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News and Views on Caffeine, Creatine Kinase Levels, and Sickle Cell Trait

Eichner, E. Randy MD, FACSM

doi: 10.1249/JSR.0000000000000426
Pearls and Pitfalls

Address for correspondence: E. Randy Eichner, MD, FACSM, 321 Baudin Way, Sonoma, CA; E-mail:

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Balzac said that, upon drinking coffee, ideas march in like armies, memories arrive at full gallop, shafts of wit start up like sharpshooters, and the paper is covered with ink. Sounds good, but it does not always work for me. I do, however, see myself in what David Letterman once said: “If it weren’t for the coffee, I’d have no identifiable personality whatsoever.”

Anyway, I try to keep up with the pros and cons of caffeine, health, and sports medicine. However, hundreds of articles exist on this, and new ones arrive at full gallop. I cover and comment on a new caffeine study here. I also cover news and views on creatine kinase (CK) levels in football players and on young athletes and sickle cell trait.

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Caffeine and Performance

Research on caffeine for sports goes back more than a century. It is fair to say that ingestion of caffeine can enhance endurance and middle-distance performance, along with some forms of sprinting and even muscular strength (4,12). The new study asked: does habitual consumption of caffeine lessen the performance benefit from acute caffeine ingestion?

Studied were 40 male competitive cyclists who, in a double-blind, crossover, counterbalanced design, performed on an ergometer simulated cycling time-trials (a set amount of work) in the fastest time possible after ingestion of caffeine (6 mg·kg−1), placebo, or no supplement. They were classified by questionnaire into tertiles of habitual caffeine intake. Performance was significantly better on caffeine than on placebo (2.4% better) or on no supplement (3.3% better), but these differences were small. Contrary to the hypothesis of the researchers, cycling performance was not influenced by the level of habitual caffeine consumption (6).

In other words, caffeine boosted performance even in those who habitually consumed a lot of caffeine. The boost was small, however, and the dose of caffeine was large, equivalent to about four cups of coffee. I do not endorse large doses of caffeine to “enhance performance,” however, especially for the general public. It seems almost silly, if not maybe risky.

Granted, it is hard to kill yourself by drinking coffee. They say Balzac drank 50 cups a day. Also, a world record was set in 1927 by a Minnesota porter named Gus Comstock, who drank 85 cups in a day. How Gus slept that night is lost to history.

The poison, however, is in the dose. Large doses of caffeine can cause annoying central nervous system and gastrointestinal effects. In some people and some settings, large doses may increase cardiac ectopy (2,9). Massive doses can trigger fatal arrhythmia. Deaths have occurred from massive doses of caffeine in tablets or in pure caffeine powder bought on the Internet. In prior columns, I covered three such deaths, one a 16-yr-old high school wrestler. In April 2017, a 16-yr-old boy in South Carolina drank three caffeine-laced drinks in 2 h, then collapsed in class at school and soon died. At autopsy, his heart was normal; the medical examiner and a forensic toxicologist agreed his caffeine intake was excessive, and his death was from cardiac arrhythmia. We need more awareness of the risk of massive caffeine dosage, and I think the sale of pure caffeine powder, which is difficult to dose, dangerous to use, and has no redeeming virtue, should be banned (5).

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CK Levels

I am asked about serum CK levels in an African-American college football player, and whether to let him play. His serum CK was 1,200 U·L−1 on a hospital admission unrelated to football, falling to 500 U·L−1 by discharge. Checked again during winter workouts, his CK was 3,500 U·L−1, even though he had no muscle symptoms. After heat cramping in the spring game, his CK was again 3,500 U·L−1. Thereafter, it was checked five to six times, at relative rest and during training, and ranged from about 600 to about 900 U·L−1. He continues to deny muscle symptoms, and his renal function is normal. Should he play football?

Serum CK levels wax and wane in healthy football players, typically higher in blacks than whites. In fact, baseline serum CK levels in healthy black men may be as high as 600 to 700 U·L−1 (7). The rise in CK after an exercise bout, however, is proportionally similar in blacks and whites (10). A serum CK of 3,500 U·L−1 during major heat cramping in football is not unusual. We once checked six Sooner football players who were heat cramping early in summer camp: CK levels ranged from 1,900 to 3,600 U·L−1.

