1.1. The Benefits of Vegetarian Diets on Health and Performance
1.3. Purpose of Creatine in Anaerobic Energy System Pathways
2. How Does Creatine Supplementation Affect Omnivores?
3. Differences in Creatine Levels in Muscle, Brain, and Blood in Vegetarians Versus Omnivores
4. Systematic Review of Creatine Supplementation in Vegetarians
4.1. Systematic Review Methodology
4.2. Systematic Review Results
4.3. Systematic Review Discussion
Conflicts of Interest
- Barr, S.I.; Rideout, C.A. Nutritional considerations for vegetarian athletes. Nutrition 2004, 20, 696–703. [Google Scholar] [CrossRef]
- Rogerson, D. Vegan diets: Practical advice for athletes and exercisers. JISSN 2017, 14, 36. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Melina, V.; Craig, W.; Levin, S. Position of the Academy of Nutrition and Dietetics: Vegetarian Diets. J. Acad. Nutr. Diet. 2016, 116, 1970–1980. [Google Scholar] [CrossRef] [PubMed]
- Barnard, N.D.; Cohen, J.; Jenkins, D.J.; Turner-McGrievy, G.; Gloede, L.; Jaster, B.; Seidl, K.; Green, A.A.; Talpers, S. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care 2006, 29, 1777–1783. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Schmitz, H.; Chevaux, K. Defining the role of dietary phytochemicals in modulating human immune function. In Nutrition and Immunology; Humana Press: New York, NY, USA, 2000; pp. 107–119. [Google Scholar]
- Gleeson, M. Can nutrition limit exercise-induced immunodepression? Nutr. Rev. 2006, 64, 119Y31. [Google Scholar] [CrossRef]
- Fuhrman, J.; Ferreri, D. Fueling the Vegetarian (Vegan) Athlete: Corrigenda. Curr. Sports Med. Rep. 2010, 9, 313. [Google Scholar] [CrossRef] [PubMed]
- Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets. J. Am. Diet. Assoc. 2003, 103, 748–765. [CrossRef]
- Neacsu, M.; Fyfe, C.; Horgan, G.; Johnstone, A.M. Appetite control and biomarkers of satiety with vegetarian (soy) and meat-based high-protein diets for weight loss in obese men: A randomized crossover trial. Am. J. Clin. Nutr. 2014, 100, 548–558. [Google Scholar] [CrossRef][Green Version]
- Loucks, A.B. Energy balance and body composition in sports and exercise. J. Sports Sci. 2004, 22, 1–14. [Google Scholar] [CrossRef]
- Clarys, P.; Deliens, T.; Huybrechts, I.; Deriemaeker, P.; Vanaelst, B.; De Keyzer, W.; Hebbelinck, M.; Mullie, P. Comparison of nutritional quality of the vegan, vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diet. Nutrients 2014, 6, 1318–1332. [Google Scholar] [CrossRef]
- Venderley, A.M.; Campbell, W.W. Vegetarian diets: Nutritional considerations for athletes. Sports Med. 2006, 36, 293–305. [Google Scholar] [CrossRef]
- Kniskern, M.A.; Johnston, C.S. Protein dietary reference intakes may be inadequate for vegetarians if low amounts of animal protein are consumed. Nutrition 2011, 27, 727–730. [Google Scholar] [CrossRef] [PubMed]
- Young, V.R.; Pellett, P.L. Plant proteins in relation to human protein and amino acid nutrition. Am. J. Clin. Nutr. 1994, 59, 1203S. [Google Scholar] [CrossRef]
- Balestrino, M.; Adriano, E. Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle. Med. Res. Rev. 2019, 39, 2427–2459. [Google Scholar] [CrossRef] [PubMed]
- Delanghe, J.; De Slypere, J.P.; De Buyzere, M.; Robbrecht, J.; Wieme, R.; Vermeulen, A. Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin. Chem. 1989, 35, 1802–1803. [Google Scholar] [CrossRef]
- Lukaszuk, J.M.; Robertson, R.J.; Arch, J.E.; Moore, G.E.; Yaw, K.M.; Kelley, D.E.; Rubin, J.T.; Moyna, N.M. Effect of creatine supplementation and a lacto-ovo-vegetarian diet on muscle creatine concentration. Int. J. Sport Nutr. Exerc. Metab. 2002, 12, 336–348. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Solis, M.Y.; De, S.P.; Artioli, G.G.; Roschel, H.; Otaduy, M.C.; Gualano, B. Brain creatine depletion in vegetarians? A crosssectional 1H-magnetic resonance spectroscopy (1H-MRS) study. Br. J. Nutr. 2014, 111, 1272–1274. [Google Scholar] [CrossRef][Green Version]
- Mahmood, L. The metabolic processes of folic acid and Vitamin B12 deficiency. J. Health Res. Rev. 2014, 1, 5. [Google Scholar] [CrossRef]
- Stekol, J.A.; Weiss, S.; Smith, P.; Weiss, K. The synthesis of choline and creatine in rats under various dietary conditions. J. Biol. Chem. 1953, 201, 299–316. [Google Scholar]
