Relative Energy Deficiency in Sport (RED-S): A Comprehensive Clinical Framework for the Modern Clinician

Dr Neeraj Manikath , claude.ai

Abstract

Relative Energy Deficiency in Sport (RED-S) represents a paradigm shift from the outdated "female athlete triad" concept, recognizing that inadequate energy availability affects athletes of all sexes across multiple physiological systems. This review synthesizes current evidence on RED-S pathophysiology, clinical presentation, diagnostic strategies, and management approaches essential for internal medicine practitioners encountering athletes and physically active patients.

Introduction

The evolution from "female athlete triad" to RED-S reflects our growing understanding that chronic energy deficiency in athletes extends far beyond the classical triad of menstrual dysfunction, low energy availability, and decreased bone mineral density. First introduced by the International Olympic Committee (IOC) in 2014 and updated in 2018, RED-S encompasses a syndrome of impaired physiological functioning caused by relative energy deficiency, affecting metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health, and psychological well-being (1,2).

The fundamental issue is deceptively simple: when energy intake chronically fails to meet the energy expenditure demands of daily living plus athletic training, the body enters a state of low energy availability (LEA), typically defined as <30 kcal/kg fat-free mass per day (3). However, the clinical manifestations are protean, often subtle, and frequently missed in routine medical practice.

Epidemiology and At-Risk Populations

RED-S affects 22-58% of female athletes and 15-50% of male athletes depending on sport type and diagnostic criteria used (4,5). Contrary to popular belief, this is not exclusively a condition of elite athletes or those with eating disorders. Weekend warriors, military personnel, dancers, and recreational fitness enthusiasts all demonstrate vulnerability.

Pearl: Male athletes often present later in the disease course because practitioners fail to consider RED-S in men, and because menstrual dysfunction—an early warning sign in females—has no male equivalent.

High-risk sports include:

Weight-class sports (wrestling, rowing, combat sports)
Aesthetic sports (gymnastics, figure skating, diving)
Endurance sports (distance running, cycling, triathlon)
Sports emphasizing leanness (cross-country skiing, ski jumping)

Pathophysiology: Beyond Simple Caloric Mathematics

The body's response to chronic LEA represents an elegant, if clinically problematic, adaptive mechanism. When faced with insufficient energy, the hypothalamic-pituitary axis downregulates non-essential functions to preserve survival (6). This creates a cascade:

Hypothalamic suppression: Reduced GnRH pulsatility leads to functional hypothalamic amenorrhea in females and hypogonadotropic hypogonadism in males
Thyroid axis suppression: Decreased T3 conversion (euthyroid sick syndrome) reduces basal metabolic rate
Growth hormone resistance: Despite elevated GH, IGF-1 levels fall, impairing bone formation and soft tissue repair
Cortisol dysregulation: Chronic elevation contributes to immune suppression and catabolic state
Metabolic adaptation: Progressive reduction in resting energy expenditure beyond that predicted by body composition changes alone (7)

Oyster: The body becomes remarkably efficient at low energy availability—athletes may maintain training performance for months or even years before decompensation occurs, masking the underlying problem until serious complications arise.

Clinical Presentation: Recognizing the Red Flags

Primary Manifestations

Performance Decline The paradox of RED-S: athletes train harder yet perform worse. Look for:

Unexplained plateaus or decrements in training adaptations
Prolonged recovery times between sessions
Inability to complete previously manageable workouts
Loss of power, speed, or endurance despite maintained training volume

Bone Health Complications

Recurrent or non-healing stress fractures (particularly femoral neck, sacrum, or navicular)
Multiple fractures within a single season
Stress fractures in non-weight-bearing sites
DEXA Z-scores ≤-1.0 in premenopausal women or men <50 years

Pearl: A stress fracture in an athlete should prompt RED-S screening, not just orthopedic management. Studies show 40-50% of athletes with stress fractures have underlying RED-S (8).

Reproductive Dysfunction

Females: Primary or secondary amenorrhea, oligomenorrhea (cycles >35 days), anovulation with regular cycles, luteal phase defects
Males: Low libido, erectile dysfunction, decreased morning erections (often underreported)

Hack: Ask female athletes: "How many periods have you had in the past year?" rather than "Are your periods regular?" Many athletes normalize irregular cycles and won't volunteer this information.

Secondary Manifestations

Cardiovascular Changes

Resting bradycardia beyond athletic adaptation (<40 bpm with symptoms)
Orthostatic intolerance
Reduced heart rate variability (impaired parasympathetic tone)
ECG abnormalities (QTc prolongation in severe cases)

Immunological Impairment

Increased frequency/severity of upper respiratory infections
Prolonged illness duration
Impaired wound healing
Recurrent soft tissue injuries

Psychological Sequelae

Depression and anxiety (may precede or result from RED-S)
Irritability and emotional lability
Impaired concentration
Disturbed sleep patterns
Obsessive thinking about food, weight, or training

Metabolic Disturbances

Cold intolerance
Hair loss
Dry skin
Brittle nails
Constipation
Peripheral edema (in severe refeeding)

Diagnostic Evaluation: Laboratory and Beyond

Oyster: Normal laboratory values do not exclude RED-S. The diagnosis remains clinical, supported rather than confirmed by testing.

