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PQQ, Berberine and Other Mitochondrial Enhancers

Your diet is one of the most important tools you can use to take control of your health. But supplements can also be useful, especially when it comes to improving mitochondrial function. In this interview, Dr. Michael Murray, a naturopathic physician and author of several books, discusses some of the most useful supplements for mitochondrial optimization, including PQQ and berberine. 

Murray graduated from Bastyr University in 1985 — the oldest naturopathic university in the U.S. and widely regarded as one of the best — and has also served on Bastyr's faculty and board of trustees during his 30-year career.

"As I was going through my education process in the early '80s, it occurred to me that if natural approaches to health and healing are based upon truth that they should be able to explain with modern scientific thought," he says. "Over the last 35 years, I personally gathered 70,000 scientific articles, which support the use of diet, lifestyle, attitude adjustment and the proper use of dietary supplements to promote health and healing. 

It's from this database that I have written over 30 books that have been instrumental in bringing many safe and effective products to North America; things like ginkgo, St. John's wort, quercetin, curcumin, deglycyrrhizinated licorice (DGL), enteric-coated peppermint oil, glucosamine sulphate, PGX and PharmaGABA. These are just some of the products I helped introduce." 

The Benefits of PQQ

PQQ stands for pyrroloquinoline quinone. This compound was identified as an essential nutritional component in 1994. Eventually, it will be classified as a vitamin. It's particularly important for the health of the mitochondria. "It appears that PQQ is really the spark of life," Murray says. "Our mitochondria definitely require this compound to produce energy. It's also critical in protecting the mitochondria from damage." 

Mitochondrial DNA is quite prone to damage from free radicals and pro-oxidants. Most of the free radicals in the body are produced within the mitochondria themselves, which is why they're so susceptible. The free radicals are an unavoidable artifact of burning food for fuel, and your food is ultimately metabolized in your mitochondria. 

PQQ has been shown to protect against this kind of damage. PQQ is found in minute quantities in food, but research shows that when taken in supplement form, you can dramatically boost your PQQ level and really see remarkable effects. While your mitochondria are susceptible to damage, they also have built-in repair and replication mechanisms. The key is to activate those mechanisms, which is what PQQ allows you to do. Murray explains:

"Reactive oxygen species (ROS) are produced during energy production. There are mechanisms that the mitochondria use to protect itself. One of those mechanisms is PQQ. I know your audience is very familiar with the term "antioxidant." The thing is everybody thinks all antioxidants are the same. They're really not. You have to look at the type of pro-oxidant and free radical that is involved.

You have to look at how many times an antioxidant can be used to really get a sense of how profound it is in protecting our cells. PQQ is really a profoundly effective antioxidant. Every time an antioxidant neutralizes a free radical, that's called a catalytic conversion. Some antioxidants just aren't used very often.

For example, vitamin C is only capable of going through four catalytic conversions. That means after it's used four times, it's no longer effective as an antioxidant. The number of catalytic conversions that PQQ can be utilized for is in the realm of over 20,000 times … It also plays a huge role in a process called mitochondrial biogenesis (regeneration of new mitochondria).

It does a great job in killing off mitochondria that are not functioning properly and then stimulating the replication of the healthy mitochondria. It's really a cellular regenerator. It does this through its action on mitochondria. This is really exemplified in studies that have looked at the influence of PQQ in enhancing brain function and brain connections, and forming new brain cells. That translates to just having your brain function at a much higher level." 

The Role of Polyphenols for Health

Before we go further, I want to remind you that indiscriminately suppressing free radicals with general antioxidants is typically not a good idea. Yes, free radicals are often considered damaging, but the same can be said for exercise. It too causes damage if done excessively without enough recovery. The key is moderation and balanced recovery.

ROS are actually important biological signaling molecules. If you indiscriminately suppress their formation, you can interrupt profoundly important biologic pathways. So, there's a fine balance to prevent damage. This is one of the reasons why I recommend focusing on your diet. When you eat a diet high in healthy fats, low in net carbs, with moderate amounts of protein, you naturally limit the production of ROS in the first place, which means you typically don't need to worry about excessive damage taking place.

Additionally, an alternative to using a potent antioxidant like PQQ is to use hormetic agents such as molecular hydrogen, CBD oil — both of which activate the Nrf2 pathway — and resveratrol (found in grape skins, for example). Hormetic agents are not antioxidants by themselves, rather, they induce oxidative stress on the system that causes your body to produce its own antioxidants. This helps ensure a more ideal balance of free radicals and antioxidants. 

As a quick side note, increasing Nrf2 — a biological hormetic that upregulates superoxide dismutase, catalase and all the other beneficial intercellular antioxidants — is helpful mainly because it lowers inflammation, improves your mitochondrial function and stimulates mitochondrial biogenesis. Both PQQ and berberine (discussed below) have a positive effect on Nrf2 expression. Murray weighs in on this subject, saying:

"Flavonoids, polyphenols, are quite interesting to mitochondrial function. There's wisdom in the body. There's wisdom in nature. If we look at the way flavonoids are transported in the body, they are not transported in a free form. They are bound to either sulfur or glucuronic acid. In this bound form, they become inactive. 

This is really important because we want to make sure that when we take something that is getting delivered not only to the tissues but also to the cell and to the parts of the cell that really needs the greatest support. The latest science shows that when we ingest these polyphenols — whether they come from grapes, berries, raw cacao or any of the other rich sources — they are bound to glucuronic acid and they are inactive. 

But at sites of inflammation, sites of infection, or when cells aren't functioning properly, the cells release an enzyme called glucuronidase. This liberates the flavonoid or polyphenol and allows that polyphenol to enter the cell, enter the mitochondria and affect change. This has been demonstrated with mitochondria. It causes mitochondria to experience stress. 

When the mitochondria experience that stress, it causes release of glucuronidase, and that ultimately leads to flavonoids entering in the mitochondria, protecting the mitochondria from free radical damage, and actually activating certain genomes that will allow the mitochondria to function much more efficiently and to reduce the inflammation and the stress."

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