Vitamin-Like PQQ Offers Antioxidant, Neuroprotective, and Mitochondrial Health Benefits

PQQ (Pyrroloquinoline quinone) may be the first new vitamin to be identified in over five decades. While the compound was first identified in 1979, its presence and function in animals has only started to be understood in the last decade. It’s been found to have antioxidant and neuroprotective properties as well as contributing to mitochondrial health. It is thought to work as as enzyme cofactor somewhat like vitamin B3 (niacin) and vitamin B2 (riboflavin) and so someday may be grouped as one of the B vitamins which, like PQQ, are also water-soluble nutrients.

(from PQQ is the first new vitamin in 55 years)

PQQ was discovered in 1979 from a bacterium, and afterward it was reported to be in common foods. Because PQQ-deprived mice showed several abnormalities, such as poor development and breakable skin, PQQ has been considered as a candidate for vitamin. It was a mystery, however, with what enzyme PQQ is connected, preventing PQQ from being recognized as a vitamin. In this study, we discovered a mammalian PQQ-linked enzyme. The enzyme was involved in the degradation of the amino acid lysine, and it required PQQ to function normally. This brand-new vitamin will be also important for humans, and we are hoping for a great contribution in medical fields.

PQQ’s Effects on Mitochondria

Recent research suggests it helps mitochondria function better (somewhat like the antioxidant and coenzyme CoQ10) and to form new mitochrondia. The mitochondria are chemical energy factories in cells. Human cells can have from a few to hundreds per cell. Aging humans suffer from damage to their mitochondria and declining numbers of mitochondria. Mitochondrial damage and depopulation is thought to be a major factor in some diseases, particularly those involving energy-intensive organs like the brain, heart, and liver. PQQ appears to both help mitochondria avoid oxidative damage and to help form new mitochondria.

Research reported in 2006 shows that PQQ-deficient mice suffer a reduction in the number of mitochondria in their liver cells:

(from Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice)

When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but otherwise nutritionally complete basal diet, it improves growth-related variables in young mice. We examined PQQ and mitochondrial function based on observations that PQQ deficiency results in elevated plasma glucose concentrations in young mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ-deficient weanling mice had a 20–30% reduction in the relative amount of mitochondria in liver; lower respiratory control ratios, and lower respiratory quotients than PQQ-supplemented mice (2 mg PQQ/kg diet).

PQQ’s Effects on Brain Function

Research published in 2007 shows that PQQ works together with CoQ10, another nutrient critical for mitochondrial function, to improve learning ability in rats and helped counter the effects of hyperoxia (elevated blood oxygen) that impairs brain function and memory by causing oxidative damage to neurons. Damage to neurons from oxidation is suspected to be involved in neurodegenerative conditions including Alzheimer’s disease and Parkinson’s disease.

PQQ supplementation appears to help form new memories in rats learning mazes.

(from Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats)

CoQ10 did not improve the learning function of the rats, so that no synergistic efficacy was observed by the concurrent supplementation of PQQ and CoQ10. At the late stage of the trials, the rats fed a PQQ-, CoQ10- and (PQQ + CoQ10)-supplemented diets showed higher learning rates than the control rats. However, the efficacies of the supplementations showed no significant difference. From these results, PQQ is likely more effective in improving the learning ability of the rats using space cognition than CoQ10 itself.

It also appears that PQQ helps retain memories despite oxidative stress on the rats.

(from Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats)

After the rats learned the location of the platform in the pool, the effect of hyperoxia as oxidative stress on memory function was assessed. When the rats were subjected to hyperoxia as oxidative stress for 48 h, they retained their memories within four days after the oxidative stress treatment. However, their memories suddenly declined five days after the oxidative stress treatment, as previously reported [8]. The rats fed either the PQQ- or CoQ10-supplemented diet showed memory retention even after the oxidative stress treatment for 48 h. Furthermore, the rats fed the concurrent diet of PQQ and CoQ10 showed marked the memory retention (Fig. 2).

PQQ In Diet

PQQ in the diet is not yet well understood. Some are characterizing it as similar to B family nutrients like biotin and folic acid in its presence in food. But PQQ easily transforms into other related compounds that may obscure the total amount of PQQ consumed, so some estimates are that the typical human PQQ consumption per day without supplements might be as high as 1 to 2 milligrams. It is believed to be well-absorbed (around 85% absorption) and not toxic in dosages of less than 60mg per day in humans based upon testing that included complete blood chemistry, liver, and kidney function tests. Some mice and rat studies suggest that the toxicity doesn’t become apparent except with daily dosages of beyond 250mg per kg of body mass.

Some foods that appear to be high in PQQ, along with approximate concentrations in nanograms of PQQ per gram of food, include:


Natto is a good source for PQQ

Natto (fermented soybeans) – 61
Parsley – 34
Green tea – 30
Oolong tea – 28
Green pepper – 28
Papaya – 27
Kiwi fruit – 27
Tofu – 24
Spinach – 22
Broad bean – 18
Potato – 17
Carrot – 17
Miso (fermented soybeans) – 17
Cabbage – 16
Banana – 13
Soybean – 9
Tomato – 9
Egg (yolk) – 7
Orange – 7
Celery – 6
Apple – 6
Egg (white) – 4
Milk – 3

It’s clear that many of the best sources of PQQ are not commonly consumed foods in most Western nations. The Japanese diet tends to include a number of foods high in PQQ, including natto, green tea, tofu, miso, and soybeans.

