- Journal List
- J Obes Metab Syndr
- v.29(3); 2020 Sep 30
- PMC7539343
As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsem*nt of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more: PMC Disclaimer | PMC Copyright Notice
J Obes Metab Syndr. 2020 Sep 30; 29(3): 166–173.
Published online 2020 Jul 23. doi:10.7570/jomes20028
PMCID: PMC7539343
PMID: 32699189
Jaecheol Moon1 and Gwanpyo Koh1,2,*
Author information Article notes Copyright and License information PMC Disclaimer
Abstract
Several clinical trials have found that consuming more protein than the recommended dietary allowance not only reduces body weight (BW), but also enhances body composition by decreasing fat mass while preserving fat-free mass (FFM) in both low-calorie and standard-calorie diets. Fairly long-term clinical trials of 6–12 months reported that a high-protein diet (HPD) provides weight-loss effects and can prevent weight regain after weight loss. HPD has not been reported to have adverse effects on health in terms of bone density or renal function in healthy adults. Among gut-derived hormones, glucagon-like peptide-1, cholecystokinin, and peptide tyrosine-tyrosine reduce appetite, while ghrelin enhances appetite. HPD increases these anorexigenic hormone levels while decreasing orexigenic hormone levels, resulting in increased satiety signaling and, eventually, reduced food intake. Additionally, elevated diet-induced thermogenesis (DIT), increased blood amino acid concentration, increased hepatic gluconeogenesis, and increased ketogenesis caused by higher dietary protein contribute to increased satiety. The mechanism by which HPD increases energy expenditure involves two aspects: first, proteins have a markedly higher DIT than carbohydrates and fats. Second, protein intake prevents a decrease in FFM, which helps maintain resting energy expenditure despite weight loss. In conclusion, HPD is an effective and safe tool for weight reduction that can prevent obesity and obesity-related diseases. However, long-term clinical trials spanning more than 12 months should be conducted to further substantiate HPD effects.
Keywords: High protein diet, Weight loss, Obesity, Satiation
INTRODUCTION
Prevalence of obesity around the world have increased rapidly in recent years. This phenomenon poses serious health risks because obesity can progressively cause a wide range of diseases such metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular diseases.1 To resolve obesity, a negative energy balance, in which energy expenditure is greater than energy intake, must be encouraged. This can be achieved via an energy-restricted diet.2 However, an energy-restricted diet carries the risk of post-loss weight regain because it increases hunger and decreases fullness. Furthermore, weight loss through an energy-restricted diet reduces fat mass and fat-free mass (FFM), which hinders a continuous negative energy balance. To overcome this, lowering energy intake while maintaining fullness and FFM is crucial, and a high-protein, energy-restricted diet is one important strategy.3,4 In this review article, we examine the clinical evidence for the weight-loss effects and side effects of high-protein diet (HPD) and introduce various mechanisms through which HPD increases satiety and induces weight loss while preserving FFM.
CLINICAL OUTCOMES WITH HPD
Protein is a component of the human body, a source of energy, and an essential nutrient that facilitates growth and development. The recommended dietary allowance of protein to avoid protein deficiency in adults is 0.80 g/kg body weight (BW)/day, which translates to about 48–56 g/day and about 10%–15% of the total daily energy expenditure.5 To date, many clinical trials have attempted to regulate BW through high protein consumption more than the recommended dietary allowance (Table 1).
