Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation

Darren G Candow, Scott C Forbes, Philip D Chilibeck, Stephen M Cornish, Jose Antonio, Richard B Kreider, Darren G Candow, Scott C Forbes, Philip D Chilibeck, Stephen M Cornish, Jose Antonio, Richard B Kreider

Abstract

Sarcopenia, defined as the age-related decrease in muscle mass, strength and physical performance, is associated with reduced bone mass and elevated low-grade inflammation. From a healthy aging perspective, interventions which overcome sarcopenia are clinically relevant. Accumulating evidence suggests that exogenous creatine supplementation has the potential to increase aging muscle mass, muscle performance, and decrease the risk of falls and possibly attenuate inflammation and loss of bone mineral. Therefore, the purpose of this review is to: (1) summarize the effects of creatine supplementation, with and without resistance training, in aging adults and discuss possible mechanisms of action, (2) examine the effects of creatine on bone biology and risk of falls, (3) evaluate the potential anti-inflammatory effects of creatine and (4) determine the safety of creatine supplementation in aging adults.

Keywords: dynapenia; exercise; functionality; mechanisms; safety; sarcopenia.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Endogenous creatine synthesis. Adopted from Kreider and Jung [14]. ATP = Adenosine Triphosphate. ADP = Adenosine Diphosphate.
Figure 2
Figure 2
Forest plot for sit-to-stand performance. SD = Standard Deviation; CI = Confidence Interval. The large diamond on the Forest plot indicates the mean effect across studies. The effect is significant if the diamond does not cross the “zero” point on the x-axis.

References

    1. Anker S.D., Morley J.E., von Haehling S. Welcome to the ICD-10 code for sarcopenia. J. Cachexia Sarcopenia Muscle. 2016;7:512–514.
    1. Cruz-Jentoft A.J., Bahat G., Bauer J., Boirie Y., Bruyere O., Cederholm T., Cooper C., Landi F., Rolland Y., Sayer A.A., et al. Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2 Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31. doi: 10.1093/ageing/afy169.
    1. Dent E., Morley J.E., Cruz-Jentoft A.J., Arai H., Kritchevsky S.B., Guralnik J., Bauer J.M., Pahor M., Clark B.C., Cesari M., et al. International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management. J. Nutr. Health Aging. 2018;22:1148–1161.
    1. Marty E., Liu Y., Samuel A., Or O., Lane J. A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease. Bone. 2017;105:276–286. doi: 10.1016/j.bone.2017.09.008.
    1. Dalle S., Rossmeislova L., Koppo K. The Role of Inflammation in Age-Related Sarcopenia. Front. Physiol. 2017;8:1045.
    1. Reginster J.Y., Beaudart C., Buckinx F., Bruyere O. Osteoporosis and sarcopenia: Two diseases or one? Curr. Opin. Clin. Nutr. Metab. Care. 2016;19:31–36. doi: 10.1097/MCO.0000000000000230.
    1. Larsson L., Degens H., Li M., Salviati L., Lee Y.I., Thompson W., Kirkland J.L., Sandri M. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol. Rev. 2019;99:427–511.
    1. Baker B.A. Efficacy of age-specific high-intensity stretch-shortening contractions in reversing dynapenia, sarcopenia, and loss of skeletal muscle quality. J. Funct. Morphol. Kinesiol. 2018;3:36. doi: 10.3390/jfmk3020036.
    1. Clark B.C., Manini T.M. What is dynapenia? Nutrition. 2012;28:495–503.
    1. Clark B.C., Manini T.M. Sarcopenia ≠ dynapenia. J. Gerontol. A Biol. Sci. Med. Sci. 2008;63:829–834.
    1. Wyss M., Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol. Rev. 2000;80:1107–1213.
    1. Jung S., Bae Y.S., Kim H.J., Jayasena D.D., Lee D.D., Park H.B., Heo K.N., Jo C. Carnosine, anserine, creatine, and inosine 5′-monophosphate contents in breast and thigh meats from 5 lines of Korean native chicken. Poult. Sci. 2013;92:3275–3282. doi: 10.3382/ps.2013-03441.
