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Does Creatine Affect Your Kidneys

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Does Creatine Affect Your Kidneys – Cross-sectional association of dietary patterns and dietary supplement intake with the incidence and gray-scale median of carotid plaque – A comparison between women and men in the population-based Hamburg City Health Study

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Does Creatine Affect Your Kidneys

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How Creatine Impacts My Glucose Levels And Metabolism

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By Igor Longobardi Igor Longobardi Scilit Preprints.org Google Scholar 1 , Bruno Gualano Bruno Gualano Scilit Preprints.org Google Scholar 1, 2 , Antonio Carlos Seguro Antonio Carlos Seguro Scilit Preprints.org Google Scholar 3 and Hamilton Roschel Hamilton Roschel Scilit Preprints.org Google Academic 1, 2, *

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Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, School of Medicine, University of Sao Paulo, Sao Paulo 01246-903, SP, Brazil

Department of Rheumatology, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo 01246-903, SP, Brazil

Division of Nephrology, Hospital das Clinicas HCFMUSP, Faculty of Medicine, Universidade de São Paulo, Sao Paulo 01246-903, SP, Brazil

Received: 21 February 2023 / Revised: 13 March 2023 / Accepted: 15 March 2023 / Published: 18 March 2023

Creatine Loading: How To Do It And Is It Necessary?

Creatine has become one of the most popular dietary supplements among a wide range of healthy and clinical populations. However, its potential adverse effects on kidney health remain a cause for concern. This is a narrative review of the effects of creatine supplementation on kidney function. Despite some case reports and animal studies suggesting that creatine may affect kidney function, clinical trials using controlled models do not support this claim. Creatine supplementation may increase serum creatinine (Crn) in some individuals, but does not necessarily indicate impaired renal function, as creatine is spontaneously converted to Crn. Based on studies that evaluate kidney function using reliable methods, creatine supplements have been shown to be safe for human consumption. Further studies are needed in people who already have kidney disease.

Creatine (α-methyl-guanidine-acetic acid) is one of the most popular dietary supplements with a wide range of potential applications [1]. Creatine is a central player in the phosphagen system, which is essential for cellular bioenergetics, especially in tissues with high and fluctuating energy demands [2]. Its oral administration can increase muscle creatine content [3], consistent evidence shows that creatine supplementation can benefit performance in some sports [4] and improve some clinical symptoms, for example in rheumatic diseases [5, 6], metabolic disorders [7, 6 ]. 8], myopathy [9, 10], neurodegenerative diseases [11], chronic obstructive pulmonary disease [12] and congestive heart failure [13, 14].

However, the potential adverse effects of creatine, particularly on the kidneys, are still a matter of debate. The first concerns about the possible damage of creatine supplementation to the kidney came from a series of case studies that retrospectively associated its use with kidney disease [15, 16, 17, 18, 19, 20, 21]. In addition, some animal studies also question the safety of creatine supplementation [22, 23, 24]. On the other hand, a growing number of randomized controlled trials, mostly involving healthy people, have found no harmful effects of this supplement on kidney function.

In this narrative review, we discuss the latest on the effect of creatine supplementation on kidney health, describe gaps in the literature, and provide evidence-based recommendations for safe creatine consumption.

Low Creatinine Levels

Kidneys are vital organs that are actively involved in several physiological processes and play a central role in maintaining body homeostasis. They participate in endocrine pathways; regulates osmolarity, extracellular fluid volume, and blood pressure; maintains electrolyte and acid-base balance; and excrete wastes and foreign substances (eg, toxins and drugs) [25].

