Coffee and Caffeine Consumption for Human Health Printed Edition of the Special Issue Published in Nutrients www.mdpi.com/journal/nutrients Juan Del Coso Edited by Coffee and Caffeine Consumption for Human Health Coffee and Caffeine Consumption for Human Health Special Issue Editor Juan Del Coso MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Special Issue Editor Juan Del Coso Rey Juan Carlos University Spain Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Nutrients (ISSN 2072-6643) (available at: https://www.mdpi.com/journal/nutrients/special issues/ Coffee Caffeine Health). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year , Article Number , Page Range. 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Contents About the Special Issue Editor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Juan Del Coso, Juan Jos ́ e Salinero and Beatriz Lara Effects of Caffeine and Coffee on Human Functioning Reprinted from: Nutrients 2020 , 12 , 125, doi:10.3390/nu12010125 . . . . . . . . . . . . . . . . . . . 1 Juan Jos ́ e Salinero, Beatriz Lara, Ester Jim ́ enez-Orme ̃ no, Blanca Romero-Moraleda, Ver ́ onica Gir ́ aldez-Costas, Gabriel Baltazar-Martins and Juan Del Coso More Research Is Necessary to Establish the Ergogenic Effect of Caffeine in Female Athletes Reprinted from: Nutrients 2019 , 11 , 1600, doi:10.3390/nu11071600 . . . . . . . . . . . . . . . . . . 7 Mill ́ an Aguilar-Navarro, Gloria Mu ̃ noz, Juan Jos ́ e Salinero, Jes ́ us Mu ̃ noz-Guerra, Mar ́ ıa Fern ́ andez- ́ Alvarez, Mar ́ ıa del Mar Plata and Juan Del Coso Urine Caffeine Concentration in Doping Control Samples from 2004 to 2015 Reprinted from: Nutrients 2019 , 11 , 286, doi:10.3390/nu11020286 . . . . . . . . . . . . . . . . . . . 11 Alejandro F. San Juan, ́ Alvaro L ́ opez-Samanes, Pablo Jodra, Pedro L. Valenzuela, Javier Rueda, Pablo Veiga-Herreros, Alberto P ́ erez-L ́ opez and Ra ́ ul Dom ́ ınguez Caffeine Supplementation Improves Anaerobic Performance and Neuromuscular Efficiency and Fatigue in Olympic-Level Boxers Reprinted from: Nutrients 2019 , 11 , 2120, doi:10.3390/nu11092120 . . . . . . . . . . . . . . . . . . 23 Domingo Jes ́ us Ramos-Campo, Andr ́ es P ́ erez, Vicente ́ Avila-Gand ́ ıa, Silvia P ́ erez-Pi ̃ nero and Jacobo ́ Angel Rubio-Arias Impact of Caffeine Intake on 800-m Running Performance and Sleep Quality in Trained Runners Reprinted from: Nutrients 2019 , 11 , 2040, doi:10.3390/nu11092040 . . . . . . . . . . . . . . . . . . 39 Sandro Venier, Jozo Grgic and Pavle Mikulic Caffeinated Gel Ingestion Enhances Jump Performance, Muscle Strength, and Power in Trained Men Reprinted from: Nutrients 2019 , 11 , 937, doi:10.3390/nu11040937 . . . . . . . . . . . . . . . . . . . 49 Michal Wilk, Aleksandra Filip, Michal Krzysztofik, Adam Maszczyk and Adam Zajac The Acute Effect of Various Doses of Caffeine on Power Output and Velocity during the Bench Press Exercise among Athletes Habitually Using Caffeine Reprinted from: Nutrients 2019 , 11 , 1465, doi:10.3390/nu11071465 . . . . . . . . . . . . . . . . . . 63 Blanca Romero-Moraleda, Juan Del Coso, Jorge Guti ́ errez-Hell ́ ın and Beatriz Lara The Effect of Caffeine on the Velocity of Half-Squat Exercise during the Menstrual Cycle: A Randomized Controlled Trial Reprinted from: Nutrients 2019 , 11 , 2662, doi:10.3390/nu11112662 . . . . . . . . . . . . . . . . . . 75 Michal Wilk, Michal Krzysztofik, Aleksandra Filip, Adam Zajac and Juan Del Coso The Effects of High Doses of Caffeine on Maximal Strength and Muscular Endurance in Athletes Habituated to Caffeine Reprinted from: Nutrients 2019 , 11 , 1912, doi:10.3390/nu11081912 . . . . . . . . . . . . . . . . . . 85 Michal Wilk, Michal Krzysztofik, Aleksandra Filip, Adam Zajac and Juan Del Coso Correction: Wilk et al. “The Effects of High Doses of Caffeine on Maximal Strength and Muscular Endurance in Athletes Habituated to Caffeine” Nutrients, 2019, 11(8), 1912 Reprinted from: Nutrients 2019 , 11 , 2660, doi:10.3390/nu11112660 . . . . . . . . . . . . . . . . . . 