Effects of high protein diets on human health - a systematic review of the literature

In recent years, high-protein diets can be included among the most discussed ways of eating, not only among nutritionists, but also among the lay population. Higher protein intake is associated with more effective weight loss, better preservation of muscle mass and an increased feeling of satiety, which makes it an attractive choice not only for weight reduction, but also in the field of sports. On the other hand, there are concerns about possible side effects, especially in connection with kidney function, cardiovascular health, or changes in the intestinal microbiota. The topic of the impact of a high-protein diet on health is therefore extremely relevant. In an era when conflicting information is often presented in the media, it is important to rely on scientifically based knowledge. The aim of this publication is to systematically review the available literature and provide an overview of how increased protein intake affects various aspects of human health - from body weight and metabolism to kidney function, cardiovascular system and gut microbiota.

Methodology

The search and processing of scientific studies was carried out in order to collect and evaluate current scientific knowledge about the impact of a high-protein diet on various aspects of health. The search was carried out in the renowned databases PubMed, Scopus, Web of Science and additionally through Google Scholar.

Studies published in the period 2018–2025 were analyzed, with preference given to the most recent systematic reviews, meta-analyses and randomized controlled trials published in peer-reviewed scientific journals.

Selection criteria were scientific articles investigating the effects of a high-protein diet on adults (healthy or overweight/obese) and studies evaluating at least one of the following aspects: body weight, metabolic indicators, kidney function, cardiovascular health or gut microbiota.

Results

High protein diets represent a significant aspect of research in nutrition and metabolic health. Scientific works published in recent years focus on how increased protein intake affects body weight, body composition, metabolism, kidney function, cardiovascular health or intestinal microbiota. Based on a systematic analysis of the available literature, several relevant studies were identified that provide an overview of the effects of this form of diet on various aspects of human health. The following sections summarize the main findings of the individual authors and point to areas of scientific agreement as well as issues that remain open to debate.

Diets with a high protein content have been shown to be an effective tool in reducing body weight in recent years. Several meta-analyses confirm that an increased proportion of protein in the diet leads to slightly greater weight loss and better maintenance of muscle mass compared to normal protein intake. Although this effect is small to moderate, it is consistent across randomized control trials (Hansen et al., 2021; Kokura et al., 2024). Other meta-analyses of randomized controlled trials confirm that diets with a higher protein content have modest but statistically significant beneficial effects on body composition and some cardiometabolic indicators compared to low-protein diets. A meta-analysis of 54 RCTs (more than 4,500 participants in total) found that increased protein intake was associated with greater loss of body weight (−0.79 kg; 95% CI −1.23 to −0.36 kg) and fat mass (−0.87 kg; 95% CI −1.36 to −0.38 kg) compared with control groups. In addition, the authors noted a slight decrease in systolic blood pressure (−1.76 mm Hg) and an improvement in the lipid profile, namely a decrease in total cholesterol (−0.13 mmol/l) and triacylglycerols (−0.12 mmol/l). These effects were manifested without significant differences in energy intake, which indicates that a higher proportion of protein can also favorably affect metabolic health independently of caloric restriction (Vogtschmidt et al., 2021).

In older adults without renal impairment, the combination of strength training with increased protein intake has been shown to have beneficial effects on body composition without negative health effects. In an eight-week randomized study of former professional soldiers (mean age 61 years), consumption of approximately 1.6 g protein/kg/day resulted in greater gains in muscle mass and strength compared to a control group (0.8 g/kg/day). At the same time, no adverse changes in kidney or liver function parameters were detected. Another study by the same team of authors produced similar results, in which resistance-trained men consumed 1.6 g or 3.2 g of protein/kg/day for 16 weeks. Even with such a high protein intake, no negative effects on kidney, liver function or lipid profile were demonstrated, while improvements in strength and body composition were similar in both groups. The authors conclude that a high protein intake (up to 3.2 g/kg/day) is safe and well tolerated in healthy, physically active men when combined with regular training (Bagheri et al., 2023a,b).