    1. Buford T.W., Kreider R.B., Stout J.R., Greenwood M., Campbell B., Spano M., Ziegenfuss T., Lopez H., Landis J., Antonio J. International Society of Sports Nutrition position stand: Creatine supplementation and exercise. J. Int. Soc. Sports Nutr. 2007;4:6.
    1. Kreider R.B., Jung Y.P. Creatine supplementation in exercise, sport, and medicine. J. Exerc. Nutr. Biochem. 2011;15:53–69. doi: 10.5717/jenb.2011.15.2.53.
    1. Hultman E., Soderlund K., Timmons J.A., Cederblad G., Greenhaff P.L. Muscle creatine loading in men. J. Appl. Physiol. (1985) 1996;81:232–237. doi: 10.1152/jappl.1996.81.1.232.
    1. Harris R.C., Soderlund K., Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin. Sci. (Lond.) 1992;83:367–374.
    1. Balsom P.D., Soderlund K., Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Med. 1994;18:268–280. doi: 10.2165/00007256-199418040-00005.
    1. Brosnan M.E., Brosnan J.T. The role of dietary creatine. Amino Acids. 2016;48:1785–1791. doi: 10.1007/s00726-016-2188-1.
    1. Schlattner U., Klaus A., Ramirez Rios S., Guzun R., Kay L., Tokarska-Schlattner M. Cellular compartmentation of energy metabolism: Creatine kinase microcompartments and recruitment of B-type creatine kinase to specific subcellular sites. Amino Acids. 2016;48:1751–1774.
    1. Ydfors M., Hughes M.C., Laham R., Schlattner U., Norrbom J., Perry C.G. Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise. J. Physiol. 2016;594:3127–3140. doi: 10.1113/JP271259.
    1. Hunter G.R., McCarthy J.P., Bamman M.M. Effects of resistance training on older adults. Sports Med. 2004;34:329–348.
    1. Janssen I. Evolution of sarcopenia research. Appl. Physiol. Nutr. Metab. 2010;35:707–712. doi: 10.1139/H10-067.
    1. Gualano B., Rawson E.S., Candow D.G., Chilibeck P.D. Creatine supplementation in the aging population: Effects on skeletal muscle, bone and brain. Amino Acids. 2016;48:1793–1805.
    1. Candow D.G. Sarcopenia: Current theories and the potential beneficial effect of creatine application strategies. Biogerontology. 2011;12:273–281.
    1. Candow D.G., Forbes S.C., Little J.P., Cornish S.M., Pinkoski C., Chilibeck P.D. Effect of nutritional interventions and resistance exercise on aging muscle mass and strength. Biogerontology. 2012;13:345–358. doi: 10.1007/s10522-012-9385-4.
    1. Forbes S.C., Little J.P., Candow D.G. Exercise and nutritional interventions for improving aging muscle health. Endocrine. 2012;42:29–38.
    1. Chilibeck P.D., Kaviani M., Candow D.G., Zello G.A. Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: A meta-analysis. Open Access J. Sports Med. 2017;8:213–226. doi: 10.2147/OAJSM.S123529.
    1. Devries M.C., Phillips S.M. Creatine supplementation during resistance training in older adults-a meta-analysis. Med. Sci. Sports Exerc. 2014;46:1194–1203. doi: 10.1249/MSS.0000000000000220.
    1. Candow D.G., Chilibeck P.D. Differences in size, strength, and power of upper and lower body muscle groups in young and older men. J. Gerontol. A Biol. Sci. Med. Sci. 2005;60:148–156.
    1. Candow D.G., Chilibeck P.D., Forbes S.C. Creatine supplementation and aging musculoskeletal health. Endocrine. 2014;45:354–361.
    1. Stout J.R., Sue Graves B., Cramer J.T., Goldstein E.R., Costa P.B., Smith A.E., Walter A.A. Effects of creatine supplementation on the onset of neuromuscular fatigue threshold and muscle strength in elderly men and women (64–86 years) J. Nutr. Health Aging. 2007;11:459–464.