Table 1
Summary of studies on HPD
| Variable | Wycherley et al. (2012)4 | Santesso et al. (2012)6 | Skov et al. (1999)7 | Weigle et al. (2005)8 | Westerterp- Plantenga et al. (2004)9 | Lejeune et al. (2005)10 | Clifton et al. (2008)11 | Layman et al. (2009)12 |
|---|---|---|---|---|---|---|---|---|
| Remark | Controlled, energy-restricted diet | Controlled, nonenergy-restricted diet | Ad libitum diet | Weight regain after initial weight loss was assessed | ||||
| Study design | Meta-analysis | Meta-analysis | Randomized parallel | Single-arm trial | Randomized parallel | Randomized parallel | Randomized parallel | Randomized parallel |
| Protein quantity (% of total energy) | ||||||||
| HPD | 27–35 | 16–45 | 25 | 30 | 18 | 18 | 34 | 30 |
| Control diet | 16–21 | 5–23 | 12 | - | 15 | 15 | 17 | 15 |
| Number | 1,063 | 1,577 | 65 | 19 | 148 | 113 | 79 | 130 |
| Duration (mo) | ≥1 | ≥1 | 6 | 3 | 4 | 7 | 15 | 12 |
| Body weight (kg) | –0.79 (–1.50 to –0.08) | –0.36 (–0.56 to –0.17) | –3.7 (–6.2 to –1.3) | –4.9± 0.5 | NS | –2.9 | NS | NS |
| BMI (kg/m2) | - | –0.37 (–0.56 to 0.19) | - | - | –0.9 –1.0 | - | - | |
| Waist circumference (cm) | - | –0.43 (–0.69 to –0.16) | - | - | –3.0 –1.7 | - | - | |
| Fat mass (kg) | –0.87 (–1.26 to –0.48) | - | –3.3 (–5.5 to –1.1) | –3.7± 0.4 | –3.4 | –2.6 | NS | –1.7 |
| FFM (kg) | 0.43 (0.09 to 0.78) | - | - | - | NS | NS | - | NS |
| REE (kJ/day) | 595.5 (67.0 to 1,124.1) | - | - | NS | NS | - | - | - |
| SBP (mmHg) | –0.21 (–0.32 to –0.09) | –0.21 (–0.32 to –0.09) | - | - | - | - | - | - |
| DBP (mmHg) | –0.18 (–0.29 to –0.06) | –0.18 (–0.29 to –0.06) | - | - | - | - | - | - |
| TC (mg/dL) | NS | NS | - | - | - | - | - | - |
| Triglycerides (mg/dL) | –20.3 (–29.2 to –10.6) | –45.1 (–69.0 to –21.2) | - | - | –16.6 | - | NS | - |
| HDL-C (mg/dL) | NS | 9.6 (2.7 to 16.9) | - | - | - | - | NS | - |
| LDL-C (mg/dL) | NS | NS | - | - | - | - | NS | - |
| Fasting glucose (mg/dL) | NS | NS | - | NS | NS | NS | NS | - |
| Fasting insulin (μIU/mL) | NS | –0.03 (–0.05 to –0.01) | - | NS | NS | NS | - | - |
| HbA1c (%) | - | NS | - | - | - | - | - | - |
| FFA (μmol/L) | - | - | - | NS | NS | NS | NS | - |
| C-reactive protein (mmol/L) | - | NS | - | - | - | - | - | - |
| Comment | 52% Less weight regain, only consisting of FFM | 64% Less weight regain, only consisting of FFM | Protein intake was directly related to weight loss and change. Lipids, glucose, insulin, and C-reactive protein all improved with weight loss. | For completers, the mean weight loss was 23% greater for HPD group. HPD group showed sustained favorable effects on serum triglycerides and HDL-C. |
Values are presented as mean (95% confidence interval) or mean± standard deviation.
HPD, high-protein diet; NS, not significant; BMI, body mass index; FFM, fat-free mass; REE, resting energy expenditure; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; FFA, free fatty acids.
Wycherley et al.4 conducted a meta-analysis of 24 randomized controlled trials (RCTs) that compared HPD and standard-protein diet (SPD) with isocaloric, energy-restricted diets. Subjects in the HPD group consumed 1.07–1.60 g protein/kg BW/day (27%–35% of total energy intake consumed as protein), and subjects in the SPD group consumed 0.55–0.88 g/kg BW/day (16%–21% of total energy intake consumed as protein), with the two groups having a difference less than 1,250 kJ/day in total energy intake. A total of 1,063 participants were enrolled, and the mean (±standard deviation) diet duration was 12.1±9.3 weeks. Compared with subjects in the SPD group, those in the HPD group showed a significant reduction in BW (–0.79 kg; 95% confidence interval [CI], –1.50 to –0.08 kg), fat mass (–0.87 kg; 95% CI, –1.26 to –0.48 kg), and blood triglycerides (–20.3 mg/dL; 95% CI, –29.2 to –10.6 mg/dL) and a significant increase in FFM (0.43 kg; 95% CI, 0.09–0.78 kg) and resting energy expenditure (REE; 595.5 kJ/day; 95% CI, 67.0– 1,124.1 kJ/day). Santesso et al.6 conducted a meta-analysis of 74 RCTs with less than 5% difference in calorie intake between the two study groups regardless of energy restriction. Compared with subjects in the SPD group who consumed protein as 5%–23% of their daily total energy, subjects in the HPD group who consumed protein as 16%–45% of their daily total energy showed a significant decrease in BW (–0.36 kg; 95% CI, –0.56 to –0.17 kg), body mass index (–0.37 kg/m2; 95% CI, –0.56 to 0.19 kg/m2), waist circumference (–0.43 cm; 95% CI, –0.69 to –0.16 cm), and blood pressure (systolic: –0.21 mmHg; 95% CI, –0.32 to –0.09 mmHg and diastolic: –0.18 mmHg; 95% CI, –0.29 to –0.06 mmHg), but the degree of improvement was small.