In terms of metabolism, diets with a higher protein content have a beneficial effect on insulin sensitivity and glycemic control in several studies. A 2024 systematic review and meta-analysis that included randomized controlled trials in women with polycystic ovary syndrome (PCOS) demonstrated that a high-protein diet significantly reduced fasting insulin levels (−3.12 mIU/L; 95% CI −5.21 to −1.02) and improved the HOMA-IR insulin resistance index (−0.59; 95% CI −0.94). to −0.24) compared to control diets. The effect on body weight and hormonal parameters was less pronounced, but the trend was towards their improvement. The authors conclude that an increased proportion of protein in the diet can contribute to a better control of insulin resistance in women at metabolic risk if the diet is balanced and long-term (Wang et al., 2024). Several clinical studies show that diets with a higher protein content can favorably affect metabolic parameters, especially insulin sensitivity and glycemic control. A randomized controlled trial by Tettamanzi et al. (2021) compared the effects of a high-protein diet with a Mediterranean diet in women with obesity and insulin resistance over 12 weeks. Participants in the high-protein diet group received approximately 30% of their energy from protein, while in the Mediterranean group it was around 18%. The results showed that the high-protein diet significantly improved insulin sensitivity, as shown by a decrease in HOMA-IR index by -1.78 (95% CI -3.03 to -0.52; p < 0.01) and a decrease in fasting insulin level by -6.98 µIU/mL (95% CI -12.30 to -1.65). In addition, there was also a reduction in glycemic variability (–3.13 mg/dL; p = 0.0004), indicating better stability of glucose levels throughout the day. The authors conclude that a high-protein diet may be more effective than a traditional Mediterranean diet in improving insulin sensitivity and glycemic control in obese subjects, if it is properly balanced and individually adjusted.

From the point of view of renal function, scientific reviews show that in healthy adults with intact kidney function, a high-protein diet can lead to a temporary increase in glomerular filtration rate (GFR), which is an adaptive response of the body to a higher burden of nitrogenous substances. The results of the meta-analysis showed that although GFR may be slightly higher after increased protein intake (SMD 0.19; 95% CI 0.07 to 0.31), the change in GFR between the increased and standard protein intake groups was not statistically significant (SMD 0.11; 95% CI –0.05 to 0.27) suggesting that high protein intake did not have a marginally negative effect on renal function in the short term. studies in healthy subjects (Devries et al., 2018). On the other hand, a reduced or moderate protein intake is recommended in individuals with pre-existing chronic kidney disease (CKD), as a higher nitrogen load and possible glomerular hyperfiltration may contribute to the progression of damage with reduced kidney function. As a result, protein restriction to approximately 0.8 g/kg/day or less is often recommended in CKD, depending on the stage of the disease (Cheng et al., 2024). It follows from practice that in a healthy adult with normal kidney function who does not have risk diseases (such as diabetes, hypertension, kidney damage), increased protein intake within reasonable values ​​(e.g. 1.2–1.6 g/kg or more) appears to be safe according to current data. Nevertheless, it is important to monitor individual health status, kidney function (e.g. eGFR, creatinine), protein source (vegetable vs. animal), and overall diet with adequate intake of fiber and hydration (Devries et al., 2018).

