Research Review By Novella Martinello©

Date Posted:

May 2010

Study Title:

Dietary Protein, Weight Loss, and Weight Maintenance


Westerterp-Plantega MS, Nieuwenhuizen A, Tomé D, Soenen S, & Westerterp KR

Author's Affiliations:

Department of Human Biology, Nutrim, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands; TIFN, Wageningen, The Netherlands; AgroParisTech, Department of Life Sciences and Health, Nutrition Physiology and Ingestive Behavior, Paris, France.

Publication Information:

Annual Review of Nutrition 2009; 29: 21-41.

Background Information:

Obesity is a serious concern as we all know. We also know that many patients who successfully lose weight have trouble maintaining their new, lower weight. The required conditions for weight maintenance after weight loss are sustained satiety, sustained energy expenditure, and sparing fat free mass while subjects are in negative energy balance. High-protein diets act on these metabolic targets. For example, doubling the relative protein content of a diet from the normal level of 10-15% to 20-30% reduces food intake under ad libitum conditions, which results in immediate weight loss.

Therefore, an increase in the relative protein content of the diet, irrespective of protein type, reduces the risk of a positive energy balance and the development of overweight conditions. Increasing protein intake also increases the chance of maintenance of body weight after weight loss induced by an energy-restricted diet. One of the mechanisms contributing to successful weight maintenance is a sparing effect of fat-free mass.

This review of the literature examines the effects of relatively high-protein diets during energy balance, weight loss, and weight maintenance as it relates to satiety, energy expenditure, protein and amino acid metabolism, and gluconeogenesis. As well, effects on body weight and body composition and potential risks of high-protein diets are discussed.


Protein-Induced Satiety by Acute High-Protein Meals and Medium-Term High-Protein Diets:

Protein is the most satiating macronutrient and the first to metabolize (1). Protein can be consumed through a mix of meat, fish, dairy products, and plants. In subjects with stable weight, consuming mixed proteins in a single meal, in a range of amounts, has shown a dose-dependent satiating effect (1, 6). Persistent protein-induced satiety has been shown when a mixed high-protein diet is given for 24 hours up to several days.

The average “normal” protein intake is a range of 10% to 15% of energy per meal. Meals with an average of 20% to 30% of energy from protein are representative of high-protein diets when consumed in energy balance. In healthy individuals, it has been demonstrated that after a high-protein lunch, satiety and energy expenditure is significantly higher than after a normal-protein lunch.

Outcomes differ when it comes to the satiating power of a high-protein meal due to the type or quantity of protein intake, or both. Proteins with high concentrations of casein or soy are more satiating, as well as complete proteins (proteins with all essential amino acids), as compared to incomplete proteins, and pea protein hydrolysate (PPH) or whey protein (WP) as compared to milk protein.

When different proteins or amino acids are consumed at very high levels, satiety is very high and differences in satiating effects are no longer observed (4, 5). This has been demonstrated using casein, whey protein, and whey protein with and without glyco-macropeptide (GMP).

Studies comparing protein-containing drinks, such as chocolate milk and whey protein drinks, against control drinks, such as soda, have demonstrated that the effects of protein appear when sufficient protein and energy are present in the drinks.

Taken together, these results indicate that protein amount and concentration are significant, in that relatively more protein is more satiating and promotes less energy intake, supported by relatively elevated amino acid concentrations, anorexigenic hormones, or energy expenditure feeding back on the central nervous system.

The individual amino acids involved in protein consumption may have significant effects on satiety. Research shows that tryptophan (and hence, serotonin) is unlikely to play a role in this effect. The amino acid tyrosine can be converted into the neurotransmitters dopamine and norepinephrine, both of which have shown to be involved in food-intake regulation but there is no direct evidence of a role for tyrosine in protein-induced satiety.

Histamine (the neurotransmitter histidine) is suggested to decrease food intake through activation of hypothalamic H1 receptors since the anorectic effect of histamine can be blocked by the H1-receptor antagonist ?-fluoromethylhistidine (FMH).

Finally, when high-protein menus are offered to healthy subjects at each meal for one to several days, the metabolic reactions of a high-protein diet are established and higher satiety is shown throughout the day in comparison to a normal-protein diet, which is primarily related to elevated energy expenditure (1, 6).

Energy Expenditure:

Diet-induced energy expenditure (DEE) is related to the stimulation of energy-requiring processes during the postprandial period. Studies have shown a high-protein diet to have greater effects on DEE than a high fat diet, in both healthy and obese subjects, in which it was concluded that a high DEE diet can contribute to the prevention of weight gain.

Sleeping metabolic rate (SMR) has been shown to increase as a result of protein intake in studies where one carbohydrate source has been replaced with a protein like meat or soy, and when using a high-protein diet in comparison of a normal-protein diet, over a period of three days. However, animal proteins may have more of an effect in this respect than soy protein due to protein synthesis. This effect can be explained by the fact that the body has no storage capacity to cope with high intakes of protein and therefore has to process it metabolically.

Therefore, the increase in SMR may be the increase in protein turnover. Protein intake is the most important dietary determinant of whole-body protein turnover. Whole-body protein synthesis is affected not only by protein intake but by exercise as well, especially in the period after exercise. In practice, exercise induces an increase in food intake and thus protein intake remains sufficient when it comprises a minimum of 10% of energy intake.