Most clinical trials examining the effects of HPD used controlled diets, which were provided by the investigators. However, Skov et al.7 and Weigle et al.8 conducted clinical trials involving ad libitum diets. Skov et al.7 conducted a six-month randomized dietary intervention trial, where participants were divided into an HPD (protein as 25% of total energy intake, n=25), high-carbohydrate diet (protein as 12% of total energy intake, n=25), or control group (n=15), with fat intake set to 30% of total energy intake. Although the participants followed an ad libitum diet at designated restaurants, they were instructed to strictly adhere to the required diet composition. In contrast to other controlled feeding trials, the withdrawal rate was very low (<10%). After 6 months, participants in the high-protein group significantly lost BW (–3.7 kg; 95% CI, –6.2 to –1.3 kg) and fat mass (–3.3 kg; 95% CI, –5.5 to –1.1 kg) compared with those in the high-carbohydrate diet group. Similar results were observed in the study by Weigle et al.8 That study was a single-arm trial involving a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for the first 2 weeks, an isocaloric HPD (30% protein, 20% fat, and 50% carbohydrate) for the next 2 weeks, and an ad libitum HPD (30% protein, 20% fat, and 50% carbohydrate) for the next 12 weeks. After HPD, satiety increased, while BW (–4.9± 0.5 kg) and fat mass (–3.7±0.4 kg) significantly decreased.
Some studies examined the effect of HPD on weight regain after weight loss. Westerterp-Plantenga et al.9 induced weight loss through a 4-week, very low-energy diet in 148 mildly obese participants, after which protein was additionally administered at 48.2 g/day for 3 months. The participants in the group given additional protein consumed 18% of their daily total energy as protein, while the control group consumed 15% of their daily total energy as protein. Participants in the protein group showed 50% less weight regain compared with control-group participants. Weight regain constituted FFM in the protein-group participants and fat mass in the controlgroup participants. Lejeune et al.10 also observed less weight regain in participants consuming 30 g/day of protein for 6 months (0.8 vs. 3.0 kg; P<0.05). Clifton et al.11 and Layman et al.12 compared HPD and high-carbohydrate diet for nine and 12 months, respectively, and they confirmed a correlation between protein intake and weight loss and between protein intake and fat-mass reduction, respectively.
In conclusion, many clinical trials have shown that consuming more protein than the recommended dietary allowance induces weight loss and improves body composition regardless of total energy intake. HPD was also observed to have long-term weight-loss effects and to prevent weight regain following initial weight loss.
