The review aims to explore the potential benefit and risk of high-protein diets (HPD) regarding the comorbidity of sarcopoenia and CVD in the setting of cardiac rehabilitation (CR). CR is standard care for individuals who have experienced a cardiac event, but the current practice of predominantly aerobic exercise, a lower-fat diet and weight loss poorly addresses the issue of sarcopoenia. HPD, especially when combined with resistance exercise (RE), may be valuable adjuncts to current CR practice and benefit both muscle and cardiovascular health. Meta-analyses and randomised controlled trials of HPD and CVD risk show beneficial but variable effects regarding weight loss, the lipid profile, insulin resistance and lean body mass in those living with or high risk of CVD. Meta-analyses of prospective cohort studies on hard CVD endpoints favour lower- and plant-protein diets over higher animal protein, but the evidence is inconsistent. HPD augment the strength and muscle gaining benefits of RE in older populations, but there are no published data in those living with CVD providing promising opportunities for CR research. HPD raise concern regarding renal and bone health, the microbiome, branched chain amino acids and environmental sustainability and findings suggest that plant-based HPD may confer ecological and overall health advantages compared to animal-based HPD. However, incorporating RE with HPD might alleviate certain health risks. In conclusion, a largely plant-based HPD is deemed favourable for CR when combined with RE, but further research regarding efficacy and safety in CR populations is needed.

The ingestion of excess lipids often produces the accumulation of liver fat. The modulation of diet energy partition affects this process and other metabolic responses, and oestrogens and androgens are implied in this process. Ten-week-old male and female rats were fed with either standard rat chow (SD), SD enriched with coconut oil (high-fat diet, HF), SD enriched with protein (high-protein diet, HP) or a ‘cafeteria’ diet (CAF) for 1 month. HF and CAF diets provided the same lipid-derived percentage of energy (40 %), HP diet protein energy derived was twice (40 %) that of the SD. Animals were killed under anaesthesia and samples of blood and liver were obtained. Hepatic lipid content showed sex-related differences: TAG accumulation tended to increase in HF and CAF fed males. Cholesterol content was higher only in the CAF males. Plasma oestradiol in HF and HP males was higher than in CAF. Circulating cholesterol was inversely correlated with plasma oestradiol. These changes agreed with the differences in the expression of some enzymes related to lipid and energy metabolism, such as fatty acid synthetase or phosphoglycolate phosphatase. Oestrogen protective effects extend to males with ‘normal’ diets, that is, not unbalanced by either lipid or protein, but this protection was not enough against the CAF diet. Oestradiol seems to actively modulate the liver core of 2C-3C partition of energy substrates, regulating cholesterol deposition and lactate production.

Prebiotic supplements and high-protein (HP) diets reduce body weight and modulate intestinal microbiota. Our aim was to elucidate the combined effect of an inulin/oligofructose (FOS) and HP diet on body weight gain, energy metabolism and faecal microbiota. Forty male C57BL/6NCrl mice were fed a control (C) diet for 2 weeks and allocated to a C or HP (40 % protein) diet including no or 10 % inulin/FOS (C + I and HP + I) for 4 weeks. Inulin/FOS was added in place of starch and cellulose. Body weight, food intake, faecal energy and nitrogen were determined. Indirect calorimetry and faecal microbiota analysis were performed after 3 weeks on diets. Body weight gain of HP-fed mice was 36 % lower than HP + I- and C-fed mice (P < 0⋅05). Diet digestibility and food conversion efficiency were higher in HP + I- than HP-fed mice (P < 0⋅01), while food intake was comparable between groups. Total energy expenditure (heat production) was 25 % lower in HP + I- than in C-, HP- and C + I-fed mice (P < 0⋅001). Carbohydrate oxidation tended to be 24 % higher in HP- than in HP + I-fed mice (P < 0⋅05). Faecal nitrogen excretion was 31–45 % lower in C-, C + I- and HP + I- than in HP-fed mice (P < 0⋅05). Faecal Bacteroides–Prevotella DNA was 2⋅3-fold higher in C + I- and HP + I- relative to C-fed mice (P < 0⋅05), but Clostridium leptum DNA abundances was 79 % lower in HP + I- than in HP-fed mice (P < 0⋅05). We suggest that the higher conversion efficiency of dietary energy of HP + I but not C + I-fed mice is caused by higher digestibility and lower heat production, resulting in increased body mass.

