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Editor’s Notes: This post was updated March 24, 2019.
Pyrroloquinoline Quinone (PQQ) is a substance that is neither antioxidant nor vitamin, but rather a cofactor for enzymes that enhances the formation of new mitochondria and increases cellular energy production. It works much like an antioxidant, as it does help with the biogenesis of mitochonidria and provides many of the same types of benefits. It is also a recommended supplement on the popular Cusack Protocol for Ehlers-Danlos Syndrome (EDS).
PQQ is an essential nutrient, meaning your body cannot make its own. It is a natural substance that can be found in many plants in varying quantities. It is especially concentrated in fermented foods, soybeans, spinach, field mustard, green tea, green peppers, parsley and kiwi. However, the PQQ content of these foods is minuscule in comparison to the amount you can get from a supplement (5-20mg) and this is what I recommend for spoonies and zebras alike who hope to reap its many benefits.
The Benefits of PQQ Supplementation
For Zebras and spoonies, there are many benefits to taking PQQ. Although much research still needs to be done on this substance, it is clear from the research done to date that it has a powerful effect on the multiplication of our mitochondria, protects us against free radicals, significantly decreases inflammation, improves cognitive function and memory loss, improves sleep issues and more.
In trials, Healthy humans who took 20mg of PQQ (for a 150-pound male) resulted in significant decreases in the levels of C-reactive protein (by 45% after 3 weeks) and IL-6. A lower dosage didn’t decrease inflammation (R). Reduced inflammation can mean a reduction in a number of symptoms for us, including pain, stiffness, headaches, fever, fatigue, swelling in any number of major body systems, and loss of appetite.
At 10 weeks on PQQ at 20 mg per day, everything I am experiencing bespeaks to a significant reduction in inflammation and it was exactly what I needed to take my wellness to the next level. I’ve been struggling with inflamed bowels (especially my colon) for so long, my stools (when I actually managed to produced a solid one) would come out pencil thin. Now, I actually have normal sized stools and for the first time in years, I am without constant abdominal pain. I’m also experiencing a significant reduction in head pain, just as I always have with the introduction of steroids capable to breeching the blood/brain barrier. Even the osteoarthritis pain and redness in my knees has become significantly reduced. The only drawback that I can tell to this significant reduction in inflammation is that my joints seem to be slightly less stable, something I’m working to resolve through exercise.
In the same study, various urinary markers of oxidative stress also improved, which is consistent with enhanced mitochondria-related functions (R). Too much oxidative stress can cause cancer, brain disorders, heart problems, and more. Cell death and loss of cell production are the primary mechanisms of aging, so PQQ can only benefit your long term health.
Along similar lines, PQQ also helps your body generate new mitochondria, something thought impossible until recent times. The creation of new mitochondria by PQQ occurs through the activation of CREB and PGC-1alpha, pathways known to increase mitochondrial biogenesis (R). PGC-1a is a “master regulator” that directly stimulates genes that promote mitochondrial and cellular respiration, growth, and proliferation (R).
As a result of activation of the PGC-1alpha pathway, PQQ increased NRiF-1 and NRF-2, proteins (transcription factors) that protect us from free radicals by increasing our internal antioxidant production and can protect us from toxins, UV, etc. and we have a particular need to protect ourselves against these harmful outside influences as our bodies can be particularly sensitive to environmental factors.
By increasing cellular metabolism, it favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity. Great news for those of us who struggle with hormone regulation, dysautonomia and dietary issues that make regulating these things difficult. It took a full 8-10 weeks to begin to see the autonomic benefits of taking PQQ, but my blood pressure is coming up, my need for medication is decreasing and unlike the past, the more activity I do does not equate to needing to take in more electrolytes or medication to keep my autonomic system stable. Not only am I seeing less dizziness, I’m seeing a lot less fatigue and at 10 weeks, post-exertional malaise seems almost a thing of the past. I even went hiking and felt only a slight drag on my energy levels the next day, but was able to operate normally the next day and was back to normal the day after. Just last year, hiking itself would have been completely out of the question and a trip to the grocery store would have required a day of rest to recuperate. Of course, it’s not the PQQ alone that got me here, but it certainly was the final step.
PQQ can also give you a big boost in the area of cognitive function and memory. PQQ triggers the DNA reading protein CREB, which plays a key role in growth and gene expression. CREB also stimulates the growth of new mitochondria and increases BDNF (R1, R2). It also stimulates the production and release of nerve growth factors in cells that support neurons in the brain and increases Schwann cells by increasing the PI3K/Akt signal pathway (R). PQQ also prevents aggregation of alpha-synuclein and amyloid-beta, proteins associated with Parkinson’s and Alzheimer’s diseases, respectively (R1, R2). It also protects nerve cells from the toxic effects of the proteins that are already there and is a neuroprotective compound that has been shown in a small number of preliminary studies to protect memory and cognition in aging animals and humans (R). It’s no wonder then that it has been shown to reverse cognitive impairment caused by chronic oxidative stress in animal models and improve performance on memory tests (R1, R2).
Changes in cognitive function seemed most remarkable at three and eight weeks, though they are gradual and subtle. I began to notice that I had an easier time remembering things without referring to my calendar or relying on my GPS. My writing is becoming clearer and requires less editing and my verbal communication skills are much smoother because I don’t have to hunt for words. It’s actually a pleasure to engage in conversation and I no longer fear sounding like an idiot when dealing with people face to face. I can even “multitask” again.
