By Dr. Mercola

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."

PQQ Boosts Brain Health

So, it's important to get the right type of antioxidants and not just use a shotgun approach where you're loading your body up with them. For health, you really need targeted support for key cellular compartments, especially your mitochondria. As for PQQ, Murray notes that PQQ is stored in your mitochondria, where it is used appropriately. "When you supplement with PQQ, it increases the number and the health of your mitochondria, which in turn increases the need for PQQ," he says.

Both animal and human studies using doses between 10 and 20 milligrams (mg) of PQQ shows significant improvement in mental processing and memory.

One study using the Stroop test found PQQ in combination with Coenzyme Q10 (CoQ10) produced better results than either of these nutrients alone, so there appears to be some synergistic effects with CoQ10. (The Stroop test is where you're looking at words spelling out various colors while the word itself is also colored. You're supposed to name the color you see. The test is timed, which gives you an indication of your brain's processing speed.)

"A lot of times the energy production [in the brain] is turned down like a dimmer switch. What PQQ, CoQ10 and other mitochondrial enhancers do is they basically just brighten up the brain. They turn up that dimmer switch. They increase the energy production in the brain cells, so that they function more efficiently.

That leads to better memory, better cognitive function and feeling better as well," Murray says. "That's what they're showing with these clinical studies with PQQ. In regards to brain health, these studies have used a combination of [a daily dose of] 20 mg of PQQ with 300 mg of CoQ10."

I recommend using the reduced form of CoQ10, called ubiquinol, as it is more readily available for your body. It's fat-soluble, so it's best taken with a small amount of fat in your meal rather on an empty stomach. In addition to being a powerful antioxidant in its own right, CoQ10/ubiquinol also facilitates the recycling (catalytic conversion) of other antioxidants.

PQQ Lowers Inflammation and Improves Blood Lipids

Research looking at PQQs influence on energy metabolism and markers of inflammation showed a single dose was able to dramatically lower C-reactive protein, a marker for inflammation. Other studies have shown it lowers low-density lipoprotein (LDL) cholesterol on par with statins, but without any side effects. "I think the list of potential applications for PQQ is extremely long," Murray says.

"If you look at some of the metabolic effects of PQQ, they go well beyond improving mitochondrial function. PQQ can lead to activation of an enzyme called adenosine monophosphate-activated protein kinase (AMPK). This enzyme, I think, is really a molecular target for modern humans.

As we age, the level of this enzyme drops. Certain dietary practices — too much of the wrong types of fats, not enough of the good types of fats, not enough of the flavonoids, not enough of the metabolic enhancers and mitochondrial enhancers — lead to a reduction in AMPK activity.

Insulin resistance is probably the major cause of reduction in AMPK activity. This enzyme plays a huge role in body fat composition. In your body, it plays a huge role in inflammation [and] blood lipids. It's not surprising with PQQ activating this enzyme that we see improved blood sugar control, we see excess body fat, particularly visceral fat, decline, and we see drops in LDL cholesterol."

How PQQ Helps Lower Risk of Parkinson's and Alzheimer's

AMPK also stimulates mitochondrial autophagy (mitophagy) and mitochondrial biogenesis, as well as five other critically important pathways: insulin, leptin, mammalian target of rapamycin (mTOR), insulin-like growth factor 1 (IGF-1) and proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α). According to Murray, it also increases nerve growth factor and helps protect against the type of oxidative stress that leads to Parkinson's disease.

One of the mechanisms by which it does this is by protecting against the self-oxidation of a gene called DJ-1, which is damaged by various compounds. When damaged, it leads to Parkinson's disease. According to Murray, PQQ has been shown to be protective against every known inducer of damage to DJ-1, including mercury and other heavy metals, as well as a variety of neurotoxins.

"[PQQ] protects against the development of alpha-synuclein, a protein associated with Parkinson's," Murray says. "It also protects the brain from the development of Alzheimer's disease [via] multiple mechanisms, including protecting the formation of beta-amyloid [and] the damage that beta-amyloid can cause in the brain.

