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How IL1B Gene Variations Influence Fatigue and What You Can Do About It

Fatigue is more than feeling tired. It is a persistent lack of energy that is not easily relieved by rest and can interfere with daily life, focus, work, and mood. One factor that can influence fatigue is inflammation. The IL1B gene controls production of Interleukin-1 beta (IL-1β), an immune signaling protein that helps coordinate inflammatory responses. While inflammation is essential for fighting infection and healing, chronically elevated IL-1β can affect brain systems that regulate energy, motivation, and mood, contributing to long-term or “central” fatigue.

PlexusDx provides genetic information to help you understand predispositions linked to fatigue. This educational article explains how IL1B variation at rs1143643 can influence fatigue risk, and offers practical, evidence-informed lifestyle, diet, supplement, and testing recommendations to help manage inflammation and support healthy aging. This content is for education only. PlexusDx does not provide medical advice. Always consult your healthcare provider before making changes to medications, supplements, or clinical care.

How IL1B and IL-1β Affect Energy and Fatigue

IL-1β is a signaling molecule the immune system uses to coordinate inflammation. Elevated IL-1β can:

  • Promote sickness behaviors such as low motivation, reduced activity, and sleep alterations.
  • Interact with brain regions that control energy and mood, contributing to feelings of persistent tiredness.
  • Amplify fatigue during chronic illness or prolonged stress by sustaining a low-level inflammatory state.

Genetic variation at rs1143643 in the IL1B gene can influence how strongly your body produces IL-1β. Depending on your genotype, you may have a higher predisposition to inflammation-related fatigue when facing chronic disease or stress.

Managing Inflammation-Related Fatigue: Practical Steps

Regardless of genotype, many lifestyle and dietary strategies reduce chronic inflammation and can help improve energy levels over time. Use these as a starting point and work with your healthcare provider for personal guidance.

Diet

  • Follow an anti-inflammatory pattern focused on whole foods: plenty of vegetables and fruits, legumes, whole grains, lean proteins, nuts, seeds, and healthy fats such as olive oil and fatty fish.
  • Minimize processed foods high in added sugars, refined grains, and industrial seed oils.
  • Include fatty fish (salmon, sardines, mackerel) or algae-based sources for omega-3s to help modulate inflammatory pathways.
  • Consider foods with polyphenols and antioxidants such as berries, dark leafy greens, turmeric, ginger, and green tea.

Sleep and Circadian Health

  • Prioritize regular sleep routines: consistent bed and wake times, 7 to 9 hours nightly for most adults.
  • Create sleep-friendly habits: limit screen time before bed, keep the bedroom cool and dark, and avoid large meals or caffeine close to bedtime.

Exercise and Movement

  • Engage in regular moderate exercise such as brisk walking, cycling, swimming, or strength training 3 to 5 times per week.
  • For chronic fatigue or advanced conditions, start slowly and build activity gradually to avoid post-exertional setbacks. Work with a clinician or physical therapist as needed.

Stress Management

  • Practice stress-reduction techniques that work for you: mindfulness, breathing exercises, yoga, progressive muscle relaxation, or spending time in nature.
  • Social connection and purposeful activity can buffer stress and reduce inflammatory signaling over time.

Hydration and General Wellness

  • Stay hydrated, prioritize routine medical care, and address treatable contributors to fatigue such as anemia, thyroid disorders, sleep apnea, and medication side effects with your provider.

Supplements to Discuss with Your Healthcare Provider

  • Omega-3 fatty acids (EPA and DHA) to support anti-inflammatory pathways.
  • Vitamin D if you have low levels; Vitamin D influences immune regulation.
  • Magnesium for sleep quality, muscle relaxation, and nervous system support.
  • B vitamins (B6, B12, folate) for energy metabolism and nervous system health.

Useful Blood Tests to Consider

  • High sensitivity C-reactive protein (hs-CRP) to assess systemic inflammation.
  • 25-hydroxy Vitamin D to check Vitamin D status.
  • Complete blood count and thyroid-stimulating hormone to evaluate common causes of fatigue.
  • Ferritin and iron studies if iron deficiency is suspected.

What Your rs1143643 Genotype Means

TT — Two effect alleles (higher predisposition to fatigue with chronic disease)

If your genotype is TT, you carry two copies of the effect allele at rs1143643. This pattern is associated with a greater tendency toward higher IL-1β production in certain contexts. When IL-1β is elevated, especially during chronic illness or prolonged stress, it can promote persistent central fatigue by affecting neural circuits that regulate energy and mood. For people with this genotype, proactive inflammation management becomes especially relevant. Focus on anti-inflammatory lifestyle habits, address sleep and stress, consider blood testing to monitor inflammation and nutrient status, and discuss targeted supplementation such as omega-3s and Vitamin D with your healthcare provider. Monitoring and early intervention during periods of illness or high stress may help reduce the duration or intensity of fatigue episodes.

CT — One effect allele (likely increased fatigue with chronic disease)

If your genotype is CT, you carry one copy of the effect allele. This genotype is associated with a likely increased susceptibility to inflammation-linked fatigue compared to the non-effect genotype. Your body may produce somewhat higher IL-1β under inflammatory stressors, which can contribute to central fatigue during chronic conditions. Applying anti-inflammatory strategies can be beneficial: prioritize a whole-foods, anti-inflammatory diet, maintain consistent sleep and activity habits, practice stress reduction, and consider routine blood tests such as hs-CRP and Vitamin D to guide interventions. Discuss any supplements with your provider and tailor plans to your personal health history and current conditions.

CC — Zero effect alleles (typical IL1B-related inflammatory response)

If your genotype is CC, you carry two copies of the non-effect allele. This suggests typical IL-1β production and no increased genetic predisposition to inflammation-related fatigue from this specific variant. That said, fatigue is multifactorial. Environmental factors, chronic disease, sleep habits, diet, stress, and other genes also influence energy. Maintaining an anti-inflammatory lifestyle remains valuable for preventing fatigue and supporting healthy aging. Use general wellness strategies, screen for common medical causes of fatigue, and consult your healthcare provider if fatigue persists or worsens.

Next Steps and When to Seek Care

  • If fatigue is persistent, worsening, or limits daily activities, schedule an evaluation with your healthcare provider. Genetic predisposition is only one piece of the puzzle.
  • Share your PlexusDx genetic results with your clinician to help guide personalized testing and management choices.
  • Before starting any new supplement or major lifestyle change, check with your healthcare provider, especially if you take medications or have chronic health conditions.

Remember, PlexusDx provides educational genetic information to help you understand potential predispositions. This information is not medical advice. Always consult your healthcare provider for diagnosis and personalized treatment plans.