This protocol was developed for practitioners using Fullscript in the United States and the templates cannot be applied to accounts operating outside of the United States

Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through D-quality evidence.

Class
Qualifying studies
Minimum requirements
A
Systematic review or meta-analysis of human trials
 
B
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
C
RDBPC human trials
1 study
D
Non-RDBPC human or In-vivo animal trials
 

Introduction

What Is Healthspan?

Healthspan describes the period of life spent in good health, free from the chronic diseases and disabilities of aging. It focuses on the period of good health and functionality in which individuals remain healthy, active, independent, and productive both mentally and physically. Ultimately, the goal of improving healthspan is remaining healthier for longer, ideally delaying the onset of chronic disease. (Masfiah 2025)

Why Muscle Health Matters

Skeletal muscle is the body’s largest tissue mass in the human body and functions as an endocrine tissue, secreting signaling molecules called myokines into systemic circulation. These myokines regulate metabolic function in distant organs, including the brain, liver, and gut. (Horvath 2025)

Muscle health is a key predictor of longevity and systemic resilience. Low skeletal muscle mass is strongly associated with increased all-cause mortality and functional disability, while maintaining muscle integrity supports metabolic health, insulin sensitivity, and overall physical performance. This underscores the role of muscle as a central pillar of systemic resilience, influencing multiple aspects of long-term health. (Feng 2025)(Wang 2023)

Purpose of the Clinical Guide

The Muscle Health clinical guide was designed to:

  1. Simplify decision-making using standardized, evidence-rated nutrient and lifestyle interventions.
  2. Integrate laboratory and biomarker data to identify modifiable contributors to muscle health.
  3. Serve as the foundation for individualized care plans aimed at maintaining muscle health through the lifespan.

Essential Labs

Nutrients and Inflammation

Vitamin D 

Vitamin D is clinically relevant as a pro-hormone that modulates bone mineralization, immune function, and skeletal muscle physiology. It supports muscle health by influencing protein synthesis in fast-twitch fibers and facilitating calcium transport for contraction. Consequently, deficiency is linked to proximal muscle weakness and an increased risk of injuries. (Sist 2023) 

Magnesium RBC 

Magnesium acts as a vital cofactor for over 300 enzymes and is essential for energy metabolism, where it binds with ATP to form the bioactive Mg-ATP complex. It regulates the mechanics of muscle contraction and relaxation by functioning as a physiological calcium channel blocker. Magnesium supports muscle mass maintenance and repair by modulating the IGF-1/PI3K/Akt/mTOR (Insulin-like Growth Factor-1/Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin) anabolic signaling pathway and facilitating the differentiation of satellite cells. It provides anti-inflammatory and analgesic benefits by lowering pro-inflammatory cytokines and blocking N-methyl-D-aspartate receptor (NMDA) receptors to prevent central pain sensitization. (Liguori 2024) 

High-Sensitivity C-Reactive Protein (hs-CRP) 

Hs-CRP is a sensitive biomarker of systemic inflammation. Elevated hs-CRP levels are associated with sarcopenia, frailty, and impaired physical function, all of which contribute to reduced muscle mass, strength, and recovery in older adults. Monitoring hs-CRP can help clinicians identify individuals at higher risk for muscle decline, guide interventions aimed at reducing chronic inflammation, and track response to lifestyle or therapeutic strategies targeting muscle preservation and functional resilience. (Lai 2025)

Hormones

Testosterone, Free and Total 

Testosterone is a potent anabolic-androgenic hormone that promotes muscle growth by stimulating protein synthesis and inhibiting protein breakdown, supporting hypertrophy, strength, and functional capacity. Acute resistance exercise can increase circulating testosterone in men, enhancing adaptations to training, though this response declines with age. In women, testosterone levels are lower and the exercise-induced response is less consistent, but it still contributes to muscle maintenance. Monitoring testosterone can help identify individuals at risk for age-related muscle loss (sarcopenia) or impaired training response, guiding targeted interventions to preserve muscle health. (Vingren 2010)

Dehydroepiandrosterone Sulfate (DHEA-S) 

DHEA-S is the sulfated, circulating form of the steroid hormone DHEA and serves as a key precursor for both androgen and estrogen synthesis. Peak levels occur in young adulthood and decline progressively with age, with larger decrements linked to reduced physical vitality and functional capacity. Lower-than-age-expected DHEA-S levels are associated with reduced muscle strength, slower gait speed, impaired lower-body function, and increased frailty, reflecting diminished systemic resilience and anabolic signaling. DHEA-S also exerts anti-inflammatory and immunoregulatory effects, which may indirectly support muscle maintenance and recovery. (Rendina 2017)