Of common Western foods, parsley, green peppers, and spinach are among the better sources. A little research suggests that a typical bunch of parsley weighs about 60 grams and contains about 2mg of PQQ. A whole green pepper weights about 200 grams and contains about 6mg of PQQ. A bunch of spinach typically weighs about 450 grams and contains about 10mg of PQQ. These foods have nutritional value beyond their PQQ, too, so if you like salads then consider putting in some parsley, green peppers, and spinach to help boost your intake of PQQ and other nutrients without adding much in the way of calories to your meal. I’d suggest eating them fresh as it is possible (though I’m not sure yet) that cooking will degrade the PQQ.

Where to Find More PQQ Information

The article Potential Physiological Importance of Pyrroloquinoline Quinone (PQQ) has a reasonably complete summary of recent research on PQQ, including summaries of dosage and toxicity studies in humans and animals. If you’re interested in learning more about this nutrient and are comfortable reading scientific papers then this is a good place to start.

PQQ Supplements

It is still difficult to find supplements with PQQ in them, especially outside of Japan. Life Extension has recently introduced three new product formulations with PQQ:

Mitochondrial Energy Optimizer with BioPQQ™

Mitochondrial Basics with BioPQQ™

PQQ Caps with BioPQQ™

Each contains 10mg of PQQ per dose. That’s well above the amount most people get in their diet, but not so high as to be a danger according to toxicity studies on PQQ.


Mitochondrial Basics w/ Bio PQQ - Life Extension

PQQ Caps with BioPQQ - Life Extension

Further Reading

Low Cortisol, Low CoQ10, and Mitochondrial Dysfunction Often Found in Adrenal Fatigue, Chronic Fatigue Syndrome, Fibromyalgia, and Myalgic Encephalomyelitis Patients

Potential Physiological Importance of Pyrroloquinoline Quinone (PQQ)

PQQ is the first new vitamin in 55 years

Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice

Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats


These statements have not been evaluated by the Food and Drug Administration. The products mentioned in this post and on this website are not intended to diagnose, treat, cure or prevent any disease. The information presented here is for educational purposes and does not constitute medical advice. Please obtain medical advice from qualified healthcare providers.


Comments

Vitamin-Like PQQ Offers Antioxidant, Neuroprotective, and Mitochondrial Health Benefits — 37 Comments

  1. Pingback: Free Webinar on Anti-Aging Supplements Including PQQ | EmediaHealth

  2. I purchased 4 bottles of PQQ and am hoping it will help my husband who has myopathy-severe pain for 1 year due to the drug Lovastatin which depleted the CoQ10 in his muscle cells I am speculating from all the research. He is going on Permanent disability but perhaps this will turn it around. He will be getting a muscle biopsy due to my persistence ( begging the doctor). This sheds some hope! I am wondering if he should start it after the muscle biopsy in case it may affect the results. Also is there any research on how long it may take to make new mitochondrial cells? This is exciting.

    • Susanne,

      I’ve got an answer for your question — see the end of this comment — but want to put your situation in context so other readers can understand the implications of statins, CoQ10, cholesterol-lowering therapies, and how PQQ plays in this mix. What has happened to your husband is alarmingly common. I’ve seen statins cause muscle wasting and strength, some of the symptoms of CoQ10 deficiency that they often induce, and believe this class of drugs is being pushed on the public by greedy big pharma companies and poorly trained doctors who do not understand the harm that statins can cause.

      Statin drugs are a known and well-documented cause for depleted CoQ10. They can cause a huge amount of damage by lowering CoQ10 severely. Perhaps surprisingly they can also cause damage from lowering cholesterol levels too much in some patients. That’s why I think statins should be used more as a last resort, not a mainstay therapy.

      There are so many other cholestrol-lowering supplements with solid backing in research studies that have less risk of causing damaging side effects and are inexpensive. Among these are high dosage niacin (should monitor liver function via regular
      Chemistry Panel & Complete Blood Count (CBC) blood tests
      when starting or increasing dosages until it’s clear it is not causing problems), plant sterols (they work by competing with cholesterol for absorption in the digestive tract), digestive fiber products, vitamin E tocotrienols, and red yeast rice all have good evidence for effectiveness with lower risk of side effects than statins.

      Statins are derived from a single component of red yeast rice supplements known as monacolin K — in fact US courts have ruled in favor of the FDA that red yeast rice supplements must have all lovastatin (the drug name for monacolin K) removed from them to be sold in the US, apparently to support the patent-based profits on the compound for Merck, one of the big companies that buys favoritism from the FDA and its employees via the mutually beneficial and monopolistic FDA drug study and approval process that can turn natural substances into proprietary drugs and then ban everybody else from selling or using them. This has gotten so out of control that even natural B6 vitamin variants such as pyridoxamine and pyridoxal 5 phosphate that occur in many common foods (turkey, for instance) are being targeted by the FDA and its drug industry buddies who want patents on them so they can make consumers pay a lot of money for something that is relatively cheap today.

      I pointed out this FDA situation because fundamentally the reason statins are being pushed so hard is because of the FDA and drug companies. They both stand to gain big revenue streams from the never-ending minor variants of statin drugs that the FDA charges user fees to review and the drug companies can patent and then ram down the throats of unsuspecting consumers to rip them and insurance companies off while actually in many cases hurting people’s health.

      Statins are often administered in excessive dosages. Drug companies want to make sure they will have the effect of lowering cholesterol drastically and they didn’t adequately study lower dosages. It appears the effects of statins are not linear. In other words, 20mg of a statin drug may not get anywhere near twice as much a reduction in cholesterol than 10mg, but it may have much worse side effects such as CoQ10 depletion.