- Wallimann, T.; Tokarska-Schlattner, M.; Schlattner, U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids 2011, 40, 1271–1296. [Google Scholar] [CrossRef][Green Version]
- Branch, J.D. Effect of Creatine Supplementation on Body Composition and Performance: A Meta-analysis. Int. J. Sport Nutr. Exerc. Metab. 2003, 3, 198–226. [Google Scholar]
- Mielgo-Ayuso, J.; Calleja-Gonzalez, J.; Marqués-Jiménez, D.; Caballero-García, A.; Córdova, A.; Fernández-Lázaro, D. Effects of Creatine Supplementation on Athletic Performance in Soccer Players: A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 757. [Google Scholar] [CrossRef][Green Version]
- 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. [Google Scholar] [CrossRef]
- Dorrell, H.F.; Gee, T.I.; Middleton, G. An Update on Effects of Creatine Supplementation on Performance: A Review. Sports Nutr. Ther. 2016, 1, 2473–6449. [Google Scholar] [CrossRef][Green Version]
- 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. [Google Scholar] [CrossRef][Green Version]
- Lanhers, C.; Pereira, B.; Naughton, G.; Trousselard, M.; Lesage, F.X.; Dutheil, F. Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis. Sports Med. 2017, 47, 163–173. [Google Scholar] [CrossRef][Green Version]
- Lanhers, C.; Pereira, B.; Naughton, G.; Trousselard, M.; Lesage, F.X.; Dutheil, F. Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses. Sports Med. 2015, 45, 1285–1294. [Google Scholar] [CrossRef]
- Kaviani, M.; Abassi, A.; Chilibeck, P.D. Creatine monohydrate supplementation during eight weeks of progressive resistance training increases strength in as little as two weeks without reducing markers of muscle damage. J. Sports Med. Phys. Fit. 2019, 59, 608–612. [Google Scholar] [CrossRef]
- Clark, J.F. Creatine: A review of its nutritional applications in sport. Nutrition 1998, 14, 322–324. [Google Scholar] [CrossRef]
- 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 50 -monophosphate contents in breast and thigh meats from 5 lines of Korean native chicken. Poult. Sci. 2013, 92, 3275–3282. [Google Scholar] [CrossRef]
- Solis, M.Y.; Artioli, G.G.; Otaduy, M.C.G.; Leite, C.D.C.; Arruda, W.; Veiga, R.R.; Gualano, B. Effect of age, diet, and tissue type on PCr response to creatine supplementation. J. Appl. Physiol. 2017, 123, 407–414. [Google Scholar] [CrossRef][Green Version]
- Blancquaert, L.; Baguet, A.; Bex, T.; Volkaert, A.; Everaert, I.; Delanghe, J.; Petrovic, M.; Vervaet, C.; De Henauw, S.; Constantin-Teodosiu, D.; et al. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: A randomised trial. Br. J. Nutr. 2018, 119, 759–770. [Google Scholar] [CrossRef]
- Shomrat, A.; Weinstein, Y.; Katz, A. Effect of creatine feeding on maximal exercise performance in vegetarians. Eur. J. Appl. Physiol. 2000, 82, 321–325. [Google Scholar] [CrossRef]
- Maccormick, V.M.; Hill, L.M.; Macneil, L.; Burke, D.G.; Smith-Palmer, T. Elevation of creatine in red blood cells in vegetarians and nonvegetarians after creatine supplementation. Can. J. Appl. Physiol. 2004, 29, 704–713. [Google Scholar] [CrossRef]
- Watt, K.K.; Garnham, A.P.; Snow, R.J. Skeletal muscle total creatine content and creatine transporter gene expression in vegetarians prior to and following creatine supplementation. Int. J. Sport Nutr. Exerc. Metab. 2004, 14, 517–531. [Google Scholar] [CrossRef]
- Layec, G.; Malucelli, E.; Le Fur, Y.; Manners, D.; Yashiro, K.; Testa, C.; Cozzone, P.J.; Iotti, S.; Bendahan, D. Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: A 31P MRS study in three muscle groups in humans. NMR Biomed. 2013, 26, 1403–1411. [Google Scholar] [CrossRef]
- Han, C.H.; Sillerud, L.O. Synthesis of [guanidino-13C] creatine and measurement of the creatine phosphokinase reaction in vitro by 13C NMR spectroscopy. Magn. Reson. Med. 1986, 3, 626–633. [Google Scholar] [CrossRef]
- Benzi, G.; Ceci, A. Creatine as nutritional supplementation and medicinal product. J. Sports Med. Phys. Fit. 2001, 41, 1–10. [Google Scholar]
- Rodríguez-Gandullo, J.A.; Álvarez-Barbosa, F. Effects of strength training and supplementation in vegetarian people: Systematic review. Retos 2018, 34, 247–251. [Google Scholar]