Albumin

Albumin serves as the primary carrier for many hormones, including adrenal and sex steroids, as well as drugs and nutrients. Approximately 90% of adrenal androgens (DHEA, DHEA-S, androstenedione) circulate weakly bound to albumin. Only unbound (“free”) steroids are biologically active, capable of interacting with target tissues or being metabolized. (Papadopoulou-Marketou 2023)

Sex Hormone Binding Globulin (SHBG)

SHBG binds sex steroids, particularly testosterone and estradiol, with high affinity, regulating the proportion of hormone that remains free and biologically active. Binding to SHBG controls steroid availability for target tissues. (Papadopoulou-Marketou 2023)

Estradiol 

In animal models, estrogen deficiency reduces mitochondrial function, antioxidant capacity, and insulin sensitivity, while increasing susceptibility to muscle injury. Estrogen decline after menopause is associated with reduced muscle protein synthesis, decreased muscle mass, and diminished sensitivity to anabolic stimuli, contributing to age-related sarcopenia and frailty. (Chidi-Ogbolu 2019)

Specialty Labs

Insulin-Like Growth Factor 1 (IGF-1) 

IGF-1 is a key anabolic hormone that promotes protein synthesis and inhibits muscle protein degradation, playing a central role in maintaining skeletal muscle mass and function. Levels peak in early adulthood and naturally decline with age, contributing to sarcopenia and age-related muscle weakness. Low IGF‑1 (≤88 ng/mL) is linked to increased frailty risk in men, with similar trends in women, though these findings are population-specific and may not generalize. Combined aerobic and resistance training is most effective for increasing IGF‑1 in older adults. Resistance training alone is moderately effective, while aerobic training alone shows minimal effect. Interpretation of IGF‑1 should rely on lab-specific, age- and sex-adjusted reference ranges, as values vary by assay and population. (Chu 2025)

Essential Ingredients

Branched Chain Amino Acids (BCAA) 

Dosing: 5.6–6.1 g of isolated BCAAs, 2:1:1 ratio (leucine:isoleucine:valine) (Kaspy 2024)

Supporting evidence:

  • Activates mechanistic Target of Rapamycin Complex 1 (mTORC1) to increase protein synthesis, enhance BCAA uptake, reduce muscle protein breakdown, preserve fiber size, and support mitochondrial biogenesis and function (Bifari & Nisoli, 2017)(Kaspy 2024)(Mănescu 2025)
  • Meta-analysis of 12 randomized controlled trials (RCTs) (n = 459) found that combined BCAA supplementation and resistance training helped significantly increase skeletal muscle index, but did not improve functional outcomes or total body composition. (Li 2026)
  • In older adults with pre‑sarcopenia/sarcopenia, 5 weeks of BCAA supplementation (3.6 g twice per day) helped improve skeletal muscle mass index, grip strength, gait speed, and other sarcopenic parameters, but benefits diminished after discontinuation. (Ko 2020)

Creatine Monohydrate 

Dosing: Loading protocol: 20 g/day divided doses for 5–7 days then 3–5 g for maintenance. Gradual protocol: 3 g/day for 28 days (fewer side effects such as GI distress, but takes longer to saturate muscle stores). (Paoli 2024)

Supporting evidence:

  • Enhances ATP regeneration via phosphocreatine, supports higher training volume, and activates satellite cells to stimulate muscle growth and protein synthesis. (Mănescu 2025)(Paoli 2024)
  • A systematic review and meta-analysis of 10 RCTs examining 44 outcomes in healthy adults found that creatine supplementation combined with resistance training led to a small increase in site-specific skeletal muscle hypertrophy (0.10–0.16 cm). (Burke 2023)
  • Creatine supplementation combined with exercise training in older adults helped significantly improve 1 rep max (1RM) strength and reduced body fat percentage, but had no significant effect on total body bone mineral density. (Sharifian 2025)

Omega-3 Fatty Acids 

Dosing: >2 g/day of EPA or DHA for 6 months (Moon & Bu, 2023)

Supporting evidence:

    • Inhibits NF‑κB, reduces pro-inflammatory cytokines, supports muscle energy metabolism, and enhances acetylcholine sensitivity for faster neuromuscular signaling. (Moon & Bu, 2023)(Tomczyk 2024)
    • In older adults, 3.36 g/day (1.86 g EPA + 1.50 g DHA) for 6 months showed  increased muscle volume & handgrip strength. (Moon & Bu, 2023)
    • In a 10-week RCT (n = 21), EPA+DHA improved upper- and relative lower-body 1RM vs. placebo, with modest, non-significant changes in body composition. (Heileson 2023)

