18 Best Natural Ways to Improve Mitochondrial Function 2024
The common denominator for overall health—including longevity, brain health,
gut health, liver health, immune health, and kidney health—is mitochondrial
health.
Mitochondria are involved in many vital processes in human cells, including
energy production, fatty-acid oxidation, and the Tricarboxylic Acid (TCA)
cycle, calcium signaling, apoptosis (cellular death), and heat production.
However to simplify things let’s talk about energy and longevity which is what
their function translates to for practical purposes. And to help this occur,
we can review the health practices, along with the
best supplements to improve mitochondrial health.
Proper mitochondrial functioning is crucial for every nucleated cell in a body. A number of diseases are characterized by dysfunction of muscular or neural systems or metabolic reactions. All these diseases and pathophysiological conditions are developed against a specific genetic background, together with environmental factors.
Mitochondria produce energy as ATP (adenosine triphosphate), which your body then uses to fuel your daily activities. Some cells have more mitochondria than others. Your brain, muscles, and heart cells are full of mitochondria. Putting diseases and aging to the side: you want your mitochondria working at full strength to keep your energy levels up, your brain sharp, and your muscles and heart at their peak performance. The creation of new mitochondria (mitochondrial biogenesis) is needed for optimal aging, which we now call our healthspan. Not to be repetitive, but always remember this is mandatory to keep your energy levels at a peak. It’s also a part of what’s needed to protect you from oxidative stress. As you would predict, mitochondrial dysfunction tanks your energy and contributes to numerous physical ailments.
Here are the mitochondrial supplements that have been studied and proven effective.
Some studies have shown that CoQ10 supplementation can improve mitochondrial
respiratory function and reduce oxidative stress (Nature 2019,
CASI 2022)
Note: It would be impossible to review all the studies on the internet;
rather, we have focused on, curated and evaluated the information that
appear to have the greatest clinical utility. This article is a
work-in-progress article as new evidence might be added from time to
time.
Contents
- Mitochondria: Why do we care?
- Best Mitochondrial Support Supplements
- CoQ10
- PQQ
- L-carnitine
- NAD Boosting Supplements
- Glycine and NAC
- Vitamin D3 and K2
- Magnesium and Molecular Hydrogen
- D-ribose
- Phospholipids
- Melatonin
- Miscellaneous supplements
- What happens when mitochondria malfunction?
- What about mitochondrial function and aging in general?
- Mitochondria boosting health practices
- Mitochondrial specific exercise
- Final words
Mitochondria: Why do we care?
First, let’s discuss the “energy part.” Mitochondria produce Adenosine Triphosphate (ATP). In the cell, the energy in the form of ATP is produced in two ways: in the cytosol as a product of glycolysis and in the mitochondria as a product of oxidative phosphorylation. The substrates, in the form of fatty acids and pyruvate, are oxidized via fatty acid β-oxidation and the TCA cycle, respectively. The Nicotinamide Adenine Dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) produced by these reactions are used by the electron transport chain to generate ATP. Just remember from this complex discussion of energy production that you need ATP and you need NAD+/NADH to make that ATP, so you feel as if you have enough energy.Proper mitochondrial functioning is crucial for every nucleated cell in a body. A number of diseases are characterized by dysfunction of muscular or neural systems or metabolic reactions. All these diseases and pathophysiological conditions are developed against a specific genetic background, together with environmental factors.
Mitochondria produce energy as ATP (adenosine triphosphate), which your body then uses to fuel your daily activities. Some cells have more mitochondria than others. Your brain, muscles, and heart cells are full of mitochondria. Putting diseases and aging to the side: you want your mitochondria working at full strength to keep your energy levels up, your brain sharp, and your muscles and heart at their peak performance. The creation of new mitochondria (mitochondrial biogenesis) is needed for optimal aging, which we now call our healthspan. Not to be repetitive, but always remember this is mandatory to keep your energy levels at a peak. It’s also a part of what’s needed to protect you from oxidative stress. As you would predict, mitochondrial dysfunction tanks your energy and contributes to numerous physical ailments.
The best supplements to improve mitochondrial function
I see people perk right up within (literally) 24 hours of proper mitochondrial supplementation. If someone has a chronic and/or fatiguing illness or are just suffering from age-related mitochondrial failure, supplementation absolutely works. It sure beats energy drinks which end up causing adrenal issues and potentiating energy problems.Here are the mitochondrial supplements that have been studied and proven effective.