    1. Rawson E.S., Wehnert M.L., Clarkson P.M. Effects of 30 days of creatine ingestion in older men. Eur. J. Appl. Physiol. Occup. Physiol. 1999;80:139–144. doi: 10.1007/s004210050570.
    1. Gotshalk L.A., Volek J.S., Staron R.S., Denegar C.R., Hagerman F.C., Kraemer W.J. Creatine supplementation improves muscular performance in older men. Med. Sci. Sports Exerc. 2002;34:537–543.
    1. Gotshalk L.A., Kraemer W.J., Mendonca M.A., Vingren J.L., Kenny A.M., Spiering B.A., Hatfield D.L., Fragala M.S., Volek J.S. Creatine supplementation improves muscular performance in older women. Eur. J. Appl. Physiol. 2008;102:223–231. doi: 10.1007/s00421-007-0580-y.
    1. Chami J., Candow D.G. Effect of Creatine Supplementation Dosing Strategies on Aging Muscle Performance. J. Nutr. Health Aging. 2019;23:281–285. doi: 10.1007/s12603-018-1148-8.
    1. Lobo D.M., Tritto A.C., da Silva L.R., de Oliveira P.B., Benatti F.B., Roschel H., Niess B., Gualano B., Pereira R.M. Effects of long-term low-dose dietary creatine supplementation in older women. Exp. Gerontol. 2015;70:97–104.
    1. Baker T.P., Candow D.G., Farthing J.P. Effect of Preexercise Creatine Ingestion on Muscle Performance in Healthy Aging Males. J. Strength Cond. Res. 2016;30:1763–1766. doi: 10.1519/JSC.0000000000001254.
    1. Canete S., San Juan A.F., Perez M., Gomez-Gallego F., Lopez-Mojares L.M., Earnest C.P., Fleck S.J., Lucia A. Does creatine supplementation improve functional capacity in elderly women? J. Strength Cond. Res. 2006;20:22–28.
    1. Safdar A., Yardley N.J., Snow R., Melov S., Tarnopolsky M.A. Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol. Genom. 2008;32:219–228. doi: 10.1152/physiolgenomics.00157.2007.
    1. Willoughby D.S., Rosene J.M. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Med. Sci. Sports Exerc. 2003;35:923–929. doi: 10.1249/01.MSS.0000069746.05241.F0.
    1. Deldicque L., Louis M., Theisen D., Nielens H., Dehoux M., Thissen J.P., Rennie M.J., Francaux M. Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med. Sci. Sports Exerc. 2005;37:731–736. doi: 10.1249/01.MSS.0000162690.39830.27.
    1. Parise G., Mihic S., MacLennan D., Yarasheski K.E., Tarnopolsky M.A. Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J. Appl. Physiol. (1985) 2001;91:1041–1047. doi: 10.1152/jappl.2001.91.3.1041.
    1. Candow D.G., Little J.P., Chilibeck P.D., Abeysekara S., Zello G.A., Kazachkov M., Cornish S.M., Yu P.H. Low-dose creatine combined with protein during resistance training in older men. Med. Sci. Sports Exerc. 2008;40:1645–1652. doi: 10.1249/MSS.0b013e318176b310.
    1. Johannsmeyer S., Candow D.G., Brahms C.M., Michel D., Zello G.A. Effect of creatine supplementation and drop-set resistance training in untrained aging adults. Exp. Gerontol. 2016;83:112–119.
    1. Sestili P., Martinelli C., Colombo E., Barbieri E., Potenza L., Sartini S., Fimognari C. Creatine as an antioxidant. Amino Acids. 2011;40:1385–1396. doi: 10.1007/s00726-011-0875-5.
    1. Johnston A.P., De Lisio M., Parise G. Resistance training, sarcopenia, and the mitochondrial theory of aging. Appl. Physiol. Nutr. Metab. 2008;33:191–199.