It's really far reaching. I think that PQQ is going to be a real superstar in the dietary supplement field. It's really going to revolutionize natural therapies for many different health conditions.

We highlighted its synergy with CoQ10. I think we're going to learn that various cocktails of PQQ in combination with other compounds are going to produce better results than PQQ on its own. It makes a lot of sense when you start digging in and looking at how PQQ works, and how it's synergistic with all these other wonderful compounds that we have available to us now."

The Benefits of Berberine

Another beneficial and vastly underappreciated supplement is berberine. It has many of the same benefits as the diabetic drug metformin, but without the drawbacks and side effects. Historically, berberine-containing plants such goldenseal, goldthread, Oregon grape root and barberry have been used in the treatment of Type 2 diabetes, gastrointestinal infections, liver problems and a number of other health conditions.

Berberine is an alkaloid, which tend to be stronger in their effect than the flavonoids. Flavonoids are neutralized fairly quickly in the body by binding to glucaronic acid or sulfur. Alkaloids circulate in two to three forms and therefore tend to be stronger. Like PQQ, berberine benefits mitochondrial function and is a powerful AMPK activator.

"The research on berberine right now is really focusing on its ability to improve blood sugar control, to lower blood pressure and cholesterol. If this were a drug, it'll hit big numbers, because it's kind of a holy grail. The drug companies would love to have a drug that would hit that triad of high blood pressure, high cholesterol and Type 2 diabetes.

There were 27 double-blind, placebo-controlled trials with berberine for those conditions. The results were on par with the individual drug for those three conditions (metformin, statins and blood pressure-lowering drugs) … You're looking at clinical trials involving thousands of patients now. The results show [berberine is] very safe [and] a very effective natural alternative to drugs used for these common conditions."

The typical dose is 500 mg of berberine two or three times daily. It's best taken right before meals as it also helps improve digestion and will address parasitic infections in the gastrointestinal tract.

Berberine is actually poorly absorbed by your body, and many of its benefits appear to be related to its beneficial impact on the gut microbiome, which we now know plays an important role in metabolism and even insulin sensitivity. In addition to its beneficial effects on blood pressure, cholesterol and blood sugar, berberine is also a powerful neuroprotector, in part by improving mitochondrial health and function.

The Benefits of Mulberry Leaves and Grape Seed Extract

Another plant that can help improve blood sugar control is mulberry leaves. Murray cites a study in which mulberry leaves were compared to glyburide, a Type 2 diabetes medication, and mulberry performed far better than the drug. In addition to improving blood sugar control, lowering A1C levels and improving fasting blood sugar levels, mulberry also increases the level of antioxidants in your blood and lowers both LDL and total cholesterol.

"It just seems to work much better than the drug," Murray says. "It's just that there's no money to advertise mulberry or mulberry extract. It's really a very important approach I think. [Berberine and mulberry] are good answers for these epidemic conditions that people are suffering from out there, whether it's high blood pressure, high cholesterol or diabetes."

Murray also cites research demonstrating the effects of grape seed extract on high blood pressure. Two double-blind studies found 300 mg of grape seed extract per day lowered blood pressure in people with mild to moderate hypertension, bringing them back into the normal range. "We're not talking about a few points that we typically see with some of the natural approaches. We see dramatic clinically relevant reductions just by taking a simple dietary supplement," he says.

"My key message is that there are safe and effective alternatives [to drugs]," Murray says. "We use those safe and effective alternatives until the diet and lifestyle and attitude adjustments have a chance to take hold. But we don't lose focus. We focus on those real key areas that really lead to the condition arising in the first place — diet, lifestyle and attitude."

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"In this day and age, people have fallen in love with technology. I love technology as much as anybody, but the greatest technology in the universe is nothing that man has created; it's nature," he says.

"The way in which we commune with nature on a daily basis is through the food we eat. It's truly amazing and beautiful and just harmonious the way in which food is designed to work in our body. We need to make healthier food choices.

We need to take advantage of some of these concentrated nutrient-dense foods, and when appropriate, use effective herbal approaches and supplement approaches to try kick-start our health — really make dramatic improvements, and avoid the use of potentially harmful pharmaceuticals."