1. CoQ10
CoQ10 is an essential electron carrier in the mitochondrial respiratory chain. In other (more complex) words, CoQ10 passes electrons between NADH-ubiquinone oxidoreductase, succinate-ubiquinone oxidoreductase, or succinate-cytochrome C oxidoreductase.
Basically, CoQ10 can be found in both oxidized (ubiquinone) and reduced
(ubiquinol) forms, and the conversion between these oxidized and reduced
states allows it to act as a cofactor of enzymatic reactions via the
transfer of electrons.
CoQ10 is a critical part of the mitochondrial oxidative phosphorylation
system. Over ten well-done studies show that supplementation with this
vitamin-like antioxidant compound in individuals with reduced CoQ10 levels
results in increased energy production and reduced fatigue. The most
dramatic results are in those individuals with degenerative
diseases.
Ubiquinone, also known as Coenzyme Q10, is an important cofactor in the
mitochondrial electron transport chain and a potent antioxidant. Both
ubiquinol and ubiquinone are forms of CoQ10 (coenzyme Q10).
Levels of CoQ10 in the heart can decrease with age, statin use, or due to
genetic factors.
In patients with heart failure, CoQ10 treatment has been shown to
significantly reduce major adverse cardiovascular events20 and lower the
death rate. (source)
PQQ decreases oxidative stress (production of ROS) and inflammation which, by definition, will
protect mitochondria. It also increases mitochondrial biogenesis, which
is the formation of new, young-acting mitochondria. It is
neuroprotective, too. Here’s how. Recall that you have read about GABA
versus glutamate or inhibitory (relaxing) versus excitatory (too
stimulating) neurotransmitter activity. We want more GABA than
glutamate, plain and simple. Too much glutamate damages brain cells. PQQ
protects neurons by preventing the long-term over-activation of the
glutamate (NMDA) receptors, which results in toxic excitotoxicity of
neurons. This over-stimulation of brain cells is associated with many
neurodegenerative diseases and seizure disorders.
Clinical studies show that L-carnitine supplementation may also be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer. Note: L-carnitine is the nomenclature used for many clinical studies, but due to l-carnitine’s ability to increase TMAO, experts suggest that all human supplementation be done with acetyl-l-carnitine.
Oral NADH supplementation can reduce symptoms in patients with chronic fatigue. One study on patients with chronic fatigue syndrome treated participants with micro-encapsulated, oral NADH or a placebo for a month’s time. 8 of 26 study participants (about 1/3) responded positively with increased well-being and energy levels to the NADH compared with 2 of 26 (8%) in the placebo group.
This supplement also shows promise for neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. The increase in measured NADPH levels correlates with a marker for aging: an increase in telomere length.
NAD will stimulate the SIRT1 pathway which is notably dysfunctional in those with metabolic syndrome, diabetes, and more. When you stimulate the SIRT1 pathway, you lower leptin levels, making it again possible to lose weight, improve blood sugar, cholesterol, and triglyceride levels, and in fact, all aspects of metabolic syndrome.
“B vitamins are absolutely critical for mitochondrial function — especially niacin, riboflavin and folate. Orally speaking, with niacin, I typically start them at 100 to 200 milligrams a day [but] you can go up to 2,000 mg easy on some patients. I use a B complex because I like to balance it out, but I'm focusing primarily on niacin, folate and riboflavin.”
Typically, when a deficiency of B vitamins is the cause of decreased mitochondrial function, I will see improved readings within two to three weeks, although the level of improvement can vary tremendously from one person to the next. An important caveat here is that mitochondria are vulnerable to any number of assaults, including emotional stress.
Vitamin B12 is needed to form red blood cells and DNA. It is also a key player in the function and development of brain and nerve cells. However, we believe the most important function it provides is methylation. If you don’t know what methylation is, allow us to briefly explain. Methylation is a biochemical process which is involved in a wide range of bodily functions, and is essential to our overall well-being. When methylation is out of balance, many different health problems may arise.
Decreased vitamin D levels reduce mitochondrial activity and ATP production from oxidative phosphorylation and increase oxidative stress and inflammation [205, 206]. Vitamin D–controlled mitochondrial health may also have implications for self-renewal capacity of cells [207].
Vitamin D is an important substance for skeletal muscle and bone support in humans. The regeneration of muscle includes complex mechanisms comprising the restoration of mitochondrial functions [207]. More specifically, vitamin D3 therapy increased mitochondrial oxidative phosphorylation in muscle cells after exercise in symptomatic, vitamin D–deficient subjects [208].
