A literature review of biomarkers used for diagnosis of relative energy deficiency in sport
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic-ecollection
Document type Journal Article, Systematic Review
PubMed
39070233
PubMed Central
PMC11273787
DOI
10.3389/fspor.2024.1375740
Knihovny.cz E-resources
- Keywords
- REDs, athletes, low energy availability, markers, relative energy deficiency in sport,
- Publication type
- Journal Article MeSH
- Systematic Review MeSH
INTRODUCTION: The review aims to summarize the markers used in diagnosing relative energy deficiency in sport (REDs) and compare them with the REDs CAT2 score. METHODS: A systematic search was performed in the PubMed, Web of Science, and SPORTDiscus databases during April 2023. The descriptors used were "athlete" AND "REDs," along with respective entry terms. The selection process followed the PRISMA 2020 recommendations, identifying 593 records, from which 13 studies were ultimately selected. Seventy-nine markers were identified and categorized into six groups: bone mineral density (BMD), metabolic resting rate, blood biomarkers, anthropometrics, nutritional intake, and performance parameters. The most frequently utilized biomarkers included BMD, anthropometric parameters (e.g., body mass index, body mass, and fat mass), and the triiodothyronine (T3) concentration. RESULTS: According to the REDs CAT2 pointed indicators, the biomarkers varied among the studies, while 7 out of the 13 included studies achieved a ≥60% agreement rate with this tool. The prevalence of low energy availability, an etiological factor in the development of REDs, was detected in 4 out of 13 studies, with an average of 39.5%. CONCLUSION: In conclusion, this review highlights the most commonly used markers in diagnosing REDs, such as BMD, anthropometric parameters, and T3 hormone concentration. Due to the current inconsistencies, standardizing diagnostic methodologies is crucial for future research. By focusing on widely used markers, this review aids future research planning and result interpretation and points out the ongoing need for methodological consistency in evolving diagnostic tools. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/, PROSPERO (CRD42022320007).
See more in PubMed
Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, et al. The IOC consensus statement: beyond the female athlete triad–relative energy deficiency in sport (RED-S). Br J Sports Med. (2014 Apr) 48(7):491–7. 10.1136/bjsports-2014-093502 PubMed DOI
Malina RM, Spirduso WW, Tate C, Baylor AM. Age at menarche and selected menstrual characteristics in athletes at different competitive levels and in different sports. Med Sci Sports. (1978) 10(3):218–22. PubMed
Yeager KK, Agostini R, Nattiv A, Drinkwater B. The female athlete triad: disordered eating, amenorrhea, osteoporosis. Med Sci Sports Exerc. (1993) 25(7):775–7. 10.1249/00005768-199307000-00003 PubMed DOI
Souza MJD, Nattiv A, Joy E, Misra M, Williams NI, Mallinson RJ, et al. 2014 female athlete triad coalition consensus statement on treatment and return to play of the female athlete triad: 1st international conference held in San Francisco, California, May 2012 and 2nd international conference held in Indianapolis, Indiana, May 2013. Br J Sports Med. (2014) 48(4):289. 10.1136/bjsports-2013-093218 PubMed DOI
Sundgot-Borgen J, Meyer NL, Lohman TG, Ackland TR, Maughan RJ, Stewart AD, et al. How to minimise the health risks to athletes who compete in weight-sensitive sports review and position statement on behalf of the ad hoc research working group on body composition, health and performance, under the auspices of the IOC Medical Commission. Br J Sports Med. (2013) 47(16):1012–22. 10.1136/bjsports-2013-092966 PubMed DOI
Hamer J, Desbrow B, Irwin C. Are coaches of female athletes informed of relative energy deficiency in sport? A Scoping Review. Women Sport Phys Act J. (2021) 29(1):38–46. 10.1123/wspaj.2020-0062 DOI
