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Understanding Fatigue and Your TRPM8 Genotype

Fatigue is a persistent feeling of low energy that can affect physical, mental, and emotional well-being, often making daily tasks challenging. Genetics is one piece of the puzzle. The TRPM8 gene, best known for sensing cold, also influences nerve signaling, immune responses, and inflammation. Variations in TRPM8 may change how sensory information and immune signals are processed, and some variations have been observed more often in people with chronic fatigue.

How TRPM8 Can Influence Energy

  • TRPM8 encodes a protein that responds to cold stimuli and contributes to nerve cell activity.
  • Differences in TRPM8 can influence immune signaling and inflammation, both of which affect energy and recovery.
  • Genetic predisposition is not destiny. Lifestyle, environment, sleep, stress, and other genes all shape fatigue risk and symptom severity.

Practical Steps to Support Energy and Healthy Aging

Whether your genetic test shows an increased predisposition or not, these evidence-informed habits can help support energy levels and resilience over time.

Diet

  • Focus on an anti-inflammatory pattern: plenty of vegetables, fruits, legumes, whole grains, lean protein, and healthy fats (olive oil, avocados, nuts).
  • Prioritize protein at each meal to support muscle and metabolic health.
  • Limit highly processed foods, excess added sugars, and refined carbohydrates that can promote energy crashes and inflammation.
  • Include omega-3 rich foods such as fatty fish, chia seeds, and walnuts.
  • Stay consistent with meal timing; avoid long periods without food if that triggers fatigue for you.

Hydration

  • Even mild dehydration can reduce energy and cognitive function. Aim for regular fluid intake across the day.
  • Water is best; include herbal teas or mineral water as needed for variety.

Supplements (Discuss with Your Healthcare Provider)

  • Vitamin D: Many people are low; adequate levels support immune and musculoskeletal health.
  • B Vitamins: B12 and B6 support energy metabolism and nervous system function.
  • Magnesium: May help with sleep quality and muscle relaxation.
  • Omega-3 fatty acids: Support inflammation balance and brain health.
  • Use laboratory testing and professional guidance before starting supplements to pick appropriate doses and rule out interactions.

Sleep and Stress Management

  • Prioritize regular, restorative sleep. Aim for consistent bed and wake times and a dark, cool sleep environment.
  • Practice stress reduction: mindfulness, deep breathing, progressive muscle relaxation, or short daily walks can reduce symptom burden.

Exercise and Pacing

  • Engage in moderate, regular activity—walks, gentle strength training, yoga—to build stamina without overexertion.
  • Use pacing strategies: break tasks into smaller steps, alternate activity with rest, and monitor for post-exertional symptom increases.

Temperature and Comfort

  • TRPM8 is sensitive to cold. Keep environment and clothing comfortable to avoid unnecessary sensory stress.
  • Layer clothing and control ambient temperature where possible to reduce thermal discomfort that may impact energy.
2 effect alleles (AA) — Increased genetic predisposition to chronic fatigue

Your rs11563204 genotype: AA (two copies of the effect allele). This variant in the TRPM8 gene has been associated with a higher likelihood of chronic fatigue in some studies. TRPM8 influences cold sensing, nerve signaling, and immune modulation. Variants found more frequently in individuals with chronic fatigue suggest altered sensory processing and inflammation may contribute to persistent low energy.

What this means for you

  • You may have a higher genetic susceptibility to ongoing fatigue compared to people without this variant.
  • This does not mean you will develop chronic fatigue. Lifestyle, environment, coexisting health conditions, and other genes heavily influence outcomes.
  • Early attention to sleep, pacing, nutrition, and stress can reduce the likelihood or severity of prolonged fatigue.

Actionable suggestions

  • Consider baseline lab work for vitamin D, B12, thyroid function, and basic metabolic panel with your clinician.
  • Start a gradual activity program with pacing to build endurance without provoking setbacks.
  • Prioritize anti-inflammatory foods and discuss targeted supplementation with your healthcare provider.
  • Monitor environmental temperature and comfort to reduce sensory-triggered symptom flares.
1 effect allele (AG) — Likely increased risk compared to non-carriers

Your rs11563204 genotype: AG (one copy of the effect allele). Carrying one A allele is associated with a moderate increase in genetic predisposition toward fatigue related to TRPM8 functions. The protein produced by TRPM8 affects cold sensation, nerve signaling, and inflammation, and some variations appear more often in people with chronic fatigue.

What this means for you

  • You have a modestly increased genetic risk, but most people with this genotype will not develop chronic fatigue solely because of this variant.
  • Environmental triggers, sleep habits, stress, and other health conditions remain central determinants of your energy levels.

Actionable suggestions

  • Optimize sleep and stress management practices to reduce the chance of becoming symptomatic.
  • Adopt anti-inflammatory eating patterns and maintain hydration.
  • Talk with your clinician about screening labs and whether supplements like vitamin D, B vitamins, or magnesium are appropriate.
  • Use pacing for activity increases and keep environmental temperature comfortable.
0 effect alleles (GG) — Typical genetic susceptibility

Your rs11563204 genotype: GG (two copies of the non-effect allele). This is the most common genotype and is associated with typical susceptibility to fatigue related to TRPM8 variations. Research has identified TRPM8 differences in some people with chronic fatigue, but your result indicates you do not carry these specific variants.

What this means for you

  • Your TRPM8-related genetic risk for fatigue is typical for the population.
  • Non-genetic factors such as sleep quality, diet, stress, activity patterns, and medical conditions remain key drivers of fatigue risk.

Actionable suggestions

  • Continue healthy lifestyle practices to support energy: balanced diet, regular movement, restful sleep, and stress reduction.
  • If you experience persistent fatigue, work with your healthcare provider to evaluate medical causes and appropriate testing.
  • Maintain comfortable environmental temperatures and attention to hydration and nutrient sufficiency.

When to Talk with Your Healthcare Provider

  • If fatigue is persistent, worsening, or limiting daily function, seek medical evaluation to identify treatable causes.
  • Ask about laboratory testing for vitamin D, B12, thyroid function, complete blood count, metabolic panel, and other targeted tests your clinician deems appropriate.
  • Discuss any supplements before starting them, especially if you take medications or have chronic health conditions.

PlexusDx provides genetic information for education and empowerment. This content is not medical advice. Always consult your healthcare provider to interpret genetic results in the context of your medical history, current health, medications, and lifestyle before making health changes.