Improve mitochondrial function

One of the keys to mitochondrial function is diet. As we have seen, overeating, eating too often, or eating the wrong things, especially high calorie low nutrient dense foods and refined carbohydrates has a very detrimental effect on our mitochondria. By improving our diets, we can very much improve the health of our mitochondria.

Mediterranean diet

• olive oil polyphenols which support the mitochondrial electron transport chain, stimulate mitochondrial biogenesis[1] [2]
• olive oil polyphenols can also increase neurotrophins to protect against neurodegeneration and depression[3] [4]
• in addition to olive oil, the UNESCO definition of the Mediterranean diet includes communal preparation and consumption – using crockery and glasses produced locally
• social enrichment from a strong sense of community is another driver of brain-supportive neurotrophins[5]

Ketogenic diet

• ketones, derived from fats, are especially supportive to the mitochondrial electron transport chain, and mitochondrial biogenesis
• mitochondria do better with ketones than with glucose, providing a better fuel to produce ATP
• ketones trigger epigenetic changes that improve mitochondria number and function[6] [7] [8]
• however ketogenic diets don’t work for everyone, and for some, especially those with excessively damaged mitochondria, it can be too hard on the system

Vegetarian diet 

• rich in fruit and vegetables which contain many mitochondria supporting phytonutrients 
• be careful to include sufficient vitamin B12 and choline

Read more about correcting your nutrition for better mental health. 

Certain nutrients are vital to protecting our mitochondria from inflammation, ROS and dysfunction.

Coq10 

Works as an essential cofactor within the Electron Transport Chain (ETC), which is vital for sufficient ATP and protects against ROS.[9]

Vitamin E

• in animal models, vitamin E supplementation has been found to reverse age-related declines in ATP and increases in mitochondrial ROS in the hippocampus and frontal cortex – both implicated in depression
• vitamin E was able to restore mitochondrial mass in the hippocampus and maintain synaptic mitochondrial biogenesis[10]

Vitamin A

• acting via retinoic acid receptors, vitamin A can help support mitochondrial biogenesis and the utilisation of fat for energy (beta oxidation)[11]
• essential for thyroid hormone action[12], which is also important for mitochondria
• important for nerve regeneration, particularly the outgrowth of axons[13]
• lessens microglial activation, thereby reducing inflammation in the brain[14]
• can also enhance acetylcholine, the neurotransmitter essential to memory and cognitive function[15]
• mitochondria have nicotinic acetylcholine receptors – when activated these acetylcholine receptors inhibit mtDNA release from mitochondria and block inflammasome activation[16]

B vitamins

• folate deficiency has been linked with depression[17]
• folate metabolism within mitochondria supports mtDNA synthesis and consequently mitochondrial integrity[18]
• vitamins B1,  B6 and biotin all play vital roles in maintaining ATP production within mitochondria[19]

Choline

• choline is an important component of phospholipids which help to build cell membranes, synapses and the inner mitochondrial membrane[20] [21]
• a choline-deficient diet will compromise the synthesis of cardiolipin, the ‘glue’ that holds the mitochondrial electron transport chain together[22]
• choline is required for the neurotransmitter acetylcholine which acts via the vagus nerve to reduce inflammation and support mitochondria[23]

Taurine

• plays an important role in stabilising mtDNA gene transcription[24]
• is an effective mitochondrial antioxidant[25]

MCT oil

• a readily available source of mitochondrial energy that does not require active transport into mitochondria
• Medium-chain triglycerides (MCTs) can trigger diarrhoea in some individuals and have been linked to EFA deficiencies when supplemented long-term[26]
• MCTs used in support of a ketogenic diet help with neurotransmitter and mitochondrial function in the CNS[27]
• protect against insulin resistance and metabolic syndrome[28]
• support mitochondrial biogenesis[29]

Vitamin C

• mitochondria have a high need for vitamin C to neutralise the reactive oxygen species (ROS) they produce[30]
• mitochondria have their own C transporters[31]

A-lipoic acid

• increases glutathione
• improves insulin sensitivity
• is an integral part of the Kreb’s cycle within mitochondria
• promotes mitochondrial biogenesis
• is neuroprotective

[32]

Astaxanthin

• effective at protecting mitochondria from oxidative stress[33]

Curcumin

• can help increase ATP in hippocampal cells and support mtDNA and biogenesis[34]
• can protect tau proteins and help maintain the integrity of the cytoskeleton and ensure mitochondrial ATP transport to neurons[35]

Certain phytochemicals 

• resveratrol[36] (found in grapes, berries, nuts and cocoa) and equol[37] (a soy metabolite from gut fermentation) have been found to benefit mitochondrial health and function

Green tea

• epigallocatechin-3-gallate, a polyphenol found in green tea, has been shown to dramatically improve mitochondrial function in a study researching neurodegeneration[38]

Vitamin K

• found in green leafy vegetables 
• protects against neurodegeneration and inflammation[39]
• in combination with vitamin C, vitamin K can help bypass blocks in mitochondrial metabolism[40]
• helps to maintain the integrity of the myelin sheath[41]

Vitamin D 

• acting through its receptor (VDR) vitamin D regulates mitochondrial oxidative phosphorylation and so protects against ROS[42]
• Deficiency increases the risk of depression in later life[43]

Magnesium

• protects mitochondria 
• helps keep calcium in check
• helps to regulate glutamate receptors and excitotoxicity

[44]

