Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle

Abstract

Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease‐modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta‐analysis, shows that it improves muscular strength and general well‐being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment‐resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy‐duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo‐controlled trials showing that creatine supplementation is safe up to 20 g/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.

Creatine for Prevention of Statin Myopathy

“…emphasize that creatine is a legally available, widely used dietary supplement, and that double-blind, placebo-controlled trials have demonstrated its safety even in people of more advanced age [36,[69][70][71]. Thus, we believe that in view of its safety and easy availability creatine supplementation should be trialed, on a case-by-case basis and under medical supervision, in those patients at risk for cardiovascular diseases whom statin myopathy prevents from reaching their cholesterol goals.…”

“…In those rare conditions, usual dietary creatine is not sufficient to meet the need for creatine by the tissues, and severe symptoms occur [35]. Dietary supplementation can then replenish creatine stores, but much higher amounts than usual are needed, up to 800 mg/Kg/day for an infant, or 10 g/day for an adult [36], compared to 1-2 g that are usually obtained through the normal diet [37].…”

Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review

“…This means the protein is missing essential amino acids, including leucine, valine, phenylalanine, histidine, lysine, methionine, isoleucine, threonine, and tryptophan [14]. Of concern, methionine is a precursor of creatine [15], a natural compound with proven benefits on sport performance.…”

“…As a result, there is decreased intake among vegetarian athletes [2]. Dietary intake of creatine is significantly reduced in individuals following a vegetarian diet (egg and dairy products may contribute to provide very small amounts of creatine), while in vegan diets, almost no exogenous source of creatine is consumed [15]. The amount of creatine is lower in serum, plasma, red blood cells, and muscle, but not in the brain in vegetarians versus omnivores [16][17][18][19].…”

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis

“…While there have been more than eighty reviews reporting the ergogenic or therapeutic effect of creatine supplementation, only thirty-four reviews have addressed the safety of this supplement. Some of these reviews have been highly specific, targeting particular areas of interest [ 15 , 16 , 17 , 18 ], but none have been sex specific. There have only been two systematic reviews to date, one which focused on renal function [ 19 ] and the other on fluid dynamics [ 20 ] both were conducted in mixed sex populations.…”