 

CoQ10 (Ubiquinone)

Dosing: 100–300 mg/day (Talebi 2024)

Supporting evidence:

  • Helps reduce muscle damage and supports recovery by lowering CK, decreasing reactive oxygen species (ROS), and optimizing redox status, particularly during short-term supplementation. (Talebi 2024)(Zhang 2026)
  • Meta-analysis of 28 RCTs (n = 830) showed CoQ10 supplementation helped reduce exercise-induced muscle damage and oxidative stress with decreases in CK, LDH and myoglobin, with each 100 mg/day further lowering these markers. (Talebi 2024)
  • In a double-blind RCT, 8 weeks of CoQ10 supplementation combined with high-intensity interval training (HIIT) led to greater improvements in lower-body strength and power compared to placebo, with no additional benefits observed for grip strength, balance, mobility, or aerobic endurance. (Bagheri 2025)

β-Hydroxy β-Methylbutyrate (HMB)

Dosing: 3 g/day > 12 weeks (Durkalec-Michalski 2017)(Rathmacher 2020)

Supporting evidence:

  • In a 12-week RCT in trained athletes, HMB supplementation (3 g/day) helped increase lean mass, reduced fat mass, and improved both aerobic and anaerobic performance compared to placebo. (Durkalec-Michalski 2017)
  • A 12-month double blind RCT found HMB (3 g/day) + vitamin D3 (2,000 IU/day) increased lean mass, strength, and physical function in older adults—even without exercise. (Rathmacher 2020)

HMB promotes muscle protein synthesis while inhibiting muscle protein breakdown, supporting a net anabolic effect. (Li 2025)

Urolithin A 

Dosing: 500–1000 mg/day (Singh 2022)

Supporting evidence:

  • In a 4-month double-blind RCT (n = 66, ages 65–90), 1000 mg/day urolithin A improved muscle endurance and reduced inflammatory and mitochondrial-related biomarkers but did not significantly enhance 6-minute walk distance or maximal ATP production compared to placebo. (Liu 2022)
  • In a 4-month RCT in middle-aged adults, urolithin A improved muscle strength (~12%), aerobic endurance, 6-minute walk performance, and mitophagy-related biomarkers, without affecting peak power. (Singh 2022)

Lifestyle Recommendations

Nutrition

Risk Factors

Inadequate protein intake, poorly timed carbohydrates, and uncorrected electrolyte disturbances are key modifiable contributors to loss of muscle mass, strength, and physical function in adults and older adults. Low intake of high-quality protein accelerates age-related muscle loss due to reduced appetite and anabolic resistance. Insufficient carbohydrate intake can impair glycogen availability, reduce exercise performance, and increase fatigue and protein oxidation. Electrolyte imbalances—particularly abnormalities in sodium, potassium, calcium, and magnesium—can cause muscle weakness, cramps, and impaired neuromuscular function, and in severe cases may contribute to myopathy or rhabdomyolysis. (Habumugisha 2025)(Henselmans 2022)(Bordoni 2025)

Interventions

To support muscle protein synthesis and counter anabolic resistance, adults should consume at least 1.2 g/kg/day of protein, exceeding the RDA of 0.8 g/kg/day. Intake should be distributed evenly across meals, targeting ~0.4 g/kg per meal (25–40 g) to provide approximately 3 g of leucine, which helps stimulate muscle protein synthesis. Animal proteins generally provide higher digestibility and essential amino acid content, though well-planned plant-based diets can also meet requirements. For exercise lasting longer than 60 minutes, consuming 30–60 g of carbohydrate per hour supports performance and glycogen preservation. After exercise, rapid glycogen restoration is optimized with ~1.2 g/kg/hour of carbohydrate for the first 4 hours, particularly when combining multiple carbohydrate sources such as glucose and fructose. (Bonilla 2020)(Henselmans 2022)(Jeukendrup 2014)(Orrù 2018)(Traylor 2018)

Adequate electrolyte intake is also important for muscle contraction and fluid balance. During exercise lasting less than 3 hours, beverages containing 0.5–0.7 g/L sodium are generally sufficient, while longer exercise sessions may require 0.7–1.0 g/L sodium to replace sweat losses. Electrolyte supplementation should be individualized, particularly in patients with heart failure, chronic kidney disease, or hypertension. (Bonilla 2020)(Henselmans 2022)(Jeukendrup 2014)(Orrù 2018)(Traylor 2018)