Lodge MT, Ackerman KE, Garay J. Knowledge of the female athlete triad and relative energy deficiency in sport among female cross-country athletes and support staff. J Athl Train. (2022) 57(4):385–92. 10.4085/1062-6050-0175.21 PubMed DOI PMC
Loucks A. Energy availability, not body fatness, regulates reproductive function in women. Exerc Sport Sci Rev. (2003) 31:144–8. 10.1097/00003677-200307000-00008 PubMed DOI
Heikura IA, Uusitalo ALT, Stellingwerff T, Bergland D, Mero AA, Burke LM. Low energy availability is difficult to assess but outcomes have large impact on bone injury rates in elite distance athletes. Int J Sport Nutr Exerc Metab. (2018) 28(4):403–11. 10.1123/ijsnem.2017-0313 PubMed DOI
Sim A, Burns SF. Review: questionnaires as measures for low energy availability (LEA) and relative energy deficiency in sport (RED-S) in athletes. J Eat Disord. (2021) 9(1):41. 10.1186/s40337-021-00396-7 PubMed DOI PMC
Gould RJ, Ridout AJ, Newton JL. Relative energy deficiency in sport (RED-S) in adolescents—a practical review. Int J Sports Med. (2023) 44(4):236–46. 10.1055/a-1947-3174 PubMed DOI
Areta JL, Taylor HL, Koehler K. Low energy availability: history, definition and evidence of its endocrine, metabolic and physiological effects in prospective studies in females and males. Eur J Appl Physiol. (2021) 121(1):1–21. 10.1007/s00421-020-04516-0 PubMed DOI PMC
Mountjoy M, Ackerman KE, Bailey DM, Burke LM, Constantini N, Hackney AC, et al. 2023 International Olympic Committee’s (IOC) consensus statement on relative energy deficiency in sport (REDs). Br J Sports Med. (2023) 57(17):1073–98. 10.1136/bjsports-2023-106994 PubMed DOI
Stellingwerff T, Mountjoy M, McCluskey WT, Ackerman KE, Verhagen E, Heikura IA. Review of the scientific rationale, development and validation of the International Olympic Committee relative energy deficiency in sport clinical assessment tool: v.2 (IOC REDs CAT2)—by a subgroup of the IOC consensus on REDs. Br J Sports Med. (2023) 57(17):1109–21. 10.1136/bjsports-2023-106914 PubMed DOI
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Br Med J. (2021) 372:n71. 10.1136/bmj.n71 PubMed DOI PMC
Hooper DR, Mallard J, Wight JT, Conway KL, Pujalte GGA, Pontius KM, et al. Performance and health decrements associated with relative energy deficiency in sport for division I women athletes during a collegiate cross-country season: a case series. Front Endocrinol. (2021) 12:524762. 10.3389/fendo.2021.524762 PubMed DOI PMC
Õnnik L, Mooses M, Suvi S, Haile DW, Ojiambo R, Lane AR, et al. Prevalence of triad–RED–S symptoms in high-level Kenyan male and female distance runners and corresponding control groups. Eur J Appl Physiol. (2022) 122(1):199–208. 10.1007/s00421-021-04827-w PubMed DOI
Torstveit MK, Fahrenholtz IL, Lichtenstein MB, Stenqvist TB, Melin AK. Exercise dependence, eating disorder symptoms and biomarkers of relative energy deficiency in sports (RED-S) among male endurance athletes. BMJ Open Sport Exerc Med. (2019) 5(1):e000439. 10.1136/bmjsem-2018-000439 PubMed DOI PMC
Keay N, Francis G, Entwistle I, Hind K. Clinical evaluation of education relating to nutrition and skeletal loading in competitive male road cyclists at risk of relative energy deficiency in sports (RED-S): 6-month randomised controlled trial. BMJ Open Sport Exerc Med. (2019) 5(1):e000523. 10.1136/bmjsem-2019-000523 PubMed DOI PMC
Stenqvist TB, Torstveit MK, Faber J, Melin AK. Impact of a 4-week intensified endurance training intervention on markers of relative energy deficiency in sport (RED-S) and performance among well-trained male cyclists. Front Endocrinol. (2020) 11:512365. 10.3389/fendo.2020.512365 PubMed DOI PMC
Keay N, Francis G, Hind K. Low energy availability assessed by a sport-specific questionnaire and clinical interview indicative of bone health, endocrine profile and cycling performance in competitive male cyclists. BMJ Open Sport Exerc Med. (2018) 4(1):e000424. 10.1136/bmjsem-2018-000424 PubMed DOI PMC
Stenqvist TB, Melin AK, Garthe I, Slater G, Paulsen G, Iraki J, et al. Prevalence of surrogate markers of relative energy deficiency in male Norwegian Olympic-level athletes. Int J Sport Nutr Exerc Metab. (2021) 31(6):497–506. 10.1123/ijsnem.2020-0368 PubMed DOI