99 v Hamdi Chtourou, Khaled Trabelsi, Achraf Ammar, Roy Jesse Shephard and Nicola Luigi Bragazzi Acute Effects of an “Energy Drink” on Short-Term Maximal Performance, Reaction Times, Psychological and Physiological Parameters: Insights from a Randomized Double-Blind, Placebo-Controlled, Counterbalanced Crossover Trial Reprinted from: Nutrients 2019 , 11 , 992, doi:10.3390/nu11050992 . . . . . . . . . . . . . . . . . . . 101 Juan Del Coso, Beatriz Lara, Carlos Ruiz-Moreno and Juan Jos ́ e Salinero Challenging the Myth of Non-Response to the Ergogenic Effects of Caffeine Ingestion on Exercise Performance Reprinted from: Nutrients 2019 , 11 , 732, doi:10.3390/nu11040732 . . . . . . . . . . . . . . . . . . . 115 Paulo Estev ̃ ao Franco-Alvarenga, Cayque Brietzke, Raul Canestri, M ́ arcio Fagundes Goethel, Bruno Ferreira Viana and Fl ́ avio Oliveira Pires Caffeine Increased Muscle Endurance Performance Despite Reduced Cortical Activation and Unchanged Neuromuscular Efficiency and Corticomuscular Coherence Reprinted from: Nutrients 2019 , 11 , 2471, doi:10.3390/nu11102471 . . . . . . . . . . . . . . . . . . 123 Akbar Shabir, Andy Hooton, George Spencer, Mitch Storey, Olivia Ensor, Laura Sandford, Jason Tallis, Bryan Saunders and Matthew F. Higgins The Influence of Caffeine Expectancies on Simulated Soccer Performance in Recreational Individuals Reprinted from: Nutrients 2019 , 11 , 2289, doi:10.3390/nu11102289 . . . . . . . . . . . . . . . . . . 137 Juan Mielgo-Ayuso, Diego Marques-Jim ́ enez, Ignacio Refoyo, Juan Del Coso, Patxi Le ́ on-Guere ̃ no and Julio Calleja-Gonz ́ alez Effect of Caffeine Supplementation on Sports Performance Based on Differences Between Sexes: A Systematic Review Reprinted from: Nutrients 2019 , 11 , 2313, doi:10.3390/nu11102313 . . . . . . . . . . . . . . . . . . 159 Juan Mielgo-Ayuso, Julio Calleja-Gonzalez, Juan Del Coso, Aritz Urdampilleta, Patxi Le ́ on-Guere ̃ no and Diego Fern ́ andez-L ́ azaro Caffeine Supplementation and Physical Performance, Muscle Damage and Perception of Fatigue in Soccer Players: A Systematic Review Reprinted from: Nutrients 2019 , 11 , 440, doi:10.3390/nu11020440 . . . . . . . . . . . . . . . . . . . 177 Satoshi Tsuda, Tatsuya Hayashi and Tatsuro Egawa The Effects of Caffeine on Metabolomic Responses to Muscle Contraction in Rat Skeletal Muscle Reprinted from: Nutrients 2019 , 11 , 1819, doi:10.3390/nu11081819 . . . . . . . . . . . . . . . . . . 193 Antonella Samoggia and Bettina Riedel Consumers’ Perceptions of Coffee Health Benefits and Motives for Coffee Consumption and Purchasing Reprinted from: Nutrients 2019 , 11 , 653, doi:10.3390/nu11030653 . . . . . . . . . . . . . . . . . . . 207 Regina Wierzejska, Mirosław Jarosz and Barbara Wojda Caffeine Intake During Pregnancy and Neonatal Anthropometric Parameters Reprinted from: Nutrients 2019 , 11 , 806, doi:10.3390/nu11040806 . . . . . . . . . . . . . . . . . . . 229 Hyeong Jun Kim, Min Sun Choi, Shaheed Ur Rehman, Young Seok Ji, Jun Sang Yu, Katsunori Nakamura and Hye Hyun Yoo Determination of Urinary Caffeine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities Reprinted from: Nutrients 2019 , 11 , 1947, doi:10.3390/nu11081947 . . . . . . . . . . . . . . . . . . 239 vi Ki-Young Ryu and Jaesook Roh The Effects of High Peripubertal Caffeine Exposure on the Adrenal Gland in Immature Male and Female Rats Reprinted from: Nutrients 2019 , 11 , 951, doi:10.3390/nu11050951 . . . . . . . . . . . . . . . . . . . 255 Marina Sartini, Nicola Luigi Bragazzi, Anna Maria Spagnolo, Elisa Schinca, Gianluca Ottria, Chiara Dupont and Maria Luisa Cristina Coffee Consumption and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Studies Reprinted from: Nutrients 2019 , 11 , 694, doi:10.3390/nu11030694 . . . . . . . . . . . . . . . . . . . 