Each kidney consists of 0.8–1.2 million nephrons [26]. Each nephron, in turn, consists of a glomerulus (a ball-like group of capillaries) and a renal tubule (consisting of Bowman’s capsule, proximal and distal convoluted tubules, loop of Henle, and collecting duct) composed of a single layer of epithelium. cells that regulate urine volume and osmolarity [26]. Initially, plasma is filtered from the glomerulus into Bowman’s capsule. Additional segments of renal tubules then change the filtered fluid before it is excreted as urine. Water, electrolytes (e.g. Na

), and some organic compounds (e.g. glucose, amino acids, etc.) can be reabsorbed from the renal tubules into the blood according to the needs of the individual, while K

, other organic compounds (e.g., urea, citric acid cycle intermediates, etc.) and xenobiotics (e.g., penicillin) are secreted from the extracellular fluid into the renal tubule [ 25 , 27 , 28 ]. All these processes are specifically and strictly controlled by local and/or systemic mechanisms.

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In particular, the filtration process mainly depends on the capillary pressure and the permeability of the glomerular filtration barrier, which is relatively selective and quite robust. Three filtration barriers (fenestrated endothelial cells, the glomerular basement membrane, and specialized cells called podocytes) allow most plasma components to enter the lumen of the tubules, except for blood cells and large plasma proteins (eg, albumin), which are retained and float. into the world. peritubular capillaries [25]. Leakage of such macromolecules into urine is a strong indicator of impaired glomerular permeability [29, 30]. Importantly, the kidneys have a significant reserve capacity and kidney function is a dynamic process that is continuously adapted to changes in the internal environment. It is estimated that at least three quarters of the kidney’s functional capacity must be lost before homeostasis begins to seriously deteriorate [31].

Glomerular filtration rate (ie, the amount of fluid filtered into Bowman’s capsule per unit time) is considered a central point in the assessment of kidney function. Although it cannot be measured directly, glomerular filtration rate can be inferred from the elimination of a filtered solute. The gold standard method for its assessment is the measurement of exogenous filtration biomarkers (ie, measured glomerular filtration rate; mGFR), which are continuously infused intravenously from timed blood and urine samples [32]. As these biomarkers are not produced by the body (e.g. inulin,

Cr-EDTA, etc.), it can be assumed that their clearance is equal to the glomerular filtration rate because they are freely filtered, but neither reabsorbed nor excreted by the renal tubules. Unfortunately, mGFR is generally limited to specialized facilities, so in medical practice, glomerular filtration rates are usually estimated from serum levels of endogenous biomarkers (ie, estimated glomerular filtration rate; eGFR), without requiring a direct clearance measurement [32]. For example, serum levels of creatinine (Crn) and cystatin C (CysC) have been associated with renal function and progression of renal diseases [ 33 , 34 ]. However, eGFR is directly affected by the rate at which such biochemical markers are produced by metabolic processes, their tubular secretion and reabsorption, and their excretion. Despite great progress in recent years, there are still many sources of bias and error associated with eGFR methods that can increase their inaccuracy (eg, smoking, inflammation, medications, thyroid hormone and corticosteroid levels, fat, muscle mass, diet); which may limit their ability to accurately assess renal function for some groups [32, 35].

This is the case for people who take creatine supplements. Serum Crn is the parameter most often used to assess renal function, either by itself or as a means of estimating glomerular filtration rate [34, 35]. Crn is an end product of creatine metabolism [36]. Creatine is spontaneously (ie, non-enzymatically) and irreversibly degraded to Crn at a rate of approximately 2% of total body per day [36]. Since chronic creatinine intake increases the total creatine content in the body, it is likely that a physiological increase in Crn occurs in the blood after creatine administration, without necessarily causing any damage to the kidneys (Figure 1). It is worth noting that the opposite is also true. Vegetarians show lower serum clearance of Crn and Crn, due to low intake of creatine in the diet [37]. Consequently, creatinine intake is a known confounder of Crn levels. This is why Crn clearance calculated from equations that only consider serum Crn (ie, without considering its concentration in urine) may be inappropriate for those taking creatine supplements. Whenever this bias is overlooked, it can lead to misinterpretation of test results and misdiagnosis

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