The Science

Bemben M.G., Bemben D.A., Loftiss D.D., Knehans A.W. Creatine Supplementation during Resistance Training in College Football Athletes. Med. Sci. Sports Exerc. 2001;33:1667–1673. doi: 10.1097/00005768-200110000-00009. [PubMed] [CrossRef] [Google Scholar]

Conclusions: Our findings indicate that creatine, supplemented concurrently with resistance and anaerobic training, may positively affect cell hydration status and enhance performance variables further than augmentation seen with training alone.

Burke D.G., Chilibeck P.D., Parise G., Candow D.G., Mahoney D., Tarnopolsky M. Effect of Creatine and Weight Training on Muscle Creatine and Performance in Vegetarians. Med. Sci. Sports Exerc. 2003;35:1946–1955. doi: 10.1249/01.MSS.0000093614.17517.79. [PubMed] [CrossRef] [Google Scholar]

Conclusions: These findings confirm an ergogenic effect of creatine during resistance training and suggest that subjects with initially low levels of intramuscular Cr (vegetarians) are more responsive to supplementation.

Candow, D.G.; Forbes, S.C.; Chilibeck, P.D.; Cornish, S.M.; Antonio, J.; Kreider, R.B. Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation. J. Clin. Med. 2019, 8, 488. [Google Scholar] [CrossRef]

Conclusions: Accumulating evidence indicates that creatine supplementation, with and without resistance training, has possible anti-sarcopenic and anti-dynapenic effects. Specifically, creatine supplementation increases aging muscle mass and strength (upper- and lower-body), possibly by influencing high-energy phosphate metabolism, muscle protein kinetics and growth factors. Creatine supplementation has shown potential to enhance bone mineral

Hall M., Trojian T.H. Creatine Supplementation. Curr. Sports Med. Rep. 2013;12:240–244. doi: 10.1249/JSR.0b013e31829cdff2. [PubMed] [CrossRef] [Google Scholar]

Conclusions: Creatine monohydrate is a dietary supplement that increases muscle performance in short-duration, high-intensity resistance exercises, which rely on the phosphocreatine shuttle for adenosine triphosphate. The effective dosing for creatine supplementation includes loading with 0.3 g·kg·d for 5 to 7 days.

Kreider, R.B.; Kalman, D.S.; Antonio, J.; Ziegenfuss, T.N.; Wildman, R.; Collins, R. 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. [Google Scholar] [CrossRef] [PubMed]

Synopsis: Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection.

Kreider, R.B.; Stout, J.R. Creatine in Health and Disease. Nutrients 2021, 13, 447.

Synopsis: The benefits of creatine monohydrate supplementation go well beyond increasing muscle Cr and PCr levels and thereby enhancing high-intensity exercise and training adaptations. Research has clearly shown several health and/or potential therapeutic benefits as we age and in clinical populations that may benefit by enhancing Cr and PCr levels.

Rawson E.S., Volek J.S. Effects of Creatine Supplementation and Resistance Training on Muscle Strength and Weightlifting Performance. J. Strength Cond. Res. 2003;17:822–831. [PubMed] [Google Scholar]

Conclusions: there is substantial evidence to indicate that creatine supplementation during resistance training is more effective at increasing muscle strength and weightlifting performance than resistance training alone

Artioli, G.; Gualano, B.; Smith, A.; Stout, J.; Lancha, A.H. Role of β-alanine supplementation on muscle carnosine and exercise performance. Med. Sci. Sports Exerc. 2010, 42, 1162–1173. [Google Scholar] [CrossRef]

Synopsis: BA may increase power output and working capacity, decrease the feeling of fatigue and exhaustion, and have of positive effect on body composition and carnosine content.

Saunders, B.; Elliott-Sale, K.; Artioli, G.G.; Swinton, P.A.; Dolan, E.; Roschel, H.; Sale, C.; Gualano, B. β-Alanine supplementation to improve exercise capacity and performance: A systematic review and meta-Analysis. Br. J. Sports Med. 2017, 51, 658–669. [Google Scholar] [CrossRef]

Synopsis: β-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors.

