Mitochondrial Biogenesis – Fix Your ATP, Fix Your Life

Now that you’ve read Mitochondria – Fix Your ATP, Fix Your Life,  you should know that mitochondria put the “vital” in “vitality.”

If you didn’t know this, then I suggest you go back and try reading at a slower pace.

This article is going to focus on something called Mitochondrial Biogenesis.

Mitochondrial Biogenesis is the growth or division of pre-existing mitochondria(S).

It causes the mitochondria to either grow in mass or increase in numbers.

What Increases Mitochondrial Biogenesis?

Multiple systems are involved in this, but the one we are going to really be focused on increasing is…

PGC-1α

Peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) – say that 5 times fast – is a part of the family of transcription coactivators, where it plays a pivotal role in the regulation of cellular energy metabolism(S).

What does it do?

To name a few:

• Increases mitochondrial biogenesis and respiration rates
• Increases the uptake of nutrients
• Increases the speed of which these nutrients are processed into ATP
• Coactivates mutliple transciption factors that govern energy metabolism
• Increases fat-burning
• PGC-1 alpha overexpression promotes recovery from mitochondrial dysfunction and cell injury(S)
• It is deeply involved in the Circadian Rhythm.

Most of us know that the Circadian Rhythm is our bodies 24 hour sleep and wake cycle, but there is much more to it than that.  PGC-1α is responsible for stimulating the expression of “clock genes(S).”  Clock genes are components of the circadian clock responsible for generating oscillations of gene expression(S).

PGC-1α is “a key component of the circadian oscillator that integrates the mammalian clock and energy metabolism(S).”

This means that problems in the Circadian Rhythm can lead to Metabolic problems, and Metabolic problems can lead to Circadian Rhythm problems(S).

Upon activation,  PGC-1α also induces the transcription of NRF-1 and NRF-2(S).

NRF-2 is specifically known for its role in increasing the genes that are responsible for increasing our bodies own antioxidant system.

***This is the reason why increasing mitochondrial number and mass does not equate to increased ROS and cell damage.***

The same factor (PGC-1α) that drives mitochondrial biogenesis also increases our bodies’ ability to control  ROS (NRF-2)(S).

Side note:  You can increase mitochondria without activating the PGC-1α pathway.  However, in mice that had this pathway silenced – the mitochondria showed a reduced resilience to stressful conditions.  In other words, mitochondria are stronger with PGC-1α.

Ok, now for the fun part!.

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Mitochondrial Boosters

Free Methods:

1) DIET : Ok, so food isn’t exactly free, but you have to eat anyway – so it’s not exactly an added expense like adding a supplement would be…  The food you choose to eat can be directly responsible for stimulating PGC-1α and mitochondrial biogenesis.

However, the opposite is also true.  The food you choose to eat can be directly responsible for stifling PGC-1α and mitochondrial biogenesis.

The first dietary mean to improve your mitochondria is through…

A. Ketones/Ketosis/Ketogenic Diet –  Basically a ketogenic diet is one that restricts carbohydrates and forces your body to use fat-driven ketones as energy instead of carb-driven glucose.

The Ketogenic Diet is shown to increase mitochondrial respiration (energy production), increase the NRF-2 antioxidant pathway, decrease reactive oxygen species, decrease anxiety, decrease markers of brain atrophy, be neuroprotective, increase glutathione(the master antioxidant), decrease inflammation, upregulate stress response genes, and increase mitochondrial biogenesis(though maybe not through PGC-1α)(S)(S)(S).

If you don’t feel like switching up your diet, evidence suggests that you can still receive the benefits of ketosis through supplementing with MCT Oil, Butyrate, or something like KetoForce (S).

The other type of food that can add some fight to your mitochondria is…

B. Resistant Starch – I’ve discussed Resistant Starch in my “Gut Health”  article, but I did not mention that Resistant Starch can increase mitochondrial biogenesis and the expression of PGC-1α!

When your gut bacteria digest the resistant starch, they produce Short Chain Fatty Acids(SCFA) and Medium Chain Fatty Acids(MCFA or MCT).

Mitochondria gobble these fats up like candy.

This SCFA and MCFA consumption increases mitochondrial respiratory capacity and mitochondria biogenesis(S).  In this rat study, they showed that PGC-1α expression was increased, yet they weren’t sure of the exact mechanism(S).

So you can consume foods that I mention in “Gut Health” like: “cooked then cooled potatoes and rice, green bananas, plantains aka macho bananas, chickpeas, etc.”

Or you can consider eating tiger nuts…

No, I’m not talking about eating a tiger’s testicles…I’m talking about Tiger Nuts.

