Is Chronic Fatigue Genetic?

What is Chronic Fatigue?

Chronic fatigue is a complex disorder characterized by extreme fatigue that lasts for at least six months and that cannot be fully explained by an underlying medical condition.

The fatigue worsens with physical or mental activity but doesn’t improve with rest.

Symptoms can significantly disrupt daily activities and quality of life.

What is Exercise Fatigue?

Exercise fatigue, also known as exercise intolerance, refers to a condition where you are unable to sustain a workout or activity due to the onset of fatigue or even dyspnea (shortness of breath).

It’s normal to feel tired after a rigorous workout, but exercise fatigue is a feeling of exhaustion that makes it difficult to function at your normal capacity during or after exercise.

What are the Primary Causes of Exercise Fatigue?

Exercise fatigue can be attributed to various factors, which can broadly be categorized into physical and psychological causes.

Physical Causes

1. Muscle Glycogen Depletion: The human body uses glycogen as its primary fuel source during strenuous exercise. As these glycogen stores deplete, muscle fatigue sets in, which is one of the main reasons athletes hit the wall during prolonged physical exertion.
2. Accumulation of Metabolic Byproducts: High-intensity exercise can lead to the accumulation of metabolic byproducts such as lactic acid, which can impair muscle contraction and contribute to fatigue.
3. Dehydration and Electrolyte Imbalance: Water and electrolytes are crucial for maintaining cell function and supporting muscle contractions. Dehydration and electrolyte imbalances can severely impact performance and induce fatigue.
4. Muscle Damage: Intense or prolonged exercise can cause microscopic tears in the muscle tissue, leading to inflammation, pain, and fatigue.

Psychological Causes

1. Central Fatigue: Central fatigue refers to a form of fatigue associated with changes in the neurochemical systems of the brain. It is believed to play a role in the regulation of exercise performance to prevent the harmful effects of extreme exertion.
2. Perceived Effort: This is the subjective feeling of how hard one feels the body is working. It is influenced by various factors, including muscle soreness, mental state, and even environmental conditions. High perceived effort can lead to an early onset of fatigue.
3. Stress and Anxiety: High levels of stress and anxiety can increase fatigue levels during exercise. This is due to the energy-demanding nature of the stress response, which can detract from the energy available for physical exertion.

Understanding these factors can help you manage and mitigate exercise-induced fatigue and improve your physical performance.

Is Chronic Fatigue Genetic? Exploring Key Genes

Chronic fatigue syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a complex, multi-system, chronic medical condition characterized by unexplained persistent fatigue¹.

The precise cause of CFS is still unclear, but it is believed to result from a combination of factors, and it may be triggered by an infection².

Emerging research suggests a potential genetic predisposition towards CFS in some individuals³.

These genetic factors may not cause CFS directly but can heighten the risk or influence the severity of the condition.

HSPA1A

The HSPA1A gene belongs to the heat shock protein 70 (Hsp70) family, involved in protein folding and safeguarding cells from stress.

Variants in this gene, like rs1043618, have been associated with an increased risk of developing CFS⁴.

Which HSPA1A gene variants do you have? Check your Ancestry DNA, 23andMe raw data

TNF

The TNF gene, responsible for encoding a pro-inflammatory cytokine, promotes inflammation when activated.

Certain TNF gene variants like rs1800629 have been connected with increased inflammation levels, which could contribute to CFS symptoms⁵.

Which TNF gene variants do you have? Check your Ancestry DNA, 23andMe raw data

IL10

The IL10 gene produces an anti-inflammatory cytokine, counteracting inflammation in the body.

Some people with CFS carry IL10 gene variants such as rs1800896, which could impact its function and associate with the condition⁶.

Which IL10 gene variants do you have? Check your Ancestry DNA, 23andMe raw data

IL6 and IL6R

The Interleukin 6 (IL6) gene and its receptor gene IL6R are crucial for immune response modulation.

The altered function of these genes, possibly through variants like rs1800795 in IL6 and rs2228145 in IL6R, could disrupt this balance, leading to inflammation—an underlying feature of CFS⁷.

Which IL6 & IL6R gene variants do you have? Check your Ancestry DNA, 23andMe raw data

AMPD1

The AMPD1 gene regulates energy production within cells by encoding the enzyme adenosine monophosphate deaminase, which is involved in purine metabolism.

Variants in this gene, such as rs17602729, can disrupt energy production, leading to muscle weakness and fatigue—a characteristic of CFS⁸.

Which AMPD1 gene variants do you have? Check your Ancestry DNA, 23andMe raw data

Gene	SNP	Risk Allele	Association with Chronic Fatigue
IL6R	rs2228145	A	The ‘A’ allele is associated with higher levels of IL6R protein in the blood. Increased IL6R levels may lead to an exaggerated inflammatory response, which can contribute to symptoms of chronic fatigue.
AMPD1	rs17602729	T	The ‘T’ allele is associated with a deficiency of the AMPD1 enzyme. This enzyme is critical in energy metabolism, and its deficiency can contribute to muscle weakness and fatigue.
IL6	rs1800795	G	The ‘G’ allele has been associated with higher levels of IL6, a pro-inflammatory cytokine. Higher levels of this cytokine can stimulate the inflammatory response, contributing to fatigue.

Section Summary

While these genes may influence the risk of CFS, they do not definitively predict the condition’s onset.

Environmental factors, non-genetic biological elements, and potentially undiscovered genetic factors all play integral roles in this complex condition’s manifestation⁹.

Non-Genetic Factors that Influence Chronic Fatigue

Several non-genetic factors can also influence the development and severity of chronic fatigue. These include:

Lifestyle Factors

Poor sleep habits, a sedentary lifestyle, and high-stress levels can all contribute to chronic fatigue.