Movement

Risk Factors

Sedentary behavior, defined as waking activities performed while sitting or reclining with energy expenditure ≤1.5 metabolic equivalent of tasks (METs), contributes to declines in muscle strength, physical performance, and functional capacity. Prolonged sedentary time in older adults is associated with increased risk of mobility limitations, falls, cardiometabolic disease, and all-cause mortality. Insufficient resistance exercise is another major contributor to reduced muscular fitness. Current global guidelines recommend performing resistance exercises involving all major muscle groups at least twice per week. Poor lower-body function—reflected by reduced gait speed, impaired balance, or poor chair-rise performance—is also associated with increased risk of disability and loss of independence. (Bull 2020)(Mahato 2024)

Interventions

Adults should perform resistance training targeting all major muscle groups at least two times per week, with ≥10 total sets per muscle group weekly and sets performed near muscular failure to stimulate strength and hypertrophy. Both lighter loads (<60% 1RM) and heavier loads (>60% 1RM) can improve muscle strength, particularly when progressive overload is applied. (Bernárdez-Vázquez 2022)(Bhatia & Kayser, 2019)(Grant 2020) (Liu 2016)(MacInnis 2017)(Sadaqa 2023)(Shen 2023)(Schoenfeld 2016)(Wei 2025)

Combining resistance training with aerobic and balance exercises provides the greatest functional benefits, improving strength, gait speed, chair-rise performance, and overall mobility. HIIT can further enhance mitochondrial function and metabolic efficiency. In deconditioned individuals, protocols may include a 5-minute warm-up followed by 2 × 10-minute intervals of 15-second high-intensity efforts (rate of perceived exertion [RPE] 7–9) alternating with 15-second recovery periods. More trained individuals may perform 4 × 5-minute intervals at approximately 65% peak power output (Wpeak) with 2.5-minute recovery periods, typically 2–3 sessions per week. In addition, minimizing sedentary time through frequent walking, standing, or light movement and incorporating balance and mobility exercises can help maintain muscle loading and reduce fall risk. (Bernárdez-Vázquez 2022)(Bhatia & Kayser, 2019)(Grant 2020) (Liu 2016)(MacInnis 2017)(Sadaqa 2023)(Shen 2023)(Schoenfeld 2016) (Wei 2025)

Recovery 

Risk Factors

Insufficient recovery between physical stressors can impair muscle repair, performance, and adaptation. Sleep plays a central role in muscle maintenance by supporting protein synthesis, circadian regulation, glucose metabolism, and anti-inflammatory pathways. Acute sleep deprivation has been shown to reduce postprandial muscle protein synthesis by approximately 18%, while increasing cortisol and contributing to anabolic resistance. High training intensity, repetitive eccentric loading, inadequate rest intervals, and elevated oxidative stress can further delay tissue repair and impair recovery when mitochondrial energy production and antioxidant defenses are insufficient. (Lin 2022)(Lamon 2021(Qiu 2025)

Interventions

Adults should aim for at least 7 hours of sleep per night and maintain consistent sleep–wake timing to support recovery and metabolic health. Exposure to bright morning light, limiting naps to ≤1 hour and avoiding naps after 3 PM, minimizing evening screen exposure, and maintaining a cool, dark, and quiet sleep environment (60–70°F) can improve sleep quality. (Cheatham 2015)(Ferraresi 2016)(Laukkanen & Kunutsor, 2024)(Leonardi 2025)(Shadgan 2018)(Siraji 2023)(Vitale 2019)(Watson 2015)

Additional recovery strategies may include heat therapy, cold exposure, contrast therapy, and photobiomodulation. Sauna use at 80–100°C (176–212ºF) for 15–20 minutes, 3–7 times per week may support mitochondrial function and recovery. Cold immersion at ~5°C (41ºF) for 5 minutes may reduce inflammation and pain. Contrast therapy typically alternates 3–4 minutes of hot water at 37.8–40°C (100–104°F) with 1 minute of cold water at 7.8–12.8°C (46–55°F) for 4–6 cycles, ending on cold. Red and near-infrared light therapy (630–660 nm or 808–950 nm) applied for 3–5 minutes before and after exercise may enhance ATP production and reduce markers of muscle damage. Patients should be screened for cardiovascular or neurological conditions prior to implementing these modalities. (Cheatham 2015)(Ferraresi 2016)(Laukkanen 2024)(Leonardi 2025)(Shadgan 2018)(Siraji 2023)(Vitale 2019)(Watson 2015)

Disclaimer

The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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