Fatigue Flashcards
Fatigue
Fatigue = physical and mental exhaustion that is not relieved by rest. * Fatigue is the symptom experienced when energy demand exceeds energy delivery. If more energy is spent than can be generated, it will lead to death!
- Thus, the body manifests uncomfortable symptoms to prevent this happening.
- While mild fatigue can be caused by a range of factors, moderate to severe persistent fatigue involves cellular energy systems — the hallmark of chronic fatigue syndrome and other intractable fatigue states.
Mitochondrial energy production
Mitochondria make over 90% of the body’s energy as ATP. This energy is crucial to sustain life and support organ function.
- Mitochondrial energy production is the result of two closely coordinated metabolic processes the Krebs cycle and electron transport chain.
- If cells function slowly, then organs function slowly i.e., the start of organ failures such as heart failure and dementia.
- If the immune system functions slowly then healing and repair is slow, increasing risk of infection and cancer.
- If all cells in the body are affected, the clinical picture of chronic fatigue syndrome and premature ageing emerges
Mitochondrial dysfunction
ATP cannot be stored — therefore, the mitochondria need to function continuously, every second of every day.
- Mitochondria are highly susceptible to nutrient deficiencies, environmental toxins and oxidative damage.
- Environmental toxins — mitochondria have very high metabolic activity so are particularly susceptible to toxin exposure.
- Oxidative stress in cells — the primary source of ROS (reactive oxygen species) are those generated by the mitochondria themselves, which leak out.
- Mitochondrial damage occurs when ROS production outpaces antioxidant activity.
- Hyperglycaemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction.
- Inflammatory mediators such as TNF-α have been associated with mitochondrial dysfunction and increased ROS generation.
‒ Consider why inflammatory mediators are raised, e.g., intestinal mucosal degradation (LPS leakage), pro-inflammatory diet (high omega 6:3 etc.), glucose dysregulation, raised homocysteine (increases TNF-α expression), TNF SNP, smoking, obesity, etc
Factors associated with increased mitochondrial damage
Primary ways mitochondria are protected from oxidative stress:
- Optimising levels of antioxidant enzymes — superoxide dismutase (manganese), glutathione peroxidase (selenium), glutathione reductase (B3), catalase (iron).
- Coenzyme Q10, vitamin E.
Factors associated with increased mitochondrial damage:
- ROS leaked while ATP is produced.
- Ageing (accumulated oxidative damage to mitochondrial DNA).
- Genomic susceptibility.
- Toxic metals, persistent organic pollutants (POPs), alcohol.
- Many prescription drugs e.g., antibiotics, aspirin, NSAIDs, statins
Key nutrients required for atp production (other than oxygen)
Key strategies to improve mitochondrial function
Key strategies to improve mitochondrial function:
- Optimise nutrients required for ATP production and antioxidant properties to protect the mitochondria from oxidative stress.
- Focus on blood sugar regulation (prevent chronic hyperglycaemia).
- Reduce levels of inflammatory mediators — optimise intestinal health, anti-inflammatory foods, optimise weight etc.
- Decrease toxin exposure e.g., consume organic food, avoid plastic packaging, carefully select cleaning products, cosmetics and personal care items; avoid alcohol and pharmaceuticals.
- Strength training — increase muscle mass to increase mitochondria number and function
Coenzyme Q10
Dosage: 100–300 mg / day (solubilised)
- Transports high energy electrons in the ETC supporting mitochondrial function and energy production.
- Deficiency reduces ATP production and increases electron loss causing increased oxidative damage and fatigue.
- Production of ROS, which can damage cellular lipids, proteins and DNA, is a direct consequence of the ET process.
- CoQ10 is an efficient intra-mitochondrial antioxidant, playing a vital role in neutralising ROS.
- Ability to produce CoQ10 strongly correlates with longevity.
Alpha lipoic acid (ALA)
Dosage: 300–600 mg / day.
- Is a co-factor for several mitochondrial enzymes involved in glucose oxidation and ATP generation.
- As an antioxidant, protects mitochondrial structures.
Acetyl Lcarnitine.
Dosage: 500–2000 mg / day.
- Essential for the transport of long chain fatty acids across the mitochondrial membrane for subsequent β-oxidation and generation of ATP.
- Increases mitochondrial oxidative phosphorylation, thereby increasing ATP production and reducing mtROS.
Magnesium (as citrate or malate).
Dosage:200 ‒400 mg / day
- Plays a fundamental role in energy production where it transfers phosphate groups between ADP and ATP.
- Magnesium insufficiency or deficiency can result in a symptom picture reflective of chronic fatigue syndrome.
- Malic acid is a Krebs cycle cofactor, so magnesium malate may be better, and is researched to improve fibromyalgia.
B complex vitamins High dose combination
- B1 is needed in the Krebs cycle. B2 (energy carriers FAD, FMN) and B3 (coenzymes NAD and NADP). Required for Krebs cycle and for conversion of fatty acids to ATP.
- Possibly consider even higher even dose B2/B3 — 100mg+
