I have reading Miochondria and the future of medicine by Lee Know, ND. A very detailed look at how mitochondria, the powerhouse of the cell, are intricate in all life on earth. Here is my short summary. The book is divided into three parts with part 1 looking at function and action of mitochondria, part 2 discusses what happens when this function goes wrong and it implication in disease and ageing and then part 3 is about what you can do to improve mitochondrial health.
Summary points
Part 1
Mitochondria have own DNA independent of nucleas All mitochondia inherited maternally.The workings of mitochondria in relation to energy production via Electrom transport chain (eletron transport chain) results in production of ATP. This ETC is managed by several complexes (protiens in the mitochondrial membrane) which are are coded by mitochondrial DNA and nucleas DNA. This allows mitochondria to act independantly and also increase/decrease ATP production by changing amount and number of the complexes.
Mitochondrial theory of aging. As mitochondria replicate this can cause mutations in the mitochondrial DNA (mDNA). As each mitochondria has five copies of mDNA and replicates independentaly this results a mosaic of mitochondrial mutation in cells i.e different mitochondria with different types and levels of mutation in one cell. When this mosaic reaches point of inefficency in energy production the this results is mitochondrial death and then apoptosis (cell death) and then resultant ageing, as more cells die within an organ.
Antooxidants can have a negative effect as high levels as free radicals are a feedback for mitochondrial production and also efficiency. So careful not to consume high levels of antioxidants.
Caloric reduction i.e reduction in food intake has shown to reduce the ETC and thus reduce free radical production and long term increase life span. I.e fasting. Mitochondria also able to produce heat together with uncoupling protiens by pumping protons to produce heat . This is know as non shivering thermogenis occurs more in brown fat.
Therefore mitochondria in brown fat together with uncoupling protiens produce heat and reduce free radical production. As brown fat is higher in populations exposed to cold this means less free radical production and lower incidence of degenerative diseases in these populations. This could explain lower levels of degenerative diseases in the Intuit populations and higher in populations from warmer climates closer to the equator Therefor if your maternal ancestry from the equator or warmer climates then cold exposure is a way to increase brown fat tissue.
Part 2
The second part of the book called “The Dark Side of the Force” explores what happens when there is a dysfunction within the Mitochondrial process. A very simplified view would be to consider mitochondria the battery of a cell and in the same was as a battery can go wrong it can for instance go flat, it can be the wrong type of battery, you may not have enough batteries, or it could even leak and expose its toxic substances out and cause damage to the component it is supposed to power.
Here are some of the health conditions listed and how mitochondrial dysfunction can be attributed to thier etiology.
Cardiac disease- The relaxation of any smooth muscle, such as in the heart during diastole, requires large amounts of ATP to be broken down to release energy to remove calcium ions from the cell. ATPase is an enzyme which breaks down ATP and this requires magnesium to function. If you do not have enough ATP or a functioning ATPase enzyme the heart muscle is unable to fully relax and this can lead to hypertophy and congestive heart failure. This is in effect whereby the battery (mitochondria) is going flat.
Stroke- In a stroke the brain is starved of oxygen. The brain has high energy demands and continues to use ATP and convert it to ADP. As ADP increases and ATP decreases two ADP molecules are used to create ATP and AMP resulting in increase levels of AMP which is then eliminated from the cell. This reduces the available energy in the brain cell and also increases free radicals which then trigger cell death or apoptosis. This is the senario where the battery is effectly overused and then leaks.
Neurological diseases . including Alzheimers, Huntingtons and Parkinsons and Aging- in all of these conditions the one common factor is free radical production in ALzheimers disease the brain tries to reduce the impact of the free radicals by producing amyloid which then replaces much of healthy brain tissue and leads to the symptoms. In Parkinsons the Substantia Nigra ( part of brain controlling movement) has increased mutations in mDNA which causes malfuction in the ETC and results in free radicals which then damage the cells in this area and result in erratic movements. Coenzyme Q10 has been shown to help in these conditions and is neuroprotective
Depression- one of the theories for depression is the lack of neuroplasticity (the ability of the brain to change neural networks and adapt) in the brain to stress people with less functioning mitochondria seem to have reduced neuroplastic adaption to stress.
ADHD- an imbalance in Astrocytes in the brain leads to extication followed by energy deficiencies. The overexcitation phase can lead to mitochondria pushed to the limit and then effectly burn out resulting in apoptosis.
Chronic fatigue syndrome -When ATP is depleted use of glycogen to produce ATP results in the production of lactic acid production although people with CFS are unable to remove lactic acid and thus end in a constant state of fatigue.
Type 2 Diabetes – the pancreatic cells require large amounts of energy to produce insulin which pushes the mitochondria and results in production of free radicals and oxides which causes multiorgan pathogenesis.
Mitochondrial disease – essentialy a mutation in the mDNA causing a malfunction in the mitochondria and can cause issues in several organs
Age related hearing loss and wrinkles – reduced function of mitochondria and also reduced numbers can lead to damage to cells in the ears and also in skin which resultant age related issues.
