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Peptides for Endurance Athletes

Running 50 miles a week breaks your body down. So does cycling centuries or stacking back-to-back swim sessions.

Running 50 miles a week breaks your body down. So does cycling centuries or stacking back-to-back swim sessions. Endurance training is a controlled form of damage -- micro-tears in muscle fibers, oxidative stress on mitochondria, inflammation in tendons and joints that never quite settles between sessions.

That reality has pushed a growing number of distance runners, cyclists, triathletes, and ultra-endurance athletes toward peptide research. The logic is straightforward: if certain peptides can accelerate tissue repair, improve mitochondrial efficiency, or modulate inflammation, they might help endurance athletes recover faster and train harder without breaking down.

But the science is complicated. Some peptides have real clinical data behind them. Others ride on animal studies and speculation. And many are banned by WADA, which means competitive athletes face career-ending consequences for using them.

This guide breaks down what the research actually says -- peptide by peptide -- so you can have an informed conversation with your doctor.

Table of Contents

Why Endurance Athletes Are Interested in Peptides

Endurance sports create a unique set of physiological demands that differ from strength or power sports. The primary concerns are:

Mitochondrial efficiency. Your mitochondria are the engines that produce ATP -- the energy currency your muscles burn during every stride, pedal stroke, or swim lap. Over time, oxidative stress from prolonged exercise damages these structures. Anything that improves mitochondrial function could translate to better endurance capacity.

Connective tissue durability. Runners absorb 2-3 times their body weight with every footstrike. Over a marathon, that's roughly 25,000 impacts. Tendons, ligaments, and cartilage bear this load, and they heal much slower than muscle. IT band syndrome, Achilles tendinopathy, plantar fasciitis, and patellar tendonitis are the toll booth fees of distance running.

Recovery between sessions. Elite endurance athletes often train 15-25 hours per week. The gap between sessions is where adaptation happens -- or where overtraining takes hold. Faster recovery means more productive training.

Body composition. In endurance sports, power-to-weight ratio is everything. Carrying extra body fat up a mountain pass or through mile 20 of a marathon costs real time.

These four areas map directly onto specific peptide research. Let's look at what the data shows.

MOTS-c: The Mitochondrial Exercise Peptide

If any peptide was built for endurance athletes, it's MOTS-c. This mitochondrial-derived peptide is encoded within mitochondrial DNA and plays a direct role in metabolic homeostasis, insulin sensitivity, and exercise capacity.

What the Research Shows

MOTS-c activates the AMPK pathway -- the same master switch for cellular energy metabolism that endurance training itself triggers [1]. This is not a coincidence. Your body produces more MOTS-c during and after exercise, suggesting it's part of the natural signaling cascade that drives endurance adaptations.

A 2021 study published in Nature Communications found that MOTS-c treatment improved physical performance in mice of all ages -- young, middle-aged, and old. On treadmill tests, treated mice showed 12-15% improvements in running time and distance after a single dose [2].

In human subjects, skeletal muscle MOTS-c levels increased nearly 12-fold after cycling exercise, while plasma levels rose roughly 50% during and after the session [3]. A separate study measuring circulating mitochondrial-derived peptides found that acute endurance exercise stimulates MOTS-c levels in plasma, while resistance exercise does not -- pointing to a specific relationship between MOTS-c and aerobic work [4].

Professional athletes show different MOTS-c patterns than sedentary people. A study of 75 professional athletes found that serum MOTS-c levels correlated with aerobic capacity and endurance training load [5]. Long-term endurance training (4-8 weeks of voluntary running in rodents) increased MOTS-c protein expression 1.5 to 5-fold in skeletal muscle, and those levels stayed elevated even after 4-6 weeks of detraining [6].

The Endurance Angle

For runners and cyclists, MOTS-c's mechanism hits at the heart of what limits performance: mitochondrial capacity. By activating the AMPK/PGC-1alpha pathway, MOTS-c may promote mitochondrial biogenesis, improve fatty acid oxidation, and improve mitochondrial respiratory function [7]. These are the same adaptations you chase through long slow distance runs and tempo work.

