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How IGF-II and rs680 Affect Muscle Damage and Recovery

Muscle damage from exercise happens when intense or new activities cause tiny tears in muscle fibers. That damage leads to soreness, swelling, and temporary reductions in strength and performance. The IGF-II gene plays an important role in muscle repair and growth. Variations at the rs680 location in IGF-II can influence how efficiently your body heals and rebuilds muscle tissue after exercise.

This article explains what the rs680 genotypes mean for exercise-induced muscle damage, and provides practical, evidence-informed steps you can use to support recovery. Remember: PlexusDx does not provide medical advice. This information is educational only. Always consult your healthcare provider before starting new supplements, changing diet patterns, or altering your training plan.

Why IGF-II Matters for Muscle Repair

Insulin-like growth factor 2, commonly called IGF-II, helps regulate cellular growth, differentiation, and tissue repair. After exercise-related microtears occur, signaling pathways involving IGF-II influence the speed and quality of muscle regeneration. Variants at rs680 may change expression or activity of IGF-II, which can alter the typical recovery process. The practical result is differences in soreness, inflammation, and time needed to return to peak strength.

Common Symptoms of Exercise-Induced Muscle Damage (EIMD)

  • Muscle soreness that peaks 24 to 72 hours after exercise
  • Temporary loss of muscle strength or reduced range of motion
  • Mild swelling and stiffness
  • Possible increase in inflammatory markers or muscle enzymes after intense activity

General Recovery Principles (Useful for Everyone)

Regardless of genotype, these core strategies support faster, safer recovery:

  • Prioritize protein: Aim for adequate daily protein distributed across meals to support repair and muscle protein synthesis.
  • Include anti-inflammatory foods: Fatty fish, walnuts, flax, berries, leafy greens, turmeric, and ginger help modulate inflammation.
  • Stay hydrated: Fluid balance supports nutrient delivery and metabolic waste removal.
  • Plan rest and progressive loading: Allow sufficient rest days and increase training volume or intensity gradually, especially when introducing new movements.
  • Use targeted recovery tools: Sleep, compression, gentle mobility work, and active recovery (light aerobic activity) aid tissue healing.
  • Consider supplements carefully: Omega-3 fatty acids and antioxidants can reduce excessive inflammation and may speed repair when used appropriately.

Genetic Interpretations for rs680 (IGF-II)

2 effect alleles (TT) — Higher risk of exercise-induced muscle damage

If your genotype is TT, you carry two copies of the effect allele at rs680. This pattern is associated with a greater likelihood of more pronounced muscle damage after intense or unfamiliar exercise, particularly in men. You may experience stronger or longer-lasting soreness, and temporary reductions in strength may last longer than average.

Practical Recommendations

  • Adjust training volume: Reduce frequency or intensity when introducing new exercises. Use a slower progression to allow repair pathways more time to adapt.
  • Prioritize protein timing: Target 20 to 40 g of high-quality protein within 1 to 2 hours after training and distribute 3 to 5 protein-containing meals across the day.
  • Emphasize anti-inflammatory nutrition: Include omega-3 rich foods (salmon, mackerel, chia), colorful vegetables and fruits, and spices like turmeric and ginger.
  • Supplement suggestions: Consider omega-3 supplements (EPA + DHA) and antioxidant support such as vitamin C or polyphenol-rich extracts. Discuss doses with a healthcare provider.
  • Recovery protocols: Prioritize sleep, incorporate light aerobic or mobility sessions on sore days, and use contrast baths or cold therapy cautiously based on how they affect your performance goals.
  • Monitor and test: If you experience unusually severe or persistent weakness, discuss blood tests or clinical evaluation with your healthcare provider to rule out other causes.
1 effect allele (GT) — Moderate predisposition to exercise-induced muscle damage

If your genotype is GT, you carry one copy of the effect allele. This suggests a moderate genetic predisposition to exercise-induced muscle damage. Your recovery may be somewhat less efficient than people without the T allele but not as strongly affected as those with two copies.

Practical Recommendations

  • Progress gradually: Increase training intensity and volume stepwise to reduce the risk of large, sudden muscle insults.
  • Maintain adequate daily protein: Aim for regular protein intake spread across meals to support ongoing repair.
  • Anti-inflammatory focus: Add omega-3 rich foods and plenty of vegetables and fruits to your meals.
  • Consider supplements: Low-to-moderate dose omega-3 supplementation and antioxidant-rich supplements may help. Check with your provider for personalized dosage.
  • Use recovery strategies: Prioritize sleep, hydration, and active recovery sessions after heavy workouts to reduce prolonged soreness.
0 effect alleles (GG) — Typical response to muscle damage and repair

If your genotype is GG, you carry two copies of the non-effect allele. Your genetic profile suggests a standard or typical response to exercise-induced muscle damage and repair. You are less likely to experience unusually severe or prolonged soreness specifically due to IGF-II variation.

Practical Recommendations

  • Follow standard recovery practices: Balanced protein intake, anti-inflammatory foods, good hydration, and progressive training remain important.
  • Optimize sleep and stress: These factors affect repair processes and overall recovery capacity.
  • Use targeted supplements as needed: Omega-3s and antioxidants can provide general anti-inflammatory support, particularly around periods of increased training load.
  • Listen to your body: Even with a typical genetic profile, sudden increases in training intensity or volume can cause significant soreness. Scale appropriately.

Practical Meal and Supplement Tips

  • Post-workout protein: A mix of whey or plant protein with carbohydrate can promote recovery; aim for 20 to 40 g protein after resistance workouts.
  • Daily protein target: Adjust to body size and goals—general ranges 1.2 to 2.0 g/kg body weight per day for active individuals, higher during intense training phases.
  • Omega-3 guidance: Food first approach with fatty fish 2 to 3 times per week; consider supplements if intake is low. Discuss dose with your clinician.
  • Antioxidant-rich choices: Berries, citrus, leafy greens, nuts, and green tea help manage oxidative stress without blunt training adaptations when used sensibly.

When to Talk to Your Healthcare Provider

  • If soreness or weakness is severe, persists longer than expected, or limits daily activities
  • If you are considering high-dose supplements or combining multiple anti-inflammatory agents
  • If you have underlying medical conditions, are pregnant, breastfeeding, or taking medications that could interact with supplements

PlexusDx provides educational genetic insights to help you understand potential predispositions. This information is not medical advice. Always consult your healthcare provider before making changes to your diet, supplement routine, or exercise program.