- Sterne, J.A.C.; Savović, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.-Y.; Corbett, M.S.; Eldridge, S.M.; et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ 2019, 366, l4898. [Google Scholar] [CrossRef][Green Version]
- Lukaszuk, J.M.; Robertson, R.J.; Arch, J.E.; Moyna, N.M. Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration. J. Strength Cond. Res. 2005, 19, 735–740. [Google Scholar]
- Burke, D.G.; Candow, D.G.; Chilibeck, P.D.; MacNeil, L.G.; Roy, B.D.; Tarnopolsky, M.A.; Ziegenfuss, T. Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. Int. J. Sport Nutr. Exerc. Metab. 2008, 18, 389–398. [Google Scholar] [CrossRef][Green Version]
- Benton, D.; Donohoe, R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br. J. Nutr. 2011, 105, 1100–1105. [Google Scholar] [CrossRef][Green Version]
- Rae, C.; Digney, A.L.; McEwan, S.R.; Bates, T.C. Oral creatine monohydrate supplementation improves brain performance: A double-blind, placebo-controlled, cross-over trial. Proc. Biol. Sci. 2003, 270, 2147–2150. [Google Scholar] [CrossRef][Green Version]
- Harris, R.C.; Söderlund, K.; Hultman, E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin. Sci. 1992, 83, 367–374. [Google Scholar] [CrossRef][Green Version]
- Farthing, J.P.; Borowsky, R.; Chilibeck, P.D.; Binsted, G.; Sarty, G.E. Neuro-physiological adaptations associated with cross-education of strength. Brain Topogr. 2007, 20, 77–88. [Google Scholar] [CrossRef]
- Jones, A.M.; Carter, H.; Pringle, J.S.; Campbell, I.T. Effect of creatine supplementation on oxygen uptake kinetics during submaximal cycle exercise. J. Appl. Physiol. 2002, 92, 2571–2577. [Google Scholar] [CrossRef][Green Version]
|Solis et al. ||8 male, 6 female vegetarians (4 vegan, 9 lacto–ovo, 1 ovo); duration vegetarian ~10 y|
11 male, 6 female omnivoresMean age ~30 y
Approximately equal number in each group classified as having low, moderate, and high levels of physical activity
|Non-randomized cross-over study|
Participants were given placebo for 7 d, then 0.3 g Cr/kg/d for 7 d
|Gastrocnemius PCr increased by 25% after Cr supplementation in vegetarians with no increase in omnivores.|
Gastrocnemius PCr was about 5% lower before Cr supplementation in vegetarians but 17% higher after Cr supplementation versus omnivores.
Brain PCr: no change in either group with Cr supplementation.
|Blancquaert et al. ||40 female omnivores|
Mean age ~26 y
n = 10 controls
n = 15 given a lacto–ovo vegetarian diet for 6 months + 1 g Cr/d
n = 15 given lacto–ovo vegetarian diet for 6 months + placebo
|After 3 months:|
Vastus lateralis TCr decreased 15% with vegetarian + placebo; increased 9.7% with vegetarian + Cr; increased 6.8% with control.
After 6 months:
Plasma Cr decreased 46% with vegetarian + placebo; increased 195% with vegetarian + Cr; no change with control.
Performance on an incremental cycling test to exhaustion: no change. over the 6 months
|Shomrat et al. ||7 male vegetarians|
17 male omnivores
Active, but not highly trained
Mean age ~28 y
9 omnivores and the 7 vegetarians received 3 × 7 g Cr/d for 6 d
8 omnivores received placebo
|Performance on 3 × 20 s modified Wingate maximal cycling tests with 4 min recovery between bouts:|
Mean power output increased 5% in vegetarians and omnivores supplemented with Cr, but not with placebo.
Peak power output increased 5% only in omnivores on Cr.
|MacCormick et al. ||6 female vegetarians|
6 female omnivores
Mean age ~22 y
Physically active, but not athletes
Participants were given 0.3 g Cr/kg LTM/d for 5 d
|Vegetarians increased Cr in erythrocytes (140%) and plasma (258%); omnivores increased Cr in erythrocytes (53%) and plasma (116%).|
At 5 d, vegetarians had 89% higher plasma Cr compared to omnivores.
|Watt et al. ||7 male vegetarians (4 vegans, 3 lacto–ovo vegetarians), at least 6 months duration vegetarian; mean age 23 y|
7 male omnivores, mean age 28 y
|Randomized cross-over study|
0.4 g Cr/kg/d or placebo for 5 d
|Vastus lateralis TCr increased 76% in vegetarians with Cr supplementation versus 35% in omnivores.|
Vastus lateralis PCr increased by ~31% in both groups with Cr supplementation.
