Fatigue - Lecture 9 Flashcards
(34 cards)
What can cause mitochondria dysfunction?
- Environmental toxins — mitochondria have very high metabolic activity so are particularly susceptible to toxin exposure.
- Oxidative stress in cells — the primary source of ROS 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. When the immune system is activated inflammatory mediators are activated or when someone has allergies or AI.
‒ 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.
Nutrients for mitochondria function
Antioxidant = superoxide dismutase (manganese), Glutathione Peroxidase (selenium), B3, iron
CoQ10, Vit E, Vit D, Vit K, Melatonin, Vit C
Factors associated with mitochondrial damage ?
ROS
Ageing
Genomic susceptibility
Toxic metals
Prescription drugs
Key nutrients required for glycolysis?
Magnesium and B3
Key nutrients required for Acetyl CoA
B1, B5 and alpha lipoid acid
Key nutrients required for Krebs cycle
Magnesium, Vita D, Mangenese, Iron, B1, B2, B3, CoQ10
Key nutrients required for ETP
iron, B2, sulphur, CoQ10, Copper
Key nutrients required for beta oxidation of fats
carnitine
Key nutrients required for energy carriers
b3, b2
Key strategies to optimise mitochondria functions?
- 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 can damage mitochondria (aluminium for example)
- Strength training — increase muscle mass to increase mitochondria number and function.
CoQ10 dose and usage
Coenzyme Q10
Dosage: 100–300 mg / day
- 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.
- As we age we should all take coq10
Alpha lipoic acid (ALA) dosage and use
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.
- Glutathione is similar – both multitasking tool. As we age and in any disease process very helpful for patients
Acetyl L- carnitine dosage and use
Acetyl L- carnitine.
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.
- Is very rich in meat (if patient can digest meat properly), if patient id vegetarian or vegan high chance they will need L-carnitine
Magnesium dosage and use
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.
Calcium and magnesium compete with each other and takin a lot of calcium deplete of magnesium. Dairy products are 10x calcium for 1x magnesium and that is why dairy products are a risk factor for heart disease
B complex vitamins dosage and use
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+
CFS = chronic fatigue syndrome. ME = myalgic encephalomyelitis.
Signs and characteristics
CFS and ME are terms often used interchangeably though ME is sometimes defined as CFS + inflammation.
* Characterised by long-term physical and cognitive fatigue, not alleviated by rest.
* Other symptoms include post-exertional malaise, muscle and joint pain, unrefreshing sleep, flu-like symptoms with sore throat and tender lymph nodes, mood disturbances.
* While mitochondrial dysfunction is recognised as a key player, there are a number of proposed contributing factors.
* Post exertion malaise (do something one day and pay for it the next)
* Inflammation can be joint pain, neck pain, fibromyalgia, feeling ill (malaise)
* Mitochondrial health is central to both
Proposed aetiologies of CFS and ME
- Infectious organisms — in particular EBV (high antibody titres in patients with symptoms indicative of CFS). Other: Human herpes virus-6, Borrelia burgdorferi (Lyme’s).
- Immunological — e.g., increased cytokines, NK cell abnormalities, decreased CD8 suppressor cells. Imbalances that collectively suggest chronic, low level activation of the immune system.
- Abnormal HPAA functioning — association with hypocortisolism.
- Mitochondrial dysfunction and high oxidative stress — associated with ↓ GPO and SOD. Also low melatonin (sleep dysregulation).
- Serotonin studies have concluded:
‒ Increased 5-HT autoimmune activity is associated with activation of inflammatory pathways and increased bacterial translocation. A reduction in 5 HT neurons has been noted.
‒ Proposed upregulation of the serotonin transporter (5-HTT) in astrocytes, reducing extracellular serotonin (5-HT) levels. - A breakdown in the bidirectional communication between the brain and the gut mediated by bacteria and their metabolites. CFS / ME are commonly associated with GI symptoms (see next slide).
- The key to that is to ensure a good connection between the gut and the brain
- Findings in relation to intestinal health and CFS:
– High relative abundance of bacterial species such as clostridium and ruminococcus in CFS / ME; decreased faecalibacterium abundance.
– Metabolic endotoxaemia as a driver for CFS / ME.
Natural approach to CFS and ME - what to avoid / what to include?