267 vii About the Special Issue Editor Juan Del Coso is the Director of the Exercise and Training Laboratory at Rey Juan Carlos University and he lectures on athletics and sports performance assessment. During the last 15 years, he has been working in the field of exercise physiology, devoted to developing new strategies to increase sports performance. After he obtained a bachelor’s degree in Sport Sciences (2002, Castilla La Mancha University), he started to investigate the benefits of merging rehydration, carbohydrate intake, and caffeine intake on endurance performance and this was the topic of his Ph.D. dissertation in sports performance (2007, Castilla La Mancha University). He obtained two post-doc fellowships at the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas and UT Southwestern Medical Center (2007) and in the Spanish Anti-Doping Agency (2008). Then, he became the Director of the Exercise Physiology Laboratory at Camilo Jose ́ Cela University (2010), where he spent 9 years building a research group focused on studying sports nutrition, genetics, and doping behaviors. He has just started a new s t ep in his career at Rey Juan Carlos University where he will collaborate to expand the knowledge on evidence-based, safe, and legal approaches to enhance sport performance. ix nutrients Editorial E ff ects of Ca ff eine and Co ff ee on Human Functioning Juan Del Coso 1, *, Juan Jos é Salinero 2 and Beatriz Lara 2 1 Centre for Sport Studies, Rey Juan Carlos University, Fuenlabrada, 28943 Madrid, Spain 2 Exercise Physiology Laboratory, Camilo Jos é Cela University, 28692 Madrid, Spain; jjsaalinero@ucjc.edu (J.J.S.); blara@ucjc.edu (B.L.) * Correspondence: juan.delcoso@urjc.es; Tel.: + 34-918444694 Received: 17 December 2019; Accepted: 20 December 2019; Published: 2 January 2020 As expected, 2019 has been a prolific year in terms of new evidence regarding the e ff ects of co ff ee and ca ff eine consumption on diverse aspects of human functioning. A search in PubMed for published studies in 2019 on the e ff ects of ca ff eine or co ff ee on humans, following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [ 1 ], showed a total of 202 manuscripts that contained “co ff ee” (n = 65, which represents 32.2% of the total) or “ca ff eine” (n = 137, which represents 67.8% of the total) in the title of the manuscript (Figure 1). In the group of studies that investigated the e ff ect of co ff ee intake, 58 (89.2%) were related to the use of this beverage to modify one or more health outcomes, five (7.7%) were related to the use of co ff ee to improve human performance and two (3.1%) assessed regular intake of co ff ee. In the group of studies that investigated the e ff ect of ca ff eine intake (in most cases measured as the sum of all the sources containing ca ff eine such as co ff ee, tea, chocolate, energy drinks, etc.), 79 (57.7%) were associated with the use of ca ff eine with health variables, 52 (38.0%) were associated with the use of ca ff eine with ergogenic purposes, six (4.4%) were associated with regular ca ff eine intake. Briefly, this analysis shows the elevated amount of new information published each year regarding the utility of co ff ee and ca ff eine to produce a change in human functioning while reveals that most of the indications of co ff ee and ca ff eine are associated with producing a benefit on health or with enhancing human performance. Figure 1. Number of articles published in 2019 that investigated the e ff ects of co ff ee or ca ff eine on humans. This special edition in Nutrients has brought together a variety of investigation that imitates the pattern of published manuscripts commented above. This issue entitled “Co ff ee and Ca ff eine Nutrients 2020 , 12 , 125; doi:10.3390 / nu12010125 www.mdpi.com / journal / nutrients 1 Nutrients 2020 , 12 , 125 Consumption for Human Health” gathered 20 manuscripts; two (10.0%) were associated with co ff ee intake and 18 (90%) were associated with ca ff eine intake. In the manuscripts associated with the use of co ff ee, one original investigation was geared to study the perceptions of consumers regarding the health benefits that they might obtain with the regular consumption of this beverage [ 2 ]. Interestingly, 75.2% of the study sample perceived co ff ee as negative