Recommended Initial Workup

Hormonal Assessment

LH, FSH: Often inappropriately low or low-normal given the hypogonadal state
Estradiol (females)/Total testosterone (males): Low to low-normal
TSH, free T3, free T4: TSH may be low-normal; T3 typically reduced with normal T4 (euthyroid sick pattern)
Prolactin: Exclude hyperprolactinemia
25-OH vitamin D: Assess for deficiency compounding bone health risk
IGF-1: May be low despite normal/elevated GH

Metabolic Panel

Complete metabolic panel (electrolytes can be abnormal in severe restriction or purging behaviors)
Complete blood count (anemia may indicate micronutrient deficiency; leukopenia in severe cases)
Iron studies (ferritin <30 ng/mL impairs performance independent of anemia)

Bone Health

DEXA scan of lumbar spine and hip (dual-energy X-ray absorptiometry)
Consider trabecular bone score for additional fracture risk assessment
Bone turnover markers (CTX, P1NP) if available—typically show suppressed formation with variable resorption

Additional Assessments

ECG (particularly if bradycardia, dizziness, or concerning history)
Resting metabolic rate measurement (if available—typically 10-30% below predicted)
Menstrual history diary (retrospective and prospective)

Pearl: Order LH and FSH in the early follicular phase (days 2-5) in menstruating females. In amenorrheic athletes, timing is less critical but serial measurements may help assess recovery.

Differential Diagnosis

Critical alternative diagnoses to consider:

Primary hypogonadism (elevated LH/FSH)
Hyperprolactinemia
Thyroid disease (TSH typically more markedly abnormal)
Polycystic ovary syndrome (elevated androgens, LH:FSH ratio typically >2:1)
Pregnancy
Celiac disease or inflammatory bowel disease
Chronic infections
Malignancy (rarely)

Management: A Multidisciplinary Imperative

Hack: The single most common management error is prescribing rest and oral contraceptives to amenorrheic athletes without addressing energy availability. This approach treats symptoms while ignoring etiology and often delays recovery.

Energy Balance Restoration: The Cornerstone

Target: Achieve energy availability ≥45 kcal/kg fat-free mass/day (3). This typically requires:

Increasing caloric intake by 300-600 kcal/day above current intake
Reducing training volume by 10-20% initially, or
Combination approach

Pearl: Many athletes resist reducing training. Frame it as "optimizing the training you do" rather than "doing less." Strategic rest often improves performance more than additional volume in the RED-S state.

Nutrition Intervention

Registered dietitian involvement is mandatory, ideally one specializing in sports nutrition and eating disorders. Focus areas:

Calculating individualized energy needs
Meal timing optimization (particularly around training)
Macronutrient distribution (minimum 1.2-1.6 g/kg protein; adequate fat ≥20% of total calories)
Micronutrient sufficiency (calcium 1000-1500 mg/day, vitamin D 600-2000 IU/day minimum)
Practical strategies for increasing intake without gastrointestinal distress

Hack: For athletes struggling with increased food volume, recommend calorie-dense foods: nut butters, avocados, olive oil, dried fruit, and liquid calories (smoothies, milk, juice).

Psychological Support

Mental health evaluation and treatment are first-line interventions, not afterthoughts. Athletes with RED-S commonly have:

Disordered eating behaviors (may not meet full eating disorder criteria)
Body image disturbances
Perfectionism and anxiety
Exercise compulsion

Cognitive-behavioral therapy, particularly eating disorder-specialized approaches, demonstrates efficacy (9). Some athletes require higher-level eating disorder treatment.

Pharmacological Considerations

Bone Health

Oral contraceptives: NOT recommended as first-line for bone health. They mask amenorrhea without addressing underlying energy deficiency and show minimal bone density benefit in LEA states (10).
Transdermal estrogen: Emerging evidence suggests physiologic estrogen replacement (with cyclic progestogen) may benefit bone health while maintaining the menstrual marker of recovery (11).
Bisphosphonates: Generally avoided in premenopausal women of childbearing potential
Teriparatide: Case reports show benefit in severe cases with multiple fractures; off-label use

Vitamin D: Supplement to achieve 25-OH vitamin D >30 ng/mL (>40 ng/mL optimal for athletes)

Oyster: Resumption of menses is the best biomarker of energy balance restoration in females—maintain vigilance that pharmacological suppression of this marker doesn't create false reassurance.