Researchers at Baylor College of Medicine also looked into
supplementation with a combination of glycine and N-acetylcysteine
(NAC), two glutathione precursors known as GlyNAC when taken together.
Anytime your skin is exposed to natural sunlight, however, you can be sure you’re receiving the necessary wavelengths of near-infrared to generate melatonin in your mitochondria. Conversely, when indoors under artificial lighting, you can be certain you’re not getting any. This is because most window glass is low-e and filters out a good portion of the near-infrared, so even sitting near a window is not going to provide you with this benefit.
A 2022 systematic review showed that curcumin helped improve metabolic syndrome objectively (reducing BMI, triglycerides, total cholesterol, and insulin resistance).
Here are some examples.
In studies using Alzheimer’s disease models, CoQ10 administration
significantly delays brain atrophy and characteristic β-amyloid
plaquing. In a 4 month clinical study on around 100 Alzheimer’s
patients who took an oral mixture of vitamins E, C, CoQ10, and
α-lipoic acid, the group receiving supplementation showed significant
reductions in oxidative stress markers and subsequent DNA damage.
Individuals with Parkinson’s disease tend to show increased levels of oxidized (and by definition: damaged) CoQ10. They also have significant increases in markers of oxidative stress and damage in their brains, which is partially reversible with CoQ10 administration.
One last important clinical note: recall that the heart is filled with mitochondria which are partially powered by CoQ10. If you are taking a statin drug, please be aware that they deplete your body of CoQ10, so supplementation is a must.
Individuals with Parkinson’s disease tend to show increased levels of oxidized (and by definition: damaged) CoQ10. They also have significant increases in markers of oxidative stress and damage in their brains, which is partially reversible with CoQ10 administration.
One last important clinical note: recall that the heart is filled with mitochondria which are partially powered by CoQ10. If you are taking a statin drug, please be aware that they deplete your body of CoQ10, so supplementation is a must.
2. PQQ
Pyrroloquinoline quinone (PQQ) is contained in fruits and vegetables
such as kiwi fruit and green peppers. It has received a lot of
research attention in the past several years. PQQ can reduce reactive
oxygen species (ROS) levels and improve the apoptosis (death) of tumor
cells. PQQ protects tissues by regulating the redox (electron
transfer) reaction. Moreover, PQQ protects overall tissue function by
improving the mitochondrial function of the liver, neurons, and other
important tissues. It can also reduce atrophy in mouse skeletal
muscles.
Recall again that you have the largest concentration of mitochondria
in your brain, heart, and skeletal muscles. The brain “wins” pound for
pound by a little edge, which is why you feel tired after using your
brain all day. With this in mind, remember that when we protect the
brain, we’re protecting brain mitochondria. PQQ protects the brain (to
a certain extent) against neurotoxicity induced by mercury and other
potent toxins such as
mold mycotoxins. Lastly, it too helps to prevent the accumulation of amyloid tau and
beta proteins associated with Parkinson’s and Alzheimer’s diseases.
3. Acetyl-l-carnitine
Acetyl-l-carnitine is a naturally occurring fatty acid transporting
amino acids. L-carnitine supplementation has long been studied and
then used in many mitochondrial dysfunction disorders. These disorders
are also characterized by low concentrations of serum l-carnitine levels such as heart disease, diabetes, kidney disease,
and overwhelming infections. An important cellular longevity function
of l-carnitine has been to increase the rate of mitochondrial oxidative
phosphorylation (ATP production) that declines with age. A study
where old rats were fed acetyl-l-carnitine resulted in the reversal of age-related decreases
in l-carnitine levels, an increase in fatty acid metabolism, and an
increase in mitochondrial activity. Acetyl-l-carnitine also reverses
the age-related decline in muscle mitochondria.
Clinical studies show that L-carnitine supplementation may also be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer. Note: L-carnitine is the nomenclature used for many clinical studies, but due to l-carnitine’s ability to increase TMAO, experts suggest that all human supplementation be done with acetyl-l-carnitine.
4. NAD and B Vitamins
NAD is now the big news, thanks largely to the research by Dr. David
Sinclair and his best-selling book, “Lifespan.” Recall the mentions
throughout this article about the conversion of NAD+ to NADH, and
vice versa, as essential reactions in creating ATP. Recall that ATP
is cranked out by mitochondria, and gives cells (and you) energy.