The catch: human intervention trials are still limited. Most of the performance data comes from mouse models, and MOTS-c is not currently available as an approved therapeutic.

BPC-157: The Recovery Peptide

BPC-157 is the most widely discussed recovery peptide in endurance sports, and for good reason. This pentadecapeptide -- derived from a protective compound found in human gastric juice -- has shown tissue-healing effects across tendons, ligaments, muscles, and bones in over 100 animal studies [8].

Why It Matters for Endurance Athletes

Endurance athletes don't usually blow out a knee in one explosive movement. They break down gradually. Achilles tendinopathy from mileage accumulation. Plantar fasciitis from foot mechanics under fatigue. Patellar tendonitis from thousands of descents.

BPC-157 addresses these chronic overuse patterns through several proposed mechanisms:

  • Angiogenesis: BPC-157 promotes the formation of new blood vessels at injury sites, potentially improving nutrient and oxygen delivery to damaged tissues [8].
  • Growth hormone receptor expression: One study found BPC-157 increased growth hormone receptor activity in tendon cells up to sevenfold by day three, which could accelerate tissue regeneration [9].
  • Anti-inflammatory signaling: The peptide modulates inflammatory cytokines, which may help resolve the low-grade chronic inflammation that plagues overuse injuries [8].
  • Collagen synthesis: BPC-157 appears to stimulate fibroblast activity and collagen formation through the FAK-paxillin pathway -- directly relevant to tendon and ligament repair [10].

The Evidence Gap

Here's the honest picture: BPC-157's preclinical data is consistently positive across dozens of animal studies. A 2025 systematic review in orthopaedic sports medicine confirmed improved functional, structural, and biomechanical outcomes in muscle, tendon, ligament, and bony injuries in animal models [11]. One small human pilot study found that 7 of 12 participants with chronic knee pain reported relief lasting over six months after a single BPC-157 injection [8].

But there are no randomized controlled trials in human athletes. The peptide is also banned by WADA since 2022 and is not FDA-approved. Its safety profile in humans remains formally unknown, though animal studies across wide dose ranges (6 mcg/kg to 20 mg/kg) found no toxic or lethal dose and no organ toxicity [11].

For a deeper look at recovery-focused peptides, see our guide on best peptides for athletic performance.

TB-500: Tissue Repair and Angiogenesis

TB-500 is a synthetic fragment of thymosin beta-4, a 43-amino-acid peptide found in nearly all human cells. Its primary function is regulating actin -- a protein critical for cell movement and tissue repair.

How It Works

TB-500 binds to G-actin, maintaining a pool of actin monomers ready for rapid assembly when tissue repair is needed [12]. For an endurance athlete with micro-damage accumulating across weeks of training, this cellular readiness matters.

Beyond actin regulation, TB-500 research shows:

  • Reduced scarring: Treated wounds in rat models healed with organized collagen fibers and minimal scarring, with no loss in wound breaking strength [13].
  • Ligament repair: A 2013 study found that local TB-500 administration significantly improved both the histological appearance and mechanical properties of healing medial collateral ligaments in rats at 4 weeks post-surgery [14].
  • Muscle regeneration: TB-500 acts as a chemoattractant for myoblasts -- the precursor cells that repair damaged muscle fibers [15].
  • Anti-inflammatory effects: TB-500 reduces NF-kB translocation and decreases pro-inflammatory cytokines like IL-6 and IL-8 [12].

Many athletes and clinicians combine BPC-157 and TB-500 for injury recovery, as they work through complementary mechanisms. For more on this strategy, see our peptide stacking guide.

TB-500 is banned by WADA and is not FDA-approved for therapeutic use. Like BPC-157, most evidence comes from preclinical models.

SS-31 (Elamipretide): Targeting Mitochondrial Efficiency

SS-31 is a synthetic tetrapeptide that targets the inner mitochondrial membrane. For endurance athletes, its mechanism is directly relevant: it binds to cardiolipin, a phospholipid that stabilizes the electron transport chain where ATP is produced [16].