Return-to-Sport Criteria

Evidence-based return-to-play protocols remain limited, but expert consensus suggests graduated return when (2):

Increasing weight trend for ≥1 month (if underweight)
Improved eating behaviors and psychological state
Medical complications resolved or improving (normal ECG, normalized electrolytes)
Menstrual function restored or improving (at least one menses if previously amenorrheic, though full recovery may take 6-12 months)
Bone health stable or improving (if applicable)

Maintain reduced training loads (70-80% of pre-RED-S volume) during initial recovery with gradual progression over 2-3 months.

Prevention: Proactive Screening

Pearl: Pre-participation examinations should include specific RED-S screening. Simple questions:

"How many periods have you had in the past 12 months?" (females)
"Have you ever tried to lose weight to improve performance?"
"Do you feel you need to control your weight?"
"Has anyone recommended you lose weight?"
"Have you had a stress fracture?"

Validated screening tools include the Low Energy Availability in Females Questionnaire (LEAF-Q) and the Relative Energy Deficiency in Sport Clinical Assessment Tool (RED-S CAT), though the latter requires clinical expertise to interpret (12).

Education Initiatives

Athletes, coaches, and athletic trainers benefit from education on:

Performance optimization through adequate fueling (not restriction)
Recognition of early warning signs
Long-term health consequences of chronic LEA
"Relative health" model: optimal performance requires optimal health

Long-Term Consequences and Prognosis

Untreated RED-S carries significant morbidity:

Irreversible bone density loss (BMD Z-score may not fully normalize even with treatment)
Stress fracture recurrence risk
Cardiovascular complications (rarely, sudden cardiac death in severe cases)
Infertility or subfertility
Impaired growth in adolescents

However, with appropriate intervention, most athletes demonstrate substantial improvement within 6-12 months, with continued recovery over 1-2 years. The key prognostic factor is treatment adherence—athletes who successfully increase energy availability show restored menstrual function, improved bone markers, enhanced performance, and better psychological health (13).

Conclusion: A Call to Clinical Vigilance

RED-S represents a critical diagnosis that internal medicine physicians, sports medicine practitioners, and primary care clinicians must recognize and manage competently. The condition's high prevalence, protean manifestations, and potentially severe consequences demand systematic screening in athletic and active populations.

Final Pearl: Suspect RED-S in any athlete with unexplained performance decline, menstrual irregularity, or recurrent injuries. The diagnosis may be subtle, but clinical consequences are substantial. Early recognition and comprehensive, multidisciplinary intervention offer the best outcomes.

Final Hack: Document "Relative Energy Deficiency in Sport" explicitly in the medical record. This ICD-10 codable diagnosis (use E63.1 - nutritional deficiency, or F50.89 - other eating disorder depending on presentation) ensures appropriate billing and communicates clearly with consulting specialists.

References

Mountjoy M, et al. IOC consensus statement on relative energy deficiency in sport (RED-S): 2018 update. Br J Sports Med. 2018;52(11):687-697.
Mountjoy M, et al. International Olympic Committee's consensus statement on Relative Energy Deficiency in Sport (RED-S). Br J Sports Med. 2014;48(7):491-497.
Loucks AB, Thuma JR. Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women. J Clin Endocrinol Metab. 2003;88(1):297-311.
Tenforde AS, et al. Parallels with the female athlete triad in male athletes. Sports Med. 2016;46(2):171-182.
Melin A, et al. Energy availability in athletics: health, performance, and physique. Int J Sport Nutr Exerc Metab. 2019;29(2):152-164.
Nattiv A, et al. The female athlete triad: the inter-relatedness of disordered eating, amenorrhea, and osteoporosis. Clin Sports Med. 1994;13(2):405-418.
Koehler K, et al. Low energy availability in exercising men is associated with reduced leptin and insulin but not with changes in other metabolic hormones. J Sports Sci. 2016;34(20):1921-1929.
Tenforde AS, et al. Association of the female athlete triad risk assessment stratification to the development of bone stress injuries in collegiate athletes. Am J Sports Med. 2017;45(2):302-310.
Plateau CR, et al. Effectiveness of cognitive behavioural therapy compared to specialist supportive clinical management for adult anorexia nervosa. Eur Eat Disord Rev. 2022;30(5):737-746.
Rickenlund A, et al. Effects of oral contraceptives on body composition and physical performance in female athletes. J Clin Endocrinol Metab. 2004;89(9):4364-4370.
Heikura IA, et al. 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):403-411.
Melin AK, et al. Direct and indirect impact of low energy availability on sports performance. Scand J Med Sci Sports. 2024;34(1):e14327.
De Souza MJ, et al. High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Hum Reprod. 2010;25(2):491-503.

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