Therefore NAD and its substrates are crucial for cellular energy,
mitochondrial biogenesis and it turns out; cellular longevity. All
that remains to be seen, is proof positive that one “form” of NAD is
superior to another. Here are some of the data.
Oral NADH supplementation can reduce symptoms in patients with chronic fatigue. One study on patients with chronic fatigue syndrome treated participants with micro-encapsulated, oral NADH or a placebo for a month’s time. 8 of 26 study participants (about 1/3) responded positively with increased well-being and energy levels to the NADH compared with 2 of 26 (8%) in the placebo group.
This supplement also shows promise for neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. The increase in measured NADPH levels correlates with a marker for aging: an increase in telomere length.
NAD will stimulate the SIRT1 pathway which is notably dysfunctional in those with metabolic syndrome, diabetes, and more. When you stimulate the SIRT1 pathway, you lower leptin levels, making it again possible to lose weight, improve blood sugar, cholesterol, and triglyceride levels, and in fact, all aspects of metabolic syndrome.
Taken orally, NMN (nicotinamide mononucleotide) is rapidly absorbed
and converted to NAD+. In numerous studies, supplementation with NMN
increases NAD+ biosynthesis, suppresses age-related fatty tissue
inflammation, enhances insulin secretion and its action, improves
overall mitochondrial function, and in the brain, it improves
mitochondrial as well as neuronal function. In animal studies, it
extends lifespan. In fact, NMN given to mice does quite a bit.
Before I discuss NMN, let me give a shoutout to nicotinamide
riboside- also converted to NAD+. As well as NMN? We don’t know, and
the research continues. Meanwhile, we have a lot of data from mice
studies.
Orally administered NMN is rapidly converted to NAD+ in mice. NMN
has been shown to enhance energy metabolism and physical activity,
suppress age-associated weight gain, improve insulin sensitivity and
even improve ocular function. It improves mitochondrial metabolism
and prevents age-related negative changes in gene expression. In
mice bred to be obese or diabetic, NMN improved both the action and
secretion of insulin.
NMN also protects the mouse heart from ischemia and/or reperfusion
injury. It restores skeletal muscle mass in aging mice. Of special
interest to those of us who treat many patients with brain issues,
it has been shown to slow cognitive decline in a mouse model of
Alzheimer’s disease, by improving the survival of neurons, improving
energy metabolism, and reducing oxidative stress. It may also help
maintain the integrity of the blood-brain barrier.
NMN also probably suppresses the increase in systemic inflammation
associated with aging based on the studies which show that it lowers
adipose tissue inflammation associated with age. In fact,
surprisingly enough, older mice appear to be more responsive to NMN,
in comparison with younger mice.
Dr. Frank Shallenberger, author of “Bursting With Energy: The Breakthrough Method to Renew Youthful
Energy and Restore Health,” explains:
“B vitamins are absolutely critical for mitochondrial function — especially niacin, riboflavin and folate. Orally speaking, with niacin, I typically start them at 100 to 200 milligrams a day [but] you can go up to 2,000 mg easy on some patients. I use a B complex because I like to balance it out, but I'm focusing primarily on niacin, folate and riboflavin.”
Typically, when a deficiency of B vitamins is the cause of decreased mitochondrial function, I will see improved readings within two to three weeks, although the level of improvement can vary tremendously from one person to the next. An important caveat here is that mitochondria are vulnerable to any number of assaults, including emotional stress.
“I have literally seen patients have great mitochondrial
function, be under stress for two months, and have their
mitochondria wiped out just from emotional stress,” he says. “I
haven't done the studies, but I'm pretty sure that if you get
under a lot of emotional stress, I bet your mitochondria suffer
a measurable hit within 48 hours.”
Vitamin B12
Vitamin B12 is needed to form red blood cells and DNA. It is also a key player in the function and development of brain and nerve cells. However, we believe the most important function it provides is methylation. If you don’t know what methylation is, allow us to briefly explain. Methylation is a biochemical process which is involved in a wide range of bodily functions, and is essential to our overall well-being. When methylation is out of balance, many different health problems may arise.
5. Magnesium and Molecular Hydrogen
Magnesium
Magnesium can help increase oxidative capacity, the ability of
your mitochondria to produce ATP from oxygen. Most people only
tend to focus that oxidative capacity only depends on the
availability of oxygen, however, the truth is this activity also
critically relies on your mitochondria.