      There is some evidence that the full mix of red yeast rice rather than the single component used in the statin drugs may help lower LDL cholesterol levels without as much risk. Anybody taking either statins or red yeast rice should periodically check their CoQ10 levels with a CoQ10 blood test to ensure they are not being seriously impaired. The risk of such impairment appears to be much lower with red yeast rice and low-dosage statin therapy rather than the dangerous dosages many doctors are prescribing.

      The way statins and monacolin K and also vitamin E tocotrienols work is by impeding an enzyme known as HMG-CoA reductase that participates in a chemical synthesis chain to make mevalonate which is a precursor to both cholesterol and CoQ10. That’s right, the two compounds are related! This may seem odd given how often cholesterol gets a bad rap and the praise being given to CoQ10, but in fact cholesterol is not inherently bad. If you didn’t have any cholesterol, you would die as a result. The body uses cholesterol as a precursor for steroid hormones (testosterone and its relatives and also estrogen compounds that are derived from them) and other functions in the body such as producing bile to help digest and absorb fat-soluble nutrients.

      The evidence for effectiveness for vitamin E tocotrienols is not at well developed yet as for monacolin K / lovastatin and red yeast rice, but what is neat about tocotrienols is that they are also potent antioxidants and have other health benefits as a result. Recall that one of the major theories of aging is the oxidation theory in which biochemical compounds and cells and their components are damaged by oxidation and that loading up the body with higher levels of antioxidants can slow down the aging process at a microscopic level. While I think anybody taking high-dosage tocotrienols should also monitor cholesterol and CoQ10 levels, it appears to me the extra antioxidant benefits make it very worthwhile to try this approach in combination with other cholesterol lowering techniques before resorting to statin drugs.

      There’s a supplement called Sytrinol sold by several vendors that mixes tocotrienols with citrus extracts. There are claims with research support indicating it helps lower LDL cholesterol and triglycerides and raise HDL (protective) cholesterol. The Swanson brand of Sytrinol 150mg softgels is the best priced version of this supplement that I found when I looked for it from various suppliers. There are may other brands of it, but I think they are all essentially the same except for packaging as they apparently all use the same proprietary mix owned by a company called KGK Synergize and produced by Pharmachem Laboratories. So I’d shop for this on price since there’s not likely to be much variation in the actual softgels you’d get from any vendor.

      Niacin, plant sterols, and fiber products work entirely differently than the HMG-CoA enzyme inhibitors including statins, monacolin K, and tocotrienols. They are unlikely to do anything severe to CoQ10 levels.

      Niacin’s most common side effect is an unpleasant red flushing, heat, and itching sensation — I’ve experienced this and would have been alarmed if I had not known of the effect. It seems to take about 30 to 60 minutes after consuming niacin for this effect to appear, and then it passes in about another 30 minutes. It’s not dangerous but can be annoying. Small dosages of aspirin (81mg) or white willow bark can help prevent this, as can taking niacin in divided doses over the course of the day (something that should be done anyway if you’re using standard release niacin) and consuming it along with food. High dosage niacin can cause liver dysfunction in some people, so this should be monitored. Adding in safe and widely used liver-promoting supplements like NAC and silymarin is likely to help reduce the chances of adverse affects from high dosage niacin.

      Off the top of my head I can’t think of anything really adverse likely to happen from plant sterols.

      Fiber products can produce some digestive side effects, but sometimes people actually don’t view these as side effects and instead like how fiber helps make their digestive function become more regular and consistent. Possibly the biggest risk from fiber products is choking when consuming high quantities of them. You need to take them with plenty of water.

      Eating a diet rich with fresh or steamed vegetables and fiber might be among the least risky of the approaches for treating high LDL cholesterol. That’s because most people don’t get enough of these things in the first place. Plants don’t produce cholesterol, they produce plant sterols which are chemically similar but do not have the same harmful effects in excess as cholesterol does. Certain fiber supplements like chitosan, glucomannan, and propolmannan are very good at mopping up fats in the digestive tract. This has two benefits. First, it helps impeded absorption of LDL cholesterol from foods. But even if you eat a low-cholesterol diet (say 200mg per day or less) compared to typical Westerners, you can still have high cholesterol.

      This is where the second benefit of fiber comes in. Bile, necessary for digesting fats, is a fatty substance that contains a lot of cholesterol that is generally reabsorbed by the digestive tract along with whatever fat soluble nutrients it has picked up from your food intake. But if you take a large amount of fiber along with the most fatty meal of the day, not only will much of the fat in the meal be passed through the body undigested but also a significant amount of bile, rich with cholesterol, may be sopped up and passed out of the body rather than being reabsorbed. This is great news as it means you can actually get rid of some the the cholesterol already in your body via your digestive tract by using digestive fibers that are resistant to breaking down.

      Life Extension’s new propolmannan fiber products are very interesting. I’ve used chitosan, glucomannan, oat bran, apple and citrus pectin, psyllium husk, and other fiber products myself and find that chitosan seems to work really well. Life Extension claims that their brand of propolmannan products are better than most fiber products, including glucomannan products which are probably the most similar to it. The reason is that the fat-blocking and absorption effects are enhanced because the fiber is specially processed to get rid of digestive enzymes that would allow it to break down in the digestive tract and release some of its fat payload. They have a capsule product called LuraLean® Caps that seems to be comparable to glucomannan in many ways.