Infertility – Mitochondria are required to produce hugh amounts of energy for fertility the Oocyte and the sperm both require large amounts of energy. Mitochondria in sperm are know to mutate due to high metabolism. The mDNA from mitochondrial sperm is elminated post fertilisation by autopahgosomes if this process does not happen then the zygote can be terminated as the sperm mDNA can be incompatible with the nucleas DNA in the egg.
Cancer- whereby apoptosis does not occur for mutated cells. Apoptosis requires large amount of ATP so malfunctions in mitochondria can reduce apoptosis of mutated cells and result in growth of a tumour.
Part 3
Supplementation – nurturing the force this part looks at what supplements and factors can help with mitochondiral function and dysfunction
D-ribose – component of ATP, Improves energy synthesis helps recovery post exercise and also shown to help recovery in post heart attacks.
PQQ pyrroloquinoline Quinone – essential component in the biogenisis of mitchondria and found in high levels in dark chocolate.
Coenzyme Q10 – antioxidant and essential component in the ETC. Preventive against congeestive heart failure. Lowers high Blood pressure by increasing levels of nitric oxide which help blood vessels dilate, minimises oxidation of LDL and increases levels of ATP. In statin therapy, statins reduce the formualtion of CoQ10 and as we age body produces less.
L – carnitine – main function is the tranport of fats, together with acyl-CoA into the cell for production of ATP. Also increases lactic acid clearance. An omivorous diet gives good levels although can supplement. Is synthesized in the body from lysine and methoinine ( essential amino acids)
Magnesium – This mineral is implicated in over 300 different reactions in the body. One major reaction is the stablisation of ATP which is used in muscle relaxation. Magnesium deficiency can lead to ischemic heart disease, congesetive heart failure, diabetes, metabolic syndrome as well as many other issues.
Alpha- Lipoic Acid – involved in the final stages of glycolosis and also acts as an antioxidant. Helps restore balance of NAD/NADH and thus reduces free radical production. Also activates genes called sirtuins which are involved in longevity and antiaging.
Creatine- Creatine phosphate donates a phosphate molecule to convert ADP to ATP. Supplementation can hep with energy levels and also be neuroprotective and cardioprotective.
B Vitamins – B1 – involved in the conversion of pyruvate to acetyl-coA lack of B1 can cause Beriberi the stymptoms of which include sensory disturbances and impaired memory.
B2 – Riboflavin – is a major component of co factors in complex I
B3 Niacinamide – is a precursor to NAD molecules is begining to be used for treatment of neurodegenerative diseases and diabetes.
B5 pantothenic acid – is a precursor to coenzyme A and also in heme for haemoglobin. Is essential in metabolism.
B6 Pyridoxine – essential for haem systhesis and also neuological function.
B12 Cobalamin – involved in the synthesis of SAMe ( S-adenosyl methionine) which supports formation of creatine. Also makes up some of the complexes in the ETC, which is why B12 injections increase energy levels.
Iron- essential mineral found in haem and also several complexes in the ETC. Only take Iron if shown to be deficient via blood test.
Reveratrol and Pterostilbene- both compounds work in synergistic fashion and minic caloric restriction which could help support lipid panel. Also some research to show that they are epigenetic ( modify gene expression)
Ketogenic Diet and Calorie Restirction- Ketones are three water soluble molecules which are the byproducts when fats are broken down. (acetone, acetoacetic acid and beta-hydroxybutyric acid). Both the heart and brain use ketones as energy source and in calorie restriction the brains ketone use jumps substantially. In the brains of patients with Alzheimers and Parkinsons reduced mitochondrial function. Ketones are efficiently used by brain mitochondria a ketone diet may help protect from these diseases. Various ways to induce a ketone diet including MCT or coconut oil use and fasting. Calorie restriction has been shown to increase lifespan in animal studies. Calorie restriction reduces free radical production and can be effective in disease prevention and calorie restricted animals stay biologically younger.
Diabetes- mitochondrial deterioration in the pancreas Beta cells can lead to reduced insulin production and type 2 diabetes. calorie restriction and exercise can help to reduce the doward spiral.
Massage and hydrotherapy- brown fat tissue is more thermogenic and contains more mitochondria per cell, white fat tissue can be induced to brown fat by cold exposure or physiological stimulation.
Cannabis and Phyocannbinoids- cannabidiol (CBD) and tetrahydrocannabinol (THC) Found in cannabis. Mitochondria contain cannbiod receptors. Have a biphasic response in low levels stimulate in higher levels sedate. THC shows some evidence in reducing amyloid plaques in the brain and CBD shown to induce mitochondrial biogenesis.
Exercise and Physical activity- at the right level increases the demand for mitochondrial biogensis in very high levels increases free radical prodcution and thus inflammation. So right levels with correct rest and recovery essential. HIIT high intensity interval training seems to show best levels ot induce mitochondrial biogenesis and keep inflammation low .