Conclusions: Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks)

Wilson, J.M.; Wilson, G.J.; Zourdos, M.C.; Smith, A.E.; Stout, J. Beta-alanine supplementation improves aerobic and anaerobic indices of performance. Strength Cond. J. 2010, 32, 71–78. [Google Scholar] [CrossRef]

Conclusions: Beta-alanine combined with creatine may augment performance to a greater extent than when administered separately (11,26,31), most likely as a result of a decreased accumulation of H+ ions during submaximal and maximal intensity exercises.

Furlong, J. Acetyl-L-Carnitine: Metabolism and Applications in Clinical Practice. Altern. Med. Rev. 1996, 1, 9. [Google Scholar]

Conclusions: As  Acetyl-L-Carnitine is easily transported across the blood-brain barrier, multiple benefits in CNS function have been observed in human stud- ies. Models of aging, stroke, Alzheimer’s de- mentia, diabetic neuropathy and neuropeptide release have been positively influenced by ALC administration. Acetyl-L-Carnitine is able to exert profound effects on some de- pressed patients with high cortisol levels and participates in immunomodulatory mecha- nisms which hold promise in the treatment of HIV infection.

Montgomery, S.A.; Thal, L.J.; Amrein, R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimers disease? Int. Clin. Psychopharmacol. 2003, 18, 61–71. [Google Scholar] [CrossRef]

Synopsis: A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases.

Zanelli, S.A.; Solenski, N.J.; Rosenthal, R.E.; Fiskum, G. Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann. N. Y. Acad. Sci. 2005, 1053, 153–161. [Google Scholar] [CrossRef]

Synopsis: The data obtained show that acetylcarnitine can have significant clinical neuroprotective effects when administered shortly after the onset of focal or global cerebral ischemia.

Cheuvront SN, Kenefick RW. Dehydration: physiology, assessment, and performance effects. Compr Physiol 4: 257–285, 2014. doi:10.1002/cphy.c130017. 
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Synopsis: sodium, and perhaps also of potassium, may be important for rehydration after exercise.

Maughan RJ, Leiper JB. Sodium intake and post-exercise rehydration in man. Eur J Appl Physiol Occup Physiol 71: 311–319, 1995. doi:10.1007/BF00240410. 
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Synopsis: These results suggest that the fraction of the ingested fluid that was retained was directly related to the sodium concentration.

Maughan RJ, Merson SJ, Broad NP, Shirreffs SM. Fluid and electrolyte intake and loss in elite soccer players during training. Int J Sport Nutr Exerc Metab 14: 333–346, 2004. doi:10.1123/ijsnem.14.3.333. 
Crossref | PubMed | ISI | Google Scholar

Shirreffs SM, Maughan RJ. Rehydration and recovery of fluid balance after exercise. Exerc Sport Sci Rev. 2000 Jan;28(1):27-32. PMID: 11131686.

Synopsis: Restoration of water and electrolyte balance is an essential part of the recovery process after exercise that results in sweat loss. Ingestion of plain water results in a fall in plasma sodium concentration and osmolality, reducing the drive to drink and stimulating urine output. Addition of sodium and potassium to rehydration fluids will decrease urine output in the hours after rehydration.

Maughan RJ, Shirreffs SM, Merson SJ, Horswill CA. Fluid and electrolyte balance in elite male football (soccer) players training in a cool environment. J Sports Sci 23: 73–79, 2005. doi:10.1080/02640410410001730115. 
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Merson SJ, Maughan RJ, Shirreffs SM. Rehydration with drinks differing in sodium concentration and recovery from moderate exercise-induced hypohydration in man. Eur J Appl Physiol 103: 585–594, 2008. doi:10.1007/s00421-008-0748-0. 
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Conclusions: The addition of 40 or 50 mmol/l of sodium chloride to a rehydration beverage reduced subsequent urine output, thereby providing more effective rehydration than a sodium-free drink.