      But I’m personally looking forward to friends and family trying out the product called Calorie Control Weight Management Formula that mixes the propolmannan fiber with compounds like white kidney bean extract and Irvingia gabonensis extract that helps block complex carbohydrate absorption and prevent glycemic spikes that make you eat more from meal-induced hunger. I hope to be able to report more on it from actual usage experience in the next few months. In the meantime if it sounds interesting, take a look at the article Reverse Age-Related Weight Gain for information on a study they did with the Calorie Control Weight Management Formula product that showed the propolmannan fiber significantly improves outcomes for people who were using a similar formula without the fiber and were not losing much weight no matter what they did with diet and exercise.

      Here’s the really surprising thing — although the US RDA for cholesterol in the diet is 300mg, the body itself typically produces over 1000mg of cholesterol per day. That means the cholesterol your body is producing is far beyond the amount you are likely to get in even an unhealthy typical Western diet. That’s why HMG-CoA blockers are so effective. They severely disrupt the production of mevalonate and thereby much less is available to make cholesterol and cholesterol production plummets. Unfortunately, anything else coming from melvonate is also likely to plummet and in many people the CoQ10 deficiency is a major result.

      My hope is that for many people special use of dietary fibers can help suck the cholesterol-laden fats and bile out of the digestive tract and that combined with safer alternatives to statins that many will be able to get a sufficiently enhanced cholesterol lowering effect without adversely impacting CoQ10 and requiring high-dosage CoQ10 supplementation. CoQ10 supplements can be very expensive compared to the multivitamins and herbal supplements that many people are used to using, and that’s another hidden cost of statins that must be considered.

      Low CoQ10 levels can cause a huge amount of health damage including not just the myopathic pain and muscle weakness your husband is experiencing but also neurological effects, too. Depression and confusion are sometimes symptoms of low CoQ10 and/or low cholesterol associated with statin usage. Since CoQ10 is essential to the functioning of the energy-producing mitochondria that make about 95% of the energy used in the human body, organs that are heavy in energy usage are particularly susceptible to disruption. These include the brain, heart, liver, and kidney in particular as all are high energy usage organs. And as was theoretically predicted, CoQ10 deficiencies have been linked to problems in all these organs.

      Perhaps the most frightening of these is the impairment to brain function. Research in the last several years suggests that mitochondrial problems are involved in Alzheimer’s disease:

      Mitochondrial aging and dysfunction in Alzheimer’s disease

      Disruptions in energy metabolism have been suggested to be a prominent feature, perhaps even a fundamental component, of Alzheimer’s disease (AD). These abnormalities in cerebral metabolism precede the onset of neurological dysfunction as well as gross neuropathology of AD. These changes may stem from inhibition of mitochondrial enzymes including pyruvate dehydrogenase, cytochrome c oxidase, and alpha-ketoglutarate dehydrogenase. Several lines of evidence also suggest a role for oxidative stress in the neuropathology associated with the disease state. Because mitochondria are the major site of free radical production in cells, they are also a primary target for oxidative damage and subsequent dysfunction. This link between mitochondrial dysfunction and the pathophysiology of AD is supported by several lines of evidence.

      Prog Neuropsychopharmacol Biol Psychiatry. 2005 Mar;29(3):407-10

      I suspect you already know much of the above, but wanted to make sure other readers understand it all, too.

      Given all of this, I’d strongly recommend CoQ10 supplementation and monitoring for people who are experiencing symptoms of mitochondrial dysfunction and/or low CoQ10 levels.

      PQQ has the potential to significantly boost mitochondrial function as it exerts antioxidant and protective effects that complement CoQ10, making the combination get better results than either alone.

      I haven’t found a definitive answer for your question about how long it will take for PQQ to get some results in increased mitochondrial function and quantity, but did find this study which suggests the reseachers were looking at effects from PQQ exposure for 1 to 2 days time before retesting mice liver cells to see the effect:

      (from Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis through cAMP Response Element-binding Protein Phosphorylation and Increased PGC-1α Expression)

      Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species. Previously studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Therefore, we hypothesized that PQQ can induce mitochondrial biogenesis in mouse hepatocytes. Exposure of mouse Hepa1–6 cells to 10–30 μM PQQ for 24–48 h resulted in increased citrate synthase and cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content, and cellular oxygen respiration. The induction of this process occurred through the activation of cAMP response element-binding protein (CREB) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a pathway known to regulate mitochondrial biogenesis. PQQ exposure stimulated phosphorylation of CREB at serine 133, activated the promoter of PGC-1α, and increased PGC-1α mRNA and protein expression. PQQ did not stimulate mitochondrial biogenesis after small interfering RNA-mediated reduction in either PGC-1α or CREB expression. Consistent with activation of the PGC-1α pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA expression. Moreover, PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction.

      I don’t have access to the full article, but the abstract suggests they did notice effects in markers related to improved mitochondrial replication and also noticed protection against compounds that would normally block such mitochondrial replication. It appears that their short study time of 1-2 days exposure was not enough to increase the number of mitochondria. I don’t consider this to be alarming as most treatments take far longer than a couple of days to be effective unless they are treating severe critical deficiencies like administering oxygen to a patient who has been suffocating.

      So this study suggests to me that PQQ may start to act very quickly, but because it is playing a role in chemical processes that were not entirely failed in the first place that it may take several weeks or months for the effect to become apparent.

      Looking for more information, I found several mentions of this study:

      Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style 21 2009;13(7):50-53

      But I have been unable as of yet to find a copy or abstract of it. I did see some comments that it was run over a period of 12 weeks and involved supplementation with both PQQ and CoQ10, but I don’t have much in the way of details yet.