Environmental Factors

Exposure to toxins, chronic infections, or a traumatic event can trigger chronic fatigue in susceptible individuals.

How to Beat Fatigue? Lifestyle Tips Based on Your Genes

Genetics can significantly influence your susceptibility to chronic fatigue, and understanding these genetic predispositions can guide lifestyle changes that help combat fatigue.

Physical Activity and the ACTN3 Gene

The ACTN3 gene produces a protein found in fast-twitch muscle fibers, contributing to powerful, explosive movements.

The variant rs1815739 can influence the response to resistance training, with people carrying the CC variant typically showing improved fatigue resistance following this type of exercise.

Lifestyle tip:

Regular resistance training, therefore, can be beneficial for individuals with the CC genotype to improve fatigue resistance.

Sleep Quality and the PER3 Gene

The PER3 gene plays a crucial role in regulating circadian rhythms, and the variant rs57875989 has been linked to sleep duration.

PER3 gene has a type of polymorphism called variable number of tandem repeats (VNTR). Individuals can have either a four repeat allele PER3^4/4 or a five repeat allele PER3^5/5.

Geek Out!
Variable Number of Tandem Repeats (VNTRs) are sections of a DNA sequence that repeat themselves. The number of repetitions varies among individuals. These can impact gene function and are often used in genetic profiling.

Lifestyle tip:

Individuals with the PER3^5/5, 5-repeat allele, are often “morning types” and require more sleep.

Maintaining a consistent sleep schedule can improve sleep quality and decrease fatigue levels in these individuals.

Stress Management and the COMT Gene

The COMT gene helps break down dopamine, a neurotransmitter involved in mood regulation and response to stress.

The rs4680 variant can influence the rate of dopamine breakdown, with the GG genotype associated with slower breakdown and potentially greater stress response.

Lifestyle tip:

For those with the GG genotype, stress management techniques like mindfulness and yoga can be especially beneficial in managing fatigue.

Caffeine Metabolism and the CYP1A2 Gene

The CYP1A2 gene determines how quickly your body metabolizes caffeine.

The variant rs762551 can affect caffeine metabolism rate, with AA individuals being ‘fast’ metabolizers and AC/CC ‘slow’ metabolizers.

Lifestyle tip:

Slow metabolizers may experience sleep disturbances and increased fatigue with excessive caffeine consumption, so moderating caffeine intake could reduce fatigue levels.

Your genes are not your destiny.

Lifestyle modifications can help manage symptoms, but if you’re dealing with persistent fatigue, it’s essential to consult with a healthcare provider to rule out other underlying health issues.

How to Beat Fatigue? Diet Tips Based on Your Genes

Understanding the interplay between genetics and diet can be instrumental in overcoming fatigue.

Here are a few ways your genes may impact your nutritional needs and how you can adjust your diet to help combat fatigue.

Vitamin B12 Absorption and the FUT2 Gene

The FUT2 gene influences the secretion of certain antigens in bodily fluids and impacts the gut microbiome, which plays a role in vitamin B12 absorption.

Variants of FUT2, such as rs601338, can lead to reduced B12 absorption, with the AA genotype associated with non-secretor status and potentially lower B12 levels.

Diet tip:

If you carry this genotype, you might benefit from a diet rich in B12 sources, like meat, fish, eggs, and fortified cereals, or consider a B12 supplement to help prevent fatigue.

Iron Metabolism and the HFE Gene

The HFE gene plays a significant role in iron metabolism, and the C282Y variant (rs1800562) is linked with hemochromatosis, a condition of iron overload.

While iron is essential for energy, the excess can lead to symptoms like fatigue.

Diet tip:

Carriers of this variant might benefit from regular monitoring of iron levels and a diet not excessively high in iron.

Lactose Intolerance and the MCM6 Gene

Lactose intolerance, which can be influenced by the MCM6 gene (specifically, the variant rs4988235), may lead to gastrointestinal symptoms, including bloating and fatigue, after consuming dairy products.

Diet tip:

People with lactose intolerance may benefit from a diet low in lactose or the use of lactase supplements to help reduce fatigue symptoms.

Folate Metabolism and the MTHFR Gene

The MTHFR gene is involved in folate metabolism, a crucial process for DNA synthesis and repair.

The C677T variant (rs1801133) in the MTHFR gene can lead to decreased enzyme activity, impacting folate metabolism and potentially leading to lower energy levels.

Diet tip:

If you carry this variant, you might benefit from a diet rich in folate, found in leafy greens, legumes, and fortified grains, or consider a folate supplement.

Section Summary

By tailoring your diet to suit your genetic makeup, you can potentially improve your fatigue symptoms.

Always remember to consult with a healthcare professional before making significant dietary changes.

Summary

References

1. NHS – Chronic fatigue syndrome (CFS) ↩
2. CDC – Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) ↩
3. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome – Light et al., 2012 ↩
4. Genetic Predisposition for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study – Smith et al., 2016 ↩
5. Association of TNF-α, TNFRSF1A, and IL-10 polymorphisms with chronic fatigue syndrome in a New Zealand cohort – van Heukelom et al., 2015 ↩
6. The Role of IL-10 and TGF-β in Chronic Fatigue Syndrome – Blundell et al., 2015 ↩
7. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue – Broderick et al., 2012 ↩
8. Association of AMPD1 gene polymorphism with Chronic Fatigue Syndrome in a Chinese Han population – Xiao et al., 2012 ↩
9. The Role of Genes in the Etiology of Chronic Fatigue Syndrome – Klimas et al., 2002 ↩