Protein and Amino Acid Metabolism, Gluconeogenesis, and Glycogen Synthesis:

Protein requirement is about one-fifth to one-tenth of the daily protein turnover of 300 gram/day in a healthy adult, depending on the type of protein (with the rate of protein turnover having an inverse relationship with age). Low protein turnover can weaken one’s response to stress due to illness. Protein turnover and metabolism are strongly influenced by protein quality because essential amino acids are needed to prevent negative protein turnover and they are essential to maintain an adequate rate of protein synthesis.

Thus, in comparison with slowly digested protein, ingestion of rapidly digested protein results in a stronger increase in postprandial protein synthesis and amino acid oxidation, with animal protein having an increased effect over soy protein (7). The metabolic efficacy of protein oxidation largely depends on the amino acid composition of the protein, since large differences exist with respect to the efficacy by which amino acids are oxidized. This relative metabolic inefficiency may contribute to the higher diet-induced energy expenditure of a high-protein meal, which, in turn, has shown to be related to subjective feelings of satiety.

The production of glucose through gluconeogenesis may play a role in postprandial amino acid metabolism. Postabsorptive protein and amino acid metabolism is strongly influenced by protein quantity and quality. Protein and amino acid metabolism may be related to body weight regulation and food intake through several physiological pathways, such as protein synthesis, protein oxidation, gluconeogenesis, and neurotransmitter release.

Body Weight and Body Composition:

The World Health Organization recommends that dietary protein should account for approximately 10% to 15% of energy when individuals are in energy balance and weight stable (8). Protein intake may be expressed in grams or as percentage of energy intake. When recommending high-protein diets, the difference between these two measures should be considered.

The absolute amount of protein is of greater importance than the percentage of protein. Results indicate that a higher protein intake changes body composition in a way that spares fat-free mass (FFM). Therefore, a high-protein diet may promote weight maintenance by its metabolic inefficiency because of the cost involved in sparing FFM.

Bodyweight loss on a sustained, relatively high-protein diet appears to be greater under conditions of ad libitum energy intake than under conditions of isoenergetic diets. This is because satiety is a key factor in applying high-protein diets. Under ad libitum conditions, subjects eat less from the high-protein diet than under isoenergetically fed conditions.

These diets contain a sufficient absolute amount of protein but lead to decreased energy intake, suggesting that in addition to metabolic effects of protein on body-weight loss, energy intake plays an important role. Most of the protein studies related to body-weight management show an improved body composition and metabolic profile with a relatively high-protein diet. The relatively high-protein negative-energy-balance diets all consist of 25% to 30% of energy from protein and imply a sustained normal protein intake in grams while energy intake is decreased.

In summary, absolute protein intake seems to be more important than the proportion (%) of protein in the diet. When energy intake is reduced, protein intake should be sustained, so that when expressed in grams/day the protein content is normal. Therefore, high-protein negative-energy balance diets should keep the grams of protein ingested at the same level despite lower overall energy intakes. Protein influences body weight regulation via its effects on satiety, thermogenesis, energy efficiency, and body composition.

These aspects are partly related to each other. When there has been a small amount of weight gain, a sustained-protein diet shows reduced energy efficiency related to the body composition of the body weight regained in favour of FFM.

Potential Risks of High-Protein Diets:
  • although there is little evidence to support this, diets very high in protein may promote renal damage
  • long-lasting high-protein diets may have blood pressure raising effects, especially in at-risk populations (elderly, those with obesity-related conditions)
  • potential interference with balance of calcium intake; however, the literature behind this is mixed

Clinical Application & Conclusions:

To review, weight loss and subsequent weight maintenance require sustained satiety, sustained energy expenditure, and sparing fat free mass while subjects are in a negative energy balance through their diet and activity. Protein intake can play a role in all of these requirements. Protein-induced sustained satiety in negative energy balance occurs mainly by oxidation of excessively ingested amino acids. Protein-induced sustained-energy expenditure occurs depending on the type of protein, mainly by net protein synthesis, or by gluconeogenesis. The possible long-term relationship between net protein synthesis and sparing fat free mass requires further research. If recommending a “high-protein, negative-energy balance diets” to clients, it should be based on keeping the amount of protein ingested at the same level, despite lower energy intakes.

Study Methods:

This study was a narrative literature review.

Additional References:

  1. Veldhorst MAB, Smeets A, Soenen S et al. Protein-induced satiety: effects and mechanisms of different proteins. Physiol. Behav 2008; 94:300–7.
  2. Diepvens K, Haberer D,Westerterp-Plantenga MS. Different proteins and biopeptides differently affect satiety and anorexigenic/orexigenic hormones in healthy humans. Int. J. Obes 2008; 32:10–18.
  3. Luhovyy BL, Akhavan T, Anderson GH. Whey proteins in the regulation of food intake and satiety. J Am Coll Nutr 2007; 26:704–12S.
  4. 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: 2913–19.
  5. Burton Freeman BM. Glycomacropeptide (GMP) is not critical to whey-induced satiety, but may have a unique role in energy intake regulation through cholecystokinin (CCK). Physiol Behav 2008; 93:379–87.
  6. Westerterp-Plantenga MS, Natalie Luscombe-Marsh N, Lejeune MPGM et al. Dietary protein, metabolism, and body-weight regulation: dose-response effects. Int J Obes 2006; 30:S16–23.
  7. Dangin M, Boirie Y, Guillet C, Beaufrere B. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr 2002; 132(10):3228–33S.
  8. World Health Organ. Tech. Rep. Ser. 2000. Obesity: preventing and managing the global epidemic. Report of WHO consultation. 894:i–xii, 1–253.