    1. Barbieri E., Guescini M., Calcabrini C., Vallorani L., Diaz A.R., Fimognari C., Canonico B., Luchetti F., Papa S., Battistelli M., et al. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity. Oxid. Med. Cell. Longev. 2016;2016:5152029.
    1. Bell K.E., Snijders T., Zulyniak M.A., Kumbhare D., Parise G., Chabowski A., Phillips S.M. A multi-ingredient nutritional supplement enhances exercise training-related reductions in markers of systemic inflammation in healthy older men. Appl. Physiol. Nutr. Metab. 2018;43:299–302. doi: 10.1139/apnm-2017-0533.
    1. Crockett K., Kontulainen S.A., Farthing J.P., Chilibeck P.D., Bath B., Baxter-Jones A.D.G., Arnold C.M. Differences in Function and Fracture Risk in Postmenopausal Women with and Without a Recent Distal Radius Fracture. J. Aging Phys. Act. 2018;26:136–145. doi: 10.1123/japa.2016-0132.
    1. Antolic A., Roy B.D., Tarnopolsky M.A., Zernicke R.F., Wohl G.R., Shaughnessy S.G., Bourgeois J.M. Creatine monohydrate increases bone mineral density in young Sprague-Dawley rats. Med. Sci. Sports Exerc. 2007;39:816–820. doi: 10.1249/mss.0b013e318031fac4.
    1. Cornish S.M., Candow D.G., Jantz N.T., Chilibeck P.D., Little J.P., Forbes S., Abeysekara S., Zello G.A. Conjugated linoleic acid combined with creatine monohydrate and whey protein supplementation during strength training. Int. J. Sport Nutr. Exerc. Metab. 2009;19:79–96.
    1. Louis M., Lebacq J., Poortmans J.R., Belpaire-Dethiou M.C., Devogelaer J.P., Van Hecke P., Goubel F., Francaux M. Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve. 2003;27:604–610. doi: 10.1002/mus.10355.
    1. Tarnopolsky M.A., Mahoney D.J., Vajsar J., Rodriguez C., Doherty T.J., Roy B.D., Biggar D. Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology. 2004;62:1771–1777. doi: 10.1212/01.WNL.0000125178.18862.9D.
    1. Walker J.B. Creatine: Biosynthesis, regulation, and function. Adv. Enzymol. Relat. Areas Mol. Biol. 1979;50:177–242.
    1. Heyden G., From S.H. Enzyme histochemistry and its application in comparative studies of adenosinetriphosphatase (ATPase) and some oxidative enzymes in bone, cartilage and tooth germs. Odontol. Revy. 1970;21:129.
    1. Shapiro I.M., Debolt K., Funanage V.L., Smith S.M., Tuan R.S. Developmental regulation of creatine kinase activity in cells of the epiphyseal growth cartilage. J. Bone Miner. Res. 1992;7:493–500.
    1. Ch’ng J.L., Ibrahim B. Transcriptional and posttranscriptional mechanisms modulate creatine kinase expression during differentiation of osteoblastic cells. J. Biol. Chem. 1994;269:2336–2341.
    1. Somjen D., Kaye A.M. Stimulation by insulin-like growth factor-I of creatine kinase activity in skeletal-derived cells and tissues of male and female rats. J. Endocrinol. 1994;143:251–259. doi: 10.1677/joe.0.1430251.
    1. Gerber I., Ap Gwynn I., Alini M., Wallimann T. Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures. Eur. Cells Mater. 2005;10:8–22. doi: 10.22203/eCM.v010a02.
    1. Chang E.J., Ha J., Oerlemans F., Lee Y.J., Lee S.W., Ryu J., Kim H.J., Lee Y., Kim H.M., Choi J.Y., et al. Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption. Nat. Med. 2008;14:966. doi: 10.1038/nm.1860.
    1. Mirandaa H., De Souzaa R.A., Tosatoc M.G., Simaob R., Oliveriraa M.X., De Limaa F.M., Ferraria E., Ribeiroa W., Moreirad L.M., Martinc A.A. Effect of different doses of creatine on the bone in thirty days of supplementation in mice. Spectroscopy. 2011;25:225–233. doi: 10.1155/2011/212038.
