Obesity is a serious health problem because of its co-morbidities. The solution, implying weight loss and long-term weight maintenance, is conditional on: (i) sustained satiety despite negative energy balance, (ii) sustained basal energy expenditure despite BW loss due to (iii) a sparing of fat-free mass (FFM), being the main determinant of basal energy expenditure. Dietary protein has been shown to assist with meeting these conditions, since amino acids act on the relevant metabolic targets. This review deals with the effects of different protein diets during BW loss and BW maintenance thereafter. Potential risks of a high protein diet are dealt with. The required daily intake is 0·8–1·2 g/kg BW, implying sustaining the original absolute protein intake and carbohydrate and fat restriction during an energy-restricted diet. The intake of 1·2 g/kg BW is beneficial to body composition and improves blood pressure. A too low absolute protein content of the diet contributes to the risk of BW regain. The success of the so-called ‘low carb’ diet that is usually high in protein can be attributed to the relatively high-protein content per se and not to the relatively lower carbohydrate content. Metabolic syndrome parameters restore, mainly due to BW loss. With the indicated dosage, no kidney problems have been shown in healthy individuals. In conclusion, dietary protein contributes to the treatment of obesity and the metabolic syndrome, by acting on the relevant metabolic targets of satiety and energy expenditure in negative energy balance, thereby preventing a weight cycling effect.

Dietary protein is effective for body-weight management, in that it promotes satiety, energy expenditure, and changes body-composition in favor of fat-free body mass. With respect to body-weight management, the effects of diets varying in protein differ according to energy balance. During energy restriction, sustaining protein intake at the level of requirement appears to be sufficient to aid body weight loss and fat loss. An additional increase of protein intake does not induce a larger loss of body weight, but can be effective to maintain a larger amount of fat-free mass. Protein induced satiety is likely a combined expression with direct and indirect effects of elevated plasma amino acid and anorexigenic hormone concentrations, increased diet-induced thermogenesis, and ketogenic state, all feed-back on the central nervous system. The decline in energy expenditure and sleeping metabolic rate as a result of body weight loss is less on a high-protein than on a medium-protein diet. In addition, higher rates of energy expenditure have been observed as acute responses to energy-balanced high-protein diets. In energy balance, high protein diets may be beneficial to prevent the development of a positive energy balance, whereas low-protein diets may facilitate this. High protein-low carbohydrate diets may be favorable for the control of intrahepatic triglyceride IHTG in healthy humans, likely as a result of combined effects involving changes in protein and carbohydrate intake. Body weight loss and subsequent weight maintenance usually shows favorable effects in relation to insulin sensitivity, although some risks may be present. Promotion of insulin sensitivity beyond its effect on body-weight loss and subsequent body-weight maintenance seems unlikely. In conclusion, higher-protein diets may reduce overweight and obesity, yet whether high-protein diets, beyond their effect on body-weight management, contribute to prevention of increases in non-alcoholic fatty liver disease NAFLD, type 2 diabetes and cardiovascular diseases is inconclusive.

Aim: To compare the impact of two long‐term weight‐maintenance diets, a high protein (HP) and low glycaemic index (GI) diet versus a moderate protein (MP) and moderate GI diet, combined with either high intensity (HI) or moderate intensity physical activity (PA), on the incidence of type 2 diabetes (T2D) after rapid weight loss. Materials and Methods: A 3‐year multicentre randomized trial in eight countries using a 2 x 2 diet‐by‐PA factorial design was conducted. Eight‐week weight reduction was followed by a 3‐year randomized weight‐maintenance phase. In total, 2326 adults (age 25‐70 years, body mass index ≥ 25 kg/m ² ) with prediabetes were enrolled. The primary endpoint was 3‐year incidence of T2D analysed by diet treatment. Secondary outcomes included glucose, insulin, HbA1c and body weight. Results: The total number of T2D cases was 62 and the cumulative incidence rate was 3.1%, with no significant differences between the two diets, PA or their combination. T2D incidence was similar across intervention centres, irrespective of attrition. Significantly fewer participants achieved normoglycaemia in the HP compared with the MP group ( P < .0001). At 3 years, normoglycaemia was lowest in HP‐HI (11.9%) compared with the other three groups (20.0%‐21.0%, P < .05). There were no group differences in body weight change (−11% after 8‐week weight reduction; −5% after 3‐year weight maintenance) or in other secondary outcomes. Conclusions: Three‐year incidence of T2D was much lower than predicted and did not differ between diets, PA or their combination. Maintaining the target intakes of protein and GI over 3 years was difficult, but the overall protocol combining weight loss, healthy eating and PA was successful in markedly reducing the risk of T2D. This is an important clinically relevant outcome.

Type-2 diabetes (T2D) is one of the fastest growing chronic diseases worldwide. The PREVIEW project has been initiated to find the most effective lifestyle (diet and physical activity) for the prevention of T2D, in overweight and obese participants with increased risk for T2D. The study is a three-year multi-centre, 2 × 2 factorial, randomised controlled trial. The impact of a high-protein, low-glycaemic index (GI) vs. moderate protein, moderate-GI diet in combination with moderate or high-intensity physical activity on the incidence of T2D and the related clinical end-points are investigated. The intervention started with a two-month weight reduction using a low-calorie diet, followed by a randomised 34-month weight maintenance phase comprising four treatment arms. Eight intervention centres are participating (Denmark, Finland, United Kingdom, The Netherlands, Spain, Bulgaria, Australia, and New Zealand). Data from blood specimens, urine, faeces, questionnaires, diaries, body composition assessments, and accelerometers are collected at months 0, 2, 6, 12, 18, 24, and 36. In total, 2326 adults were recruited. The mean age was 51.6 (SD 11.6) years, 67% were women. PREVIEW is, to date, the largest multinational trial to address the prevention of T2D in pre-diabetic adults through diet and exercise intervention. Participants will complete the final intervention in March, 2018.