Mathisen TF, Heia J, Raustøl M, Sandeggen M, Fjellestad I, Sundgot-Borgen J. Physical health and symptoms of relative energy deficiency in female fitness athletes. Scand J Med Sci Sports. (2020) 30(1):135–47. 10.1111/sms.13568 PubMed DOI PMC
Civil R, Lamb A, Loosmore D, Ross L, Livingstone K, Strachan F, et al. Assessment of dietary intake, energy status, and factors associated with RED-S in vocational female ballet students. Front Nutr. (2018) 5:136. 10.3389/fnut.2018.00136 PubMed DOI PMC
Lee S, Moto K, Han S, Oh T, Taguchi M. Within-day energy balance and metabolic suppression in male collegiate soccer players. Nutrients. (2021) 13(8):2644. 10.3390/nu13082644 PubMed DOI PMC
Pritchett K, DiFolco A, Glasgow S, Pritchett R, Williams K, Stellingwerff T, et al. Risk of low energy availability in national and international level paralympic athletes: an exploratory investigation. Nutrients. (2021) 13(3):979. 10.3390/nu13030979 PubMed DOI PMC
Gibson-Smith E, Storey R, Ranchordas M. Dietary intake, body composition and iron status in experienced and elite climbers. Front Nutr. (2020) 7:122. 10.3389/fnut.2020.00122 PubMed DOI PMC
Kalpana K, Cherian KS, Khanna GL. Energy availability and RED-S risk assessment among Kho-Kho players in India. Sport Sci Health. (2022) 19:1–8. 10.1007/s11332-022-00996-z PubMed DOI PMC
Limaye D, Shankar RP, Limaye V, Sydymanov A, Otzipka C, Ziesenis P, et al. Development of a quantitative scoring method for STROBE checklist. Acta Pol Pharm Drug Res. (2018) 75(5):1095–106. 10.32383/appdr/84804 DOI
Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. Br Med J. (2016) 355. 10.1136/bmj.i4919 PubMed DOI PMC
Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, et al. The IOC relative energy deficiency in sport clinical assessment tool (RED-S CAT). Br J Sports Med. (2015) 49(21):1354–1354. 10.1136/bjsports-2015-094873 PubMed DOI
Centers for Disease Control and Prevention. Body Mass Index: Considerations for Practitioners (2011). Available online at: https://www.cdc.gov/obesity/downloads/bmiforpactitioners.pdf.
Humphreys S. The unethical use of BMI in contemporary general practice. Br J Gen Pract. (2010) 60(578):696–7. 10.3399/bjgp10X515548 PubMed DOI PMC
Jeong SM, Lee DH, Rezende LFM, Giovannucci EL. Different correlation of body mass index with body fatness and obesity-related biomarker according to age, sex and race-ethnicity. Sci Rep. (2023) 13:3472. 10.1038/s41598-023-30527-w PubMed DOI PMC
Mountjoy M, Sundgot-Borgen JK, Burke LM, Ackerman KE, Blauwet C, Constantini N, et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med. (2018) 52(11):687–97. 10.1136/bjsports-2018-099193 PubMed DOI
Müller W, Fürhapter-Rieger A, Ahammer H, Lohman TG, Meyer NL, Sardinha LB, et al. Relative body weight and standardised brightness-mode ultrasound measurement of subcutaneous fat in athletes: an international multicentre reliability study, under the auspices of the IOC medical commission. Sports Med Auckl NZ. (2020) 50(3):597–614. 10.1007/s40279-019-01192-9 PubMed DOI PMC
Ackland TR, Lohman TG, Sundgot-Borgen J, Maughan RJ, Meyer NL, Stewart AD, et al. Current status of body composition assessment in sport: review and position statement on behalf of the ad hoc research working group on body composition health and performance, under the auspices of the I.O.C. Medical Commission. Sports Med Auckl NZ. (2012) 42(3):227–49. 10.2165/11597140-000000000-00000 PubMed DOI
Mathisen TF, Ackland T, Burke LM, Constantini N, Haudum J, Macnaughton LS, et al. Best practice recommendations for body composition considerations in sport to reduce health and performance risks: a critical review, original survey and expert opinion by a subgroup of the IOC consensus on relative energy deficiency in sport (REDs). Br J Sports Med. (2023) 57(17):1148–58. 10.1136/bjsports-2023-106812 PubMed DOI