Menopausal women are susceptible to osteoarthritis(OA) and memory impairment. We hypothesised that Alzheimer’s-like disease(AD) exacerbates OA and that intermittent fasting(IMF) with a high-protein(H-P) diet would enhance memory function and relieve OA symptoms in oestrogen-deficient animals induced AD and OA. The action mechanism was also explored. Ovariectomised Sprague–Dawley rats were fed high-fat(H-F) or H-P diets for 2 weeks, and then they had a hippocampal infusion of β-amyloid(25–35) for 4 weeks to induce AD and an injection of monoidoacetate(MIA) into the articular cartilage to induce OA. Non-AD groups had non-AD symptoms by hippocampal amyloid-β(35–25) infusion. IMF suppressed memory impairment in AD rats, especially those fed H-P diets. Compared with non-AD, AD exacerbated OA symptoms, including swelling, limping, slowed treadmill running speed, and uneven weight distribution in the left leg. The exacerbations were linked to increased inflammation and pain, but IMF and H-P lessened the exacerbation. Lean body mass(LBM) decreased with AD, but H-P protected against LBM loss. Histological examination of the knee joint revealed the degree of the cellular invasion into the middle zone, and the changes in the tidemark plateau were greatest in the AD-AL with H-F, while non-AD-IMF improved the cellular invasion to as much as non-AD-AL. H-P reduced the infiltration into the middle zone of the knee and promoted collagen production. In conclusion, AD exacerbated the articular cartilage deterioration and memory impairment, and IMF with H-P alleviated the memory impairment and osteoarthritic symptoms by decreasing hippocampal amyloid-β deposition and proinflammatory cytokine expressions and by increasing LBM.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48–96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Normal-weight obesity (NWO) syndrome is associated with metabolic diseases. The present study aimed to investigate the effects of 12 weeks of a high-protein (HP) v. a standard protein (SP) diet on appetite, anthropometry and body composition in NWO women. In this clinical trial, fifty NWO women were randomly allocated to HP (n 25) or SP (n 25) diet groups. Women in the HP and SP groups consumed 25 and 15 % of their total energy intake from protein for 12 weeks. Weight, fat mass (FM), lean body mass (LBM), waist circumference (WC) and appetite were evaluated at baseline and following their 3-month intervention. After 12 weeks, the LBM was higher in HP compared with no significant changes in the SP group (mean between-group difference = 1·5 kg; 95 % CI 3·1, 0·01; effect size (d) = 0·4). Furthermore, the HP group had lower FM (mean between-group difference –1·1 kg; 95 % CI 1, –3·3; d = –0·2), body fat percentage (BFP) (mean between-group difference –2 %; 95 % CI 0·7, –5·2; d = –0·3) and WC (mean between-group difference –1·4 cm; 95 % CI 0·6, –3·6; d = –0·2) at the end of the study in comparison with the SP group. In both groups, weight and appetite were unchanged over time without significant differences between groups. Twelve weeks of euenergetic diets with different dietary protein contents resulted in no significant weight loss in women with NWO. However, an HP diet significantly improved body composition (LBM, FM, BFP and WC) in this population.

The aim of this study was to investigate the effectiveness of the Hipcref (high-protein, energy-restricted, high-vitamin E and high-fibre) diet in Malaysian adults on body composition and metabolic parameters after an intervention period of 6 months. Overweight/obese Malaysian adults (n 128; BMI≥23 kg/m2) were randomised to the Hipcref (n 65) or control diet (n 63). The intervention group received Hipcref diet charts based on their personal preferences. The control group followed a generalised dietary advice based on Malaysian Dietary Guidelines, 2010. All participants were responsible for preparing their own meals. There was a significant treatment group×time effect on anthropometric parameters (P<0·05) on an intention-to-treat basis. Pairwise comparisons revealed that Hipcref diet participants had significant reduction in weight, BMI, waist circumference, fat mass and percentage body fat at months 3 and 6 compared with baseline (P<0·001). The control group had significant increase in weight and BMI at months 3 and 6 compared with baseline (P<0·05). The Hipcref diet group had higher reduction in fasting insulin, insulin resistance and C-reactive protein levels compared with the control group at month 6 (P<0·05). Post-intervention, compared with the control group, the Hipcref diet group was found to consume significantly higher percentage energy from protein, and PUFA, higher energy-adjusted vitamin E (mg) and fibre (g), and lower total energy, lower percentage energy from fat and carbohydrate (P<0·05). The success of the Hipcref diet on overweight/obese Malaysian adults may be due to the combined effect of the nutrient composition of the Hipcref diet.