The results of a systematic review and meta-analysis of prospective cohort studies show that a higher protein intake has no clear effect on the occurrence of cardiovascular diseases or on cardiovascular mortality. In an analysis involving more than 800,000 participants, no statistically significant differences in the risk of total cardiovascular events were observed between those with high and low protein intakes (OR 0.94; 95% CI 0.60–1.46). The authors emphasize that proteins have no effect on cardiovascular diseases, but the source of proteins plays a decisive role, while vegetable proteins tend to be associated with a more favorable lipid profile and a lower risk of cardiovascular disease, animal sources (especially from red and processed meat) can have the opposite effect (Mantzouranis et al., 2023). A major systematic review and meta-analysis by Naghshi et al. (2020) evaluated the relationship between the intake of different types of proteins and the risk of mortality from cardiovascular diseases. Thirty-two prospective cohort studies with more than 715,000 participants were included in the analysis, with more than 16,000 deaths from cardiovascular causes during follow-up. The results showed that the total protein intake was not significantly associated with the risk of death from cardiovascular diseases, but the protein source played a decisive role. Those with a higher intake of plant protein had a 12% lower risk of death from cardiovascular disease (HR 0.88; 95% CI 0.80–0.96) compared with those with a lower intake of plant protein. Each 3% increase in the proportion of energy from plant protein was associated with approximately a 5% reduction in the risk of all-cause mortality, including cardiovascular disease. Conversely, a higher intake of animal protein did not show significant protection and an increased risk was observed for some sources, especially from processed meat (Naghshi et al., 2020). The authors therefore concluded that a high-protein diet as such is not risky, as long as it is composed mainly of vegetable sources of protein and if it is part of an overall balanced diet. Such a combination can contribute to an improved lipid profile, lower inflammation, and overall better cardiovascular health. The relationship between total protein intake and cardiovascular health is still a matter of scientific debate. A long-term prospective study by Song et al. (2016), conducted on a set of more than 131,000 participants from the Nurses' Health Study and Health Professionals Follow-up Study cohorts, followed the effects of animal and plant proteins on mortality over more than 30 years. The results showed that total protein intake had no clear effect on the risk of death from cardiovascular causes. However, when stratified by protein source, differences emerged – higher plant protein intake was associated with a reduced risk of cardiovascular mortality (HR 0.88; 95% CI 0.80–0.97), while animal protein, particularly from red and processed meat, showed a slightly increased risk (HR 1.08; 95% CI 1.01–1.16). The authors concluded that a high-protein diet as a whole may not pose a risk for cardiovascular health, but its effects strongly depend on the origin of the proteins. A diet with a higher representation of plant proteins - for example from legumes, nuts or whole grain products - was associated with a better cardiometabolic profile, lower inflammation and more favorable lipid parameters. The results therefore support the recommendation to prioritize plant sources of protein within an overall balanced diet.

A randomized clinical trial investigated the effect of a high-protein diet on the gut microbiome in overweight and obese adults (n = 80). For eight weeks, the participants followed a reduction diet that contained either more protein (about 30% of energy) or the usual amount (about 15% of energy). During the study, stool samples were collected and microbiome composition was analyzed. The results showed that a high-protein diet increased the diversity of the gut microbiome and changed the representation of some bacteria. Higher protein intake increased the amount of "good" bacteria such as Akkermansia and Bifidobacterium, which support gut health, while Prevotella bacteria, often associated with a worse metabolic response, decreased. The authors conclude that a high-protein reduction diet can affect the gut microbiota in a way that is related to better metabolic adaptation during weight loss (Dong et al., 2020). A study by Farsijani et al. (2023) published in the journal Nutrients looked at the association between protein intake and gut microbiome composition in community-dwelling older men participating in the long-term Osteoporotic Fractures in Men Study (MrOS). 1,227 participants aged 65-85 were included in the analysis. Protein intake was assessed using 24-hour dietary records, with participants divided into quartiles according to the amount of protein consumed. The results showed that a higher protein intake was associated with a greater diversity of the gut microbiome and with an increased representation of species considered beneficial for metabolic health, such as Faecalibacterium prausnitzii and Roseburia spp., i.e. j. bacteria producing short-chain fatty acids (SCFA) with an anti-inflammatory effect. On the contrary, there were no negative changes that would indicate a disturbance in the balance of the intestinal ecosystem. The authors thus concluded that a reasonably higher protein intake (1.2–1.6 g/kg body weight per day) can be safe in older men and even contribute to maintaining a healthy gut microbiome, especially if the diet is rich in fiber and plant-based protein sources.