A study showed that at the cellular level, magnesium improved mitochondrial function with increased ATP, decreased mitochondrial ROS and Ca2+ overload, and repolarized mitochondrial membrane potential. In conclusion, Magnesium supplementation improved mitochondrial function, reduced oxidative stress, and prevented diastolic dysfunction in diabetes mellitus.
A study showed that at the cellular level, magnesium improved mitochondrial function with increased ATP, decreased mitochondrial ROS and Ca2+ overload, and repolarized mitochondrial membrane potential. In conclusion, Magnesium supplementation improved mitochondrial function, reduced oxidative stress, and prevented diastolic dysfunction in diabetes mellitus.
Molecular Hydrogen
Molecular Hydrogen provides an extra layer of protection against
sun damage and mitigates the effects of vegetable oils. It
operates at the cellular level by neutralizing harmful free
radicals, especially hydroxyl radicals. It can also penetrate
cell membranes to target inflammation and oxidative damage
directly at the source while preserving beneficial reactive
oxygen species (ROS). Beyond its protective role, H2 boosts
energy levels and enhances recovery, making it a valuable
support for cellular health, particularly when dealing with sun
exposure and dietary challenges from vegetable oils.
Note: Most Molecular Hydrogen tablets uses pure
elemental magnesium as its carrier and provides you with
approximately 80 mg of magnesium per tablet. So, you receive
also highly bioavailable magnesium for a healthy brain,
muscles, cells, kidneys, and heart.
Related: Best Molecular Hydrogen Tablets
6. Vitamin D3 and K2
Vitamin D3
Decreased vitamin D levels reduce mitochondrial activity and ATP production from oxidative phosphorylation and increase oxidative stress and inflammation [205, 206]. Vitamin D–controlled mitochondrial health may also have implications for self-renewal capacity of cells [207].
Vitamin D is an important substance for skeletal muscle and bone support in humans. The regeneration of muscle includes complex mechanisms comprising the restoration of mitochondrial functions [207]. More specifically, vitamin D3 therapy increased mitochondrial oxidative phosphorylation in muscle cells after exercise in symptomatic, vitamin D–deficient subjects [208].
Another study revealed that vitamin D deficiency is linked with
muscle atrophy, increased oxidative stress, and decreased
mitochondrial functions in the multifidus muscle in patients [209]. Regarding bone health, hypovitaminosis D represents a risk
factor for decreased bone strength in primary mitochondrial disease
in human subjects [210].
Vitamin K2, a fat-soluble vitamin, also has antioxidant effects and is neuroprotective. In one study, researchers even revealed vitamin K2 modulates mitochondrial dysfunction caused by neurotoxins (2). They exposed SH-SY5Y cells, which serve as a model for neurodegenerative disorders, to 6-hydroxydopamine (6-OHDA), a neurotoxic compound used to destroy neurons in the brain.
They then treated the cells with vitamin K2, which led to multiple improvements. While 6-OHDA induced abnormal mitochondrial changes, vitamin K2 significantly suppressed the negative changes.
Vitamin K2 also inhibited the accumulation of reactive oxygen species (ROS) and promoted mitophagy, which is the removal of damaged mitochondria via autophagy — an essential function to maintain cellular health. Writing in the journal Nutrients, the scientists explained (3):
Vitamin K2
There are two types of vitamin K: phylloquinone, or vitamin K1;
and menaquinones, or vitamin K2. Vitamin K1 is derived from green,
leafy vegetables such as spinach, kale, broccoli and cabbage, and
is best known for the role it plays in blood clotting.
Vitamin K2 is better known for its role in bone and heart health, and is found in grass fed animal products such as meat, eggs, liver and dairy, as well as in fermented foods, including sauerkraut, certain cheeses and the fermented soy food natto.
Vitamin K2 is better known for its role in bone and heart health, and is found in grass fed animal products such as meat, eggs, liver and dairy, as well as in fermented foods, including sauerkraut, certain cheeses and the fermented soy food natto.
Vitamin K2, a fat-soluble vitamin, also has antioxidant effects and is neuroprotective. In one study, researchers even revealed vitamin K2 modulates mitochondrial dysfunction caused by neurotoxins (2). They exposed SH-SY5Y cells, which serve as a model for neurodegenerative disorders, to 6-hydroxydopamine (6-OHDA), a neurotoxic compound used to destroy neurons in the brain.
They then treated the cells with vitamin K2, which led to multiple improvements. While 6-OHDA induced abnormal mitochondrial changes, vitamin K2 significantly suppressed the negative changes.