POSSIBLE HARMFUL EFFECTS OF HPD
The benefits of HPD are well known, but there have been concerns that it may be harmful to the bones and kidneys. It has long been hypothesized that HPD increases the resorption of bones, which act as buffers, by increasing the acid load in the body,13 and some researchers argued that HPD increases risk for bone fracture and osteoporosis by accelerating bone resorption and urinary calcium excretion.14 However, a meta-analysis of 74 RCTs observed that subjects in the HPD group (16%–45% of total daily energy intake as protein) were not significantly different from low-protein-diet subjects (5%–23% of total daily energy intake as protein) with regard to bone mineral density of the lumbar spine and hips.6 Furthermore, low protein intake is generally considered a nutritional deficiency. In particular, it has been described as a factor affecting osteoporosis development in older adults.15 Hannan et al.16 reported that protein intake was negatively correlated with bone loss in their Framingham Osteoporosis Study, which prospectively examined 615 older adults over four years. There have also been concerns that HPD may deteriorate renal function by increasing the glomerular filtration rate (GFR) and inducing renal hypertrophy. However, Friedman et al.17 found no declining renal function in terms of various indicators such as GFR and albuminuria when studying the safety of HPD in 307 obese adults with normal renal function over two years (24 months). Nevertheless, they reported increased calcium level in urine with neither reduction in bone mineral density nor urolithiasis, calling for further studies. Knight et al.18 also reported no association of high protein intake with change in GFR in their prospective Nurses’ Health Study, which involved 1,624 females. They noted that GFR decreased by 1.69 mL/min per 1.73 m2 in participants with mild renal insufficiency (GFR 55–80 mL/min/ 1.73 m2) when protein intake was increased by 10 g. Overall, HPD does not lead to reduced bone mineral density. On the contrary, high protein intake can help prevent bone loss in older adults who are prone to nutritional deficiency. While HPD also does not affect renal function in healthy people, it can adversely affect renal function in people with kidney disease. There is not a clear definition of the upper limit of beneficial protein intake, but Millward19 reported in their study on energy-restricted HPD that up to 1.66 g/kg BW/ day does not pose a health hazard. Martens et al.20 and Bray et al.21 studied HPD with neutral or positive energy balance, and they reported that consuming an amount of protein that accounts for 25%–30% of the total daily energy intake for 10–12 weeks did not induce any adverse effects. However, more long-term clinical trials are required to identify a safe upper limit of HPD.
MECHANISMS OF HPD-INDUCED WEIGHT LOSS
Dietary protein not only decreases BW by increasing satiety and energy expenditure, but also improves body composition by increasing FFM. Increased satiety from protein intake is associated with elevation of blood amino acid (AA) concentration, hunger-inhibiting hormones, diet-induced thermogenesis (DIT), and ketone body levels. While HPD induces a negative energy balance—a state of greater energy output than input—by increasing DIT and sleeping metabolic rate, low-protein diets promote a positive energy balance.22
Energy expenditure
HPD increases energy expenditure by increasing DIT and resting metabolism. Daily energy expenditure is divided into three elements: (1) sleeping metabolic rate or REE, (2) DIT or diet-induced energy expenditure, and (3) activity-induced energy expenditure. Protein intake generally affects DIT.2 DIT refers to the energy required for intestinal absorption of nutrients, early stages of nutrient metabolism, and nutrient storage. The total energy and protein percentage of a diet are the major determinants of DIT. In other words, DIT increases with increasing calories and protein content. DIT is known to be 0%–3% of total energy intake for fat, 5%–10% for carbohydrates, and 20%–30% for proteins.23
HPD also contributes to weight loss by preventing a decline in REE. Wycherley et al.4 performed a meta-analysis of 24 RCTs and found that, while subjects in both the HPD (1.25±0.17 g protein/ kg BW/day) and SPD (0.72±0.09 g protein/kg BW/day) groups had reduced REE, REE was higher in the HPD subjects (142 kcal/ day, 95% CI, 16–269 kcal/day). HPD is known to preserve REE by preventing lean mass loss.4
Once DIT is increased by HPD, satiety is also increased. The increased oxygen demand required to metabolize consumed protein also increases satiety.24 In a similar mechanism, people who live at high altitudes, where oxygen pressure is low, are lighter due to lower dietary intake.25
In general, dietary protein increases energy expenditure because it has a markedly higher DIT than fat and carbohydrates, and it preserves REE by preventing lean mass loss. Furthermore, increased DIT increases satiety, which also contributes to weight loss.
Satiety hormones
To the best of our knowledge, Holt et al.26 were the first to show that dietary protein increases satiety. In their study, they rated satiety for 38 foods, and protein-rich food received the highest ratings, followed by carbohydrate-rich and fat-rich foods. They further reported that a food’s protein content was proportional to its satiety index score, while fat content was inversely proportional to satiety index score.
