High protein diets (more than 1.5 grams per kilogram of bodyweight per day) and their putative detrimental effects on the kidneys is a controversial topic that has been researched and discussed ad nauseam. However, there is no conclusive answer to this question in people without kidney disease. For instance, a 2018 meta-analysis of small studies including a total of 1,358 healthy adults without kidney disease suggests that following high protein diets (1.8 g protein/kg) for up to 2 years does not worsen kidney function (measured by changes to the glomerular filtration rate GFR) when compared to low protein diets (0.9 g/kg).^[5] This analysis is limited due to lack of randomization and blinding on included studies.

Mechanistically, increased protein intake might cause kidney hyperfiltration (to clear extra nitrogen waste from the ingested proteins). This can lead to inflammation and kidney damage in some people. A few observational studies have found that increased protein intake is associated with decreased kidney function in people who develop hyperfiltration, and in those at risk for developing kidney disease (e.g., those with diabetes). Also, high animal protein intake has been associated with an increased risk of developing chronic kidney disease (CKD).^[6]

In people with existing CKD, it is generally best to avoid high-protein diets to preserve kidney function. In those with moderate to severe CKD, a low protein diet is indicated.^[7] Individualized diets in CKD should be discussed with a medical professional.

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.^[25] 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.^[26] 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.^[26]

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.^[27] 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.^[28][29]

Ultimately, the available evidence does not support the acid-ash hypothesis,^[30] 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,^[31] 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.^[32][33][34]

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.^[35] 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.^[33][35]

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.^[36] 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.^[37]

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.^[38] 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.^[5] Other data indicates that a high-protein diet does not adversely affect blood markers of kidney function or blood pressure.^[39][40]

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.^[5]

In fact, an increase in GFR in response to an increase in solute load (e.g., nitrogen from protein) is a normal adaptive mechanism.^[41] For example, GFR can increase by as much as 65% during pregnancy^[42] but does not increase the risk of CKD.^[43] 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.^[44][45][46]

While a low-protein diet is recommended for people with CKD to help prevent disease progression,^[47] 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.

Creatinine is a byproduct of the breakdown of creatine and phosphocreatine in the body. It is also a commonly used marker of kidney function.

Because supplementing with creatine can increase the blood levels of creatinine, there have been some concerns about a potential negative effect of creatine on kidney function. However, beyond a harmless increase in creatinine levels, scientific reviews on both the long- and short-term safety of supplemental creatine in people with healthy kidneys have consistently found no adverse effects on kidney function with a wide range of doses.^{[8][9][10][11][12][13][14][15]} That said, although doses of >10 g/day have been found not to impair kidney function, fewer long-term trials have assessed the safety of such high chronic daily intakes.

Similar findings have been reported in trials looking at the effect of supplemental creatine in people with kidney disease, with trials reporting no detrimental effects on kidney function.^[16][17][18] That said, long-term trials assessing the safety of supplemental creatine in people with kidney disease are lacking. Also, it’s worth keeping in mind that, because creatine can increase water retention, it could theoretically adversely affect individuals whose kidney disorder is being treated with diuretics, which cause water loss.

Overall, the available evidence suggests that short- and long-term supplementation with creatine is likely safe for people with healthy kidneys, and that short-term supplementation with creatine is likely safe for people with suboptimal kidney function. Less is known about the effects of long-term supplementation with creatine in people with suboptimal kidney function.

Also, it’s worth keeping in mind that, although elevated creatinine levels in response to supplementation with creatine are not indicative of kidney damage, creatine’s ability to raise creatinine levels could potentially mask underlying health issues.