      I also found another study regarding PQQ that mentions some of the similar markers and pathways for mitochondrial biogenesis being positively affected by caloric restriction, resveratrol, and moderate exercise:

      Mitochondrial biogenesis and healthy aging

      Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Activators of PGC-1alpha include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1alpha. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1alpha such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process.

      Life Extension just posted a new article on PQQ called Rejuvenate Your Cells by Growing New Mitochondria. It should appear in print in your monthly magazine from them in early December, but you might as well read it on the web now. It has some other useful information that helps explain how PQQ may be beneficial in several ways for mitochondria, heart health, and brain health.

      Beside statin drugs that you’ve mentioned as being responsible for the problems your husband is having, aging is also a common culprit for severely depleted CoQ10. That means nearly everybody experiences declining CoQ10 levels as they age into their 30′s and beyond unless they start taking CoQ10 supplements.

      Not all CoQ10 supplements work the same. The cheapest ones using original-style ubiquinone (this is the most commonly sold type) are usually not well absorbed. Newer formulations using water-soluble QGel CoQ10 and fat-soluble ubiquinol are much better at raising CoQ10 levels. Studies on those versions usually point to absorption levels several times that of the low-priced ubiquinone products meaning that 100mg of ubiquinol may be superior in effect to 600mg of ubquinone for many people.

      There are also ubiquinol formulations that include other ingredients helpful to mitochondrial health. Last year Life Extension introduced a ubiquinol product called Super Ubiquinol CoQ10 with Enhanced Mitochondrial Support, 100 mg, 60 softgels that contains another compound called shilajit that complements ubiquinol to help it work even better.

      Based upon CoQ10 blood tests in somebody I know using the various newer CoQ10 supplements I’ve mentioned, these new formulations do work whereas the old ubiquinone looks like it may not work well at all. His CoQ10 blood tests results of 0.28 micrograms/milliliter were below normal reference range of 0.37 to 2.2 micrograms per milliliter even without using statins when he was taking around 200mg per day of ubiquinone supplements along with 600mg of red yeast rice, around 200mg of tocotrienols, and other cholesterol-reducing supplements (niacin, fibers, and plant sterols) that shouldn’t affect CoQ10 levels.

      After switching to the newer formulation CoQ10 supplements, his results were in the middle of the normal reference range at 1.25 micrograms/milliliter. But he was using about 200mg per day of standard Kaneka QH ubiquinol, 200mg per day of QGel water-soluble CoQ10 from Tishcon, and 100mg per day of the Super Ubiquinol CoQ10 with Enhanced Mitochondrial Support, 100 mg, 60 softgels product to get to those improved results. After adding another 240mg per day of QGel (apparently there was a good sale on it), his next test a couple of months later was at 1.61 micrograms/milliliter. From this example it appears the odds are that dosages of old-style ubiquinone under 300mg per day are not going to have much effect on your CoQ10 levels. But if you use one of the newer formulations at 100mg or higher dosages, you’ll probably find you get measurable improvements.

      CoQ10 is rather expensive to take enough to get a significant effect compared to many supplements, and the amount you need is likely to vary greatly depending upon your age, health, and medicines and supplements you are taking. So I’d recommend getting a baseline CoQ10 blood test and then if it is lower than you’d like (say around 1.3 micrograms/milliliter or less) then starting at 100mg per day of ubiquinol. That dosage on a per milligram basis is usually much cheaper than 50mg softgels and many people are going to need 100mg or more to see an effect. Then retest after taking it for a couple of months to allow time for the blood levels to accumulate and stabilize. From those two measurements, you can estimate a dosage that will get your levels into the upper half of the reference range. Why the upper half? Consider that reference ranges include a lot of sick people — you don’t want to be in the lower half for something important like CoQ10.

      Make sure to take CoQ10 supplements with a meal containing some fat and apart from fiber supplements. Otherwise, you may just be wasting you money.

      Given all of the above, you might want to look into adjusting upwards the CoQ10 supplements your husband is taking, testing his CoQ10 levels periodically to monitor the effect of changes in supplements, and adding resveratrol to his supplement plan.

      Regarding the muscle biopsy, to get “clean” results not influenced by any therapy you might want to get it done before starting the PQQ. However, I’d guess that anything less than a few weeks of low-dosage PQQ is unlikely to make a significant difference in the test.

      One person I know didn’t respond well to resveratrol in even low dosages around 50mg (complained of headaches), but others are taking 500mg or even 750mg per day without any adverse effects. It might be good to try a small dosage around 50mg per day at first and ramp it up to 250mg per day over the course of a few weeks to see if he can tolerate it, then see what effect is has over the course of several months before deciding whether to continue it long-term.

      You might also want to look into adding acetyl L-carnitine and alpha lipoic acid supplements, too, preferably in combination as there are some reports that the two at low dosages work much better than either alone at several times higher dosages. Acetyl L-carnitine has some potential for stomache upset in large dosages, but I have never heard of anybody having an adverse affect from alpha lipoic acid. In theory it could drop glucose levels and that could be harmful for somebody with poor glucose control. But the risk of this in small doses doesn’t appear to be major. There are several forms of alpha lipoic acid, the best is NaRALA or sodium R Alpha Lipoic Acid. Even 200-300mg of that is likely to be more effective than 600mg or more of common alpha lipoic acid supplements.

      L-Carnosine is another supplement that may help mitochondrial health by preventing oxidative damage. Unfortunately, it is also rather expensive as for it to work well you need to take 1000mg or more per day to overcome the body’s tendency to break it down via the action of enzymes.