for their health, while the investigation determined that co ff ee users that seek potential health benefits of co ff ee are more likely to be male, young, and working. The other investigation associated with co ff ee intake was a systematic review and meta-analysis of prospective studies on the e ff ect of this beverage on the risk of colorectal cancer [ 3 ]. In this study, a total of 26 investigations were analyzed while the main finding was a weak but significant protective e ff ect of habitual co ff ee intake on the risk of su ff ering colon cancer. In addition, the regular intake of deca ff einated co ff ee exerted a protective e ff ect against colorectal cancer, suggesting that part of the positive e ff ect of co ff ee to reduce the risk of su ff ering colorectal cancer is independent of ca ff eine. Both investigations reflect the beliefs and patterns of our society because evidence shows that the regular intake of co ff ee can have a positive impact on several health outcomes [ 4 ]. Nevertheless, consumers are still cautious about drinking co ff ee because of the negative image of co ff ee-(particularly ca ff einated co ff ee), which is not based on the latest scientific evidence [ 2 ]. More e ff orts should be made to translate to our society the new pieces of evidence that support the positive e ff ect of regular co ff ee consumption on health, in addition to the caution that should be taken in terms of dose, interactions with other substances, and prevalence of side-e ff ects (e.g., stimulant-like e ff ects). The remaining 18 studies of this issue investigated the e ff ect of ca ff eine. There was a particular focus on the ergogenic e ff ect of ca ff eine as 14 (77.8% of the investigations with ca ff eine in this special issue) investigations were related to this topic. The amount of ca ff eine ingested on a regular basis was associated with two (11.1%), and the remaining two (11.1%) determined the e ff ect of ca ff eine on health variables. In the investigations that studied ca ff eine’s ergogenicity, several shared a common message because they reflect that the acute intake of ca ff eine (from ~1 to ~6 mg / kg of body mass) was e ff ective to improve di ff erent aspects of physical and sport performance [ 5 – 9 ], along with enhancement in reaction times and psychological parameters [ 6 ]. In addition, several investigations responded to an Editorial [ 10 ] that fostered investigations to assess the e ff ect of acute ca ff eine intake in female athletes because most of the current knowledge about the ca ff eine’s ergogenicity is based on investigations carried out with only-male study samples. As an answer to this call, Mielgo-Ayuso et al. [ 11 ] presented an analysis, based on a systematic review, indicating that acute ca ff eine intake exhibited a similar ergogenic benefit for aerobic performance in men and women athletes. However, the ergogenic e ff ect of ca ff eine was inferior in women than in men in strength- and power-based tests, even when the same dose of ca ff eine was being administered. This significant, although low in magnitude, e ff ect of ca ff eine to increase muscle power and force in women was confirmed by Romero-Moraleda [ 12 ], but these authors suggested that ca ff eine’s ergogenicity was similar across the menstrual cycle (by investigating placebo-ca ff eine comparisons in the early follicular, late follicular and mid-luteal phases). All these investigations have contributed to explaining the e ff ect of ca ff eine on human performance, which is present in several exercise situations and with several dosages, although further investigations should be carried out to explain the individual di ff erences in the magnitude of the ergogenic e ff ect of ca ff eine [13]. The clear evidence provided by this special issue confirming the ergogenic e ff ect of ca ff eine might be behind the slight increase in the use of ca ff eine in sports since its removal from the list of banned substances in 2004 [ 14 ]. By analyzing the concentration of ca