Zinc 

• helps protect against excitotoxicity by regulating the glutamate receptor[45]
• excitotoxicity happens when excess or unregulated glutamate allows calcium to flood the neurons, overwhelming the mitochondria, and leading to cell death[46]
• both zinc and magnesium protect against excitotoxicity by decreasing glutamate dependent neurotransmission[47]
• patients with major depressive disorder have been shown to have low zinc and low magnesium[48]

Omega 3 fatty acids 

• change the phospholipid profile of mitochondrial membranes
• DHA displaces the omega 6 fatty acid arachidonic acid in mitochondria, resulting in increased levels of the mitochondrial phospholipid cardiolipin[49]
• cardiolipin is the ‘glue’ that holds the electron transport chain together

Anthocyanin

• anthocyanin in berries is especially protective of neuronal mitochondria[50]

Rooibos tea

• aspalathin, a flavonoid found in rooibos tea, acts as a powerful mitochondrial antioxidant[51]

Melatonin

• stabilises the mitochondrial membrane potential – an indicator of mitochondrial health[52]
• melatonin is preferentially taken up by mitochondria – no other antioxidant does this[53]
• disrupted by light, even normal electric light at night and lack of sunlight during the day[54]

Read more about how to supplement for better mental health. 

There is a strong link between membrane strength and mitochondrial integrity. Damaged mitochondria and lead to damage gut and blood brain barriers, and damaged gut can compromise the mitochondria.

Soluble fibre and short-chain fatty acids

• fermentation of fibre in the gut produces short-chain fatty acids (SCFAs) 
• SCFAs improve gut and blood brain barrier integrity by reducing permeability in both[55] [56]
• SCFAs are thought to improve barrier integrity by powering mitochondria to keep barrier tight junctions intact
• SCFAs help to modulate the gut-brain axis, reducing brain inflammation and supporting neurotrophin activity[57] [58]
• the SCFA butyrate supports mitochondria by reducing ROS production[59]

Psychobiotics

• many lactobacillus and bifidobacterium species support the gut-brain axis by curbing inflammation and cortisol levels, which can result in a reduction of symptoms of depression and anxiety.[60]

Read more about how to heal your gut.

As we have seen in the section on mitochondrial dysfunction, toxins can be highly damaging to our mitochondria.

Drink ample water and fibre to support elimination of waste through the kidneys and bowels.

• sleep and exercise will upregulate the glymphatic system to clear metabolic waste from the Central Nervous System (CNS)
• in excess, the excitatory neurotransmitter glutamate is associated with mitochondrial dysfunction and excitotoxicity 
• glutamate is detoxified via the Kreb’s cycle and doubles up as a mitochondrial fuel[61]
• detoxification of the neurotransmitter dopamine accelerates as we age and can dangerously increase a dopamine metabolite called DOPAL
• DOPAL is 1000 times more toxic than dopamine and is a potent mitochondrial toxin[62] [63]
• curcumin, luteolin, quercetin, ursolic acid, rutin, catechin and berry anthocyanins and DHA are natural compounds which all have some degree of MAO-inhibitory activity
• slowing down MAO and dopamine detoxification will reduce harmful levels of DOPAL[64]
• oxidative stress also damages lipid membranes in a process called lipid peroxidation
• lipid peroxides are associated with an increased risk of depression[65]
• lipid peroxides can be detoxified by mitochondria but mitochondria can become easily damaged by them as levels increase
• high alcohol intake can compromise lipid peroxide detoxification[66]

Read more about how to detoxify for better mental health. 

As seen in mitochondria dysfunction, hormesis is a strategy where the body employs a small amount of stress to induce positive compensatory reactions, which then heal and strengthen us.

Within limits, we evolve when pushed and challenged – and grow stronger because of these beneficial challenges. However, if we go beyond our limits, this is when dysfunction ensues.

Hormesis, and more specifically, mitohormesis (mitochondrial hormesis) promote mitophagy (the digestion of damaged mitochondria) and mitochondrial biogenesis.[67]

Mitohormesis conditions our mitochondria to handle stress[68], while staying in peace time metabolism rather than going into defense mode.

Ways to promote mitohormesis:

Fasting and exercise 

• over 65s who regularly train and exercise have similar mitochondrial capacity as much younger people[69]
• exercise increases ROS and the expression of SIRT anti-ageing proteins, which are essential for mitochondrial biogenesis, especially in the hippocampus[70]
• chronic stress suppresses the expression of SIRT anti-ageing proteins, and can lead to hippocampal atrophy, which is a hallmark of depression and neurodegenerative diseases such as Alzheimer’s[71] [72] [73]

Fruit and vegetables with high polyphenol content

• plant compounds, such as polyphenols, are mildly toxic, triggering hormesis, which then triggers our own antioxidants 
• these antioxidants then in turn support mitochondria[74]

Negative ions 

• found in sea air, air ear waterfalls, after a rain
• trigger mitohormesis when breathing them[75]

Breath hold 

• hypoxia due to breath-holding practices strengthen mitochondria in the lungs through mitohormesis which upregulates endogenous antioxidants[76] [77]

Heat and cold 

• extreme heat and extreme cold (eg: saunas and/or ice therapy)[78] [79]

Red and near infrared light and uv light 

• red light interacts with mitochondria and boosts antioxidant levels[80] [81]

Romantic love and connection increase NGF (nerve growth factor) which enables mitochondria to repair neurons damaged by chronic stress.[82]