Tommy John’s Hidden Cause: How Overtraining Wrecks Redox Balance and Ligaments

[Anthony Castore]

Those who know me are well aware of my passion for cellular medicine, my English bulldog, my amazing fiance (though the running joke is she’s a mail-order bride), Marvel superheroes, great food, and, of course, the New York Yankees. It’s an interesting mix, I admit.

If you love baseball as much as I do especially if you’re a Yankees fan you’ve probably noticed the wave of injuries hitting spring training. We already have three pitchers potentially sidelined for Tommy John surgery.

I thought this would be a great opportunity to share some insights from the last Exercise Mastermind on what’s really happening with these injuries and, more importantly, what can be done to prevent them. There’s a real opportunity here to rethink training and recovery strategies.

One of the most common injuries in baseball pitchers—ulnar collateral ligament (UCL) tears requiring Tommy John surgery—is the result of cumulative biomechanical stress, exacerbated by systemic dysregulation due to overtraining and immune intolerance. This is not just a structural breakdown but a failure at multiple levels, from mitochondrial dysfunction and oxidative stress to immune dysregulation, compromised collagen integrity, and disrupted anabolic-catabolic balance.

Overtraining drives chronic elevations in cortisol via the hypothalamic-pituitary-adrenal (HPA) axis, leading to sustained glucocorticoid receptor activation in immune cells, promoting T-cell exhaustion and reducing immune surveillance. Chronic mechanical stress activates NF-κB, increasing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and perpetuating a catabolic environment. The imbalance in mTOR and AMPK signaling suppresses protein synthesis and ligament remodeling while driving excessive catabolism in response to energy deficits. Chronic stress also leads to thymic involution, reducing naïve T cells and impairing regulatory T cell (Treg) function, increasing immune intolerance. Overtraining disrupts mitochondrial function, impairing oxidative phosphorylation (OXPHOS) efficiency and increasing reactive oxygen species (ROS), which damages fibroblasts and chondrocytes in the UCL while depleting key antioxidants such as SOD2, glutathione (GSH), and catalase. This perfect storm results in a redox imbalance, where excessive ROS overwhelms the antioxidant system, leading to oxidative damage that compromises ligament integrity at a cellular level.

Loss of immune tolerance contributes to an autoimmune-like response, where damaged ligament proteins such as collagen type I and III become antigenic, triggering a cycle of chronic inflammation. Damage-associated molecular patterns (DAMPs) from repetitive stress activate TLR4 (Toll-like receptor 4), further escalating inflammation and degrading the extracellular matrix. Mast cell activation leads to histamine and prostaglandin release, impairing ligament healing and increasing vascular permeability, which disrupts nutrient delivery. Dysregulated TGF-β signaling favors excessive fibrosis over proper ligament regeneration, reducing structural integrity and increasing injury risk.

At the structural level, chronic stress disrupts collagen fibril cross-linking, reducing tensile strength and elasticity. Persistent microtrauma activates p53-mediated tenocyte apoptosis, impairing the ability of the ligament to maintain extracellular matrix integrity. VEGF signaling is also disrupted, leading to poor microvascularization and limiting the oxygen and nutrient supply necessary for tissue repair.

A targeted prophylactic protocol should focus on mitigating chronic inflammation, preserving immune tolerance, enhancing mitochondrial function, and promoting ligament regeneration.

Peptide-based interventions include BPC-157 (250-500 µg/day oral or subcutaneous) to accelerate fibroblast proliferation, reduce TNF-α and IL-6, and enhance angiogenesis; TB-500 (Thymosin Beta-4, 2 mg subcutaneous three times per week) to increase actin polymerization, upregulate SDF-1, and modulate TGF-β to prevent excessive fibrosis; GHK-Cu (2 mg/day subcutaneous or transdermal) to increase MMP-2 and MMP-9 for extracellular matrix remodeling and fibroblast proliferation; and KPV (200-500 mcg/day subcutaneous or oral) to directly suppress NF-κB and control inflammation without immunosuppression.

