# Citrate supplement facilitated muscle growth and renal maturation

## TL;DR

Citrate supplements help increase muscle mass and improve kidney function in rats through specific metabolic changes.

## Contribution

The study reveals a novel muscle-kidney interaction mechanism through citrate supplementation.

## Key findings

- Citrate supplementation increased muscle mass relative to weight gain in rats.
- Renal function development was significantly enhanced in the citrate-supplemented group.
- Metabolomic changes suggest citrate affects muscle and kidney via alanine and urea pathways.

## Abstract

Citrate supplementation is well known to alleviate muscle fatigue. Furthermore, our previous clinical study revealed that citrate supplementation prevents renal oxidative stress and dysfunction. We hypothesize that an interaction between muscle and kidney tissues underlies the effects of citrate supplementation. This study investigated the effects of a citrate agent, potassium citrate/sodium citrate (PCSC), on muscle and renal functions. Male Sprague-Dawley rats were randomly assigned to two groups (control and PCSC groups). PCSC (2000 mg/kg body weight) was administered orally administrated for one week. Kidney weight, vastus lateralis muscle weight, and renal function were compared between the groups. Subsequently, the kidney and muscle tissues were analyzed using metabolomics. The PCSC group showed a significant increase in muscle mass relative to the weight gain (p = 0.0472). Renal function development with growth was more pronounced in the PCSC group (p < 0.0001). Metabolomic analysis of muscle tissue in the PCSC group revealed increased alanine levels and decreased levels of sarcosine, creatinine, and NADPH/NADP+ ratio. In the kidney tissue, PCSC supplementation led to elevated N,N-dimethylglycine, urea, and the ratio of malic acid to aspartate, while betaine aldehyde, carnitine, and Fisher’s ratio decreased. The study concluded that PCSC supplement facilitated muscle growth metabolically through an alanine-associated pathway and renal function development by increasing intrarenal urea and accelerating the malate-shuttle and the betaine pathway. These findings indicate PCSC’s potential impact of PCSCs on muscle-kidney interactions.