      I hope this really long reply comment helps you and other readers to understand more about statins, cholesterol, CoQ10, and mitochrondrial health. Please let me know if you have more questions. I’m also happy to discuss more details about your husband’s situation if you think it would help.

      Alison

      • Alison,

        Your response to Susanne’s question was a delight. I learned a great deal from your long, informative and comprehensive reply.

        I thank you, not only for myself, but for anyone else who is fortunate enough to read your comments.

        As one who is constantly searching for additional information with which to treat my wife’s Alzheimer’s, PQQ recently came to my attention. Data like this and your additional information supports what I have been saying for a long time. The large research institutions, hospitals and other “prestigous” organizations, together with the Alzheimer’s Association always describe AD in almost identical language. It is almost as if they have some nefarious pact to denigrate the outlook for Alzheimer’s patients and their loved ones who care for them. I do not get a great deal of encouragement from their rather negative assesment of what Alzheimer’s is and how it will end.

        According to their pronouncements the disease is incurable and terrible for both the patient and loved ones in its final stages. They talk of a cure as something that may happen years in the future. They have been saying the same thing for a long time. Meanwhile, scientists from around the world have developed a remarkable understanding of the disease process and multiple contributing factors that can be addressed, if one is made aware of them. In large measure it is the individual, who loves one of the afflicted, that becomes responsible for ferreting out all the leads, trying to make sense of them and then implementing the information in some meaningful fashion. For those without scientific background this becomes a daunting task. That is why those, like you, who are willing to share knowledge, become such an important part of the process of defeating what I truly believe is a disease that can be cured or at least slowed significantly. I just wish there were more M.D.’s who were motivated by a moral imperative that challenged the monotonous conscripts of medical orthodoxy.

        Are there any sources or web sites that you would recommend to those of us who seek informed, scientific data regarding the treatment of Alzheimer’s? I look forward to your sharing more of your insights with those of us who desperately need more guidance.

        Sherwin

        • Sherwin,

          I’m glad you found that long comment helpful. I might spruce it up a bit and turn it into an article.

          Many conventional doctors get stuck in a rut and do not keep their knowledge up to date. They depend far too much on big drug companies to educate them. But big pharma doesn’t really want to cure patients, they want to milk them for years by selling expensive patented drugs that help by keeping them alive but not by curing them. After all, a cured patient is one less customer for them.

          I’ve heard from an acquaintance who suffers Parkinson’s Disease some similar comments to what you are saying about Alzheimer’s. I’ll try to write something more detailed about Alzheimer’s and alternatives to conventional medicine therapies and drugs at some point in the future. From what I know of it, it seems many of the neurodegenerative diseases feature similar problems with plaque protein buildups, damaged and deficient mitochondria, and excitotoxin damage to various brain cells. Based upon this, I’d suggest that findings in other neurodegenerative diseases should also be considered as to how they may be applicable to Alzheimer’s disease.

          One of my favorite organizations for cutting-edge supplements and letting the public know of new research is Life Extension. Visit their web site and search for topics of interest, they often have a lot of good articles and importantly they provide references to studies that have even more details.

          PubMed is also a good place to find new studies before they become widely known, but you may only be able to get abstracts for many of the articles unless you’re associated with an organization that subscribes to various medical and biological research journals. Still, it is a good place to do some investigation to uncover research that may not be known by most doctors. If you find something promising, hopefully you have a doctor who is receptive to you pointing it out to your doctor for him or her to read.

          The article Mild Cognitive Impairment: Nutrition to Stay Sharp covers a lot of the supplements with purported benefits for the brain. Probably most of these things are simply incapable of doing much to deal with Alzheimer’s and Parkinson’s already in progress, but they may be able to delay their apparent onset for years. Furthermore, given that these diseases are still accompanied in most people by the typical mental deterioration caused by aging, for people with a neurodegenerative disease it may be helpful to be able to do anything to slow down or partially reverse their decline in their mind’s functioning even if it is not a full solution.

          But this article still doesn’t cover everything that is out there. For instance, DMAE is a common inexpensive supplement that many find quite helpful at making the brain better at maintaining attention and concentration with less sleep. It’s been used in some attempts to treat Alzheimer’s and seems to be very successful at helping children and adults with ADHD without the problems caused by drugs like Ritalin.

          This may have to do with how DMAE is converted into choline and then into acetylcholine, a critical neurotransmitter of which aging people tend to have lower levels. But some researchers dispute this and claim that the DMAE cannot cross the blood-brain barrier. If that’s the case, perhaps its action could be explained by it being a “sparing agent” that frees up other biochemicals related to acetylcholine to be used in the brain that would have otherwise been used elsewhere in the body.

          It appears people with sleep deprivation may also suffer from lower levels of acetylcholine. On a personal note, I’ve experienced how DMAE can help reduce the need for sleep a little (perhaps by an hour or so depending upon the person and usage) while still feeling rested and capable of usual or better mental performance. A rat study on sleep deprivation and lowered acetylcholine levels seems to confirm this possibility. Another rat study on sleep deprivation shows that it elevates acetylcholinesterase which is the enzyme that destroys acetylcholine.

          DMAE is related to choline, the precursor to acetylcholine, and therefore various choline compounds may have similar effects to DMAE.

          An example of a study from 2003 found on PubMed that discusses this is:

          Efficacy of dimethylaminoethanol (DMAE) containing vitamin-mineral drug combination on EEG patterns in the presence of different emotional states.

