Pomegranate to feel supercharged – a potential solution to chronic fatigue and brain fog.

For the last few years I have dealt with chronic fatigue. I would sleep a full 8 hours, and wake up feeling more tired than when I went to sleep. I don’t have sleep apnea, and overall, I’m very healthy – within a normal weight, exercise 5-6 days a week, and in my early 30s. Furthermore, throughout the day I would need to nap because my brain was just tired — even when doing nothing. I had “brain fog” in the truest sense of the word. Recently, I changed my diet and have been absolutely astounded by the results — and my change in energy. When I wake up, my brain is instantly on. My energy levels are through the roof. Amazingly, this is even the case with interrupted sleep or very short sleep windows (e.g., 3-5 hours). Even more miraculously, this change happened within a matter of weeks within my diet change.

I began investigating the link between energy levels and pomegranate after I personally experienced outstanding energy from the addition of pomegranate to my morning smoothie. (Side note: my testing indicates that it was either the addition of pomegrante or wild blueberries, as the absence of both led to the return of my fatigue levels — future testing required for confirmation). I have been adding about 30-50 grams of whole pomegranate arils into my daily smoothie (including the really crunchy/tough seeds), and my chronic fatigue has just melted away. Truly, it has been life changing.

So the next step was to investigate whether pomegranate has any impact? What I’ve found seems to indicate that there is a plausible mechanism of action for the effects that I am feeling through my gut bacteria. The theorized mechanism of action is called mitophagy – a process that recycles worn-out mitochondria, the tiny powerhouses inside cells that make the chemical units of energy that fuel their work.

To date, there is increasing evidence that mitophagy is significantly impaired in several human pathologies including aging and age-related diseases such as neurodegenerative disorders, cardiovascular pathologies and cancer. Therapeutic interventions aiming at the induction of mitophagy may have the potency to ameliorate these dysfunctions.

Mitophagy: An Emerging Role in Aging and Age-Associated Diseases, Abstract.

Furthermore, mitophagy has been implicated in increasing cognition and extending lifespan with a specific mechanism of action:

mitophagy stimulation induces beneficial effect including an increase in cognition and an extended lifespan in a NIX- or PINK1 and Parkin-dependent manner 

Id., BNIP3 and NIX-Dependent Mitophagy

Urolithin A is the only molecule that can relaunch mitophagy. (1). As we age, an important process that our cells rely on for energy slows down and begins to malfunction. Mitophagy recycles worn-out mitochondria. The specific mechanism of action for mitophagy is described well in the below YouTube video by Vincere Bio:

If worn-out mitochondria are not recycled, they and their decomposing components build up inside cells, eventually causing problems in many tissues, including muscle, which gradually becomes weaker.

There is also evidence that build-up of faulty or worn-out mitochondria plays a role in the diseases of aging, such as Parkinson’s disease. Scientists have also found that defects in the Parkinson’s gene Fbxo7 also disrupt mitophagy.

It is the ellagitannins / ellagic acid content of pomegranates that are converted into urolithin A by gut bacteria. But unless you have the right bacterial species in your gut, you will not be able convert the ellagic acid into the urolithin A which is required to relaunch the mitochondrial clean-up process (mitophagy).

Based on this study, it appears Clostridium coccoides or Clostridium leptum (or certain species of Ruminococcus) are what you want in your gut in order to convert ellagic acid into urolithin A.

In addition, this study says that Gordonibacter urolithinfaciens and Gordonibacter pamelaeae convert ellagic acid into urolithin A.

Lastly, this study indicates that, while not necessary for urolithin A production, people capable of producing high levels of Urolithin A production have Akkermasia Muciniphila.

Unfortunately, it doesn’t appear that any of the previously mentioned bacteria are available as probiotics, so you must have the right bacteria at this time.

Returning to my personal anecdote, the fact that pomegranate has been further linked to the production of Urolithin A is promising as a potential mechanism of action. Furthermore, my personal microbiome test (results posted below) shows that I have many of the species needed to convert ellagic acid into urolithin A:

Clostridium Leptum in my biome sample from Viome
Gordonibacter Pamelaea in my biome sample from Viome
A variety of Ruminococcus species, unclear whether any of them are significant.
I also have three species of Akkermansia, which is correlated with high Urolithin A production

Therefore, it is plausible that the mechanism of action I am experiencing that eliminates my chronic fatigue and brain fog is a result of the consistent pomegranate dosages I have been taken.

More research is needed, but for anyone suffering with chronic fatigue and brain fog, I say give 40-60 grams of pomegranate seeds a day a try. Particularly if you have already tested your microbiome and have some beneficial species.

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