PQQ improves sleep quality and lessens the time it takes to fall asleep. One open-label human study conducted with 20mg PQQ for 8 weeks in 17 persons with fatigue or sleep-impairing disorder noted that PQQ was able to significantly improve sleep quality, with improvements in sleep duration and quality appearing at the first testing period after 4 weeks. It also led to a decrease in the time it took to fall asleep but required 8 weeks to reach significance. This has been my experience, as well. I first noticed a change in the amount of time it took me to fall asleep and I felt more refreshed in the morning. Soon I realized that I was no longer waking up to the sound of every little noise, or my husband turning or snoring. I don’t think I sleep more, but the quality of my sleep has definitely improved.
There is also evidence that PQQ can improve immune resistance. Depriving mice of dietary PPQ causes abnormal immune function e.g. dysfunctional immune response to stressors (R, R2). The addition of PQQ to the diet of mice increased levels of CD8+ cells and lymphocytes, which are important immune regulators (R). Since we all suffer some level of immune deficiency in EDS, everything we can do to boost immune response is always a good thing. I’m not sure I can speak to increased immune health or not, though I can say that I’ve been working with the general public for a month now and I’m happy to say that I have yet to pick up any illnesses. I’ve even had a couple of customers warn me that they were ill and my stepson came down with a terrible cold a couple of days after I saw him a few weeks ago, but I have yet to develop any symptoms. In the past, I may not have been so lucky as I often caught every little bug to which I was exposed
If you’re actually deficient in PQQ it could be affecting your gene expression, which is quite possible in EDS, as many of us suffer from a plethora of deficiencies due to gastrointenstinal dysfunction of one kind or another. PQQ depletion affects the way many genes are expressed (2.38% of genes studied) (R). One key gene affected by PQQ is PGC-1a. By activating PGC-1a, PQQ causes mitochondrial biogenesis, as well as a host of other beneficial effects (R).
How to Take PQQ
In a human study, 20mg PQQ caused no toxicity or adverse symptoms when taken over a 12 week period. Similarly, another study found that a week’s consumption of up to 0.3mg/kg PQQ (20mg for a 70kg male) is perfectly safe (R).
Recommended doses I have seen range from 2mg up to 40mg per day. I take a 20 mg capsule each morning.
Some articles recommend that PQQ be taken with Co-Q-10, however I have found nothing that states it’s necessary for it to do its job. One study simply saw more dramatic results with the combination, which makes sense, as Co-Q-10 is an antioxidant with common effects.
Possible Side Effects
At this time, headache was the only side effect I could find, and it was said to indicate that the dose is too high. In all honesty I have been dealing with low grade headaches over the last several months, but what I’ve dealt with for years are severe migraines, so there’s nothing that indicates to me that it’s the PQQ causing these headaches at 20mg. If anything, I feel like these headaches are what my migraines have become with the relief of the inflammation I usually have and I’m working with a headache specialist to try to resolve them.
Warnings and Contraindications of Use
Extremely high IV doses of PQQ (500-1000mg/kg bodyweight) can cause death in rats (R, R2). Additionally, almost all of the substance appears to be metabolized by the body before being passed. Additionally, even a 2mg dose appears to have benefits, so starting out low and working your way to a higher dose to find the optimal dosage, up to 40 mg, may be the best way to go for the sake of safety.
As with all supplements, consult your physician about taking this medication to be sure it’s right for you and won’t mix poorly with any of your current medications.
At this time, there are no known drug interactions with PQQ: However, that doesn’t mean there aren’t any, so proceed with caution and pay careful attention to how you feel. As with all new supplements, follow my protocol for testing new supplements.
I’m updating this post on March 24, 2019 with the name brand information of the PQQ I took so you can begin with a reliable brand. In the spirit of full disclosure, if you purchase from one of the links below, I will receive a nominal payment for the sale.
PQQ 20mg 120 Vegecaps (Pyrroloquinoline Quinone)by Health Through Nutrition was my first choice for affordability and quality in this supplement.
Now PQQ Energy,30 Veg Capsules While I’ve never taken Now’s PQQ, I’m quite comfortable offering it as a suggestion. I’ve taken many of Now’s products and have always been satisfied with the quality and efficacy.
Since there’s some debate about the efficacy of PQQ being reliant on CoQ10, or at least boosting its power, here are some combo products from makers I approve of. Note that I chose ubiquinol (the active form of CoQ10) as it may be a lot easier to absorb and utilize. For maximum absorption of ubiquinol or CoQ10, note that piperine should be added and while it hasn’t been studies, there’s a possibility it could be helpful in absorbing PQQ as well. Piperine can also increase the absorption of curcumin. The two brands below are well trusted, affordable and reliable.
PQQ + CoQ10:
Doctor’s Best High Absorption CoQ10 plus PQQ, Gluten Free, Naturally Fermented, Vegan, Heart Health and Energy Production, 60 Veggie Caps These capsules come complete with 20mg PQQ, 100mg CoQ10 and 5mg piperine all in one convenient capsule. I prefer to take 200mg of CoQ10 per day, but with the combination of PQQ and CoQ10 with the piperine to boost absorption, you may find 100mg of CoQ10 to be more than sufficient.