ff eine in post-competition urine samples, it has been found that about three out of four athletes consume ca ff eine or ca ff eine-containing products to increase performance [ 14 ]. Interestingly, the investigation by Shabir et al. [ 15 ], who used a double-dissociation experimental design where ca ff eine and a placebo were administered in situations in which participants were informed or misinformed of the substance that they had ingested, determined that part of the ergogenic e ff ect of ca ff eine on human performance is explained by the psychological impact of the expectancy of ergogenicity that ca ff eine produces in athletes. Thus, 2 Nutrients 2020 , 12 , 125 believing to have ingested ca ff eine, or feeling the stimulation that it produces, might be an important part of the actual ergogenic e ff ect of ca ff eine [ 16 ]. In this regard, ca ff eine ergogenicity can be obtained by the synergistic action of the pharmacological e ff ect of this substance on the central nervous system [ 8 ] and in other peripheral tissues [ 17 ], together with the psychological e ff ect of this potent stimulant [ 15 ]. Nevertheless, habituation to ca ff eine through the regular intake of this substance might be an important modifier for the obtaining of ca ff eine ergogenicity. The ingestion of 6 mg / kg of ca ff eine did not improve the time employed to complete an 800 m competition in athletes habituated to ca ff eine while it negatively a ff ected sleep quality [ 18 ]. Similarly, low-to-moderate doses of ca ff eine (from 3 to 9 mg / kg), were found to be ergogenic in other situations with individuals who do not consume ca ff eine or are low ca ff eine consumers [ 19 , 20 ] and seemed ine ff ective in increasing muscle performance in athletes habituated to ca ff eine intake [ 21 ]. These two investigations [ 18 , 21 ] indicate that the use of moderate doses of ca ff eine might not be ergogenic in individuals habituated to ca ff eine, likely due to the progressive tolerance to the ergogenic e ff ect of this substance when it is ingested chronically [ 22 ]. For athletes habituated to ca ff eine, the use of high doses (up to 11 mg / kg) might exert a positive e ff ect on maximal strength values, but may negatively a ff ect muscle endurance while increasing the prevalence of ca ff eine-induced drawbacks [ 23 ]. All this information taken together suggests that athletes who are consuming ca ff eine in a habitual manner should refrain from ca ff eine intake for several days to remove / reduce tolerance to the ergogenic e ff ect of this substance. For athletes habituated to ca ff eine who seek ca ff eine’s ergogenicity, the dishabituation to ca ff eine is recommended instead of using doses of ca ff eine higher than the daily habitual intake. Other contributions to science published in this issue suggest the possibility of using the measurement of urinary ca ff eine metabolites as a routine clinical examination for evaluating drug metabolic phenotypes [ 24 ], the harmful e ff ects of the administration of high doses of ca ff eine on the adrenal glands of immature rats [ 25 ], and the safety of a mean ca ff eine intake < 200 mg / day to avoid any e ff ect on neonatal weight, length, or head, and chest circumference [26]. The diversity of the articles published in this special issue highlights the extent of the e ff ects of co ff ee and ca ff eine on human functioning while it underpins the positive nature of most of these e ff ects. More work is necessary to completely understand the complex mechanisms behind each e ff ect of ca ff eine on body tissues, although this issue has greatly contributed to unveil how co ff ee and ca ff eine might be used to improve human functioning. Author Contributions: J.D.C., J.J.S., and B.L. wrote the Editorial. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Conflicts of Interest: The authors declare no conflict of interest. References 1. Moher, D.; Liberati, A.; Tetzla ff , J.; Altman, D.G. PRISMA Group Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009 , 6 , e1000097. [CrossRef] [PubMed] 2. Samoggia, A.; Riedel, B. Consumers’ Perceptions of Co ff ee Health Benefits and Motives for Co ff ee Consumption and Purchasing. Nutrients 2019 , 11 , 653. [CrossRef] [PubMed] 3. Sartini, M.; Bragazzi, N.; Spagnolo, A.; Schinca, E.; Ottria, G.; Dupont, C.; Cristina, M. Co ff ee Consumption and Risk of Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. Nutrients 2019 , 11 , 694. [CrossRef] [PubMed] 4. De Mejia, E.G.; Ramirez-Mares, M.V. Impact of ca ff eine and co ff ee on our health. Trends Endocrinol. Metab. 2014 , 25 , 489–492. [CrossRef] [PubMed] 5. Venier, S.; Grgic, J.; Mikulic, P. Ca ff einated Gel Ingestion Enhances Jump Performance, Muscle Strength, and Power in Trained Men. Nutrients 2019 , 11 , 937. [CrossRef] [PubMed] 3 Nutrients 2020 , 12 , 125 6. Chtourou, H.; Trabelsi, K.; Ammar, A.; Shephard, R.J.; Bragazzi, N.L. Acute E ff ects of an “Energy Drink”; on Short-Term Maximal Performance, Reaction Times, Psychological and Physiological Parameters: Insights from a Randomized Double-Blind, Placebo-Controlled, Counterbalanced Crossover Trial. Nutrients 2019 , 11 , 992. [CrossRef] 7. San Juan, A.F.; L ó pez-Samanes, Á .; Jodra, P.; Valenzuela, P.L.; Rueda, J.; Veiga-Herreros, P.; P é rez-L ó pez, A.; Dom í nguez, R. Ca ff eine Supplementation Improves Anaerobic Performance and Neuromuscular E ffi ciency and Fatigue in Olympic-Level Boxers. Nutrients 2019 , 11 , 2120. [CrossRef] 8. Franco-Alvarenga, P.E.; Brietzke, C.; Canestri, R.; Goethel, M.F.; Viana, B.F.; Pires, F.O. Ca ff eine Increased Muscle Endurance Performance Despite Reduced Cortical Activation and Unchanged Neuromuscular E ffi ciency and Corticomuscular Coherence. Nutrients 2019 , 11 , 2471. [CrossRef] 9. Mielgo-Ayuso, J.; Calleja-Gonzalez, J.; Del Coso, J.; Urdampilleta, A.; Le ó n-Guereño, P.; Fern á ndez-L á zaro, D. Ca ff eine Supplementation and Physical Performance, Muscle Damage and Perception of Fatigue in Soccer Players: A Systematic Review. Nutrients 2019 , 11 , 440. [CrossRef] 10. Salinero, J.J.; Lara, B.; Jim é nez-Ormeño, E.; Romero-Moraleda, B.; Gir á ldez-Costas, V.; Baltazar-Martins, G.; Del Coso, J. More Research Is Necessary to Establish the Ergogenic E ff ect of Ca ff eine in Female Athletes. Nutrients 2019 , 11 , 1600. [CrossRef] 11. Mielgo-Ayuso, J.; Marques-Jim é nez, D.; Refoyo, I.; Del Coso, J.; Le ó n-Guereño, P.; Calleja-Gonz á lez, J. E ff ect of Ca ff eine Supplementation on Sports Performance Based on Di ff erences Between Sexes: A Systematic Review. Nutrients 2019 , 11 , 2313. [CrossRef] 12. Romero-Moraleda, B.; Del Coso, J.; Guti é rrez-Hell í n, J.; Lara, B. The E ff ect of Ca ff eine on the Velocity of Half-Squat Exercise during the Menstrual Cycle: A Randomized Controlled Trial. Nutrients 2019 , 11 , 2662. [CrossRef] 13. Del Coso, J.; Lara, B.; Ruiz-Moreno, C.; Salinero, J.J. Challenging the Myth of Non-Response to the Ergogenic E ff ects of Ca ff eine Ingestion on Exercise Performance. Nutrients 2019 , 11 , 732. [CrossRef] [PubMed] 14. Aguilar-Navarro, M.; Muñoz, G.; Salinero, J.J.; Muñoz-Guerra, J.; Fern á ndez- Á lvarez, M.; Plata, M.D.M.; Del Coso, J. Urine Ca ff eine Concentration in Doping Control Samples from 2004 to 2015. Nutrients 2019 , 11 , 286. [CrossRef] [PubMed] 15. Shabir, A.; Hooton, A.; Spencer, G.; Storey, M.; Ensor, O.; Sandford, L.; Tallis, J.; Higgins, M.F.; Higgins, M.F. The Influence of Ca ff eine Expectancies on Simulated Soccer Performance in Recreational Individuals. Nutrients 2019 , 11 , 2289. [CrossRef] 16. Hurst, P.; Schipof-Godart, L.; Hettinga, F.; Roelands, B.; Beedie, C. Improved 1000-m Running Performance and Pacing Strategy With Ca ff eine and Placebo: A Balanced Placebo Design Study. Int. J. Sports Physiol. Perform. 