“Tiger nuts” are not actually nuts at all, they are a tuber and they are really high in resistant starch.

I am a HUGE fan of tiger nuts.  Hey, at least I have the balls to say it 😉 ! 

They have a unique taste that kind of reminds me of Corn Pops cereal.

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2) FASTING – Fasting, as well as “caloric restriction,” triggers your metabolic energy sensor which in turn robustly induces PGC-1α(S)!

Lack of food is a situation that requires huge energy from the body.  When consuming little to no food, your liver sends a nutrient-signal response to activate SIRT1.

SIRT1 then activates PGC-1α and increases liver gluconeogenesis (the production of glucose from non-carbohydrate sources) and fatty acid oxidative metabolism (burning of fat for fuel)(S)(S).

Intermittent fasting is great for fat loss, and works very well on a ketogenic diet.  Combine all of these and you will be well on your way to superior mitochondria.

The easiest way to Intermittently Fast is to not eat food for 16 hrs after your last meal.  So if your last meal is at 8pm, then you will eat “breakfast” at 12pm the next day. Boom.

You can still bulk while practicing intermittent fasting, you just have to make sure you consume enough calories during the feeding window.

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3) LOSING WEIGHT – The relationship between excess weight and mitochondrial function is clear-cut:  Obesity results in poor mitochondrial function, which results in metabolic dysfunction(diabetes, cardiovascular issues, inflammation, etc)(S)!

• “Both obesity and mitochondrial dysfunction are risk factors for the development of insulin resistance…
• Obese individuals have been reported to have smaller mitochondria that exhibit a compromised bioenergetic capacity”
• “It has been hypothesized that a close relationship exists among PGC-1α function, insulin sensitivity, and Type 2 diabetes, which is most likely related to the essential roles of PGC-1α in mitochondria biogenesis and glucose/fatty acid metabolism. Evidence supporting this hypothesis has been found in a number of studies.”
• “Endoplasmic reticulum (ER) and mitochondrial stress, with the consequent oxidative stress, are immediate consequences of attempts to store excess food energy“
• “Mitochondrial defects, systemic inflammation, and oxidative stress are at the root of most noncommunicable diseases such as cancer, atherosclerosis, Parkinson’s disease, Alzheimer’s disease, other neurodegenerative diseases, heart and lung disturbances, diabetes, obesity, and autoimmune diseases. Obesity and obesity-related complications as well as impairment of mitochondrial function are universally associated with these conditions(S).“
• “PGC-1α expression is restored by treatments known to normalize body weight and/or glucose homeostasis(S).”

So clean up your diet -read “Eat for Life…” – or try a Ketogenic Diet (which will be discussed early next year).

Do whatever it takes to lose that extra weight and reclaim your health!

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4) EXERCISE – It is well established that exercise increases mitochondrial biogenesis(S).

Exercise of any kind is shown to boost mitochondrial biogenesis and also PGC-1α.

Exercise activates something called AMPK – an energy sensor responsible for increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.  When AMPK is activated it then induces the expression of PGC-1α.

We all know what happens next…HARDER, BETTER, FASTER, STRONGER MITOCHONDRIA(S)!

Exercise those thighs and get your mitochondria moving to a new groove.

Or else you are  just rude…

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5) COLD EXPOSURE – PGC-1α is STRONGLY induced by cold exposure(S)!

This form of adaptive thermogenesis dissipates energy as heat!  This keeps your body warm when its cold outside.

Brown Aditpose Tissue (BAT) and Muscle Tissue are the tissues responsible for this thermogenic response.

There are two types of adipose(fat) tissues.  One is White Adipose Tissue(WAT) and the other is Brown Adipose Tissue(BAT).

The primary function of WAT is energy storage, white the primary function of BAT is energy dissipation – mostly in the form of heat.

“In fact, BAT produces ∼60% of the heat generated by nonshivering, adaptive thermogenesis.”  Humans typically have more WAT than BAT.  Having a higher BAT to WAT ratio should make someone more metabolically active.  This is why increasing BAT is being pursued as a method to prevent obesity.

As it turns out,  PGC-1α is responsible for stimulating the genes involved in developing brown adipose tissues(s)!  Imagine that…

So when someone tells you to “chill out” you should thank them, because they really just want you to optimize your BAT to WAT ratio… Duh.

The way I incorporate this is by setting the water as cold as I can at the end of my shower.  Then, I tough it out for at least 30 seconds, sometimes longer than a minute.

It is quite invigorating.

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6) BREATH HOLDING – This one I created based off of the idea that holding your breath can create a hypoxic condition in the body.