          The psychophysiological model of provoking different emotional states by watching film excerpts with various emotional contents was used to characterize drug action in 80 subjects (male/female=50%) with threshold emotional disturbance within a randomized, group-parallel, double-blind, placebo-controlled study. Analyzing the brain’s electrical reaction during presentation of 5 videoclips of 7 min duration followed by 3 minutes pause revealed a content specific representation of topographical frequency changes. This procedure was repeated after 6 and 12 weeks of daily intake of a vitamin-mineral drug combination containing dimethylaminoethanol (DMAE) (Vitagerin Geistlich N) or placebo. Subjects taking the active drug for 3 months developed significant less theta and alpha1 power in sensomotoric areas of the cortex. The grade of change and statistical significance was dependend on the content of the excerpt, but the pattern of changes in general remained the same. Since decreases in theta and alpha1 electrical power have been associated with increased vigilance and attention, subjects taking the drug combination obviously were more active and felt better. – Analysis of the emotional change in mood profile as induced by the TV session was achieved by completing two different quenstionaires (POMS and Bf-S). Both scores revealed a better mood for the active drug group thus corroborating the results from EEG analysis. Therefore the vitamine-mineral drug combination containing DMAE can be interpreted to induce a psychophysiological state of better feeling of wellbeing on both levels of analysis mood and electrical pattern of brain activity in subjects suffering from borderline emotional disturbance.

          Another interesting DMAE study on effects against cognitive impairments that is quite recent (2009) is this one:

          Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies.

          RATIONALE: Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man).

          OBJECTIVES: The present study undertook preclinical and clinical evaluations to test a potential therapeutic utility for DMAE p-Glu in cognitive impairments related to central cholinergic deficit.

          MATERIALS AND METHODS: In preclinical study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious freely moving animals, on performance of rats in the Morris water maze test of spatial memory, and on the deficit in passive avoidance behavior induced by scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive deficits induced by an intravenous injection of scopolamine in healthy young male subjects.

          RESULTS: In rat experiments, DMAE p-Glu increased the extracellular levels of choline and acetylcholine in the medial prefrontal cortex, as assessed by intracerebral microdialysis, improved performance in a test of spatial memory, and reduced scopolamine-induced memory deficit in passive avoidance behavior. Clinical study results show that scopolamine induced a memory deficit and that DMAE p-Glu produced a significant positive effect on scores in the Buschke test, as well as a slight but significant difference on choice reaction time.

          CONCLUSION: These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.

          Since DMAE is inexpensive and can’t be patented, don’t expect drug companies to do anything with it. That’s why alternative medicine is so important. It is not driven almost exclusively by the patent and drug approval processes that constrain and corrupt the big pharma companies. Therefore it is far more likely that alternative medicine will uncover and promote inexpensive and relatively simple alternatives to costly drugs that avoid some or all of their many side effects.

          Alison

  3. Wow! Thank you so much for the help. I just wandered back to this sight and didn’t realize someone had answered! We just received the PQQ last night at 8pm and he took 2 last night and 2 today (40mg) and we will continue until all 4 bottles are gone. He is also taking Alpha Lipoic Acid 100 mg. 1 per day, Coenzyme Q10 400 mg.(but I just ordered the Super Ubiquinol CoQ10 with enhanced Mitochondrial Support and it should be here in 3-4 days). He is also trying to take 1000 mg of LCarnitine spaced over the day (250 mg. at a time, but it gives him a stomach ache- so some days it may only be 250 mg.) I just want to say that I have been searching for a year for someone who knows what they are talking about. Can we meet with you and pay for an office visit? If we don’t get some help, I am sure my husband’s life will be ruined and so you can see that anything drastic would be ok and justified, even if we had to fly somewhere.

    I would like to list some other supplements that I researched about and have on hand. Please let me know if I should try to add any into the mix. I am not giving these to him now because too many is hard to swallow and I want the bang for the buck.

    B Complex which includes B1,2,5, 6,12, Calcium, Magnesium, Zinc,Amino Acids such as Glutamine, Cysteine, etc.
    Famil E-All the 8 members of the E family
    DRibose 1/2 teaspoon, Vitamin C, Selenium 200 mcg,Magnesium complex, Complete Omega 3-6-9 and Myalgia X which includes Malic Acid, Bromilian/ Magnesium and Bosweilia, Vitamineral Green, Lecithin Powder, Creatine,Curcumin, and Glutathione.

    Oh my goodness, my head is swirling and you can see why I need some help! Out of all the research I did, the D Ribose may be the one to add.

    In my research I found that the drug Fluoxitine given with Lovastatin may have bad effects. If he is taking this drug and it is also depleting CoQ10, wouldn’t that be cancelling out the CoQ10 he is trying to take? Should he ask the doctor for something else? The doctor appointment is still pending about the muscle biopsy, and should we press hard for that test? It would be nice to know if there is damage or not.

    Thanks again for your time and willingness to share to help so many in all types of situations. I am sure they are all linked.

    Susanne Baits

    • Susanne,

      I’d love to help you and your husband, but I’m not a doctor and don’t do office visits. Would be happy to discuss your particular situation via comments like this or via email if you’d like to do that. Let me know.

      Fluoxitine is in the SSRI drug class used typically for treating depression. SSRI drugs have some bad side effects, often weight gain, increased suicidal thinking during dosage changes (particularly when starting and stopping them), and negative impact on libido. What was the initial intent of the fluoxitine and how has he responded to it (both positives and negatives)? I don’t see why it would affect CoQ10 levels, but there are plenty of reasons to avoid SSRI drugs and try to use L-tryptophan, 5HTP, St. John’s Wort, high dosage omega 3 fish oil, and other similar supplements to try to deal with depression before resorting to an SSRI drug.

