Can eating too much protein be bad for you?

Last Updated:

Bone health

The acid-ash hypothesis states the following: The metabolism of certain foods — namely protein and grains — increases acid production in the body, as evidenced by an increase in urinary acidity.[7] To counteract this increase in acidity, bone is broken down to release calcium bicarbonate (a base) corresponding with an increase in urinary calcium excretion, which is thought to reflect negative body calcium balance or bone loss. Therefore, a high-protein or acid-producing diet accelerates bone loss and increases the risk of osteoporosis.

However, changes in urine pH don’t necessarily reflect changes in blood pH, which is maintained within a narrow range primarily by the renal and pulmonary systems in healthy people.[8] Additionally, variations in diet have virtually no effect on blood pH, as any nutritional influence that slightly disrupts acid-base balance is immediately corrected by biochemical buffering systems that do not involve bone.[8]

While an increase in urinary acidity has been correlated with an increase in urinary calcium excretion, dietary changes that increase urinary acidity do not lower body calcium balance.[9] Relatedly, a higher-protein diet does not negatively affect dietary calcium retention because although it increases urinary calcium excretion, it increases intestinal calcium absorption by a similar magnitude.[10][11]

Ultimately, the available evidence does not support the acid-ash hypothesis,[12] and in accordance, higher-protein diets do not have a negative effect on bone health.

Meta-analyses of prospective cohort studies have reported that a higher-protein diet was either not associated with the risk of hip fracture,[13] or, compared to the group with the lowest protein intake, there was an 11%–16% lower risk of hip fracture in the group with the highest protein intake.[14][15][16]

With respect to bone mineral density (BMD), a meta-analysis of randomized controlled trials 12–24 months long reported that a higher-protein diet had a protective effect on lumbar spine BMD.[17] A higher-protein diet also tended to have a protective effect on total hip BMD, although this finding was not statistically significant. The data from prospective cohort studies is mixed on whether higher-protein diets have a protective effect on BMD (some studies suggest a benefit with more protein, while others have reported no impact), but there is a lack of evidence indicating that higher-protein diets are associated with lower BMD.[15][17]

Concerning protein intakes significantly greater than the Recommended Dietary Allowance (RDA), there are a couple of long-term prospective cohort studies in older adults that shed light on the topic. In one four-year study that included older men and women (average age of 75), the quartile with the highest protein intake (1.24–2.78 grams of protein per kg of body weight per day) showed the least BMD loss at the femur and lumbar spine.[18] Compared to the quartile with the highest protein intake, the quartiles with the lowest (0.21–0.71 g/kg/day) and second-lowest (0.72–0.96 g/kg/day) protein intakes experienced a significant reduction in femoral neck BMD.

In a separate five-year cohort study that only included older women (average age of 75), a higher protein intake was associated with greater whole-body bone mineral content, and the tertile with the highest protein intake (about 1.6 g/kg/d) had significantly higher whole-body and appendicular bone mineral content than the tertiles with lower intakes.[19]

Kidney health

The idea that a high-protein diet puts undue stress on the kidneys stems from early research in rodents and dogs that reported increased urea excretion, renal blood flow, glomerular filtration rate (GFR; a marker of kidney function), and kidney size in animals fed a high-protein diet.[20] From this data, it was determined that a high-protein diet increases the workload of the kidneys, and thus may damage the kidneys over time and increase the risk of chronic kidney disease (CKD).

A 2018 meta-analysis of randomized controlled trials that compared the effects of a high-protein diet (1.8 grams of protein per kilogram of body weight per day, on average) to a low-protein diet (0.93 g/kg/d) in healthy adults reported that higher protein intakes may slightly increase GFR.[21] Other data indicates that a high-protein diet does not adversely affect blood markers of kidney function or blood pressure.[22][23]

Given these findings, a high-protein diet does not appear to pose a serious threat to kidney health. In further support of this conclusion, the issue at hand can be viewed through a different lens altogether; that is, is an increase in GFR a risk factor for CKD in healthy people? Such a relationship has yet to be clearly established.[21]

In fact, an increase in GFR in response to an increase in solute load (e.g., nitrogen from protein) is a normal adaptive mechanism.[24] For example, GFR can increase by as much as 65% during pregnancy[25] but does not increase the risk of CKD.[26] Also, surgical removal of a kidney is not associated with a deterioration in kidney function in the long term (> 20 years), despite the increase in workload.[27][28][29]

While a low-protein diet is recommended for people with CKD to help prevent disease progression,[30] this does not mean that a high-protein diet is harmful in all cases. The available evidence suggests that, in healthy people, a high-protein diet does not adversely affect kidney function or increase the risk of CKD.