Also, three studies of serial CK values during summer college football camps agree that elevated CK levels are common and “physiologic” for the intensity of the “sport.” In the first study, mean CK value on day 4 was about 5,000 U·L−1 (top value, 19,000 U·L−1) and on day 10 was 1,200 U·L−1 (3). In the second study, mean CK on day 3 was 1,300 U·L−1 and on day 7 was 1,560 U·L−1 (11). In the third study, mean CK on day 4 was 1,500 U·L−1, on day 7 was 1,800 U·L−1, and on day 10 was 1,460 U·L−1 (8). In all three of these studies, the football players reported no undue muscle signs or symptoms.

So, I say: Let him play!

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Sickle Cell Trait

The National Collegiate Athletic Association sickle cell trait (SCT) program has sharply cut the rate of death from exertional sickling in Division-I football conditioning, from 10 such deaths in the 10 yr (2000–2010) before the program began, to only one such death in the 7 to 8 yr of the program. Also, in that one death, the university admitted it was at fault and settled the wrongful death lawsuit. This prevention of exertional sickling death is significant by the Fisher exact test.

Alas, exertional sickling deaths continue apace in the military and in athletes younger than college level, as well as in other settings of extreme exercise. In the past 2 yr, we know of at least 11 exertional sickling deaths: six young athletes (five in high school), three military men, one firefighter recruit, and one police cadet. All 11 collapsed during intense exercise. Three of these 11 were not African-American (two were white, one was Hispanic), proving yet again that SCT is malarial, not racial.

We need more help from pediatricians to end these tragic exertional sickling deaths in young athletes. A poster on three of these deaths was presented in a subcommittee (council of sports medicine and fitness) program at the American Academy of Pediatrics annual national meeting in 2017 (1). It’s a start.

All 50 states find SCT at birth. I think all pediatricians who sign the preparticipation physical examination for kids to play sports should attest to the presence or absence of SCT. We have more work to do to end these preventable deaths of our children.

The author declares no conflict of interest and does not have any financial disclosures.

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1. Cools KS, Crowder MD, Kucera KL, et al. Sudden death in high school athletes: a case series examining the influence of sickle cell trait. Poster presented to American Academy of Pediatrics, session H1079, September 16, 2017, 11:00–11:15 am, McCormack Place West, S104 A.
2. Dixit S, Stein PK, Dewland TA, et al. Consumption of caffeinated products and cardiac ectopy. J. Am. Heart Assoc. 2016; 5:e002503. doi:10.1161/JAHA.115.002503.
3. Ehlers GG, Ball TE, Liston L. Creatine kinase levels are elevated during 2-a-day practices in collegiate football players. J. Athl. Train. 2002; 37:151–6.
4. Eichner ER. Sports medicine pearls and pitfalls: Java jolt. Curr. Sports Med. Rep. 2009; 8:42–3.
5. Eichner ER. Updates on team rhabdomyolysis, caffeine fatalities, and heat cramping. Curr. Sports Med. Rep. 2015; 14:423–4.
6. Goncalves LS, Painelli VS, Yamaguchi G, et al. Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation. J. Appl. Physiol. (1985). 2017; 123:213–20.
7. Kenney K, Landau ME, Gonzalez RS, et al. Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis. Muscle Nerve. 2012; 45:356–62.
8. Morrison KE, Godek SF, Marcinek T. Serum creatine kinase levels in Division II National Collegiate Athletic Association football players during preseason. Athl. Training Sports Health Care. 2017; 9:217–24.
9. Pelchovitz DJ, Goldberger JJ. Caffeine and cardiac arrhythmias: A review of the evidence. Am. J. Med. 2011; 124:284–9.
10. Schwane JA, Buckley RT, Dipaolo DP, et al. Plasma creatine kinase responses of 18- to 30-yr-old African-American men to eccentric exercise. Med. Sci. Sports Exerc. 2000; 32:370–8.
11. Smoot MK, Cavanaugh JE, Amendola A, et al. Creatine kinase levels during preseason camp in National Collegiate Athletic Association Division I football athletes. Clin. J. Sport Med. 2014; 24:438–40.
12. Warren GL, Park ND, Maresca RD, et al. Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med. Sci. Sports Exerc. 2010; 42:1375–87.
Copyright © 2017 by the American College of Sports Medicine.