Hypoxia – a condition in which the body or a region of the body is deprived of adequate oxygen supply(S).

Hypoxic conditions are shown to increase PGC-1α through activation of AMPK(S)(S).

Different methods for breath holding and hypoxic training exist.  This one HERE is catered to swimmers.

Experiment at your own risk.

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One-Time Purchase

1) High Altitude Mask – The Elevation 2.0 Training Mask works under the same principle as breath holding does…it causes a hypoxic state in the body.

From above: “Hypoxic conditions are shown to increase PGC-1α through activation of AMPK(S)(S).”

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2) LLLT – Near-infrared Lights, such as this 96LED IR Security Camera, are shown to improve mitochondrial biogenesis(S)!

“Transcranial low-level light/laser therapy (LLLT) has emerged as an intervention with potential to modulate neuroprotective and cognitive functions.

Transcranial LLLT is the use of light from lasers or lightemitting diodes (LEDs) in the red to near-infrared wavelengths (l = 600–1100 nm) to modulate a neurobiological function or induce a neurotherapeutic effect via stimulation of the respiratory enzyme cytochrome oxidase(S).”

The light I mention above is specified to a wavelength 850nm, which is acceptable.

Our mitochondria contain the photoacceptor –photoacceptors convert light(photons) into signals that stimulate biological processes – cytochrome oxidase whose electrons become excited when it accepts light in the 600-1,100 nm range.  This causes the electron to jump from a low energy state to a high-energy state where it then works it magic(S).

LLLT “acts as an exogenous source of highly energized electrons to the respiratory chain.

Thus, LLLT facilitates the activity of cytochrome oxidase, accelerates the electron transfer in the inner mitochondrial membrane and boosts cell respiration and energy production(S).”

LLLT works on any part of the body, but much of whats being discussed here is for cognitive mitochondrial enhancement.

This is the standard routine – Courtesy of LostFalco (whom I consider to be the founder):

“Laser Dosing Recommendations:
1. Remove glass cover and place LEDs directly on skin. They get a little warm, but nothing to worry about.
2. Laser whole brain, before bed
3. Start with 30 seconds per location. You can always increase. Minimum effective dosing is VERY important with LLLT.
4. 2 days on/1 day off OR every other day. DO NOT use every day. =)
5. 850nm, 96 LED, 9 individual “regions” on sides, top, and back of head AND 850nm, 48 LED, 5 individual spots on forehead along hairline (roughly).
Total Time: 7 minutes. Try this for 1 to 2 weeks before increasing dose time. (Note: ALL is currently provisional.)”

LLLT is an exciting biohack with lots of studies that back it’s effectiveness.  There is a lot to cover with LLLT so I will likely have an article discussing it in the future.

The Vielight-Neuro is top dog in the LLLT-derived cognitive enhancement field.  Hopefully the price drops and becomes more accessible to us peasants.

Light is the future and our future is Bright!

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Supplements

1) Methylene Blue – Methylene Blue is also very interesting.  Of course it stimulates mitochondrial biogenesis…or else I wouldn’t have put it in here 😛 !

Methylene Blue(MB) activates SIRT1 and AMPK which activates PGC-1α and results in an increase in mitochondrial biogenesis(S)(S).

MB is unique because it functions as an antioxidant, reduces ROS production, AND upregulates NRF-2 (the bodies antioxidant system)! A triple defense mechanism(S)…

• “MB has high bioavailability to the mitochondria!
• MB is an FDA-approved drug routinely prescribed as an antidote for the treatment of poison-induced methemoglobinemia(Wiki) due to its powerful antioxidant properties.
• MB readily crosses the blood–brain barrier and has great affinity for mitochondria
• MB is an electron cycler in the mitochondrial electron transport chain, with unparalleled antioxidant and cell respiration-enhancing properties(S).”

Low doses are recommended, as high doses can have the complete opposite effect.

The dosing range is: 0.5–4 mg/kg

I consider 4 mg/kg to be pretty high.  In fact, I have had a lot of success with using a 0.5 mg/kg dose.

I currently weight 165 lbs which is about 75 kg.

So, 0.5 x 75 = 37.5 mg dose.

To dose this low, you will need an accurate scale.  I use the GEMINI-20.  Cheap, effective, and classy.

Warning – MB is great for mitochondria, yet it is also great for STAINING.  It will make your urine a nice blue color.  It’s intensity is directly related to how much you consumed and how many consecutive days you took it.

Therefore, I only recommend using MB as a mitochondrial enhancer at the lowest effect dose 2-3 times a week with at least a day break in between uses.

