You know that feeling when you don’t want to be anxious, but your body has a mind of its own?
You psyche yourself up: “I’m brave, I can do this, I’m normal!” But then your brain and body just flip out anyway.
I know this too well. I had all the following symptoms a few years back.
Unwilling quivering, twitching, trouble holding eye contact, neck tightness, inner tension, etc.
Embarrassing to admit, but that happens when you have…
Low energy is a result of inadequate mitochondrial function.
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Quick recap on energy production
Your body produces energy, ATP, predominantly from glucose and fat.
Glucose and fat circulate in the blood and are taken up by the cells to produce energy. Both can be stored in the cell, in the form of glycogen and triglycerides respectively.
Glucose is broken down by glycolysis in the cytosol to produce pyruvate. Pyruvate is then transported into the mitochondria, where it’s converted to acetyl-CoA by pyruvate dehydrogenase, the rate-limited step in glucose oxidation. Fat is transported via the carnitine transporter into the mitochondria where it’s broken down by beta-oxidation into acetyl-CoA.
Acetyl-CoA enters the Kreb cycle to pump out NADH and FADH2, which feed into the electron transport chain to produce ATP. This whole process is called oxidative phosphorylation since it uses oxygen to produce ATP.
When energy production goes haywire
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When your mitochondria can’t produce energy sufficiently, many bodily functions start to suffer.
You might start to suffer from:
- Brain fog
- Memory loss
- Cogntive deterioration, which can eventually lead to neurodegeneration, such as Alzheimers, Parkinsons, dementia, Shizophrenia, etc.
- Fatty liver
- Kidney problems
- High cholesterol
- High uric acid
- Fat gains, etc, etc.
But to bring it back on topic, this study below shows very nicely that impaired mitochondrial function leads to anxiety and subordinance.
“Further insights for a key role of mitochondrial function in specific brain regions in influencing complex social behaviors have been provided by a series of studies in rats relating anxiety with diminished social competitiveness (Hollis et al., 2015; van der Kooij et al., 2017), a phenomenon that has also been highlighted in humans (Goette et al., 2015). In rats, lower mitochondrial function in the nucleus accumbens was observed in high-anxious animals compared to their less anxious littermates, and was causally implicated in their low social competitiveness (Hollis et al., 2015). More specifically, high-anxious animals that are prone to become subordinate during a social encounter exhibited reduced mitochondrial respiratory capacity, decreased ATP levels, and increased ROS production in the nucleus accumbens. Furthermore, micro-infusing specific mitochondrial electron transport chain inhibitors into the nucleus accumbens reduced social rank, recapitulating the low probability to become dominant in anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in anxious rats (Hollis et al., 2015). Additionally, treatment with a low dose of the anxiolytic diazepam was effective to facilitate social dominance, ameliorating both the competitive disadvantage and low mitochondrial function in the nucleus accumbens displayed by high-anxious rats (van der Kooij et al., 2017).” (R)
So, improving the redox balance (NAD to NADH ratio with niacinamide for example) and supporting the electron transport chain improves energy production and prevents the development of anxiety and subordinance.
- The biggest missing links to optimal brain function – part 1 (carbs)
- Hypo-intellectism: is hypothyroidism the cause? – part 2
It all comes down to energy production
This segment is exactly what I wrote in last week’s (13/8/2021) newsletter (you can check out all my old newsletters here).
Everything comes down to energy production. If your cells can’t produce energy properly, your muscles can’t contract, your testes can’t make testosterone and DHT, your adrenals can’t make DHEA and cortisol, your brain can’t make dopamine, etc. And also, your cells can’t respond to the messengers.
One example of this is that when brain function starts to go backwards, initially, messengers go up, because the cell can’t respond to them; for example, dopamine and glutamate. This can lead to neurotoxicity. Taking piracetam, which enhances the structure and energy production of the cell, restores the sensitivity to these neurotransmitters.
On a different note, a lot of people in the brain optimization sphere are obsessed with neurogenesis. Lion’s mane is often top of the list for this. However, neurogenesis is dependent on proper mitochondrial function and energy production, so if energy is low, neurogenesis will be suboptimal (R). This is why thyroid hormone, T3, significantly upregulates neurogenesis, because it enhances cellular function and energy production.