One of the important mechanisms of HPD-induced satiety involves elevation of the anorexigenic hormones glucagon-like peptide- 1 (GLP-1), cholecystokinin (CCK), and peptide tyrosine-tyrosine (PYY).27,28 Release of GLP-1, CCK, and PYY is stimulated by proteins that also stimulate the vagus nerve, thus reducing food intake.29 The enteroendocrine cells that secrete these anorexigenic hormones are situated at the luminal side of the gut. These cells detect nutrients in the gastrointestinal tract and release GLP-1, PYY, and CCK, which increase satiety and decrease food intake.30,31 Many clinical trials that compared the effects of HPD and SPD on the indices of appetite regulation and satiety found that HPD increased plasma PYY, GLP-1, and CCK levels, with a proportional increase in fullness and decrease in hunger sense.32,33
Ghrelin is an orexigenic hormone that induces food intake by increasing hunger, and its plasma concentration is decreased by protein intake.34 Bowen et al.35,36 found that liquid preloads containing protein rather than glucose significantly suppressed ghrelin release. In conclusion, dietary protein elevates GLP-1, CCK, and PYY levels, which are secreted in the gut and diminish appetite while also decreasing ghrelin levels, which increases appetite. Such changes in the release of satiety hormones constitute an important mechanism of HPD-induced weight loss.
Aminostatic hypothesis
The aminostatic hypothesis, which proposes that elevated levels of plasma AAs increase satiety and, conversely, decrease the plasma AA that induces hunger, was first introduced in 1956.37 According to this hypothesis, surplus AAs not involved in the body’s protein synthesis stimulate the brain’s satiety signaling. Multiple studies reported that HPDs significantly increased plasma AA concentration38 and satiety24,39 compared with high-fat or high-carbohydrate diets. However, the aminostatic theory has recently lost support because fasting plasma AA levels are not associated with appetite, and increased plasma AA concentration following protein intake is not consistently associated with appetite.40 Future studies should more specifically examine the homeostatic mechanism that connects peripheral organs to the central nervous system, which might explain the aminostatic hypothesis.
Gluconeogensis
Increased gluconeogenesis due to dietary protein is another mechanism of HPD-induced weight loss. With HPD, AAs remaining after protein synthesis are involved in an alternative pathway known as gluconeogenesis.41 HPD increases the expression of phosphoenolpyruvate carboxykinase, an enzyme that initiates gluconeogenesis, and glucose-6-phosphatase, an enzyme involved in the final stages of gluconeogenesis. As such, the increased energy usage in gluconeogenesis increases energy expenditure, contributing to weight loss.42 Furthermore, the elevation of glucose as a result of gluconeogenesis and the subsequent elevation of hepatic glycogen synthesis because of increased glucose level are known to intensify the sense of satiety in the brain.42,43
Ketogenesis
Compared to a standard diet, high-protein and low-carbohydrate diets increase fasting blood β-hydroxybutyrate concentration. Elevated β-hydroxybutyrate concentration is known to directly increase satiety.44 Veldhorst et al.45 reported that, although carbohydrate-free HPD increased gluconeogenesis, the mechanism did not involve appetite; rather, they speculated that the elevated β-hydroxybutyrate level triggered satiety. On the other hand, some argue that HPD does not suppress appetite, but only prevents an appetite increase. In other words, one’s appetite remains the same with both energyrestricted HPD and the standard-energy medium-protein diet, but the high-protein content in HPD contributes to weight loss by preventing excessive food intake at the next meal even if the total energy intake was low.20,46
CONCLUSION
Clinical trials with various designs have found that HPD induces weight loss and lowers cardiovascular disease risk factors such as blood triglycerides and blood pressure while preserving FFM. Such weight-loss effects of protein were observed in both energyrestricted and standard-energy diets and in long-term clinical trials with follow-up durations of 6–12 months. Contrary to some concerns, there is no evidence that HPD is harmful to the bones or kidneys. However, longer clinical trials that span more than one year are required to examine the effects and safety of HPD in more depth.
The mechanism underlying HPD-induced weight loss involves an increase in satiety and energy expenditure. Increased satiety is believed to be a result of elevated levels of anorexigenic hormones, decreased levels of orexigenic hormones, increased DIT, elevated plasma AA levels, increased hepatic gluconeogenesis, and increased ketogenesis from the higher protein intake. Protein is known to increase energy expenditure by having a markedly higher DIT than carbohydrates and fat, and increasing protein intake preserves REE by preventing FFM decrease (Fig. 1).
Schematic of the proposed high-protein diet-induced weight loss mechanism. ↑, increase; ↓, decrease; FFM, fat-free mass; DIT, diet-induced thermogenesis; GLP-1, glucagon-like peptide-1; CCK, cholecystokinin; PYY, peptide tyrosine-tyrosine; AA, amino acid; REE, resting energy expenditure.