Vitamin K2 also inhibited the accumulation of reactive oxygen species (ROS) and promoted mitophagy, which is the removal of damaged mitochondria via autophagy — an essential function to maintain cellular health. Writing in the journal Nutrients, the scientists explained (3):
“… [V]itamin K2 can reduces mitochondrial damage, and … this
effect is related to the participation of vitamin K2 in the
regulation of the mitochondrial quality-control loop, through
the maintenance of the mitochondrial quality-control system, and
repair mitochondrial dysfunction, thereby alleviating neuronal
cell death mediated by mitochondrial damage.”
7. Glycine and NAC
Glycine is a nonessential amino acid, as your body can manufacture
some on its own. However, most of us do not make enough glycine to
maximize its health benefits, which include increased longevity
and protection against age-related disease.4
While it’s long been suggested that age-related mutations in
mitochondrial DNA are responsible for making mitochondria less
efficient as you get older, Japanese researchers suggested epigenetic
changes may, instead, be the key players.
5
Further, they were able to restore gene regulation in aging
mitochondria to a more youthful state using glycine.6 According to the study, “Treatment of elderly fibroblasts
with glycine effectively prevented the expression of these aging
phenotypes.”7
Collagen — the most abundant protein in your body8 — is made mostly of glycine. It’s also a precursor to
glutathione, a powerful antioxidant that declines with age. However,
inducing autophagy and mimicking methionine restriction9 may be behind glycine’s antiaging effects. Even
intermittently restricting methionine leads to benefits like
improved glucose homeostasis, reduced obesity and protection against
fatty liver.10
They had previously shown that young mice deficient in
glutathione had mitochondrial dysfunction, and supplementing with
GlyNAC in older mice not only improved glutathione deficiency but
also mitochondrial impairment, oxidative stress and insulin
resistance.11
Additional research they conducted in HIV patients,12 and found GlyNAC supplementation improved “deficits
associated with premature aging” in this population.13 This included improvements to oxidative stress,
mitochondrial dysfunction, inflammation, endothelial dysfunction,
insulin resistance, genotoxicity, strength and cognition.14
A subsequent pilot trial in older humans found similar results,
with GlyNAC supplementation for 24 weeks correcting glutathione
deficiency and improving multiple measures of health, including
mitochondrial dysfunction, endothelial dysfunction, inflammation,
cognition, strength and more.15
8. Phospholipids
Mixtures of probiotic, phospholipid, and antioxidant preparations have shown some clinical promise in fatiguing illness. This mixture is made using antioxidant powders, probiotics, and phosphatidylserine. The bulk of the studies have been with patients who have fibromyalgia and/or chronic fatigue syndrome (CFIDS).9. D-ribose
We know that D-ribose has documented positive mitochondrial effects for those who are genetically d-ribose deficient. It’s a popular bodybuilding supplement which “hardcore” bodybuilders credit as being helpful with their muscular fatigue. Studies have looked at neurodegenerative diseases such as Multiple Sclerosis and ALS with promising results. (source)10. Melatonin
Endogenously produced melatonin diminishes during aging, further
increasing oxidative damage to mitochondrial components. More
normal mitochondrial physiology is preserved in aging neurons
with
melatonin supplementation. (Ageing Research Reviews 2024)
Melatonin is a potent antioxidant that counters free radicals and
ROS generated during cellular metabolism [25]. It protects
mitochondria by neutralizing ROS, hindering the opening of the
mitochondrial permeability transition pore, and activating
uncoupling proteins [57]. Consequently, melatonin sustains the
optimal membrane potential of mitochondria, ensuring their
functions remain intact. Furthermore, melatonin governs the
creation and movement of mitochondria. It frequently curtails
the division of mitochondria while fostering their fusion. The
rhythmic oscillation in mitochondrial dynamics mirrors
melatonin's natural secretion cycle, observed particularly in
pineal cells and likely in other cell types [58]. Recent studies
also highlight melatonin's role in promoting mitophagy and
enhancing mitochondrial equilibrium [58].
Mitochondrial melatonin production is one of the reasons why
regular sun exposure is so crucial. Most people understand
that sun exposure on bare skin generates vitamin D, courtesy
of UVB (ultraviolet B radiation). Few, however, understand
that the near-infrared spectrum, when hitting your skin,
triggers the generation of melatonin in your
mitochondria.
Anytime your skin is exposed to natural sunlight, however, you can be sure you’re receiving the necessary wavelengths of near-infrared to generate melatonin in your mitochondria. Conversely, when indoors under artificial lighting, you can be certain you’re not getting any. This is because most window glass is low-e and filters out a good portion of the near-infrared, so even sitting near a window is not going to provide you with this benefit.