    1. de Souza R.A., Xavier M., da Silva F.F., de Souza M.T., Tosato M.G., Martin A.A., Castilho J.C., Ribeiro W., Silveira L. Influence of creatine supplementation on bone quality in the ovariectomized rat model: An FT-Raman spectroscopy study. Lasers Med. Sci. 2012;27:487–495. doi: 10.1007/s10103-011-0976-0.
    1. McCreadie R., Morris M.D., Chen T.C., Sudhaker Rao D., Finney W.F., Widjaja E., Goldstein S.A. Bone tissue compositional differences in women with and without osteoporotic fracture. Bone. 2006;39:1190–1195. doi: 10.1016/j.bone.2006.06.008.
    1. Alves C.R., Murai I.H., Ramona P., Nicastro H., Takayama L., Guimaraes F., Lancha Junior A.H., Irigoyen M.C., Pereira R.M., Gualano B. Influence of creatine supplementation on bone mass of spontaneously hypertensive rats. Rev. Bras. Reumatol. 2012;52:453–461.
    1. Chilibeck P.D., Chrusch M.J., Chad K.E., Shawn Davison K., Burke D.G. Creatine monohydrate and resistance training increase bone mineral content and density in older men. J. Nutr. Health Aging. 2005;9:352–353.
    1. Murai I.H., Roschel H., Pabis L.V., Takayama L., de Oliveira R.B., Dos Santos Pereira R.T., Dantas W.S., Pereira R.M., Jorgetti V., Ballester R.Y., et al. Exercise training, creatine supplementation, and bone health in ovariectomized rats. Osteoporos. Int. 2015;26:1395–1404. doi: 10.1007/s00198-014-3017-6.
    1. Yasuda H., Shima N., Nakagawa N., Mochizuki S.I., Yano K., Fujise N., Sato Y., Goto M., Yamaguchi K., Kuriyama M., et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): A mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139:1329–1337. doi: 10.1210/endo.139.3.5837.
    1. Brose A., Parise G., Tarnopolsky M.A. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:11–19. doi: 10.1093/gerona/58.1.B11.
    1. Gualano B., Macedo A.R., Alves C.R., Roschel H., Benatti F.B., Takayama L., de Sa Pinto A.L., Lima F.R., Pereira R.M. Creatine supplementation and resistance training in vulnerable older women: A randomized double-blind placebo-controlled clinical trial. Exp. Gerontol. 2014;53:7–15. doi: 10.1016/j.exger.2014.02.003.
    1. Tarnopolsky M., Zimmer A., Paikin J., Safdar A., Aboud A., Pearce E., Roy B., Doherty T. Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS ONE. 2007;2:e991. doi: 10.1371/journal.pone.0000991.
    1. Forbes S.C., Chilibeck P.D., Candow D.G. Creatine Supplementation During Resistance Training Does Not Lead to Greater Bone Mineral Density in Older Humans: A Brief Meta-Analysis. Front. Nutr. 2018;5:27.
    1. Chilibeck P.D., Candow D.G., Landeryou T., Kaviani M., Paus-Jenssen L. Effects of Creatine and Resistance Training on Bone Health in Postmenopausal Women. Med. Sci. Sports Exerc. 2015;47:1587–1595.
    1. Pinto C.L., Botelho P.B., Carneiro J.A., Mota J.F. Impact of creatine supplementation in combination with resistance training on lean mass in the elderly. J. Cachexia Sarcopenia Muscle. 2016;7:413–421. doi: 10.1002/jcsm.12094.
    1. Candow D.G., Forbes S.C., Vogt E. Effect of pre-exercise and post-exercise creatine supplementation on bone mineral content and density in healthy aging adults. Exp. Gerontol. 2019;119:89–92. doi: 10.1016/j.exger.2019.01.025.
