High-protein and low-carbohydrate diets promote hepatic gluconeogenesis to maintain plasma glucose levels. Two key enzymes of gluconeogenesis, phosphoenolpyruvate carboxykinase PEPCK and glucosephosphatase G6P , are upregulated in rats fed a high-protein diet, suggesting that gluconeogenesis is stimulated by a high-protein diet [ 59 ].
A modulation of hepatic gluconeogenesis and increased glucose homeostasis could be responsible for the satiating effect in this animal model [ 60 ]. A recent study in humans found an increased gluconeogenesis following high-protein intake but this increase was unrelated to appetite suppression [ 62 ].
Instead, the authors observed an increased production of ketone bodies especially beta-hydroxybutyrate in response to the high-protein diet.
The increased concentration of beta-hydroxybutyrate may act as an appetite suppressing substrate [ 62 ]. The latter may be most important in contributing to increased satiety, especially if the diet is high in protein and low in CHOs. It is also well established that a decreasing level of blood glucose is an appetite stimulating state whereas amino-acid induced gluconeogenesis acts as appetite suppressant preventing hypoglycemia.
Central mechanisms include augmented activation of Pro-opiomelanocortin POMC neurons and alpha-melanocyte-stimulating hormone and decreased activation of non-POMC neurons upon acute ingestion of a high-protein diet. Intraduodenal protein can activate vagal afferent fibers and after high-protein ingestion c-Fos expression in neurons of the nucleus of the solitary tract was increased [ 58 ].
High-protein diets can help preserve lean body mass during weight loss. Mettler et al. Performance parameters were not affected in the subjects, most likely due to the short study period. In this study, the authors balanced energy by changing fat intake and not carbohydrate intake as is usually the case.
Glucose intake leads to post-prandial insulin secretion. The inhibitory effect of insulin on lipolysis in adipose tissue leads to the postprandial suppression of fat oxidation [ 64 ]. This inverse relationship between dietary carbohydrate intake and fat oxidation may explain why Mettler did not observe differences in fat loss between groups whereas others observed reductions in fat mass in non-athletic, overweight subjects on a high-protein low-carbohydrate diet [ 65 , 66 ].
Table 2 shows examples of foods high in protein relative to their carbohydrate and fat content. With regard to the macronutrient distribution, it appears that there is a difference whether protein is increased at the expense of CHO or fat. Increasing protein at the expense of CHOs leads to increased contribution of amino acids to energy expenditure with a concomitant decrease in lipogenesis due to decreased supply of dietary glucose [ 68 ] and likely has a negative impact on exercise performance and training intensity [ 69 ].
Carbohydrate supply is critical for strength and endurance performance. Athletes should therefore be aware about limited energy intake and maintenance of training levels. For obese subjects, lowering carbohydrate in favor of protein might be advantageous as dietary CHOs might impair fat oxidation [ 70 ] whereas low-CHO, high-protein diets reduce adipose tissue development [ 71 ].
Higher daily protein intake at the expense of fat intake could substantially reduce total energy intake, which could possibly translate to a healthier weight status [ 72 ]. Long-term effects of high-protein diets depend on the population studied as well as the exact composition of the diet but have generally been shown to include weight reduction and weight loss maintenance as well as beneficial effects on metabolic risk factors such total cholesterol and triacylglycerol.
Claessens et al. The authors conclude that after 12 weeks of diet intervention, the low-fat, high-protein diet was more effective for weight control. Clifton et al. The authors conclude that subjects in the high-protein group had beneficial effects on total cholesterol and triacylglycerol and achieved greater weight loss and better lipid results.
In another study, Clifton et al. The authors found no significant difference between groups regarding weight loss. Protein intake in grams derived from the dietary records, however, was directly related to weight loss [ 75 ]. Westerterp-Plantenga et al. The mechanisms by which increased long-term dietary protein intake regulate body weight are not well understood but are most likely multifactorial.
Depending on the diet, lower triacylglycerol levels and hence fat mass loss with a higher-protein diet as well as increased satiety possibly mediated by increased leptin sensitivity have been discussed [ 75 , 78 , 79 ]. Fluid loss related to reduced carbohydrate intake and overall caloric restriction have also been discussed to mediate weight loss [ 5 ].
Metabolomics studies revealed that high intake of branched-chain amino acids BCAAs, Valine, Leucine, Isoleucine and aromatic amino acids Phenylalanine, Tyrosine may be associated with the development of metabolic diseases [ 80 ]. Importantly, this only occurs in combination with a high-fat diet. High catabolic flux of these intermediates interferes with appropriate oxidation of fatty acids, possibly by allosteric inhibition of citrate synthase [ 81 ] which slows down the TCA cycle, causing buildup of incompletely oxidized substrates such as acylcarnitines.