There are two types of melatonin in your body: The melatonin
produced in your pineal gland, which traverses into your
blood, and subcellular melatonin produced inside your
mitochondria.
Importantly, the melatonin that your mitochondria produces does not escape your mitochondria. It doesn't go into your blood. So, you're not going to directly increase your blood or serum level of melatonin by sun exposure. But, bright sun exposure around solar noon will indirectly help your pineal gland to produce melatonin during the night.
It is important to understand that your blood level of melatonin is indicative of the melatonin produced in your pineal gland, and/or oral supplementation. Conversely, the melatonin produced by your pineal gland cannot enter into the mitochondria, which is why it is so important to get regular sun exposure.
Importantly, the melatonin that your mitochondria produces does not escape your mitochondria. It doesn't go into your blood. So, you're not going to directly increase your blood or serum level of melatonin by sun exposure. But, bright sun exposure around solar noon will indirectly help your pineal gland to produce melatonin during the night.
It is important to understand that your blood level of melatonin is indicative of the melatonin produced in your pineal gland, and/or oral supplementation. Conversely, the melatonin produced by your pineal gland cannot enter into the mitochondria, which is why it is so important to get regular sun exposure.
Oral supplementation, however, can enter your cells and
mitochondria.
If you supplement with melatonin, it can also enter cells and
get into the mitochondria as well. And that is also very
important ... As you age, mitochondrial melatonin diminishes.
If you supplement with melatonin, it will get into your
mitochondria and, in fact, do what melatonin does — neutralize
free radicals and protect the mitochondria's function.
11. Curcumin
Curcumin is the most commonly found in turmeric and has
antioxidant activities [50]. Studies have shown that curcumin
can boost mitochondrial fusion activity, decrease mitochondrial
fission mechanisms, and elevate mitochondrial biogenesis.
Treatment with curcumin has demonstrated enhanced mitochondrial
function and cell viability [50]. Curcumin potentially enhances
mitochondrial potential and ATP levels and might also contribute
to restoring mitochondrial fusion, likely through the
up-regulation of PGC-1α protein expression [50].
A 2022 systematic review showed that curcumin helped improve metabolic syndrome objectively (reducing BMI, triglycerides, total cholesterol, and insulin resistance).
12. Other promising supplements
Studies are increasingly showing that mitochondrial illnesses are fueled by
oxidative stress; implicating the use of antioxidants such as natural vitamin
E and NAC (the precursor to glutathione) as well as glutathione as additional
treatment considerations. We know that the sirtuin pathways are boosted by
resveratrol and ECGC-green tea extract; implying mitochondrial benefit.
Branched-chain amino acids (BCAA) and creatine are all pro-mitochondrial
health supplements as well, despite being poorly studied for this particular
issue. Finally, there is emerging data for mitochondrial health with
berberine, magnesium threonate and selenium. B vitamins are likely involved as
well.
Mitochondrial Dysfunction and Disease
Mitochondrial dysfunction, characterized by a loss of efficiency in the synthesis of ATP, is a characteristic of aging and, essentially, of all chronic diseases. Loss of function in mitochondria can result in excess fatigue and even other symptoms in just about every chronic disease you can imagine. These conditions include neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, and Amyotrophic Lateral Sclerosis.
How are mitochondrial health and metabolic syndrome related? Metabolic
syndrome, heart disease, and diabetes are all associated with mitochondrial
dysfunction. Metabolic syndrome is a group of conditions that combine
hypertension, hyperglycemia, abdominal obesity, and abnormal cholesterol or
triglyceride levels. Metabolic syndrome greatly increases the risk of
cardiovascular disease, stroke, and Type two diabetes. There are numerous
reports mentioning mitochondrial dysfunction and lower oxidative capacity in
patients with Type two diabetes compared with healthy individuals.
The cardiovascular system strongly depends on mitochondrial function. Cardiomyocytes (heart cells) have very high mitochondrial content in order to produce the necessary ATP, and mitochondrial dysfunction inevitably leads to the development of cardiovascular diseases.
There is now increasing evidence of mitochondrial dysfunction in Alzheimer’s Disease, Parkinson’s Disease, Huntington’s disease, and Amyotrophic lateral sclerosis. Even some psychiatric conditions, such as autism spectrum disorders, schizophrenia, and bipolar mood disorders, are included.