    1. Bender A., Beckers J., Schneider I., Holter S.M., Haack T., Ruthsatz T., Vogt-Weisenhorn D.M., Becker L., Genius J., Rujescu D., et al. Creatine improves health and survival of mice. Neurobiol. Aging. 2008;29:1404–1411.
    1. Aguiar A.F., Januario R.S., Junior R.P., Gerage A.M., Pina F.L., do Nascimento M.A., Padovani C.R., Cyrino E.S. Long-term creatine supplementation improves muscular performance during resistance training in older women. Eur. J. Appl. Physiol. 2013;113:987–996. doi: 10.1007/s00421-012-2514-6.
    1. Collins J., Longhurst G., Roschel H., Gualano B. Resistance Training and Co-supplementation with Creatine and Protein in Older Subjects with Frailty. J. Frailty Aging. 2016;5:126–134.
    1. Hass C.J., Collins M.A., Juncos J.L. Resistance training with creatine monohydrate improves upper-body strength in patients with Parkinson disease: A randomized trial. Neurorehabil. Neural Repair. 2007;21:107–115.
    1. Neves M., Gualano B., Roschel H., Fuller R., Benatti F.B., Pinto A.L., Lima F.R., Pereira R.M., Lancha A.H., Bonfa E. Beneficial effect of creatine supplementation in knee osteoarthritis. Med. Sci. Sports Exerc. 2011;43:1538–1543.
    1. Macrae P.G., Lacourse M., Moldavon R. Physical performance measures that predict faller status in community-dwelling older adults. J. Orthop. Sports Phys. Ther. 1992;16:123–128. doi: 10.2519/jospt.1992.16.3.123.
    1. Frank-Wilson A.W., Farthing J.P., Chilibeck P.D., Arnold C.M., Davison K.S., Olszynski W.P., Kontulainen S.A. Lower leg muscle density is independently associated with fall status in community-dwelling older adults. Osteoporos. Int. 2016;27:2231–2240.
    1. Jensen G.L. Inflammation: Roles in aging and sarcopenia. JPEN J. Parenter. Enteral Nutr. 2008;32:656–659. doi: 10.1177/0148607108324585.
    1. Abdelmagid S.M., Barbe M.F., Safadi F.F. Role of inflammation in the aging bones. Life Sci. 2015;123:25–34. doi: 10.1016/j.lfs.2014.11.011.
    1. Lawler J.M., Barnes W.S., Wu G., Song W., Demaree S. Direct antioxidant properties of creatine. Biochem. Biophys. Res. Commun. 2002;290:47–52. doi: 10.1006/bbrc.2001.6164.
    1. El-Benna J., Hurtado-Nedelec M., Marzaioli V., Marie J.C., Gougerot-Pocidalo M.A., Dang P.M. Priming of the neutrophil respiratory burst: Role in host defense and inflammation. Immunol. Rev. 2016;273:180–193. doi: 10.1111/imr.12447.
    1. Meng S.J., Yu L.J. Oxidative stress, molecular inflammation and sarcopenia. Int. J. Mol. Sci. 2010;11:1509–1526. doi: 10.3390/ijms11041509.
    1. Nomura A., Zhang M., Sakamoto T. Anti-inflammatory activity of creatine supplementation in endothelial cells in vitro. Br. J. Pharmacol. 2003;139:715–720. doi: 10.1038/sj.bjp.0705316.
    1. Almeida F.M., Oliveira-Junior M.C., Souza R.A., Petroni R.C., Soto S.F., Soriano F.G., Carvalho P.T., Albertini R., Damaceno-Rodrigues N.R., Lopes F.D., et al. Creatine supplementation attenuates pulmonary and systemic effects of lung ischemia and reperfusion injury. J. Heart Lung Transplant. 2016;35:242–250. doi: 10.1016/j.healun.2015.06.012.
    1. Tarnopolsky M.A., Bourgeois J.M., Snow R., Keys S., Roy B.D., Kwiecien J.M., Turnbull J. Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2003;285:R762–R769. doi: 10.1152/ajpregu.00270.2003.
