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Creatine Supplementation in Women's Health

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Creatine Supplementation in Women's Health nutrients Review Creatine Supplementation in Women’s Health: A Lifespan Perspective Abbie E Smith-Ryan 1,2,* , Hannah E Cabre 1,2, Joan M Eckerson 3 and Darren G Candow 4 1 Applied Physiology Laboratory, Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27713, USA; [email protected] 2 Human Movement Science Curriculum, Department of Allied Health Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27713, USA 3 Department of Exercise Science and Pre-Health Professions, Creighton University, Omaha, NE 68178, USA; [email protected] 4 Aging Muscle & Bone Laboratory, Faculty of Kinesiology & Healthy Studies, University of Regina, Regina, SK S4S 0A2, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-919-962-2574 Abstract: Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post- menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg−1·d−1); and favorable effects on bone when combined with resistance training. Pre-clinical Citation: Smith-Ryan, A.E; Cabre, and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, H.E; Eckerson, J.M; Candow, D.G. possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even Creatine Supplementation in more effective for females by supporting a pro-energetic environment in the brain. The purpose of Women’s Health: A Lifespan Perspective. Nutrients 2021, 13, 877. this review was to highlight the use of creatine in females across the lifespan with particular emphasis https://doi.org/10.3390/nu13030877 on performance, body composition, mood, and dosing strategies. Academic Editor: Patrick Diel Keywords: female; dietary supplement; menstrual cycle; hormones; exercise performance; menopause; pregnancy; mood; cognition Received: 15 January 2021 Accepted: 5 March 2021 Published: 8 March 2021 1. Introduction Publisher’s Note: MDPI stays neutral Dietary supplement use has repeatedly been reported to be highest among educated with regard to jurisdictional claims in women, and also appears to increase with age [1]. Creatine has been reported as one of published maps and institutional affil- the most commonly used dietary sports supplements. The ergogenic potential of creatine iations. can be attributed to several mechanisms, and may have different effects on males and females. Innately, creatine is an essential substrate for the creatine kinase reaction to catalyze adenosine triphosphate (ATP) production from creatine and phosphocreatine (PCr). This recycling also serves as an endogenous metabolic buffer helping to maintain Copyright: © 2021 by the authors. pH [2], and both mechanisms can support cross-bridge recycling and energy availability Licensee MDPI, Basel, Switzerland. during exercise. Creatine concentrations in the central nervous system are also notable, This article is an open access article which may support neural function in adaptations to exercise. distributed under the terms and Despite widespread use and decades of research related to creatine, its effects in conditions of the Creative Commons females are not well understood. Creatine characteristics vary between males and fe- Attribution (CC BY) license (https:// males. For example, females have/exhibit 70–80% lower endogenous creatine stores than creativecommons.org/licenses/by/ males [3]. Females have also been reported to consume significantly lower amounts of 4.0/). Nutrients 2021, 13, 877. https://doi.org/10.3390/nu13030877 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 877 2 of 17 dietary creatine compared to males [3], indicating that females may benefit from creatine supplementation as a strategy/means to increase endogenous stores. Interestingly, females Nutrients 2021, 13have, x FOR higher PEER REVIEW reported (~10%) resting levels of intramuscular creatine concentrations2 of 18 com- pared to males [4], which could theoretically lower their responsiveness to supplementation and require higher dosages compared to males [5]. In addition, creatine supplementation has not been shown[3]. Females to effectivelyhave also been reduce reported amino to consume acid significantly oxidation andlower measures amounts of ofdietary protein breakdown followingcreatine compared exercise to in males females, [3], indicating which that has females been reportedmay benefit in from males creatine [6]. supple- Therefore, mentation as a strategy/means to increase endogenous stores. Interestingly, females have the ergogenichigher potential reported of creatine (~10%) resting among levels females of intramuscular has been creatine questioned. concentrations compared The currentto males body [4], of which literature could theoretically that has evaluated lower their the responsiveness effect of creatine to supplementation supplementation and in females suggestsrequire thathigher the dosages risk-to-benefit compared to ratio males is [5]. low In [addition,7], with creatine most studies supplementation indicating has that there are numerousnot been metabolic, shown to effectively hormonal, reduce and amino neurological acid oxidation benefits. and measures The lackof protein of discussion break- and explorationdown of following creatine exercise use among in females, females which across has been the reported lifespan in males is a [6]. disadvantage Therefore, the and ergogenic potential of creatine among females has been questioned. missed opportunity,The current since abody better of literature understanding that has evaluated of creatine the effect metabolism of creatine supplementa- pre- and post- menopause yieldstion in important females suggests implications that the risk-to-benefi for improvingt ratio is health low [7], and with exercisemost studies performance indicat- for females acrossing that their there lifetime. are numerous Therefore, metabolic, the hormonal, aim of this and reviewneurological was benefits. to highlight The lack the of use of creatine in femalesdiscussion from and exploration young adulthood of creatine use to oldamong age. females across the lifespan is a disad- vantage and missed opportunity, since a better understanding of creatine metabolism pre- and post-menopause yields important implications for improving health and exercise per- 2. Creatine Homeostasisformance for females across across the Lifespantheir lifetime. Therefore, the aim of this review was to high- As a resultlight of the hormone-driven use of creatine in female changess from throughoutyoung adulthood various to old age. stages of female repro- duction, endogenous creatine synthesis, creatine transport, creatine kinase kinetics, and 2. Creatine Homeostasis across the Lifespan creatine bioavailability are altered over time, highlighting the potential positive implica- As a result of hormone-driven changes throughout various stages of female repro- tions for dietaryduction, creatine endogenous supplementation creatine synthesis, for creatine females transport, [8]. The creatine implications kinase kinetics, of hormone- and related changescreatine in creatine bioavailability kinetics are altered have beenover time largely, highlighting overlooked the potential in performance-based positive implica- studies [8]. Specifically,tions for dietary creatine creatine supplementation supplementation for females may be [8]. of The particular implications importance of hormone- dur- ing menses, pregnancy,related changes post-partum, in creatine kinetics during have and been post-menopause. largely overlooked in The performance-based menstrual cycle may influencestudies creatine [8]. Specifically, homeostasis creatine due supplementation to the cyclical may nature be of particular of sex hormone importance regulation during menses, pregnancy, post-partum, during and post-menopause. The menstrual cycle may (Figure1). Studiesinfluence conducted creatine homeostasis in animal due models to the havecyclical demonstrated nature of sex hormone that the regulation expression (Fig- of arginine-glycineure 1). aminotransferase Studies conducted in (AGAT), animal models the rate have limiting demonstrated step that of creatinethe expression synthesis, of ar- is influenced byginine-glycine estrogen and aminotransferase testosterone levels(AGAT), [9 the]. Sex rate hormones, limiting steppredominantly of creatine synthesis, estrogen is and progesterone,influenced have by been estrogen shown and testosterone to effectcreatine levels [9]. kinaseSex hormones, activities predominantly and the estrogen expression and progesterone, have been shown to effect creatine kinase activities and the expression of key enzymesof key for enzymes the endogenous for the endogenous synthesis synthesis of creatine of creatine [10 [10].]. Figure 1. A theoretical model for the interplay
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