Why Endurance Athletes Should Pay Attention

Think of cardiolipin as the structural scaffolding inside your mitochondria. When it degrades -- from aging, oxidative stress, or chronic training overload -- ATP production becomes less efficient and reactive oxygen species (ROS) increase. SS-31 stabilizes this scaffolding.

In aged mice, 8 weeks of SS-31 treatment restored redox homeostasis, improved mitochondrial quality, and increased treadmill endurance without increasing total mitochondrial content [17]. The treated mice showed greater fatigue resistance and significantly improved endurance compared to both pretreatment levels and untreated controls.

SS-31 reached a major milestone in 2025 when the FDA approved it (as elamipretide) for treating Barth syndrome, a rare mitochondrial disorder [18]. The TAZPOWER trial showed that 48 weeks of treatment significantly improved performance on the 6-Minute Walk Test and cardiac function. A separate phase I/II trial in patients with primary mitochondrial myopathy showed improvements in exercise tolerance across multiple genetic subtypes of mitochondrial disease [19].

For healthy athletes, the implications are speculative but intriguing: if SS-31 can improve ATP production per unit of oxygen consumed, it could theoretically improve running economy -- the holy grail of endurance performance. However, no trials have tested this in healthy, trained athletes.

CJC-1295 and Ipamorelin: Growth Hormone Secretagogues

CJC-1295 and Ipamorelin are two peptides frequently combined as growth hormone secretagogues. CJC-1295 is a GHRH analog that sustains growth hormone and IGF-1 levels for days, while Ipamorelin is a ghrelin mimetic that triggers shorter GH pulses [20].

The Endurance Case

Growth hormone is not typically associated with endurance sports the way it is with bodybuilding. But GH plays real roles in recovery:

  • Tissue repair: GH and IGF-1 are directly involved in muscle protein synthesis and connective tissue remodeling.
  • Fat metabolism: GH promotes lipolysis, making stored fat more available as fuel during long efforts.
  • Sleep quality: GH secretion peaks during deep sleep. Better GH signaling may improve sleep quality, which is the single most important recovery tool for any athlete.

A clinical study in healthy adults found that a single CJC-1295 injection increased plasma GH concentrations 2 to 10-fold for 6 or more days, and IGF-1 levels rose 1.5 to 3-fold for 9-11 days [20]. When combined, the two peptides may produce a 3-5 fold increase in growth hormone release compared to either alone.

The limitation: while hormone levels clearly increase, published trials demonstrating actual performance or body composition improvements in trained athletes are lacking. Both peptides are banned by WADA and are not FDA-approved for sports or anti-aging use. CJC-1295 clinical trials were discontinued after one subject died, though the death was attributed to pre-existing coronary artery disease [21].

For more on growth hormone peptides, see our guides on Sermorelin, Tesamorelin, and GHRP-6.

Semaglutide and GLP-1 Agonists: The Body Composition Question

Semaglutide and other GLP-1 receptor agonists have become the most talked-about weight loss drugs in history. For endurance athletes, the appeal is obvious: lower body weight means less mass to carry over 26.2 miles or up a mountain pass.

What the Data Shows

In the STEP-1 trial, semaglutide reduced fat mass by roughly 19.3% while lean mass decreased about 9.7% [22]. That fat-to-lean loss ratio (about 75% fat, 25% lean) has raised concerns, especially for athletes who cannot afford to lose muscle.

However, emerging research complicates this picture. A recent case series showed that athletes who combined semaglutide or tirzepatide with resistance training (3-5 days/week) and high protein intake (1.6-2.3 g/kg/day) experienced fat mass reductions of 47-62% with lean mass changes ranging from -6.9% to increases of +5.8% [23]. This suggests the muscle loss concern is manageable with proper training and nutrition.

The Problem for Endurance Athletes

The biggest risk is unintentional under-fueling. GLP-1 agonists powerfully suppress appetite. During a 90-mile training week, a runner on semaglutide might simply not feel hungry enough to eat the 3,500-4,000 calories their body needs. Over time, this creates relative energy deficiency in sport (RED-S) -- a condition linked to stress fractures, hormonal dysfunction, and degraded performance [24].