1.^Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SMA systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adultsBr J Sports Med.(2018 Mar)
3.^Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, Phillips S, Sieber C, Stehle P, Teta D, Visvanathan R, Volpi E, Boirie YEvidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study GroupJ Am Med Dir Assoc.(2013 Aug)
4.^Silva Ton WT, das Graças de Almeida C, de Morais Cardoso L, Marvila Girondoli Y, Feliciano Pereira P, Viana Gomes Schitini JK, Galvão Cândido F, Marques Arbex P, de Cássia Gonçalves Alfenas REffect of different protein types on second meal postprandial glycaemia in normal weight and normoglycemic subjects.Nutr Hosp.(2014-Mar-01)
5.^Mary C Gannon, Frank Q Nuttall, Asad Saeed, Kelly Jordan, Heidi HooverAn increase in dietary protein improves the blood glucose response in persons with type 2 diabetesAm J Clin Nutr.(2003 Oct)
6.^Mads J Skytte, Amirsalar Samkani, Amy D Petersen, Mads N Thomsen, Arne Astrup, Elizaveta Chabanova, Jan Frystyk, Jens J Holst, Henrik S Thomsen, Sten Madsbad, Thomas M Larsen, Steen B Haugaard, Thure KrarupA carbohydrate-reduced high-protein diet improves HbA 1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trialDiabetologia.(2019 Nov)
7.^Buclin T, Cosma M, Appenzeller M, Jacquet AF, Décosterd LA, Biollaz J, Burckhardt PDiet acids and alkalis influence calcium retention in boneOsteoporos Int.(2001)
9.^Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DAMeta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balanceJ Bone Miner Res.(2009 Nov)
10.^Hunt JR, Johnson LK, Fariba Roughead ZKDietary protein and calcium interact to influence calcium retention: a controlled feeding studyAm J Clin Nutr.(2009 May)
11.^Kerstetter JE, O'Brien KO, Caseria DM, Wall DE, Insogna KLThe impact of dietary protein on calcium absorption and kinetic measures of bone turnover in womenJ Clin Endocrinol Metab.(2005 Jan)
13.^Darling AL, Millward DJ, Torgerson DJ, Hewitt CE, Lanham-New SADietary protein and bone health: a systematic review and meta-analysis.Am J Clin Nutr.(2009-Dec)
16.^Inge Groenendijk, Laura den Boeft, Luc J C van Loon, Lisette C P G M de GrootHigh Versus low Dietary Protein Intake and Bone Health in Older Adults: a Systematic Review and Meta-AnalysisComput Struct Biotechnol J.(2019 Jul 22)
17.^Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CMDietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis FoundationAm J Clin Nutr.(2017 Jun)
18.^Hannan MT, Tucker KL, Dawson-Hughes B, Cupples LA, Felson DT, Kiel DPEffect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study.J Bone Miner Res.(2000-Dec)
19.^Xingqiong Meng, Kun Zhu, Amanda Devine, Deborah A Kerr, Colin W Binns, Richard L PrinceA 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal womenJ Bone Miner Res.(2009 Nov)
23.^Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TNDietary protein intake and blood pressure: a meta-analysis of randomized controlled trialsAm J Epidemiol.(2012 Oct 1)
24.^Martin WF, Armstrong LE, Rodriguez NRDietary protein intake and renal function.Nutr Metab (Lond).(2005-Sep-20)
26.^Cortinovis M, Perico N, Ruggenenti P, Remuzzi A, Remuzzi GGlomerular hyperfiltration.Nat Rev Nephrol.(2022-07)
27.^Regazzoni BM, Genton N, Pelet J, Drukker A, Guignard JPLong-term followup of renal functional reserve capacity after unilateral nephrectomy in childhood.J Urol.(1998-Sep)
28.^Higashihara E, Horie S, Takeuchi T, Nutahara K, Aso YLong-term consequence of nephrectomy.J Urol.(1990-Feb)
29.^Goldfarb DA, Matin SF, Braun WE, Schreiber MJ, Mastroianni B, Papajcik D, Rolin HA, Flechner S, Goormastic M, Novick ACRenal outcome 25 years after donor nephrectomy.J Urol.(2001-Dec)
30.^Ikizler TA, Burrowes JD, Byham-Gray LD, Campbell KL, Carrero JJ, Chan W, Fouque D, Friedman AN, Ghaddar S, Goldstein-Fuchs DJ, Kaysen GA, Kopple JD, Teta D, Yee-Moon Wang A, Cuppari LKDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update.Am J Kidney Dis.(2020-09)