In conclusion, HPD is a safe method for losing weight while preserving FFM; it is thought to also prevent obesity and obesity-related diseases, such as metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular diseases.
ACKNOWLEDGMENTS
This work was supported by the 2020 education, research, and student guidance grant, funded by Jeju National University.
Footnotes
CONFLICTS OF INTEREST
The authors declare no conflict of interest.
AUTHOR CONTRIBUTIONS
Study concept and design: GK; acquisition of data: all authors; analysis and interpretation of data: all authors; drafting of the manuscript: JM; critical revision of the manuscript: GK; obtained funding: GK; administrative, technical, or material support: GK; and study supervision: GK.
REFERENCES
1. World Health Organization. Obesity and overweight 2020 [Internet] World Health Organization; Geneva: 2020. [cited 2020 Jul 5]. Available from: https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight. [Google Scholar]
2. Westerterp-Plantenga MS, Nieuwenhuizen A, Tomé D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr. 2009;29:21–41. doi:10.1146/annurev-nutr-080508-141056. [PubMed] [CrossRef] [Google Scholar]
3. Acheson KJ. Diets for body weight control and health: the potential of changing the macronutrient composition. Eur J Clin Nutr. 2013;67:462–6. doi:10.1038/ejcn.2012.194. [PubMed] [CrossRef] [Google Scholar]
4. Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD. Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;96:1281–98. doi:10.3945/ajcn.112.044321. [PubMed] [CrossRef] [Google Scholar]
5. Fulgoni VL., 3rd Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 20032004. Am J Clin Nutr. 2008;87:1554S–1557S. doi:10.1093/ajcn/87.5.1554S. [PubMed] [CrossRef] [Google Scholar]
6. Santesso N, Akl EA, Bianchi M, Mente A, Mustafa R, HeelsAnsdell D, et al. Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. Eur J Clin Nutr. 2012;66:780–8. doi:10.1038/ejcn.2012.37. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
7. Skov AR, Toubro S, Rønn B, Holm L, Astrup A. Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity. Int J Obes Relat Metab Disord. 1999;23:528–36. doi:10.1038/sj.ijo.0800867. [PubMed] [CrossRef] [Google Scholar]
8. Weigle DS, Breen PA, Matthys CC, Callahan HS, Meeuws KE, Burden VR, et al. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005;82:41–8. doi:10.1093/ajcn/82.1.41. [PubMed] [CrossRef] [Google Scholar]
9. Westerterp-Plantenga MS, Lejeune MP, Nijs I, van Ooijen M, Kovacs EM. High protein intake sustains weight maintenance after body weight loss in humans. Int J Obes Relat Metab Disord. 2004;28:57–64. doi:10.1038/sj.ijo.0802461. [PubMed] [CrossRef] [Google Scholar]
10. Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Additional protein intake limits weight regain after weight loss in humans. Br J Nutr. 2005;93:281–9. doi:10.1079/BJN20041305. [PubMed] [CrossRef] [Google Scholar]
11. Clifton PM, Keogh JB, Noakes M. Long-term effects of a highprotein weight-loss diet. Am J Clin Nutr. 2008;87:23–9. doi:10.1093/ajcn/87.1.23. [PubMed] [CrossRef] [Google Scholar]
12. Layman DK, Evans EM, Erickson D, Seyler J, Weber J, Bagshaw D, et al. A moderate-protein diet produces sustained weight loss and long-term changes in body composition and blood lipids in obese adults. J Nutr. 2009;139:514–21. doi:10.3945/jn.108.099440. [PubMed] [CrossRef] [Google Scholar]
13. Calvez J, Poupin N, Chesneau C, Lassale C, Tomé D. Protein intake, calcium balance and health consequences. Eur J Clin Nutr. 2012;66:281–95. doi:10.1038/ejcn.2011.196. [PubMed] [CrossRef] [Google Scholar]
14. Heaney RP, Layman DK. Amount and type of protein influences bone health. Am J Clin Nutr. 2008;87:1567S–1570S. doi:10.1093/ajcn/87.5.1567S. [PubMed] [CrossRef] [Google Scholar]