Discussion

The results of the analyzed studies show that diets with a higher protein content can have modest beneficial effects on body composition, weight control and some metabolic indicators, especially compared to normal protein intake. Several meta-analyses (Hansen et. al., 2021; Vogtschmidt et. al., 2021; Kokura et al., 2024) confirm that an increased proportion of protein supports weight reduction, maintaining muscle mass and improving insulin sensitivity. However, the effects tend to be relatively small to moderate and often depend on the type of protein, energy intake and the length of the intervention. From the point of view of kidney function, the available studies (Bagheri et. al., 2023b; Cheng et al., 2024) did not show negative effects even with an intake of around 2.5-3.2 g of protein/kg/day in healthy adults and trained individuals. A short-term increase in glomerular filtration is considered a physiological adaptation, not a pathological phenomenon. Nevertheless, most authors recommend caution in persons with cardiovascular disease, where a lower protein intake (0.6–0.8 g/kg) is preferred in the long term.

When it comes to cardiovascular health, the results are less clear. A meta-analysis by Mantzouranis et al. (2023) confirmed the neutral effect of a high-protein diet on the occurrence of serious cardiovascular events, while the source of protein plays an essential role, as vegetable proteins are associated with a better lipid profile and a lower risk of cardiovascular disease, while an excess of animal proteins, especially from red meat, can have the opposite effect. Newer works on the intestinal microbiome bring interesting knowledge. According to a study by Dong et al. (2020) a high-protein diet increased the diversity of the microbiome and promoted the growth of "protective" bacteria, such as Akkermansia and Bifidobacterium, which can positively affect metabolism and gut health. However, other works (Wu et al., 2022) point out that excessive protein intake without sufficient fiber can shift the microbiome towards proteolytic fermentation, which leads to the formation of potentially harmful metabolites. This suggests that the quality and context of the diet (especially fiber intake) are crucial in evaluating the effects of a high-protein diet.

Some studies point to the short-term nature of most research, which limits the interpretation of the long-term consequences of a high-protein diet. Another limitation is the heterogeneity of the population and protein sources, as effects differ between animal and plant proteins, between trained athletes and sedentary individuals, as well as between genders and age groups. In addition, some meta-analyses include only studies with a short duration (4-12 weeks), which does not allow evaluating their impact on chronic diseases.

Based on current knowledge, it can be recommended that modest increases in protein intake (1.2–1.6 g/kg/day) are safe and potentially beneficial for most healthy adults, especially when combined with physical activity and adequate fiber intake. For persons at risk of renal dysfunction, hypertension or diabetes, however, it is advisable to consult an individual intake with a specialist. Focusing on the source of protein is also key, preferring plant, dairy and fish proteins over red and processed meat.

Conclusion

Current scientific evidence suggests that high-protein diets may have modest beneficial effects on body composition, weight control, and metabolic health for most healthy adults, especially when maintaining a total energy deficit and an active lifestyle. Data from available studies have not shown that higher protein intakes (up to about 2 g/kg/day) cause kidney damage in healthy people, although caution is warranted in those with chronic kidney disease or other metabolic disorders. The effect on cardiovascular health appears to be neutral to moderately beneficial, with the protein source being the deciding factor. From the point of view of the gut microbiome, there is no evidence of a harmful effect of a high-protein diet, as long as it contains enough fiber and plant foods. On the contrary, some studies suggest that this type of diet can promote the growth of beneficial bacteria and metabolites that are associated with better gut health. Overall, it can be concluded that a high-protein diet is safe and effective as part of a balanced diet, if individual needs are respected, a sufficient drinking regime and a varied intake of macro- and micronutrients are respected. It remains important for future research to focus on long-term effects and differences between protein sources in the context of chronic disease and gut health.