This accumulation leads to mitochondrial stress, impaired insulin action, and finally to perturbation of glucose homeostasis [ 80 ]. This connection might be highly relevant as many overweight people worldwide are effectively on a high-fat diet but might as well do weight-training and supplement with BCAAs. Therefore, in people with a high caloric intake from fat BCAA supplementation might exacerbate the risk of metabolic disease. Diets high in protein pose a potential acid load to the kidneys, mainly as sulfates and phosphates [ 82 ].
It was hypothesized that calcium and hence bone mass was lost in order to buffer this acid load [ 83 ]. Although the bone-loss hypothesis has been refuted and there is agreement that high-protein diets are actually favorable to intestinal calcium uptake, bone health and bone mineral density [ 84 ], the protein-induced acid-load to the kidneys remains, e.
This phenomenon is especially prominent in diets such as the Atkins diet which can lead to additional acid buildup from ketone bodies in response to reduced carbohydrates and concomitantly increased fat and protein intake. Frank et al. They reported significant changes in the glomerular filtration rate, the filtration fraction, albuminuria, serum uric acid, and urinary pH values in the high-protein diet group. The authors conclude that renal hemodynamics and renal excretion is altered in response to a short-term, high-protein diet.
Although depended on the source of protein, interventional studies in humans have shown that high-protein diets have the potential to increase the risk of calcium stone-formation in the urinary tract [ 82 , 86 ]. In order to maintain an acid—base balance in the body, people on a high-protein diet should consider ingestion of alkali buffers such as fruits and vegetables high in potassium alkaline-forming foods.
Glutamine or sodium bicarbonate supplements can also help to restore acid—base balance in the body. In general, people experimenting with high-protein diets are advised to monitor their renal function.
People on high-protein diets are advised to choose their source of protein very carefully i. Many protein-rich foods of animal origin e. This may put consumers of high-protein diets at higher risk for heart disease, hyperlipidemia and hypercholesterolemia [ 87 ]. Healthier proteins from vegetables soy protein, beans, tofu, seitan or nuts or fish could be a valuable alternative. Finally, all excess protein will eventually be converted to glucose via gluconeogenesis or ketone bodies [ 88 , 89 ].
This may also explain the increased gluconeogenesis in response to a high-protein diet, as described above. In a state of low energy demand, these metabolites will be stored as glycogen and fat, which is undesirable if weight loss is the goal.
Along these lines, weight loss can only be achieved by establishing a negative calorie balance, though this may be more tenable on a high-protein diet. Whereas diets high in protein have considerable beneficial effects on satiety and weight control, which is of great interest to e.
Awareness of these caveats enables individuals choosing to consume a high-protein diet to get the most benefit from it. J Am Coll Nutr. Article Google Scholar. J Am Diet Assoc. Atkins RC: Dr. Atkins' new diet revolution.
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Br J Nutr. Am J Clin Nutr. Int J Obes Lond. Schaafsma G: Advantages and limitations of the protein digestibility-corrected amino acid score PDCAAS as a method for evaluating protein quality in human diets. Tome D: Criteria and markers for protein quality assessment - a review. Acheson KJ: Influence of autonomic nervous system on nutrient-induced thermogenesis in humans. Westerterp KR: Diet induced thermogenesis. Nutr Metab Lond.
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Show references Johnston BC, et al. Comparison of weight loss among named diet programs in overweight and obese adults — A meta-analysis. Journal of the American Medical Association.
Pesta DH, et al. A high-protein diet for reducing body fat: Mechanisms and possible caveats. Atallah R, et al. Long-term effects of 4 popular diets on weight loss and cardiovascular risk factors — A systematic review of randomized controlled trials.
So what is protein? Protein is one of the three macronutrients required in ample amounts in every diet. Our hair and nails are made up of mostly protein. Proteins are also transport vehicles for hormones. This makes it critical that you consume protein daily. Eating a high protein diet has been proven to boost metabolism. It takes more energy for your body to break down protein-this is known as the thermic effect of food.
More energy required for digestion equals more calories burned. Protein is also the building block of muscle. When you have more muscle, you burn more calories. Now, that's a good cycle to be caught in when you're trying to lose weight!
Another benefit of protein consumption, especially animal proteins, is that they are rich in the type of iron that our body most readily absorbs. Iron is an essential micronutrient. When it is not present in adequate amounts or absent altogether, this can result in dizziness, tiredness, and even anemia.
Animal proteins are also high in vitamin B12, another essential micronutrient in the body. Vitamin B12 deficiency can lead to weakness, tiredness, nerve problems like tingling, or even mental issues like depression and memory loss.
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