    1. Santos R.V., Bassit R.A., Caperuto E.C., Costa Rosa L.F. The effect of creatine supplementation upon inflammatory and muscle soreness markers after a 30 km race. Life Sci. 2004;75:1917–1924. doi: 10.1016/j.lfs.2003.11.036.
    1. Bassit R.A., Curi R., Costa Rosa L.F. Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE2 after a half-ironman competition. Amino Acids. 2008;35:425–431. doi: 10.1007/s00726-007-0582-4.
    1. Deminice R., Rosa F.T., Franco G.S., Jordao A.A., de Freitas E.C. Effects of creatine supplementation on oxidative stress and inflammatory markers after repeated-sprint exercise in humans. Nutrition. 2013;29:1127–1132. doi: 10.1016/j.nut.2013.03.003.
    1. Deminice R., Jordao A.A. Creatine supplementation reduces oxidative stress biomarkers after acute exercise in rats. Amino Acids. 2012;43:709–715. doi: 10.1007/s00726-011-1121-x.
    1. Rawson E.S., Conti M.P., Miles M.P. Creatine supplementation does not reduce muscle damage or enhance recovery from resistance exercise. J. Strength Cond. Res. 2007;21:1208–1213.
    1. Cornish S.M., Peeler J.D. No effect of creatine monohydrate supplementation on inflammatory and cartilage degradation biomarkers in individuals with knee osteoarthritis. Nutr. Res. 2018;51:57–66. doi: 10.1016/j.nutres.2017.12.010.
    1. Hemati F., Rahmani A., Asadollahi K., Soleimannejad K., Khalighi Z. Effects of Complementary Creatine Monohydrate and Physical Training on Inflammatory and Endothelial Dysfunction Markers Among Heart Failure Patients. Asian J. Sports Med. 2016;7:e28578. doi: 10.5812/asjsm.28578.
    1. American College of Sports Medicine. Chodzko-Zajko W.J., Proctor D.N., Fiatarone Singh M.A., Minson C.T., Nigg C.R., Salem G.J., Skinner J.S. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med. Sci. Sports Exerc. 2009;41:1510–1530. doi: 10.1249/MSS.0b013e3181a0c95c.
    1. Candow D.G., Chilibeck P.D., Burke D.G., Mueller K.D., Lewis J.D. Effect of different frequencies of creatine supplementation on muscle size and strength in young adults. J. Strength Cond. Res. 2011;25:1831–1838. doi: 10.1519/JSC.0b013e3181e7419a.
    1. Candow D.G., Vogt E., Johannsmeyer S., Forbes S.C., Farthing J.P. Strategic creatine supplementation and resistance training in healthy older adults. Appl. Physiol. Nutr. Metab. 2015;40:689–694. doi: 10.1139/apnm-2014-0498.
    1. Trierweiler H., Kisielewicz G., Hoffmann T.J., Rasmussen R.P., Aguiar C.M., Zeghbi V.C. Sarcopenia: A chronic complication of type 2 diabetes mellitus. Diabetol. Metab. Syndr. 2018;10:25. doi: 10.1186/s13098-018-0326-5.
    1. Gualano B., de Salles Painelli V., Roschel H., Lugaresi R., Dorea E., Artioli G.G., Lima F.R., da Silva M.E., Cunha M.R., Seguro A.C., et al. Creatine supplementation does not impair kidney function in type 2 diabetic patients: A randomized, double-blind, placebo-controlled, clinical trial. Eur. J. Appl. Physiol. 2011;111:749–756. doi: 10.1007/s00421-010-1676-3.
    1. Bender A., Samtleben W., Elstner M., Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr. Res. 2008;28:172–178. doi: 10.1016/j.nutres.2008.01.001.
    1. Kreider R.B., Kalman D.S., Antonio J., Ziegenfuss T.N., Wildman R., Collins R., Candow D.G., Kleiner S.M., Almada A.L., Lopez H.L. International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. J. Int. Soc. Sports Nutr. 2017;14:18.

Source: PubMed

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