ↓Insulin, =LDL-c, ↑HDL-c, Not reported (2007)164 n = 79 Zone (30%P; 30%L; 40%CHO) -1.6 kg, ↓SBP; ↓DBP ↓TG n = 79 Learn (15%P; 30%L; -2.2 kg, ↓SBP; ↓DBP ↓Insulin, =LDL-c, ↑HDL-c, n = 76 55%CHO) -2.6 kg, ↓SBP; =DBP =TG Obese women Ornish (very-high-CHO) ↓Insulin, =LDL-c, ↑HDL-c, 1 year of intervention All diets were ad libitum ↓TG =Insulin, ↓LDL-c, ↓HDL-c, ↓TG Layman et al. n = 130 PRO-group (30%P; 30%L; BW no diﬀerences PRO-d: ↓TG, ↑HDL-c Not reported (2009)64 4-months 40%CHO) between groups CHO-d: ↓TC, ↓LDL-c, ↓HDL-c No diﬀerences in CHO-group (15%P; 30%L; PRO-group greater ↓fat compliance 55%CHO) mass between groups Noakes et al. n = 100 healthy High-P (34%P; 20%L; -7.6 kg High-P: ↓TG, ↑B-12 Both diets (2005)135 obese women 46%CHO) -6.9 kg Both diets: ↓glucose, =homocysteine, ↓CRP 12 weeks High-CHO (17%P; 20%L; 64% ↓insulin, ↓LDL-c, ↓HDL-c, CHO) ↑folate, ↑B-6 Both diets Յ10% saturated fat O’Brien et al. n = 42 Low-fat (15%P; 30%L; -4.3 Ϯ 3.5 kg; ↓SBP; Both diets: ↓insulin, Both diets ↓CRP; ↓SAA (2005)165 3 months 55%CHO) ↓DBP ↓HOMA-IR; ↓TC and Obese women Very-low-CHO (ad libitum) -7.6 Ϯ 3.2 kg; ↓SBP; ↓LDL-c. ↓DBP Only very-low-CHO ↓TG Petersen et al. n = 771 healthy Low-fat (20–25%L; -6.9 kg ↓TC, ↓LDL-c, ↓TG, ↓HDL-c Not reported (2006)56 obese adults 60–65%CHO; 15%P) -6.6 kg (changes were higher in 10 weeks High-fat (40–45%%L; this group) 60–65%CHO; 15%P) ↓TC, ↓LDL-c, ↓TG, ↓HDL-c Both groups:↓insulin Raben et al. n = 398 obese Low-fat high-CHO high-GI -1.7 kg Both diets improved glucose, Not reported (2002)44 subjects (ad libitum) -2.6 kg insulin, and fasting blood 6 months Low-fat high-CHO low-GI (ad lipids libitum)

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Table 1 Continued Reference Study data Diets Weight loss and Glucose and Inflammation and/or blood pressure lipid metabolism oxidative stress markers Seshadri et al. n = 78 severe obese Low-CHO (<30 g CHO; ad -8.5 kg ↓insulin; ↓TG ↓CRP (2004)166 subjects libitum) -3.5 kg Both diets: =TC; =LDL-c; 31 were diabetics, 36 Conventional (Յ30%L) energy =HDL-c had metabolic restricted syndrome 49 with hypertension medication and 35 with lipid-lowering medication 6 months Skov et al. n = 65 healthy High-P (25%P; 30%L; -8.9 kg ↓TG; ↓FFA Not reported (1999)31 overweight and 45%CHO) -5.1 kg obese men and High-CHO (12%P; 30%L; women 58%CHO) 6 months Sloth et al. n = 131 healthy After losing 8% of the initial There was a significant weight Low-L and MUFA groups had Not reported (2009)84 overweight and body weight, participants increase with no differences lower insulin concentrations obese subjects were instructed to follow ad between groups HbA1c increased in the control 6 months weight libitum diets: group maintenance MUFA, moderate fat (35–45%L; There were no group period >20%MUFA) differences in GLP-1; GLP-2 Low-F (20–30%L) Control (35%L; >15% SFA) Stern et al. n = 132 severe obese Low-CHO (<30 g CHO; ad -5.1 kg ↓TG; =HDL-c; ↓HBA1C Not reported 43 (2004) subjects libitum) -3.1 kg ↓HDL-c; =HBA1C urto eiw®Vl 68(4):214–231 Vol. Reviews® Nutrition 83% had diabetes or Conventional (Յ30%L) energy Both: =SBP; =DBP Both: =glucose; =insulin, =TC; metabolic restricted =LDL-c syndrome 1 year

Abbreviations: 8-iso-PGF2a, 8-isoprostane F2a; AHA, American Heart Association; AOP, total plasma antioxidant power; BW, body weight; CHO, carbohydrates; CRP, C-reactive protein; FFA, free

fatty acids; FM, fat mass; HBA1C, hemoglobin A1C; L, lipids; MDA, malondialdehyde; MUFA, monounsaturated fatty acids; ox-LDL, oxidized-LDL. Downloaded from https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 by guest on 30 September 2021 September 30 on guest by https://academic.oup.com/nutritionreviews/article/68/4/214/1846617 from Downloaded Acknowledgments overweight, insulin resistant South Asian Indian women. Asia Pac J Clin Nutr. 2008;17:669–671. Declaration of interest. Some authors (IT and JAM) have 17. Brand-Miller J, McMillan-Price J, Steinbeck K, Caterson I. Car- bohydrates - the good, the bad and the whole grain. Asia been directly involved in the SEAFOODplus project Pac J Clin Nutr. 2008;17(Suppl 1):16–19. (FOOD-CT-2004-506359), while others (AA and JAM) 18. Brehm BJ, D’Alessio DA. 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