The best place to start for optimizing cellular energy production is via diet and lifestyle optimization. Removing all foods that are gut-irritating would be step number one (since any low-grade inflammation will inhibit proper cellular function). Adding in easy-to-digest nutrient-dense foods is step number 2. Step 3 is to remove all toxins, such as mold, plastics, chemicals, etc. since they also inhibit cellular function.
All of these aspects (and more) are discussed in the Alpha Energy Male Course.
How to optimize mitochondrial function for less anxiety
For starters, eat enough protein and carbs. The brain gobbles up glucose, so be sure to give it enough.
Secondly, get enough micros, namely your vitamins and minerals. They are cofactors for almost all processes in the body, so if they are inadequate, don’t expect optimal functioning. If you think your diet is “good”, please check it on cronometer (I’m sure most people will be surprised to see that it’s not as good as they thought) or do an organic acid test (Genova ION panel for example), which will show you which micros are missing.
Thirdly is to eliminate toxins, as I mentioned above.
That will be your foundation.
Then you can add extra supplements to optimize cellular function and ATP production.
My starter stack would be CoQ10, niacinamide, magnesium, vitamin B1, pyrucet, piracetam and methylene blue.
CoQ10 (100-300mg) is essential for complex I and II of the electron transport chain. Without enough CoQ10, NADH will accumulate, NAD will decline and an excess of ROS will be produced. (iHerb, Amazon)
Niacinamide (100-500mg) helps to increase NAD, which shifts the redox balance towards oxidation and this enhances energy production. Niacinamide has long been used to reduce anxiety (R, R, R) (iHerb, Amazon)
Magnesium (1-2g) and vitamin B1 (100-600mg) are cofactors for pyruvate dehydrogenase (PDH), the rate-limited enzyme in glucose oxidation. If PDH is working suboptimally, ATP production drops and lactate production goes up. Lactate has also been shown to cause anxiety (R). Both thiamine (doses of 250mg/day) and magnesium are effective against anxiety (R, R). Niacinamide helps to increase NAD, which shifts the redox balance towards oxidation and this enhances energy production. Niacinamide has long been used to reduce anxiety (R, R, R) B1 (iHerb, Amazon) – magnesium (iHerb, Amazon)
Pyrucet (10-25 drops) is a product that contains ethyl pyruvate (EP) and ethyl acetoacetate (EA). EP stimulates PDH and EA improves the NAD to NADH ratio, thus enhancing glucose oxidation. I frequently use this product as a nootropic.
Piracetam (I like 100mg sublingually) as I mentioned above, improves cellular structure, which improves energy production and sensitivity to neurotransmitters. Piracetam has been shown to have anti-anxiety effects in rats (R). Piracetam can also potentiate the effects of other compounds, such as ketamine, most likely by improving the function of the cell (R).
Methylene blue (MB) (1-10mg) is an electron acceptor, which supports dysfunction complexes of the electron transport chain, and also speeds up ATP production, but speeding up cytochrome C oxidase. MB is also becoming more and more popular as a nootropic. (Amazon)
Lastly, two other things I also discussed in the newsletter were uridine and testosterone.
Triacetyluridine (a more oral bioavailable form of uridine) rescues brain energy deficiencies, mainly by rescuing defective oxidative phosphorylation (R, R). This is one of the reasons why it has a mood uplifting effect. (iHerb, Amazon)
Testosterone has been shown to improve mitochondrial function by enhancing the function of certain complexes of the electron transport chain.
“We investigated the effects of testosterone supplementation on mitochondrial complex V function in the substantia nigra (a brain region that regulates motor activity) in aged male rats. These rats exhibited diminished ATP levels, attenuated mitochondrial complex V activity, and reduced expression of 3 of the 17 mitochondrial complex V subunits (ATP6, ATP8 and ATP5C1) in the substantia nigra. Testosterone supplementation increased ATP levels, mitochondrial complex V activity, and ATP6, ATP8 and ATP5C1 expression in the substantia nigra of the rats. Thus, testosterone enhanced mitochondrial complex V function in the substantia nigra of aged male rats by upregulating ATP6 and ATP8. As potential testosterone targets, these two subunits may to some degree maintain nigrostriatal dopaminergic function in aged males.” (R)
There are many other compounds that can also improve energy production and the function of the electron transport chain, but I only wanted to focus on the basics in this article.
Remember, diet and lifestyle come first, then supplements.
You can also check out my Instagram post on this by clicking on the icon below.
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