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2) Baking Soda – Baking soda, also known as Sodium Bicarbonate, can increase the expression of PGC-1α after exercise(S)!

In This Study, baking soda increased the muscle glycogen utilization and blood lactate accumulation significantly more than the placebo group.  The baking soda fed group displayed higher levels of PGC-1α.

The exact mechanism that baking soda works through isn’t completely known.

Some evidence suggests that “baking soda induced chronic alkalosis promotes up-regulation of PGC-1α and its downstream targets COX-2, COX-4, Cytochrome-c and MCT1(S).”

All that really matters to me is that it works, and it is cheap.  So why not utilize it’s power?

The dose of baking soda used in the first study was quite high(0.4g/kg = 30 grams for me, YIKES!).  That’s high enough to make me vomit.

Luckily the blogger over at Suppversity discovered you can take chronic (daily) low doses and achieve a similar effect.

This low-dosing range is a much better – 0.133g/kg.

So for me that is 0.133 x 75 = 10 grams of Baking soda everyday.

10 Grams = 2 Teaspoons…Not too bad.

1 teaspoon before my workout, 1 teaspoon after my workout, and 1 for my homies.

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3) Curcumin – The active component of Turmeric, Curcumin, is potent spice that is also shown to increase PGC-1α levels(S)!

The best form of curcumin is a topic of hot debate.  However, I always use one that is high potency(>95% curcuminoids) and uses Piperine.

Piperine is needed because curcumin is not that bioavailable by itself…

After adding piperine to the mix, bioavailability increases 200%(S).

Doctor’s Best Curcumin fits the bill.

• Curcumin is “is a potent anti-inflammatory, antioxidant, anti-carcinogenic, and anti-hepatotoxic agent(S)(S).”
• It also functions as an antioxidant AND increases the antioxidant NRF-2 pathway(S)!
• It also has dual functions in fat cells:  first, it destroys White Adipose Tissue by initiating apoptosis.  Second, it increases the expression of Brown Adipose Tissue(S)!  This is pretty remarkable and would work synergistically with Cold exposure as explained above.  I learned about these cunning curcumin cheats over at Ben Greenfield‘s blog.

Curcumin is another must-have supplement!

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4) Fish Oil & Krill Oil – Fish Oil, and now Krill Oil, are well-known for their many benefits.  One of which – of course – includes increasing mitochondrial biogenesis(S)(S)(S).

Nordic Brand Fish Oil and Viva Labs Krill Oil are good brands to test out the benefits of omega-3’s.

Omega-3 Fatty Acids are shown to beneficially alter the mitochondrial membrane composition and respiration kinetics.

In This Study, fish oil consumption was shown to rapidly displace omega-6 fatty acids in the phospholipid bilayer and improve the emission of ROS from inside the cell, thus preventing oxidative damage.

“Alterations in dietary fatty acid composition are therefore thought to alter the thickness, stiffness and fluidity of the lipid bilayer, impacting metabolism.”

Aside from boosting your mitochondrial function,  omega-3’s have a a slew of health benefits.  Google it.

Omega-3’s are another must-have supplement – Alternatively,  you could eat fish like sardines(to avoid mercury) and salmon(if you like mercury)…That would work too.

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5) Nitric Oxide – My favorite, Nitric Oxide, is also shown to increase mitochondrial biogenesis(S)!

I did not know this when I wrote my article “5 Reasons Nitric Oxide is Important” so let’s make that 6 reasons!

The way nitric oxide works to increase mitochondrial biogenesis is by acting as a key messenger in cells and stimulating the PGC-1α pathway(S)(S)(S).

However, the exact mechanism that NO activates PGC-1α isn’t too clear…

You should be trying to boost your nitric oxide levels anyways though, so increasing mitochondria should be a welcome side effect!

Remember to look at my article “7 Ways to Boost Nitric Oxide Naturally” for a refresher on how to boost NO.

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6) Nicotinamide Riboside – This is a cool supplement and one of the few that actually gave me noticeable effects.  It also increases mitochondrial biogensis(S).

Niagen Brand Nicotinamide Riboside is the brand I used.

Nicotinamide Riboside works its magic by converting to NAD+ in the body.  NAD+ is shown to directly increase sirtuin(SIRT) activity(S).

” The dependence of sirtuins on NAD links their enzymatic activity directly to the energy status of the cell via the cellular NAD:NADH ratio, the absolute levels of NAD, NADH or nicotinamide or a combination of these variables(S).”