15. Bonjour JP, Schurch MA, Rizzoli R. Nutritional aspects of hip fractures. Bone. 1996;18(3 Suppl):139S–144S. doi:10.1016/8756-3282(95)00494-7. [PubMed] [CrossRef] [Google Scholar]
16. Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DP. Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res. 2000;15:2504–12. doi:10.1359/jbmr.2000.15.12.2504. [PubMed] [CrossRef] [Google Scholar]
17. Friedman AN, Ogden LG, Foster GD, Klein S, Stein R, Miller B, et al. Comparative effects of low-carbohydrate high-protein versus low-fat diets on the kidney. Clin J Am Soc Nephrol. 2012;7:1103–11. doi:10.2215/CJN.11741111. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
18. Knight EL, Stampfer MJ, Hankinson SE, Spiegelman D, Curhan GC. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med. 2003;138:460–7. doi:10.7326/0003-4819-138-6-200303180-00009. [PubMed] [CrossRef] [Google Scholar]
19. Millward DJ. Identifying recommended dietary allowances for protein and amino acids: a critique of the 2007 WHO/FAO/UNU report. Br J Nutr. 2012;108 Suppl 2:S3–21. doi:10.1017/S0007114512002450. [PubMed] [CrossRef] [Google Scholar]
20. Martens EA, Tan SY, Dunlop MV, Mattes RD, Westerterp-Plantenga MS. Protein leverage effects of beef protein on energy intake in humans. Am J Clin Nutr. 2014;99:1397–406. doi:10.3945/ajcn.113.078774. [PubMed] [CrossRef] [Google Scholar]
21. Bray GA, Smith SR, de Jonge L, Xie H, Rood J, Martin CK, et al. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial. JAMA. 2012;307:47–55. doi:10.1001/jama.2011.1918. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
22. Drummen M, Tischmann L, Gatta-Cherifi B, Adam T, WesterterpPlantenga M. Dietary protein and energy balance in relation to obesity and co-morbidities. Front Endocrinol (Lausanne) 2018;9:443. doi:10.3389/fendo.2018.00443. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
23. Tappy L. Thermic effect of food and sympathetic nervous system activity in humans. Reprod Nutr Dev. 1996;36:391–7. doi:10.1051/rnd:19960405. [PubMed] [CrossRef] [Google Scholar]
24. Westerterp-Plantenga MS, Rolland V, Wilson SA, Westerterp KR. Satiety related to 24 h diet-induced thermogenesis during high protein/carbohydrate vs high fat diets measured in a respiration chamber. Eur J Clin Nutr. 1999;53:495–502. doi:10.1038/sj.ejcn.1600782. [PubMed] [CrossRef] [Google Scholar]
25. Lippl FJ, Neubauer S, Schipfer S, Lichter N, Tufman A, Otto B, et al. Hypobaric hypoxia causes body weight reduction in obese subjects. Obesity (Silver Spring) 2010;18:675–81. doi:10.1038/oby.2009.509. [PubMed] [CrossRef] [Google Scholar]
26. Holt SH, Miller JC, Petocz P, Farmakalidis E. A satiety index of common foods. Eur J Clin Nutr. 1995;49:675–90. [PubMed] [Google Scholar]
27. Belza A, Ritz C, Sørensen MQ, Holst JJ, Rehfeld JF, Astrup A. Contribution of gastroenteropancreatic appetite hormones to protein-induced satiety. Am J Clin Nutr. 2013;97:980–9. doi:10.3945/ajcn.112.047563. [PubMed] [CrossRef] [Google Scholar]
28. Diepvens K, Häberer D, Westerterp-Plantenga M. Different proteins and biopeptides differently affect satiety and anorexigenic/orexigenic hormones in healthy humans. Int J Obes (Lond) 2008;32:510–8. doi:10.1038/sj.ijo.0803758. [PubMed] [CrossRef] [Google Scholar]
29. Davidenko O, Darcel N, Fromentin G, Tomé D. Control of protein and energy intake: brain mechanisms. Eur J Clin Nutr. 2013;67:455–61. doi:10.1038/ejcn.2013.73. [PubMed] [CrossRef] [Google Scholar]
30. Koh G. Gut hormone response to diet. Korean J Obes. 2014;23:6–15. doi:10.7570/kjo.2014.23.1.6. [CrossRef] [Google Scholar]