Vastus lateralis TCr was lower in vegetarians at baseline, but 12% higher than omnivores after 5 d Cr supplementation.
Vastus lateralis Cr transporter mRNA increased 1 d into Cr supplementation in both groups, then returned to baseline levels at 5 d.
2 × 30 s Wingate maximal cycling test with 4 min recovery between bouts:
Cr supplementation increased mean power output for both groups on the 2nd bout.
|Lukaszuk et al. [17,43]||26 male omnivores|
Mean age 23.5 y
Physically active, but not strength trained
n = 14 controls
n = 12 given lacto–ovo vegetarian diet for 26 dOn day 22:
Participants were randomized to receive 0.3 g Cr/kg or placebo
|After 21 d, participants who were given the lacto–ovo diet decreased vastus lateralis TCr (9.5%), PCr (8.7%), Cr (11%), and plasma Cr (9.1%).|
From day 22 to 27, TCr increased in the vegetarian Cr-supplemented group (20%) and the omnivorous Cr-supplemented group (10%) compared to the vegetarian placebo group (−2%) and the omnivorous placebo group (0%). Plasma Cr increased across Cr supplementation groups (13.3%) compared to placebo groups (0.5%).
|Burke et al. [18,44]||8 male, 10 female vegetarians (3 vegans, 15 lacto–ovo vegetarians; vegetarian duration at least 3 y)|
12 male, 12 female omnivores
All participants were recreational athletes (walking, jogging, swimming, cycling) with 1–5 y resistance training experience
Mean age ~33 y
n = 5 male, 5 female vegetarians and 7 male, 5 female omnivores given 0.25 g Cr/kg LTM/d for 7 d, 0.0625 Cr/kg LTM/d for 49 d
n = 3 male, 5 female vegetarians and 5 males, 7 female omnivores given placebo for 56 d
All participants engaged in a high-volume resistance training program (training all major muscle groups) for 56 d
|Vegetarians on Cr had greater increase in vastus lateralis PCr (+66%) than omnivores on Cr (+19%), vegetarians on placebo (−18%), and omnivores on placebo (+6%).|
Vegetarians on Cr had greater increase in vastus lateralis TCr (+30%) than omnivores on Cr (+8%), vegetarians on placebo (−4%), and omnivores on placebo (+4%).
Vegetarians on Cr increased lean tissue mass 2.4 kg, which was greater than omnivores on Cr (1.9 kg) and other groups (1 kg).
Vegetarians on Cr had greater increase in total work during 50 isokinetic knee extensions/flexions (30%) than omnivores on Cr (9%), vegetarians on placebo (8%), and omnivores on placebo (4%).
Both creatine groups increased bench press strength, type II vastus lateralis fiber area, and muscle insulin-like growth factor-1 more than placebo groups.
|Benton et al. ||70 female vegetarians|
51 female omnivores
Mean age ~20.3 y
Participants given either 20 g Cr/d or placebo for 5 d
|Memory was enhanced in vegetarians on Cr, but not omnivores.|
|Rae et al. ||45 vegetarians (12 males, 33 females; 18 vegans for median duration 4.6 y; 27 lacto–ovo vegetarians for median duration 14.3 y)|
Mean age ~26 y
|Randomized cross-over study|
6 weeks with 5 g Cr/d or placebo
|Working memory and intelligence were increased during creatine compared to placebo supplementation.|
|Study||Risk of Bias Domains|
|Randomization Process||Deviations from the Intended Intervention||Missing Outcome Data||Measurement of the Outcome||Selection of the Reported Result||Overall Risk of Bias|
|Benton et al. ||Some concerns||Low||Low||Low||Low||Some concerns|
|Blancquaert et al. ||Low||Low||Low||Low||Low||Low|
|Burke et al. [18,44]||Some concerns||Low||Low||Low||Low||Some concerns|
|Lukaszuk et al. [17,43]||Some concerns||Low||Low||Some concerns||Low||Some concerns|
|MacCormick et al. ||High||Some concerns||Low||Low||Low||High|
|Rae et al. ||High||Low||Low||Low||Low||High|
|Shomrat et al. ||High||Low||Low||Some concerns||Low||High|
|Solis et al. ||High||High||Some concerns||Low||Low||High|
|Watt et al. ||High||Some concerns||Some concerns||Low||Low||High|
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