This Study says:

• “NAD⁺plays a key role in regulating metabolism and circadian rhythm through sirtuins.
• NAD⁺becomes limiting during aging, affecting sirtuin’s activities.
• NAD⁺likely declines due to an NAD ⁺biosynthesis defect and increased depletion.
• Supplementing key NAD⁺ intermediates (Nicotinamide Riboside) can restore NAD⁺ levels and ameliorate age-associated pathophysiologies.”

I know Nicotinamide Riboside sounds pretty exotic, but it is actually just a variant of regular old vitamin b3.

In fact, Vitamin B3 – otherwise known as niacin – can also increase NAD+ levels(S).  However, Nicotinamide Riboside raises NAD+ levels to a higher level than any other available substance.

So technically you could use a flush-inducing Niacin supplement or the flush-free Nicotinamide(wiki) and MAYBE, just MAYBE –if you keep your fingers crossed – you can raise NAD+ to appreciable levels.  Of course that is assuming that you don’t have any obstructed pathways in your body that would prevent the natural conversion…Just saying…

Whether you choose the JET (Niagen) or the BICYCLE (Niacin), it is definitely worth optimizing NAD+.

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7) Astaxanthin – Now for the grand finale, I am proud to present to you ASTAXANTHIN!

This is my new favorite supplement.

Astaxanthin is a carotenoid that is naturally found in shrimp, salmon, algae, lobster, crab, flamingos, krill, and more!

Astaxanthin boasts an EXTREMELY HIGH antioxidant capacity:

“The ROS-scavenging capacity is 6000 times that of Vitamin C, 800 times that of coenzyme Q10, 550 times that of Vitamin E, 200 times that of polyphenols, 150 times that of anthocyanins, and 75 times that of α-Lipoic acid”  (O_O)  Woah.

Astaxanthin also:

• “Plays a role in preventing atherosclerosis(wiki) by raising good cholesterol (HDL) while lowering bad cholesterol (LDL) and by reducing the oxidation of apolipoprotein – which are responsible for binding and transporting fats.
• Maintains eye and central nervous system health.  It is one of the few antioxidants that can enter the retina and prevent oxidative damage!  It is also prevent and treat macular degeneration.
• Is a potent anti-inflammatory and pain-reliever.  It does this by inhibiting cyclooxygenase 2 (COX2) enzyme activities, which are related with many diseases, such as osteoarthritis, rheumatoid arthritis, dysmenorrhea, and acute pain.
• Affects multiple cytokines, like nitric oxide, interleukin 1-β, prostaglandin E2, C-Reactive Protein (CRP), NF-κB, and TNFα.
• Activates T-cell and inhibits autoimmune reactions.
• Is synergistic with water-soluble antioxidants. “When combining lipid-soluble antioxidants (such as astaxanthin) with water-soluble ones (such as ascorbic acid) in lower concentrations, higher efficiency on ROS removal may be expected.
• Is anti-cancer!

Astaxanthin has a 5 step plan for dealing with cancer(S):

1. It prevents cancer initiation by alleviating DNA oxidative-damage.
2. Then it promotes early check and elimination of cells undergoing malignant transformation by activating immune surveillance.
3. Next it prevents cancer cell growth in cells by boosting immune detection.
4. Then it inhibits rapid tumor cell growth by blocking tumor cell reproductive cycle and inducing tumor cell apoptosis.
5. Finally it prevents tumor cell spreading by decreasing tumor cell’s tissue-melting proteins.

It also increases mitochondria biogenesis through – can you guess it???- PGC-1α(S)(S)!

To top it all off, Astaxanthin shows NO SIDE EFFECTS or NEGATIVE RESULTS(S)!!!”

Wow.

What else is Astaxanthin capable of??

Well..

Do you remember, in “Mitochondria – Fix your ATP, Fix your Life,” when I promised that in Part II, which is this article, I would show you guys a key antioxidant that is able to mitigate sun exposure and fit in quite nicely with enhancing mitochondria?

See, I did say that…

Well this is it!  Astaxanthin protects the skin from the harmful effects UV-rays(S)(S)(S)

Believe it or not, this is just the tip of the iceberg folks.

To sum it up,

Astaxanthin kicks Ass!

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You now have many options to increase your Mitochondrial Biogenesis!

Combine a few, or combine them all!  Just be sure to DO SOMETHING!

That concludes this article!

I hope you guys enjoyed it.  If you have any questions be sure to leave a comment below.

Yours truly,

-Matt

P.S.  I alluded to Austin Powers 3 times in this article.  Let me know if you caught all of them!

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Photo Credits: Miguel Ugalde, Amenic181, Eyup Salman,

Bugtiger, Feelart, Graur Codrin,

Think4photop