31. Tan T, Bloom S. Gut hormones as therapeutic agents in treatment of diabetes and obesity. Curr Opin Pharmacol. 2013;13:996–1001. doi:10.1016/j.coph.2013.09.005. [PubMed] [CrossRef] [Google Scholar]
32. Halton TL, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr. 2004;23:373–85. doi:10.1080/07315724.2004.10719381. [PubMed] [CrossRef] [Google Scholar]
33. van der Klaauw AA, Keogh JM, Henning E, Trowse VM, Dhillo WS, Ghatei MA, et al. High protein intake stimulates postprandial GLP1 and PYY release. Obesity (Silver Spring) 2013;21:1602–7. doi:10.1002/oby.20154. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
34. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992. doi:10.1210/jcem.86.12.8111. [PubMed] [CrossRef] [Google Scholar]
35. Bowen J, Noakes M, Clifton PM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. J Clin Endocrinol Metab. 2006;91:2913–9. doi:10.1210/jc.2006-0609. [PubMed] [CrossRef] [Google Scholar]
36. Bowen J, Noakes M, Trenerry C, Clifton PM. Energy intake, ghrelin, and cholecystokinin after different carbohydrate and protein preloads in overweight men. J Clin Endocrinol Metab. 2006;91:1477–83. doi:10.1210/jc.2005-1856. [PubMed] [CrossRef] [Google Scholar]
37. Mellinkoff SM, Frankland M, Boyle D, Greipel M. Relationship between serum amino acid concentration and fluctuations in appetite. J Appl Physiol. 1956;8:535–8. doi:10.1152/jappl.1956.8.5.535. [PubMed] [CrossRef] [Google Scholar]
38. Veldhorst MA, Nieuwenhuizen AG, Hochstenbach-Waelen A, Westerterp KR, Engelen MP, Brummer RJ, et al. Comparison of the effects of a high- and normal-casein breakfast on satiety, 'satiety' hormones, plasma amino acids and subsequent energy intake. Br J Nutr. 2009;101:295–303. doi:10.1017/S0007114508003061. [PubMed] [CrossRef] [Google Scholar]
39. Poppitt SD, McCormack D, Buffenstein R. Short-term effects of macronutrient preloads on appetite and energy intake in lean women. Physiol Behav. 1998;64:279–85. doi:10.1016/S0031-9384(98)00061-4. [PubMed] [CrossRef] [Google Scholar]
40. Niijima A, Torii K, Uneyama H. Role played by vagal chemical sensors in the hepato-portal region and duodeno-intestinal canal:an electrophysiological study. Chem Senses. 2005;30(Suppl 1):i178–9. doi:10.1093/chemse/bjh172. [PubMed] [CrossRef] [Google Scholar]
41. Jungas RL, Halperin ML, Brosnan JT. Quantitative analysis of amino acid oxidation and related gluconeogenesis in humans. Physiol Rev. 1992;72:419–48. doi:10.1152/physrev.1992.72.2.419. [PubMed] [CrossRef] [Google Scholar]
42. Azzout-Marniche D, Gaudichon C, Blouet C, Bos C, Mathé V, Huneau JF, et al. Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats? Am J Physiol Regul Integr Comp Physiol. 2007;292:R1400–7. doi:10.1152/ajpregu.00566.2006. [PubMed] [CrossRef] [Google Scholar]
43. McCarty MF. Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control. Med Hypotheses. 1994;42:215–25. doi:10.1016/0306-9877(94)90120-1. [PubMed] [CrossRef] [Google Scholar]
44. Veldhorst MA, Westerterp KR, van Vught AJ, Westerterp-Plantenga MS. Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance. Br J Nutr. 2010;104:1395–405. doi:10.1017/S0007114510002060. [PubMed] [CrossRef] [Google Scholar]
45. Veldhorst MA, Westerterp KR, Westerterp-Plantenga MS. Gluconeogenesis and protein-induced satiety. Br J Nutr. 2012;107:595–600. doi:10.1017/S0007114511003254. [PubMed] [CrossRef] [Google Scholar]
46. Martens EA, Lemmens SG, Westerterp-Plantenga MS. Protein leverage affects energy intake of high-protein diets in humans. Am J Clin Nutr. 2013;97:86–93. doi:10.3945/ajcn.112.046540. [PubMed] [CrossRef] [Google Scholar]
Articles from Journal of Obesity & Metabolic Syndrome are provided here courtesy of Korean Society for the Study of Obesity