Natural approach to CFS / ME — avoid:
* Caffeine (coffee, tea, chocolate, energy drinks). Temporarily counters fatigue, but the effect is short-lived and places strain on the adrenal glands exacerbating an already fatigued body.
* Sugar — an immune system depressant. Destabilises blood glucose causing peaks and troughs in energy.
* Artificial sweeteners — interact with sweet receptors to trigger insulin release (destabilise blood glucose). Aspartame contains excitotoxins (e.g., aspartates) and methanol, which converts to formic acid — a neurotoxin. Can worsen neurological symptoms.
* Alcohol — worsening of symptoms, depletes body of nutrients
Natural approach to CFS / ME — include:
* Good quantities of essential fatty acids:
– Omega-3 is especially important for the activity of the mitochondrial membrane. EPA — anti-inflammatory properties and increases mitochondrial growth, size and distribution. DHA — essential for the structure of ETC complexes.
* Sufficient protein to allow for immune cell restoration and function.
* Individualised immune support (e.g., anti-microbials, vitamin C etc.) and GI support (e.g., digestive bitters, pro and prebiotics etc.).
Nutritional ketosis in CFS / ME how to?
Nutritional ketosis in CFS / ME — considered a beneficial dietary strategy for supporting mitochondrial function.
* Total carbohydrate intake < 50 g / day (or whatever is needed to get into ketosis).
* Moderate protein intake, around 1.5 g / kg bodyweight per day.
* Fuel as ketones come from fat AND the fermentation of fibre in the large bowel to short chain fatty acids.
* Typical macronutrient ratio — 75% fat, 20% protein, 5% carbohydrate.
* Changes the body’s primary fuel source from glucose to ketones.
* Ketones enter the mitochondria of body tissues for ATP production.
Benefits of a ketogenic diet:
- While excess levels of mitochondrial ROS (mtROS) are associated with mitochondrial
dysfunction, low concentrations of mtROS can act as signalling molecules, upregulating mitochondrial capacity and antioxidant defence — known as mitohormesis. - Ketosis causes a significant shift in energy metabolism increasing reliance on mitochondrial respiration ― this induces mitohormesis (mitohormesis = low concentrations of mitochondrial stress increase health and viability within cells).
- Ketogenic diet is also anti-inflammatory without a keto diet you won’t get rid off the fermented gut and won’t be able to absorb nutrients needed for the mitochondria.
- Further, in addition to their role as energy substrates, ketones (especially β-hydroxybutyrate) act as signalling molecules increasing expression of antioxidant enzyme systems.
Liquorice in CFS dosage and use
Liquorice
Glycyrrhiza glabra 1‒2 tsp powder daily.
- Suboptimal HPAA function and low cortisol is a common feature of CFS / ME. Liquorice is an adrenal cortex restorative, supporting cortisol production and ↓ fatigue.
- Anti-inflammatory activity — research indicates inhibitory effects on ROS-induced tissue inflammation and the COX, LOX and NF-κB inflammatory pathways.
Astragalus in CFS dosage and use
Astragalus
Astragalus membranaceus - 2.5‒3.5 g dry herb
- An adaptogen and tonic indicated for debility and CFS.
- Regulatory effect on immune function; supports aspects of innate immunity while promoting Th1 / Th2 balance.
- Reduces abnormal cytokine production.
Effect of Poor energy delivery to the body:
- Physical fatigue, poor stamina.
- Post-exertional malaise (akin to over-training in athletes) if you have to pay for your action the next day.
- Loss of muscle power — muscles heavily rely on ATP!
- Muscle pain — because of an early switch into anaerobic metabolism with production of lactic acid. If you cannot produce ATP efficiently. Anaerobic respiraction produces 2 ATP + Lactic Acid and then you need to suppress the Lactic Acid and need 6 ATP to do it if you don’t have the ATP in the tank you have muscle pain
- Variable blurred vision — the ciliary body muscles required for focusing tire easily.
- Subnormal core temperature.
Poor energy delivery to the brain:
- Mental fatigue with brain fog — the brain weighs 2% of body weight but consumes 20% of total energy.
- Light and noise intolerance demands a lot of energy the retina demands 10x energy more than the brain
- All the early symptoms of dementia