Fatigue is also commonly reported, particularly in the first weeks after dosing. For an athlete whose training demands consistent energy output, this side effect matters.

WADA currently monitors semaglutide but has not banned it. The conversation is ongoing, especially in weight-class and power-to-weight sports like cycling, marathon running, and triathlon [25].

For more on peptides and body composition, see our guide on best peptides for fat loss.

Here's a plot twist: the peptide with the strongest clinical evidence for endurance performance is legal, widely available, and costs about $30 a month.

Specific collagen peptides (SCP) have been tested in multiple randomized controlled trials measuring actual running performance -- something most other peptides on this list cannot claim.

The Clinical Evidence

A 2023 double-blind RCT in Sports Medicine - Open assigned moderately trained men to 12 weeks of concurrent training with either 15 g/day of specific collagen peptides or placebo. The collagen group ran 330 meters farther in a one-hour time trial and showed improved velocity at both the lactate threshold and anaerobic threshold [26].

An earlier RCT in women found similar results: collagen peptide supplementation combined with 12 weeks of concurrent training improved time trial performance, heart rate at the individual anaerobic threshold, and fat-free mass compared to training alone [27].

A third RCT specifically examined recovery from exercise-induced muscle damage. After 12 weeks of collagen supplementation and concurrent training, participants showed significantly improved markers of maximal, explosive, and reactive strength recovery [28].

Why It Works

The proposed mechanism involves extracellular matrix remodeling. Collagen peptides provide the specific amino acid building blocks (glycine, proline, hydroxyproline) that tendons, ligaments, and the connective tissue matrix need for repair and adaptation. A 2024 systematic review and meta-analysis concluded that 15 g/day appears to be the optimal dose for sports performance and injury prevention [29].

The major advantage: collagen peptides are explicitly permitted by WADA and USADA. They are not the same as banned peptide hormones. For competitive athletes who cannot risk WADA violations, this is the most accessible option with real performance data behind it.

AOD-9604: Fat Metabolism Without Hormonal Effects

AOD-9604 is a synthetic fragment (amino acids 177-191) of human growth hormone, designed to stimulate fat breakdown without the broader hormonal effects of full-length GH. It activates beta-3 adrenergic receptors in fat cells, preferentially mobilizing stored fat from adipose tissue without affecting IGF-1 or glucose metabolism [30].

For endurance athletes focused on optimizing power-to-weight ratio, the concept is appealing. A 12-week clinical trial found that subjects taking 1 mg/day of AOD-9604 lost an average of 2.6 kg compared to 0.8 kg in the placebo group [30]. However, a larger 24-week trial of 536 subjects failed to show significant weight loss, and drug development was terminated in 2007 [31].

AOD-9604 is banned by WADA and is not FDA-approved. Its clinical track record is mixed at best.

Peptide Comparison Table for Endurance Athletes

PeptidePrimary BenefitEvidence LevelWADA StatusHuman Trial Data
MOTS-cMitochondrial efficiency, AMPK activationModerate (animal + human observational)Not yet listedObservational only
BPC-157Tissue repair, tendon healingStrong preclinical, weak clinicalBanned (2022)1 small pilot study
TB-500Tissue repair, anti-inflammationModerate preclinicalBannedPhase I safety only
SS-31Mitochondrial ATP productionStrong (FDA-approved for Barth syndrome)Not yet listedMultiple clinical trials
CJC-1295 + IpamorelinGrowth hormone, recovery, fat metabolismModerate clinical (hormone levels)BannedHormone level studies only
SemaglutideFat loss, body compositionVery strong clinicalMonitored (not banned)Multiple large RCTs
Collagen peptidesRunning performance, tendon healthStrong clinicalPermittedMultiple RCTs with performance outcomes
AOD-9604Targeted fat metabolismWeak clinicalBannedMixed results, development discontinued

WADA Status and Competitive Athletes

If you compete in any sport with anti-doping testing -- including USATF-sanctioned races, UCI cycling events, World Triathlon events, or even CrossFit Games -- you need to understand which peptides will trigger a positive test.