Key pathophysiology of sickle cell anaemia includes compensatory erythropoiesis, vascular injury and chronic inflammation, which divert amino acids from tissue deposition for growth/weight gain and muscle formation. We hypothesised that sickle mice maintained on an isoenergetic diet with a high percentage of energy derived from protein (35 %), as opposed to a standard diet with 20 % of energy derived from protein, would improve body composition, bone mass and grip strength. Male Berkeley transgenic sickle mice (S; n 8–12) were fed either 20 % (S20) or 35 % (S35) diets for 3 months. Grip strength (BIOSEB meter) and body composition (dual-energy X-ray absorptiometry scan) were measured. After 3 months, control mice had the highest bone mineral density (BMD) and bone mineral content (BMC) (P < 0·005). S35 mice had the largest increase in grip strength. A two-way ANOVA of change in grip strength (P = 0·043) attributed this difference to genotype (P = 0·025) and a trend in type of diet (P = 0·067). l-Arginine (l-Arg) supplementation of the 20 % diet was explored, as a possible mechanism for improvement obtained with the 35 % diet. Townes transgenic sickle mice (TS; n 6–9) received 0·8, 1·6, 3·2 or 6·4 % l-Arg based on the same protocol and outcome measures used for the S mice. TS mice fed 1·6 % l-Arg for 3 months (TS1.6) had the highest weight gain, BMD, BMC and lean body mass compared with other groups. TS3.2 mice showed significantly more improvement in grip strength than TS0·8 and TS1.6 mice (P < 0·05). In conclusion, the high-protein diet improved body composition and grip strength. Outcomes observed with TS1.6 and TS3.2 mice, respectively, confirm the hypothesis and reveal l-Arg as part of the mechanism.

Dietary strategies that can help reduce hunger and promote fullness are beneficial for weight control, since these are major limiting factors for success. High-protein (HP) diets, specifically those that maintain the absolute number of grams ingested, while reducing energy, are a popular strategy for weight loss (WL) due to the effects of protein-induced satiety to control hunger. Nonetheless, both the safety and efficacy of HP WL diets have been questioned, particularly in combination with low-carbohydrate advice. Nonetheless, for short-to-medium-term intervention studies (over several months), increasing the energetic contribution of protein does appear effective. The effects of HP diets on appetite, bone health, renal function, blood pressure, cardiovascular bio-markers, antioxidant status, gut health and psychological function are discussed. Further research is warranted to validate the physiological effects of HP diets over longer periods of time, including studies that modify the quality of macronutrients (i.e. the type of carbohydrate, fat and protein) and the interaction with other interventions (e.g. exercise and dietary supplements).

Elucidating the effects of refeeding a high-protein diet after fasting on disease development is of interest in relation to excessive protein ingestion and irregular eating habits in developed countries. The objective of the present study was to address the hepatic effects of refeeding a high-protein diet after fasting. Mice were fasted for 48 h and then refed with a test diet containing 3, 15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and liver immediate-early gene expression levels were sequentially measured for the first 24 h after initiation of refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid (within 2–3 h) and abnormal elevation in serum ALT (P = 0·006) and AST (P = 0·001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ) osteosarcoma oncogene (P = 0·007) and nuclear receptor subfamily 4, group A, member 1 (P = 0·002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 % casein diets produced no substantial increases in serum ALT and AST activities in mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly increased. We conclude from these data that the consumption of a high-protein diet after fasting causes acute hepatocellular injury in healthy animals, and propose that careful attention should be paid to the use of such diets.