Ackerman KE, Stellingwerff T, Elliott-Sale KJ, Baltzell A, Cain M, Goucher K, et al. #REDS (relative energy deficiency in sport): time for a revolution in sports culture and systems to improve athlete health and performance. Br J Sports Med. (2020) 54(7):369–70. 10.1136/bjsports-2019-101926 PubMed DOI
Ackerman KE, Misra M. Neuroendocrine abnormalities in female athletes. In: Gordon CM, LeBoff MS, editors. The Female Athlete Triad: A Clinical Guide. Boston, MA: Springer; (2015). p. 85–109. 10.1007/978-1-4899-7525-6_6 DOI
De Souza MJ, Williams NI. Physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism in exercising women. Hum Reprod Update. (2004) 10(5):433–48. 10.1093/humupd/dmh033 PubMed DOI
Misra M, Miller KK, Almazan C, Ramaswamy K, Lapcharoensap W, Worley M, et al. Alterations in cortisol secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. J Clin Endocrinol Metab. (2004) 89(10):4972–80. 10.1210/jc.2004-0723 PubMed DOI
Pralong FP, Roduit R, Waeber G, Castillo E, Mosimann F, Thorens B, et al. Leptin inhibits directly glucocorticoid secretion by normal human and rat adrenal gland. Endocrinology. (1998) 139(10):4264–8. 10.1210/endo.139.10.6254 PubMed DOI
Grinspoon SK, Baum HB, Kim V, Coggins C, Klibanski A. Decreased bone formation and increased mineral dissolution during acute fasting in young women. J Clin Endocrinol Metab. (1995) 80(12):3628–33. 10.1210/jcem.80.12.8530611 PubMed DOI
Shapses SA, Heymsfield SB, Ricci TA. “Voluntary weight reduction increases bone turnover and loss.” In: Burckhardt P, Dawson-Hughes B, Heaney RP, editors. Nutritional Aspects of Osteoporosis: A Serono Symposia SA Publication. New York, NY: Springer; (1998). p. 180–4. Proceedings in the Serono Symposia USA Series. 10.1007/978-1-4612-2228-6_19 DOI
Morgan SL, Prater GL. Quality in dual-energy x-ray absorptiometry scans. Bone. (2017) 104:13–28. 10.1016/j.bone.2017.01.033 PubMed DOI
Ihle R, Loucks AB. Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res. (2004) 19(8):1231–40. 10.1359/JBMR.040410 PubMed DOI
Papageorgiou M, Elliott-Sale KJ, Parsons A, Tang JCY, Greeves JP, Fraser WD, et al. Effects of reduced energy availability on bone metabolism in women and men. Bone. (2017) 105:191–9. 10.1016/j.bone.2017.08.019 PubMed DOI
Papageorgiou M, Dolan E, Elliott-Sale KJ, Sale C. Reduced energy availability: implications for bone health in physically active populations. Eur J Nutr. (2018) 57(3):847–59. 10.1007/s00394-017-1498-8 PubMed DOI PMC
Karlsson MK, Johnell O, Obrant KJ. Bone mineral density in weight lifters. Calcif Tissue Int. (1993) 52(3):212–5. 10.1007/BF00298721 PubMed DOI
Fullmer S, Benson-Davies S, Earthman CP, Frankenfield DC, Gradwell E, Lee PSP, et al. Evidence analysis library review of best practices for performing indirect calorimetry in healthy and non-critically ill individuals. J Acad Nutr Diet. (2015) 115(9):1417–446.e2. 10.1016/j.jand.2015.04.003 PubMed DOI
De Souza MJ, Koltun KJ, Williams NI. The role of energy availability in reproductive function in the female athlete triad and extension of its effects to men: an initial working model of a similar syndrome in male athletes. Sports Med. (2019) 49(2):125–37. 10.1007/s40279-019-01217-3 PubMed DOI PMC
O’Neill JER, Corish CA, Horner K. Accuracy of resting metabolic rate prediction equations in athletes: a systematic review with meta-analysis. Sports Med. (2023) 53(12):2373–98. 10.1007/s40279-023-01896-z PubMed DOI PMC
Cunningham JJ. A reanalysis of the factors influencing basal metabolic rate in normal adults. Am J Clin Nutr. (1980) 33(11):2372–4. 10.1093/ajcn/33.11.2372 PubMed DOI
Harris JA, Benedict FG. A biometric study of human basal metabolism. Proc Natl Acad Sci U S A. (1918) 4(12):370–3. 10.1073/pnas.4.12.370 PubMed DOI PMC
Owen O, Kavle E, Owen R, Polansky M, Caprio S, Mozzoli M, et al. A reappraisal of caloric requirements in healthy women. Am J Clin Nutr. (1986) 44(1):1–19. 10.1093/ajcn/44.1.1 PubMed DOI
De Souza MJ, Hontscharuk R, Olmsted M, Kerr G, Williams NI. Drive for thinness score is a proxy indicator of energy deficiency in exercising women. Appetite. (2007) 48(3):359–67. 10.1016/j.appet.2006.10.009 PubMed DOI