Bezuglov, E.; Tikhonova, A.; Zueva, A.; Khaitin, V.; Waśkiewicz, Z.; Gerasimuk, D.; Żebrowska, A.; Rosemann, T.; Nikolaidis, P.; Knechtle, B. Prevalence and treatment of vitamin D deficiency in young male Russian soccer players in winter. Nutrients 2019, 11, 2405. [Google Scholar] [CrossRef] [PubMed]

Conclusions: Vitamin D deficiency and high level of activity in a young athlete may be the etiology to atypical multiple stress fractures. In athletes who may want to return to sport rapidly, early operative intervention and correction of vitamin D deficiency may be treatment options.

Hilger, J.; Friedel, A.; Herr, R.; Rausch, T.; Roos, F.; Wahl, D.A.; Pierroz, D.D.; Weber, P.; Hoffmann, K. A systematic review of vitamin D status in populations worldwide. Br. J. Nutr. 2014, 111, 23–45. [Google Scholar] [CrossRef]

Conclusions: One-third of the studies in the present systematic review reported mean 25(OH)D values below 50 nmol/l.

Synopsis: Vitamin D deficiency may cause deficits in strength, and lead to fatty degeneration of type II muscle fibers, which has been found to negatively correlate with physical performance. Vitamin D supplementation has been shown to improve vitamin D status and can positively affect skeletal muscles.

Myśliwec, A.; Skalska, M.; Knechtle, B.; Nikolaidis, P.T.; Rosemann, T.; Szmigiero-Kawko, M.; Lejk, A.; Jastrzębska, J.; Radzimiński, Ł.; Wakuluk, D.; et al. Acute responses to low and high intensity exercise in type 1 diabetic adolescents in relation to their level of serum 25(OH)D. Nutrients 2020, 12, 454. [Google Scholar] [CrossRef] [PubMed]

Synopsis: It is essential for athletes, both elite and recreational, to avoid vitamin D deficiency [a 25(OH)D concentration <25 nmol/l] year-round. This is particularly important when residing at latitude where UVB exposure is negligible during the winter months. Monitoring vitamin D status of athletic populations could be a useful way to identify individuals who may be at increased risk of stress fractures during intensive training and provide an opportunity to disseminate advice for improving vitamin D status. Maintaining an adequate vitamin D status may also confer additional health benefits for athletes in relation to musculoskeletal health (Lappe et al. 2008; Davey et al. 2016) and immunity (He et al. 2015).

Yagüe, M.L.P.; Yurrita, L.C.; Cabañas, M.J.C.; Cenzual, M.A.C. Role of vitamin d in athletes and their performance: Current concepts and new trends. Nutrients 2020, 12, 579. [Google Scholar] [CrossRef] [PubMed]

Synopsis: The importance and versatility of vitamin D in the organism is becoming increasingly evident. VITD plays an active role in immune function, protein synthesis, muscle function, cardiovascular function, inflammatory response, cell growth and musculoskeletal regulation

Allen, L.H.; Miller, J.W.; de Groot, L.; Rosenberg, I.H.; Smith, A.D.; Refsum, H.; Raiten, D.J. Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review. J. Nutr. 2018, 148 (Suppl. 4), 1995S–2027S. [Google Scholar] [CrossRef]

Read, M.H.; McGuffin, S.L. The effect of B-complex supplementation on endurance performance. J. Sports Med. Phys. Fitness 1983, 23, 178–184. [Google Scholar]

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Conclusions: These findings suggest a pivotal role for B12 in the control of cell growth, which may lead to coordination of cell behavior in complex multicellular systems. As key research questions emerge from host-associated and environmental microbiomes, we anticipate that B12 regulatory control of metabolism will be found to be generalizable, will be critical for coordination of individual microbe and community metabolism, and that organismal interdependencies for B12 may be pertinent to microbiome organization, stability, and overall function.

Caldeira D, Martins C, Alves LB, Pereira H, Ferreira JJ, Costa J. Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies. Heart. 2013;99(19):1383–9. PubMed Article Google Scholar 

Conclusions Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.

Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports. 1978;10(3):155–8.CAS PubMed Google Scholar 

Conclusions: Thus, the enhanced endurance performance observed in the C Trial was likely the combined effects of caffeine on lipolysis and its positive influence on nerve impulse transmission.