Banned peptides: BPC-157, TB-500, CJC-1295, Ipamorelin, AOD-9604, and all other growth hormone secretagogues and peptide hormones are prohibited under the WADA Prohibited List.

Monitored (not yet banned): Semaglutide and other GLP-1 agonists are on WADA's monitoring program. They are not currently prohibited, but WADA is studying whether they provide unfair advantages in weight-sensitive sports.

Permitted: Collagen peptides are legal and explicitly cleared by USADA. They are not peptide hormones and do not appear on any prohibited substance list.

For any competitive athlete, the safest approach is sticking to collagen peptides and working with a sports medicine physician for any other recovery interventions. The consequences of a positive test -- even from an inadvertent or contaminated source -- are severe.

Frequently Asked Questions

What is the best peptide for marathon runners?

Based on current evidence, collagen peptides are the only option with RCT data showing improved running performance in time trials. For non-competitive athletes exploring research peptides with medical supervision, MOTS-c and BPC-157 have the most relevant preclinical data for endurance and recovery, respectively.

Can peptides improve VO2 max?

No peptide has been shown to directly improve VO2 max in controlled human trials. However, MOTS-c's activation of the AMPK pathway -- the same pathway activated by endurance training -- suggests it may support the adaptations that lead to improved aerobic capacity. SS-31's ability to improve mitochondrial efficiency could theoretically improve oxygen utilization, though this hasn't been tested in healthy athletes.

Are peptides safe for endurance athletes?

Collagen peptides have a strong safety profile and are widely used. For research peptides like BPC-157 and TB-500, animal studies show favorable safety profiles with no observed toxicity across wide dose ranges, but formal human safety data is limited. Any peptide use beyond collagen should involve a qualified physician. See our guide on peptides for injury prevention in sports for more context.

How do peptides compare to traditional recovery methods?

Peptides are not a replacement for sleep, nutrition, periodized training, and manual therapy. They are, at best, an adjunct. A runner sleeping 6 hours a night and eating 2,000 calories during a 70-mile training week will not fix those problems with peptides. The fundamentals always come first.

Can I use peptides if I'm a competitive runner?

Only if they are not on the WADA Prohibited List. Currently, collagen peptides and semaglutide (monitored but not banned) are the only options that won't trigger a positive test. Everything else on this list is either banned or in a regulatory gray area.

The Bottom Line

The peptide space for endurance athletes breaks into two clear categories.

In one camp, you have collagen peptides -- legal, affordable, and backed by multiple RCTs showing real improvements in running distance, lactate threshold, and recovery. If you're a competitive runner or triathlete looking for an evidence-based edge, 15 g/day of specific collagen peptides with your training is the straightforward play.

In the other camp, you have research peptides like MOTS-c, BPC-157, TB-500, and SS-31, which have genuinely interesting mechanisms and preclinical data relevant to endurance performance. But they lack the controlled human trials needed to make confident performance claims, and most are banned in competitive sports.

The gap between these two camps will narrow as clinical trials progress. SS-31's FDA approval for Barth syndrome opens doors for studying mitochondrial peptides in broader populations. MOTS-c's role as an exercise-induced peptide makes it a natural target for endurance research. And the ongoing accumulation of BPC-157 animal data will eventually force the question of human trials.

Until then, build your training on proven foundations -- consistent mileage, proper periodization, adequate sleep, and targeted nutrition. If peptides have a role in your program, start with the ones that have the strongest evidence behind them.

References

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  2. Lee C, et al. "Exercise protein" doubles running capacity in mice. USC Leonard Davis School of Gerontology. 2021. Link

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  4. von Walden F, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. Journal of Applied Physiology. 2020;129(5):1197-1203. PubMed

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  18. FDA approves drug for treatment of rare mitochondrial disorder. Johns Hopkins Hub. 2025. Link

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  21. CJC-1295. Wikipedia. Link

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  25. Does Ozempic affect athletic performance? Triathlete. Link

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