In addition, mitochondrial dysfunction plays a significant role in the inflammatory response in acute human pathologies. Systemic Inflammatory Response Syndrome (SIRS) is a pathological state with a systemic immune reaction to severe damage, including ischemia, acute pancreatitis, trauma, and sepsis.
Autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, and systemic lupus erythematosus are all characterized by mitochondrial failure. Of course, truly fatiguing illnesses, such as CIRS (mycotoxin and mold illness and Chronic Lyme), Chronic fatigue syndrome, fibromyalgia, and Gulf War Syndrome have mitochondrial near-failure as a prominent component. Lastly, as you might predict, cancer and chronic infections round out the list of disorders. If you have any one of these disorders, you will need to improve your mitochondrial health and function in order to recover.
Mitochondria and Aging
A number of age-related processes (e.g., “normal aging of the brain”) are associated with mitochondrial dysfunction, so most of the popular aging theories take this into account. The mitochondrial theory of aging posits that the accumulation of damage to mitochondria DNA promotes the process of cellular aging of both humans and animals. The theory claims that there is a vicious cycle involving the accumulation of damage in mitochondrial DNA, which then leads to more oxidative damage due to defects in the mitochondrial respiratory chain. Let’s say that this theory is true. What, then can we do to save our precious mitochondria and therefore slow the aging in our cells and help prevent diseases?Mitochondrial health and Gut Health
Mitochondrial Dysfunction Destroys Gut Health |
13. Anti-Inflammatory Diet
Eating an anti-inflammatory diet
is one of the easiest ways to improve mitochondrial function.
Polyphenol-rich foods such as blueberries, red and purple foods (e.g.
raspberries and purple cabbage), and many fresh green foods are high in
healthy mitochondrial-boosting polyphenols.
14. Intermittent Fasting
Using intermittent fasting methods such as timed eating and intermittently
“going keto” are also mitochondrial boosters.
15. Exercising For Mitochondrial Health
Many types of exercise are mitochondria-healthy. Walking is great. Running
is great. Weight training is great. Yet, the very best type of exercise for
your mitochondria is high-intensity interval training (HIIT). This doesn’t
need to be complicated, but do get medical clearance if this is a new
activity for you.
You can do HIIT outside, too of course. If you have access to a track,
great! If not, use a treadmill if you’re inside or run in your neighborhood
if you’re outside. Whatever gets you short of breath. Then, walk until you
catch your breath and you can even lie down on your back for faster
autonomic neurological adaptation for up to 90 seconds if you need that long
to catch your breath.
16. Heat Shock Proteins
Heat shock proteins produced by extreme cold or extreme heat are great for
your mitochondria. Cold exposure is an easy way to give your mitochondria
a boost. Studies have demonstrated benefits with “ice jackets”, facial
submersion, and ice baths. Even cryotherapy tanks! And “ice swimming.”
Based on what I personally find tolerable and affordable, you can get
enough of a boost by doing the following. At the end of your daily hot
shower, just turn the temperature to cold for 30 seconds. It is mostly
quite invigorating!
Far-infrared saunas are another way to generate heat shock proteins. An
FIR is a great investment in your health, as it is also a great way to do
a bit of a detox.
17. Meditation and Yoga
Meditation and yoga also boost your mitochondrial output.
18. Other Lifestyle Strategies
Ten minutes of direct sunlight is great for a burst of mitochondrial
activity. Conversely, most data suggest that fluorescent lighting puts a
damper on ATP production and mitochondrial biogenesis. The data is
rather murky when it comes to EMFs, blue-blocking glasses, and so on,
but it’s something to watch, as there seems to be some correlation
between better health and less high-level EMF exposure, as well as less
blue light exposure.
Final words
In any good health regimen, you want to eat an anti-inflammatory diet and take
a few supplements. It makes sense to take vitamin D3 and K2 and high
antioxidant power supplements for many reasons, including mitochondrial
health. At this juncture, if you are healthy and have specific goals in mind,
you might choose, let’s say, some acetyl-l-carnitine if you are lifting
weights, or some PQQ if you have a family history of neurodegenerative
disease. And currently, if you have metabolic syndrome, SIRT pathway issues,
or fatiguing illness, it seems prudent and helpful to take NMN or other NAD
boosting supplements e.g. Nicotinamide Riboside or Niacinamide.
Sources and References:
https://kimcrawfordmd.com/2021/03/6-habits-and-the-7-best-supplements-to-improve-mitochondrial-function/
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