Kendall KL, Moon JR, Fairman CM, Spradley BD, Tai CY, Falcone PH, et al. Ingesting a preworkout supplement containing caffeine, creatine, beta-alanine, amino acids, and B vitamins for 28 days is both safe and efficacious in recreationally active men. Nutr Res. 2014;34(5):442–9.CAS PubMed Article Google Scholar 

Smith AE, Fukuda DH, Kendall KL, Stout JR. The effects of a pre-workout supplement containing caffeine, creatine, and amino acids during three weeks of high-intensity exercise on aerobic and anaerobic performance. J Int Soc Sports Nutr. 2010;7:10. PubMed PubMed Central Article CAS Google Scholar 

Fukuda DH, Smith AE, Kendall KL, Stout JR. The possible combinatory effects of acute consumption of caffeine, creatine, and amino acids on the improvement of anaerobic running performance in humans. Nutr Res. 2010;30(9):607–14. CAS PubMed Article Google Scholar 

 Conclusions: These findings suggest that the acute ingestion of this preexercise supplement may be an effective strategy for improving anaerobic performance.

Cameron M, Camic CL, Doberstein S, Erickson JL, Jagim AR. The acute effects of a multi-ingredient pre-workout supplement on resting energy expenditure and exercise performance in recreationally active females. J Int Soc Sports Nutr. 2018;15:1. PubMed PubMed Central Article Google Scholar 

Conclusions: acute multi-ingredient pre-workout supplement ingestion improved upper body muscular endurance and anaerobic capacity while improving feelings of focus following high-intensity exercise in recreationally active females.

Bergstrom HC, Byrd MT, Wallace BJ, Clasey JL. Examination of a multi-ingredient pre-workout supplement on total volume of resistance exercise andsubsequent strength and power performance. J Strength Cond Res. 2018;32(6):1479–90. PubMed Article Google Scholar 

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Synopsis: 1) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (>/= 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation.

Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R. Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land. Psychopharmacology. 2002;164(3):250–61. CAS PubMed Article Google Scholar 

Conclusions: Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

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Blusztajn, J.K.; Slack, B.E.; Mellott, T.J. Neuroprotective Actions of Dietary Choline. Nutrients 2017, 9, 815. [Google Scholar] [CrossRef] [PubMed]

Conclusion: Our present findings show novel mechanisms for the neuroprotective effects of citicoline, which cooperate to decrease brain glutamate release after ischemia.

Gareri, P.; Castagna, A.; Cotroneo, A.M.; Putignano, D.; Conforti, R.; Santamaria, F.; Marino, S.; Putignano, S. The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer’s Disease Study. J. Alzheimer’s Dis. 2017, 56, 557–565. [Google Scholar] [CrossRef]

Conclusions Citicoline may improve attentional performance in middle-aged women and may ameliorate attentional deficits associated with central nervous system disorders.

Nurk, E.; Refsum, H.; Bjelland, I.; Drevon, C.A.; Tell, G.S.; Ueland, P.M.; Vollset, S.E.; Engedal, K.; Nygaard, H.A.; Smith, D.A. Plasma free choline, betaine and cognitive performance: The Hordaland Health Study. Br. J. Nutr. 2013, 109, 511–519. [Google Scholar] [CrossRef]

Mashin VV, Belova LA, Bakhtogarimov IR, Bergelson TM, Sharafutdinova RR. Mnogotsentrovaia nabliudatel'naia programma po otsenke éffektivnosti preparata rekognan (tsitikolin) v korrektsii kognitivnykh narusheniĭ u patsientov s khronicheskoĭ tserebrovaskuliarnoĭ patologieĭ [Multicenter observational program for evaluation of the effectiveness of the recognan (citicoline) in the correction of cognitive impairment in patients with chronic cerebrovascular pathology]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(8):39-43. Russian. doi: 10.17116/jnevro20171178139-43. PMID: 28884715.

Conclusions: Citicoline reduced cognitive dysfunction and disturbances of visual/spatial coordination as well as had a positive effect on the emotional sphere decreasing the level of depression.