Staal S, Sjödin A, Fahrenholtz I, Bonnesen K, Melin AK. Low RMR ratio as a surrogate marker for energy deficiency, the choice of predictive equation vital for correctly identifying male and female ballet dancers at risk. Int J Sport Nutr Exerc Metab. (2018) 28(4):412–8. 10.1123/ijsnem.2017-0327 PubMed DOI
Sterringer T, Larson-Meyer DE. RMR ratio as a surrogate marker for low energy availability. Curr Nutr Rep. (2022) 11(2):263–72. 10.1007/s13668-021-00385-x PubMed DOI
Cunningham JJ. Body composition as a determinant of energy expenditure: a synthetic review and a proposed general prediction equation. Am J Clin Nutr. (1991) 54(6):963–9. 10.1093/ajcn/54.6.963 PubMed DOI
Martin B, Golden E, Carlson OD, Egan JM, Mattson MP, Maudsley S. Caloric restriction: impact upon pituitary function and reproduction. Ageing Res Rev. (2008) 7(3):209–24. 10.1016/j.arr.2008.01.002 PubMed DOI PMC
Elliott-Sale KJ, Tenforde AS, Parziale AL, Holtzman B, Ackerman KE. Endocrine effects of relative energy deficiency in sport. Int J Sport Nutr Exerc Metab. (2018) 28(4):335–49. 10.1123/ijsnem.2018-0127 PubMed DOI
Harvey CB, O’Shea PJ, Scott AJ, Robson H, Siebler T, Shalet SM, et al. Molecular mechanisms of thyroid hormone effects on bone growth and function. Mol Genet Metab. (2002) 75(1):17–30. 10.1006/mgme.2001.3268 PubMed DOI
Welsh KJ, Soldin SJ. How reliable are free thyroid and total T3 hormone assays? Eur J Endocrinol. (2016) 175(6):R255–63. 10.1530/EJE-16-0193 PubMed DOI PMC
Russell W, Harrison RF, Smith N, Darzy K, Shalet S, Weetman AP, et al. Free triiodothyronine has a distinct circadian rhythm that is delayed but parallels thyrotropin levels. J Clin Endocrinol Metab. (2008) 93(6):2300–6. 10.1210/jc.2007-2674 PubMed DOI
Dipla K, Kraemer RR, Constantini NW, Hackney AC. Relative energy deficiency in sports (RED-S): elucidation of endocrine changes affecting the health of males and females. Horm Athens Greece. (2021) 20(1):35–47. 10.1007/s42000-020-00214-w PubMed DOI
Sale C, Elliott-Sale KJ. Nutrition and athlete bone health. Sports Med Auckl NZ. (2019) 49(Suppl 2):139–51. 10.1007/s40279-019-01161-2 PubMed DOI PMC
Freedman LS, Commins JM, Moler JE, Willett W, Tinker LF, Subar AF, et al. Pooled results from 5 validation studies of dietary self-report instruments using recovery biomarkers for potassium and sodium intake. Am J Epidemiol. (2015) 181(7):473–87. 10.1093/aje/kwu325 PubMed DOI PMC
Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol. (1986) 124(1):17–27. 10.1093/oxfordjournals.aje.a114366 PubMed DOI
Schoeller DA. Limitations in the assessment of dietary energy intake by self-report. Metab Clin Exp. (1995) 44:18–22. 10.1016/0026-0495(95)90204-X PubMed DOI
Ndahimana D, Kim EK. Measurement methods for physical activity and energy expenditure: a review. Clin Nutr Res. (2017) 6(2):68–80. 10.7762/cnr.2017.6.2.68 PubMed DOI PMC
Welk G. Physical Activity Assessments for Health-Related Research. Champaign, IL: Human Kinetics; (2002). p. 269. Available online at: http://catalog.hathitrust.org/api/volumes/oclc/49376240.html (accessed August 30, 2023).
Torstveit MK, Ackerman KE, Constantini N, Holtzman B, Koehler K, Mountjoy ML, et al. Primary, secondary and tertiary prevention of relative energy deficiency in sport (REDs): a narrative review by a subgroup of the IOC consensus on REDs. Br J Sports Med. (2023) 57(17):1119–26. 10.1136/bjsports-2023-106932 PubMed DOI
Õnnik L, Mooses M, Suvi S, Haile DW, Ojiambo R, Lane AR, et al. Correction to: prevalence of triad–RED-S symptoms in high-level Kenyan male and female distance runners and corresponding control groups. Eur J Appl Physiol. (2022) 122(1):209. 10.1007/s00421-021-04836-9 PubMed DOI
Schofield K, Thorpe H, Sims S. Compartmentalised disciplines: why low energy availability research calls for transdisciplinary approaches. Perform Enhanc Health. (2020) 8:100172. 10.1016/j.peh.2020.100172 DOI
Todd E, Elliott N, Keay N. Relative energy deficiency in sport (RED-S). Br J Gen Pract. (2022) 72(719):295–7. 10.3399/bjgp22X719777 PubMed DOI PMC