There is growing evidence that maternal nutrition during gestation has an important effect on offspring development as well as on their gene expression with long-term effects on the metabolic state. A potential mechanism forming long-lasting gene expression patterns is DNA methylation of cytosine in CpG dinucleotides within the promoter region of distinct genes. There has been special focus on mitochondrial dysfunction by prenatal malnourishment over the recent years. To this end, we investigated the gene expression of somatic cytochrome c (CYCS), an important member of the respiratory chain, in a porcine model of gestational protein over- and undersupply at 94 d post-conception and 1, 28 and 188 d of age, and analysed the association with the DNA methylation status within the CYCS promoter. Gene expression on day 1 post natum showed a significant increase in the low protein (LP) group (P = 0·0005) and a slight increase in the high protein (HP) group (P = 0·079) compared with the control (CO) group in the liver. The mean of the methylation level over forty-seven CpG sites from nucleotide (nt) − 417 to − 10 was significantly decreased in the LP (P = 0·007) and HP (P = 0·009) groups compared with that in the CO group. Excess and restricted protein supply during pregnancy led to hypomethylation of a number of CpG sites in the CYCS promoter, including those representing putative transcription factor-binding sites, associated with elevated expression levels. However, the impact of the low-protein gestation diet is more pronounced, indicating that the offspring could better adapt to excess rather than restricted protein supply.

Increased gluconeogenesis (GNG) has been suggested to contribute to protein-induced satiety via modulation of glucose homoeostasis. The objective was to determine GNG and appetite in healthy human subjects after a high-protein v. a normal-protein diet and to assess whether GNG contributes to protein-induced satiety. A total of twenty-two healthy subjects (ten men and twelve women: age 23 (sem 1) years, BMI 22·1 (sem 0·5) kg/m2) received an isoenergetic high-protein (30/0/70 % of energy from protein/carbohydrate/fat) or normal-protein diet (12/55/33 % of energy from protein/carbohydrate/fat) for 1·5 d in a randomised cross-over design. Appetite ratings were measured using visual analogue scales (VAS); endogenous glucose production and GNG were measured via infusion of [6,6-2H2]glucose and ingestion of 2H2O. Moreover, fasting glucose and β-hydroxybutyrate concentrations were measured. Glycogen stores were lowered at the start with a glycogen-lowering exercise test. During the high-protein compared with the normal-protein diet, GNG was increased and appetite was suppressed (GNG: 148 (sem 7) v. 133 (sem 6) g/24 h, P < 0·05; and 24 h area under the curve for hunger: 694 (sem 46) v. 1055 (sem 52) mm VAS × 24 h, P < 0·001; fullness: 806 (sem 59) v. 668 (sem 64) mm VAS × 24 h, P < 0·05; desire to eat: 762 (sem 48) v. 1004 (sem 66) mm VAS × 24 h, P < 0·001). There was no correlation between appetite ratings and GNG. Glucose concentration was lower (4·09 (sem 0·10) v. 4·89 (sem 0·06) mmol/l, P < 0·001) and β-hydroxybutyrate concentration was higher (1349 (sem 139) v. 234 (sem 25) μmol/l, P < 0·001) after the high-protein compared with the normal-protein diet. In conclusion, after a high-protein diet, GNG was increased and appetite was lower compared with a normal-protein diet; however, these were unrelated to each other. An increased concentration of β-hydroxybutyrate may have contributed to appetite suppression on the high-protein diet.

High-protein (HP) diets for weight loss remain popular despite questions surrounding overall safety. In a recent study using the pig model, we showed that long-term intakes from whole proteins at 35 % energy (en %) cause moderate renal histological damage. To examine whether this observation may be species specific or more generalisable, the effect of this diet in rats was examined. Using plant and animal whole proteins, 70-d-old female Sprague–Dawley rats were randomised to either a normal-protein (NP; 15 en %) or a HP (35 en %) diet for 4, 8, 12 and 17 months. Renal function was assessed by creatinine clearance and urinary protein levels, and pathology was assessed by examination of glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis. Rats consuming the HP diet had 17 % higher kidney weights (P < 0·0001), three times higher proteinuria (P < 0·0001) and 27 % higher creatinine clearance (P = 0·0012) compared with those consuming the NP diet. Consistent with this, HP-fed rats had larger glomeruli (P < 0·0001) and more glomerulosclerosis (P = 0·0003) compared with NP-fed rats. The HP diet also resulted in altered levels of free monocyte chemoattractant protein-1 (P < 0·0001). The histological changes are consistent with those observed in the pig model. In contrast to the pig model, the elevated proteinuria and creatinine clearance observed in the rat model are also usually observed with HP consumption in human subjects. These results indicate that the rat is a useful model for HP effects on the kidney and, along with previous results using the pig model, suggest that long-term intake of high levels of protein may be detrimental to renal health.

Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

Resistance exercise is recommended to individuals following high-protein diets in order to augment changes in body composition. However, alterations in macronutrient composition may compromise physical performance. The present study investigated the effects of an isoenergetic high-protein diet on upper and lower limb strength and fatigue during high-intensity resistance exercise. Ten recreationally active women, aged 25–40 years, followed a control diet (55, 15 and 30 % of energy from carbohydrate, protein and fat, respectively) and a high-protein diet (respective values, 30, 40 and 30) for 7 d each in a random counterbalanced design. Each participant underwent strength testing of upper limb (isometric handgrip strength and endurance) and lower limb (four sets of sixteen maximal knee flexions and extensions on an isokinetic dynamometer) before and after applying each diet. Body weight, body fat and RER were significantly reduced following the high-protein diet (P < 0·05). No differences were found between diets in any of the strength performance parameters (handgrip strength, handgrip endurance, peak torque, total work and fatigue) or the responses of heart rate, systolic and diastolic arterial pressure, blood lactate and blood glucose to exercise. Women on a short-term isoenergetic high-protein, moderate-fat diet maintained muscular strength and endurance of upper and lower limbs during high-intensity resistance exercise without experiencing fatigue earlier compared with a control diet.

In subjects with untreated type 2 diabetes, we previously determined that a weight-maintenance, non-ketogenic diet containing 30 % protein, 50 % fat and 20 % carbohydrate (30:50:20) decreased the percentage total glycohaemoglobin (%tGHb) by 2·2 % glycohaemoglobin over 5 weeks compared to a diet recommended for the American public (protein–fat–carbohydrate 15:30:55). Both the fasting and postprandial glucose were decreased. The objective of the present study was to determine if increasing the carbohydrate content from 20 to 30 % at the expense of fat would still provide a similar effect on %tGHb, fasting and postprandial glucose concentration. Eight men with untreated type 2 diabetes were studied over a 5-week period. Results at the beginning (standard diet) and end of the 5-week study were analysed. Body weight was stable. Fasting glucose concentration decreased by 40 %; 24 h glucose area response decreased by 45 %. Insulin did not change. Mean %tGHb decreased by 1·7 (from 10·8 to 9·1 %), and was still decreasing linearly at 5 weeks. In conclusion, a high-protein, 30 % carbohydrate diet could be a patient-empowering method of improving the hyperglycaemia of type 2 diabetes without pharmacologic intervention. Long-term effects and general applicability of this diet remain to be determined.

This study was designed to determine whether (1) protein type and (2) the dietary carbohydrate to lipid content affected daily energy intake, body weight and adiposity in rats receiving high-protein diets ad libitum over a 25 d period. Each of the ten groups (n 8) consumed ad libitum one of the diets described below. A normal protein diet (P14C56L30, containing whole milk protein) and nine high-protein diets were used. The composition of the high-protein diets varied in terms of two parameters: macronutrient composition and protein type. Three macronutrient compositions (P55C35L10, P55C15L30 and P55L45) combined with three protein types (Milk, Whey and βLac) allowed us to test nine diets. The results show that both protein type (βLac > Whey > Milk) and the carbohydrate to lipid ratio (P55L45>P55C35L10 or P55C15L30) modulated reductions in energy intake, body weight and adiposity in rats receiving high-protein diets ad libitum, when compared with rats fed a normal diet under the same conditions. By contrast, blood lipid profiles were mainly influenced by the carbohydrate to lipid ratio (P55C15L30>P55L45 or P55C35L10). Moreover, βLac protein was also the most efficient in tending to preserve lean body mass at the expense of fat mass, and improve blood metabolism hormones (insulin, leptin). Taken together, the present results show that whey-derived protein sources, and particularly β-lactoglobulin-enriched fraction, are of considerable value because of their ability to reduce both body weight gain and the adiposity index.