Pentosan Polysulfate (250mg, 2x/week ) plays a critical role in preserving cartilage and soft tissue integrity by acting as a glycosaminoglycan mimetic, reducing fibrinogen levels and inhibiting heparanase to prevent excessive matrix degradation. Additionally, it reduces TNF-α and IL-1β, mitigating inflammation-induced collagen breakdown in the UCL while improving microvascular circulation to the ligament. Pentosan also stimulates proteoglycan synthesis, which strengthens tendon and ligament structure while preserving joint health.

Nutraceutical interventions should support mitochondrial function and redox balance while improving cellular efficiency. Ketone ester BhB (10-25g/day, dosed pre- and post-workout) reduces inflammation via inhibition of the NLRP3 inflammasome while optimizing mitochondrial function by bypassing complex I of the electron transport chain (ETC), reducing ROS production, and preserving redox homeostasis. Ketones also increase NAD+/NADPH ratios, enhancing cellular repair and metabolic efficiency, which is critical for tissue healing and injury prevention.

BDMC Curcumin (1000 mg/day) replaces standard curcumin for its superior NF-κB inhibition and COX-2 suppression while also upregulating Nrf2, leading to enhanced antioxidant defense. BDMC curcumin is particularly effective at reducing oxidative stress and fibrosis in connective tissue, making it a valuable intervention for ligament preservation.

iCell Water (daily intake tailored to hydration needs, with an emphasis on pre/post-training consumption) enhances cellular hydration, polarization, and overall tissue resilience through its blend of neutral osmolytes, which regulate cell volume, prevent dehydration stress, and optimize intracellular electrolyte balance. Proper cell polarization supports enhanced electrical conductivity within tissues, leading to improved neuromuscular efficiency and better tissue recovery post-stress.

L-Theanine (200-400 mg/day, ideally pre-sleep or post-training) enhances immune function and reduces overtraining-induced HPA axis dysregulation by modulating cortisol release and promoting parasympathetic tone. Its ability to increase GABA and regulate glutamate excitotoxicity helps control neuroinflammation, which indirectly benefits systemic inflammatory control and ligament repair.

Type II Collagen (10 mg/day, hydrolyzed or undenatured) supports immune tolerance by regulating T-cell responses and reducing autoimmune-like inflammation in connective tissues. By training the immune system to recognize type II collagen as “self,” it reduces inflammatory cytokine activation, helping to protect ligaments from excessive immune attack.

Fortigel (5-10g/day, hydrolyzed collagen peptides) specifically targets tendon and ligament regeneration, increasing fibroblast activity and improving extracellular matrix composition. Fortigel is particularly effective at stimulating collagen type I and III synthesis, which is crucial for ligament integrity.

Tendoforte (5g/day, specialized bioactive collagen peptides) enhances tensile strength and elasticity of ligaments and tendons, reducing the risk of micro-tears and chronic overuse injuries. Tendoforte has been shown to stimulate collagen fibril diameter increase, improving overall ligament durability under mechanical stress.

Idebenone (45-90 mg/day, divided dosing for sustained effects) is preferred over resveratrol due to its ability to enhance mitochondrial function and ATP production while acting as an electron donor in the ETC, particularly in hypoxic or high oxidative stress conditions. Unlike resveratrol, which has inconsistent bioavailability, idebenone directly preserves redox balance and protects against lipid peroxidation, reducing the oxidative damage that contributes to collagen degradation.

Training strategies should incorporate throwing periodization with structured high/low neural stimulus days, reducing consecutive high-load sessions to prevent chronic NF-κB activation. Isometric and eccentric loading should be emphasized to reinforce ligament resilience. Post-throwing red light therapy (660nm and 850nm, 10-15 minutes over the elbow and forearm complex) should be used to stimulate ATP production via cytochrome c oxidase activation, improve mitochondrial efficiency, and enhance local tissue repair.

By addressing immune intolerance, mitochondrial dysfunction, and chronic inflammation, this protocol restores redox balance, preserves ligament integrity, and enhances recovery. Integrating peptide therapy, nutraceutical support, and strategic training adjustments offers a comprehensive approach to preventing UCL injuries, extending career longevity, and optimizing performance.

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