2019 , in press. [CrossRef] 17. Tsuda, S.; Hayashi, T.; Egawa, T. The E ff ects of Ca ff eine on Metabolomic Responses to Muscle Contraction in Rat Skeletal Muscle. Nutrients 2019 , 11 , 1819. [CrossRef] [PubMed] 18. Ramos-Campo, D.J.; P é rez, A.; Á vila-Gand í a, V.; P é rez-Piñero, S.; Rubio-Arias, J. Á . Impact of Ca ff eine Intake on 800-m Running Performance and Sleep Quality in Trained Runners. Nutrients 2019 , 11 , 2040. [CrossRef] 19. Del Coso, J.; Salinero, J.J.; Gonz á lez-Mill á n, C.; Abi á n-Vic é n, J.; P é rez-Gonz á lez, B. Dose response e ff ects of a ca ff eine-containing energy drink on muscle performance: A repeated measures design. J. Int. Soc. Sports Nutr. 2012 , 9 , 21. [CrossRef] 20. Grgic, J.; Mikulic, P.; Schoenfeld, B.J.; Bishop, D.J.; Pedisic, Z. The Influence of Ca ff eine Supplementation on Resistance Exercise: A Review. Sports Med. 2019 , 49 , 17–30. [CrossRef] 21. Wilk, M.; Filip, A.; Krzysztofik, M.; Maszczyk, A.; Zajac, A. The Acute E ff ect of Various Doses of Ca ff eine on Power Output and Velocity during the Bench Press Exercise among Athletes Habitually Using Ca ff eine. Nutrients 2019 , 11 , 1465. [CrossRef] [PubMed] 22. Lara, B.; Ruiz-Moreno, C.; Salinero, J.J.; Del Coso, J. Time course of tolerance to the performance benefits of ca ff eine. PLoS ONE 2019 , 14 , e0210275. [CrossRef] [PubMed] 23. Wilk, M.; Krzysztofik, M.; Filip, A.; Zajac, A.; Del Coso, J. Correction: Wilk et al. “The E ff ects of High Doses of Ca ff eine on Maximal Strength and Muscular Endurance in Athletes Habituated to Ca ff eine” Nutrients, 2019, 11(8), 1912. Nutrients 2019 , 11 , 2660. [CrossRef] [PubMed] 24. Kim, H.J.; Choi, M.S.; Rehman, S.U.; Ji, Y.S.; Yu, J.S.; Nakamura, K.; Yoo, H.H. Determination of Urinary Ca ff eine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities. Nutrients 2019 , 11 , 1947. [CrossRef] [PubMed] 4 Nutrients 2020 , 12 , 125 25. Ryu, K.-Y.; Roh, J. The E ff ects of High Peripubertal Ca ff eine Exposure on the Adrenal Gland in Immature Male and Female Rats. Nutrients 2019 , 11 , 951. [CrossRef] [PubMed] 26. Wierzejska, R.; Jarosz, M.; Wojda, B. Ca ff eine Intake During Pregnancy and Neonatal Anthropometric Parameters. Nutrients 2019 , 11 , 806. [CrossRef] © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http: // creativecommons.org / licenses / by / 4.0 / ). 5 nutrients Editorial More Research Is Necessary to Establish the Ergogenic E ff ect of Ca ff eine in Female Athletes Juan Jos é Salinero, Beatriz Lara, Ester Jim é nez-Ormeño, Blanca Romero-Moraleda, Ver ó nica Gir á ldez-Costas, Gabriel Baltazar-Martins and Juan Del Coso * Exercise Physiology Laboratory, Camilo Jos é Cela University, 28692 Madrid, Spain * Correspondence: jdelcoso@ucjc.edu; Tel.: + 34-9185-3131 Received: 9 July 2019; Accepted: 12 July 2019; Published: 15 July 2019 Dear Editor-in-Chief, Today, there is a significant gap in research on the ergogenicity of ca ff eine, and on sports nutrition in general: the benefits / drawbacks for a given substance are typically assumed for the whole population of athletes when most of the evidence is supported by investigations with only male samples. As a result of this assumption, acute pre-exercise ingestion of 3–9 mg / kg of ca ff eine is considered an e ff ective strategy to increase sports performance [ 1 ], while data on urine ca ff eine concentration indicates that the use of ca ff eine in sport is similar in both sexes [ 2 ]. A few recent investigations using women as study samples, have also found that ca ff eine increases sports performance [ 3 – 6 ]. However, evidence regarding the overall ergogenicity of ca ff eine in women is much scarcer than in men, and it seems unsafe to conclude that the ergogenic e ff ect of a moderate dose of ca ff eine is of similar magnitude in men and women. A search for published studies on the e ff ects of ca ff eine on physical performance in PubMed and Scopus, following with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [ 7 ], showed a total of 362 original investigations that have compared ca ff eine to a placebo / control situation, with the measurement of at least one physical performance variable (Figure 1). Figure 1. Selection of studies. After filters were applied to remove duplicates or publications with unsuitable methodology, the