Authors: Mgr. Ján Roman, Institute of Public Health and Hygiene, UPJŠ Faculty of Medicine, Košice prof. Mgr. MUDr. Erik Dorko, PhD., MPH, MBA, Institute of Public Health and Hygiene, UPJŠ Faculty of Medicine, Košice Mgr. Anastasiia Ostafiichuk, Institute of Public Health and Hygiene, UPJŠ Faculty of Medicine, Košice prof. MUDr. Kvetoslava Rimárová, CSc., Institute of Public Health and Hygiene, UPJŠ Faculty of Medicine, Košice *** doc. MUDr. Laura Gombošová, PhD.,*** II. internal clinic UPJŠ LF and UNLP, Košice

Work supported by KEGA grant projects of the Ministry of Education, Research, Development and Youth of the Slovak Republic no. 001UPJŠ-4/2024 and no. 003UPJŠ-4/2024.

List of bibliographic references

BAGHERI, Reza. et al. 2023a. Effects of 8 weeks of resistance training in combination with a high protein diet on body composition, muscular performance, and markers of liver and kidney function in untrained older ex-military men. In Front Nutr. ISSN 2296-861X, 2023, 10, 1205310.

BAGHERI, Reza. et al. 2023b. Effects of 16 weeks of two different high-protein diets with either resistance or concurrent training on body composition, muscular strength and performance, and markers of liver and kidney function in resistance-trained males. In J Int Soc Sports Nutr. ISSN 1550-2783, 2023, 20, 1, 2236053.

DEVRIES, Michaela C. et al. 2018. Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis. In J Nutr. ISSN 1541-6100, 2018, 148, 11, 1760-1775.

DONG, Tien S. et al. 2020. A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity. In Nutrients. ISSN 2072-6643, 2020, 12, 10, 3221.

FARSIJANI, Samaneh et al. 2023. Relation Between Dietary Protein Intake and Gut Microbiome Composition in Community-Dwelling Older Men: Findings from the Osteoporotic Fractures in Men Study (MrOS). In J Nutr. ISSN 1541-6100, 2023, 152, 12, 2877-2887.

HANSEN, Thea Toft et al. 2021. Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein. In Nutrients. ISSN 2072-6643, 2021, 13, 9, 3193.

CHENG, Yu et al. 2024. Association between dietary protein intake and risk of chronic kidney disease: a systematic review and meta-analysis. In Front Nutr. PMID 38946781, 2024, 11, 1408424.

KOKURA, Yoji et al. 2024. Enhanced protein intake on maintaining muscle mass, strength, and physical function in adults with overweight/obesity: A systematic review and meta-analysis. In Clin Nutr ESPEN. ISSN 0261-5614, 2024, 63, 417-426.

MANTZOURANIS, Emmanouil et al. 2023. The Impact of High Protein Diets on Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. In Nutrients. ISSN 2072-6643, 2023, 15, 6, 1372.

NAGHSHI, Sina et al. 2020. Dietary intake of total, animal, and plant proteins and risk of all-cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of prospective cohort studies. In BMJ. ISSN 1756-1833, 2020, 370, m2412. SONG, Mingyang et al. 2016. Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality. In JAMA Intern Med. ISSN 2168-6114, 176, 10, 1453-1463.

Tettamanzi, Francesca et al. 2021. A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study. In Nutrients. ISSN 2072-6643, 2021, 13, 12, 4380.

VOGTSCHMIDT, Yakima D. 2021. Is protein the forgotten ingredient: Effects of higher compared to lower protein diets on cardiometabolic risk factors. A systematic review and meta-analysis of randomized controlled trials. In Atherosclerosis. ISSN 1879-1484, 2021, 328, 124-135.

WANG, Fang et al. 2024. Effects of high-protein diets on the cardiometabolic factors and reproductive hormones of women with polycystic ovary syndrome: a systematic review and meta-analysis. In Nutr Diabetes. ISSN 2044-4052, 2024, 14, 1, 6.

Wu, Shuang et al. 2022. Effect of dietary protein and processing on gut microbiota: a systematic review. In Nutrients. ISSN 2072-6643, 2022, 14, 3, 453.