search illustrated that a total of 5321 individuals have been tested to assess ca ff eine ergogenicity, Nutrients 2019 , 11 , 1600; doi:10.3390 / nu11071600 www.mdpi.com / journal / nutrients 7 Nutrients 2019 , 11 , 1600 since the seminal investigation by Costill et al. [ 8 ]. From this sample, 703 participants were women, which represents only 13.2% of the total sample. Although investigations on this topic have a higher tendency to include women, especially since 2013, women still represent only 16.3% of individuals participating in research carried out in 2018 (Figure 2). In addition, there is no investigation that has measured ca ff eine ergogenicity in women with doses below 1 mg / kg or above 9 mg / kg, and the number of women in investigations about ca ff eine e ff ects on speed and muscle power is very low (Table 1). Figure 2. Evolution of the number of participants ( n = total, males and females) in investigations aimed at determining the ergogenic e ff ects of ca ff eine. Table 1. Number (frequency) of male and female participants in investigations aimed at determining the ergogenic e ff ects of ca ff eine depending on dose, type of exercise, and participant’s level. Males Females Ca ff eine dose < 1 mg / kg 10 (100.0%) 0 (0.0%) 1.0–2.9 mg / kg 608 (90.2%) 66 (9.8%) 3.0–5.9 mg / kg 2295 (85.2%) 400 (14.8%) 6.0–9.0 mg / kg 1590 (87.0%) 237 (13.0%) > 9 mg / kg 115 (100.0%) 0 (0.0%) Type of exercise Speed 128 (89.5%) 15 (10.5%) Strength 527 (83.1%) 107 (16.9%) Power 98 (83.8%) 19 (16.2%) Anaerobic-like 587 (88.0%) 80 (12.0%) Endurance-like 2019 (89.0%) 249 (11.0%) Team-sport 241 (70.9%) 99 (29.1%) Other 1018 (88.4%) 134 (11.6%) Athlete’ level Trained 2777 (87.8%) 385 (12.2%) Active 1421 (85.7%) 237 (14.3%) Untrained 420 (83.8%) 81 (16.2%) Interestingly, there are no investigations measuring the ergogenic e ff ect of ca ff eine during the di ff erent phases of the menstrual cycle, despite the interactions between ca ff eine and female sex hormones [ 9 ]. In fact, it has been found that the e ff ect of ca ff eine on increasing blood pressure is higher in the follicular than in the luteal phase in female adolescents [ 10 ]. All this information indicates that it is still too early to establish that women experience the same ergogenic response to ca ff eine as men, and further research is needed to describe the optimal conditions of ca ff eine use in sport and exercise for women. With this Editorial, we want to encourage authors to provide objective information about the dose-e ff ect of ca ff eine on female athletes’ physical performance. We also want to embolden research focused to determine the magnitude of the ergogenic e ff ect of ca ff eine during the di ff erent phases of the menstrual cycle. The Nutrients’ Special Issue on “Co ff ee and Ca ff eine Consumption for 8 Nutrients 2019 , 11 , 1600 Human Health” is open to receive investigations on these topics that hold to “bridge the gap” on the ergogenicity of ca ff eine in female athletes. Author Contributions: Conceptualization, J.D.C.; methodology, J.J.S., B.L., E.J.-O., B.R.-M., V.G.-C., and G.B.-M.; formal analysis, J.J.S., and J.D.C.; writing—original draft preparation, J.D.C.; writing—review and editing, J.J.S., B.L., E.J.-O., B.R.-M., V.G.-C., and G.B.-M; supervision, J.D.C. Funding: This research received no external funding. Acknowledgments: We want to acknowledge all the authors that are investigating the e ff ects of acute ca ff eine intake in several aspects of physical performance. Conflicts of Interest: The authors declare no conflict of interest. References 1. Baltazar-Martins, J.G.; Brito de Souza, D.; Aguilar, M.; Grgic, J.; Del Coso, J. Infographic. The road to the ergogenic e ff ect of ca ff eine on exercise performance. Br. J. Sports Med. 2019 . [CrossRef] [PubMed] 2. Aguilar-Navarro, M.; Muñoz, G.; Salinero, J.J.; Muñoz-Guerra, J.; Fern á ndez- Á lvarez, M.; Plata, M.D.M.; Del Coso, J. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http: // creativecommons.org / licenses / by / 4.0 / ). 9