      There is some research such as Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats that indicates coadministering fluoxitine and lovastatin may improve the antidepressant effect. Both high and low cholesterol levels have also been linked to depression and suicidality so it is plausible there could be a connection like this. But in theory it could also go the other way, if you took somebody with normal cholesterol and depression and added lovastatin to the SSRI drug they were taking then I’d guess you might worsen their condition rather than improve it. The human body is so complex and our understanding still very rudimentary. There are so many interrelated factors to consider, it is clear that for many illnesses you have to look at many tests to find the full range of factors contributing to the illnesses as if you do not, you might only be treating a small fraction of the root cause and will not be able to get acceptable results.

      Another thought I have about your husband’s situation is that it may be worthwhile to get an amino acid blood profile. You may find that he is particularly deficient in certain amino acids and then can focus on getting those levels up to normal. People with muscle problems may in particular have low levels of branched chain amino acids (leucine, isoleucine, valine) and could particularly benefit from them. That he’s using an SSRI drug may also hint that he could suffer from a tryptophan deficiency as tryptophan is the amino acid precursor to serotonin, the neurotransmitter that SSRI drugs primarily affect.

      There’s also a chance that he could have an excess of some amino acid and that could also cause problems, but most of those situations happen with people with a genetic defect causing them to be unable to process a certain amino acid and he’d probably already be aware of this. The disease phenylketonuria is an example of such a problem that would result in a high level of an amino acid, in this case phenylalanine.

      His situation reminds me of the problems somebody I know has with low CoQ10 and depression. Possibly I can get him to join this discussion. I know he tried D Ribose previously and didn’t find it helped him much, but everybody is different and that is part of why it is so difficult to figure out what mix of foods, supplements, and drugs is ideal for any one person. There are a lot of tests that can help figure this out, but testing also is not free and you may have to test, makes changes, and retest repeatedly to home in on what is wrong and what you can do about it.

      Regarding the muscle biopsy, check to see what is included in that. I suspect it might just be a microscopic examination of the tissue sample that does not include a CoQ10 test on the sample.

      My initial thought is that a CoQ10 (Coenzyme Q10) blood test and an amino acid profile blood test may be more helpful because it sounds like you have reason to believe it is the statin drugs that have caused problems.

      That’s because it looks like muscle biopsies might not always include a CoQ10 test on the sample but instead may rely on microscopic examination of the sample looking for problems in cell structure, blood vessels, etc. in the sample. Make sure there is going to be some kind of testing for the CoQ10 levels in the blood or muscle to understand if there’s a connection with statins and CoQ10 regarding the muscle problems he’s experiencing. Also, it looks like sometimes statin-induced muscle damage shows up via elevated creatine kinase levels in a blood test. Do you know if that (elevated creatine kinase) is also a problem he is experiencing?

      Again, I’m not a doctor and certainly don’t have a full understanding of everything that has happened to your husband in terms of symptoms, tests, remedies attempted, and their results. So I’m trying to point you to things to consider, please don’t consider what I’m saying as the gospel or as medical advice.

      I did find an interesting article Muscle Coenzyme Q10 Level in Statin-Related Myopathy that you might want to read. Not everybody with suspected statin-related muscle problems had low CoQ10 levels, so there may be another mechanism at work than simply low CoQ10. One of the paragraphs near the end of the 4 page paper is particularly applicable:

      To shed some light on the role of CoQ10 in the pathogenesis of statin drug–related myopathy we studied the muscle biopsy specimens from 18 patients given standard doses of statin drugs to treat hypercholesterolemia with reports of muscle pain, cramps, and weakness (16 patients) or with increased levels of serum CK in the absence of symptoms (2 patients). We found decreased muscle CoQ10 concentration in 10 patients (56%), but the decrease was slight (1 SD of the normal mean) in 7 patients (70%) and severe (2 SDs) in only 3 patients (30%). None of the 3 patients (patients 3, 16, and 17) with the lowest CoQ10 concentrations had abnormal muscle structure or biochemical changes. Conversely, the 2 patients (patients 10 and 11) with some morphologic evidence of mitochondrial dysfunction had only modest decreases in muscle CoQ10 concentrations. In addition, both patients were older than 60 years, which raises the possibility that the few ragged red fibers and cytochrome c oxidase–negative fibers in their biopsy specimens may have been related to aging rather than to CoQ10 deficiency. The increased muscle concentrations of CoQ10 in 4 patients (patients 6, 7, 8, and 14) are difficult to explain, unless these patients were taking vitamin supplements containing CoQ10, a possibility we could not exclude with certainty.

      It would have been very helpful if the researchers running the study made sure to be aware of the use of CoQ10 supplements by each patient. It is possible that their results are tainted by some patients who would have had low CoQ10 levels but were taking CoQ10 and therefore masked this deficiency and therefore affected the study results.

      Hope this helps.

      Alison

  4. Hello,

    I just located this research paper which seems to support, in an in vivo animal model, PQQ’s ability to support and enhance cognitive function though its antioxidant and mitochondrial protective, possibly even rejuvenating metabolism. What interested me in relation to products currently available/being offered, such as by LEF, was the dosage given the test animals in order to determine and actuate these results and how these dosage sizes relate to what is contained within and suggested to be used by manufacturers such as LEF as the products seem within their potency to be grossly inadequate, offering a token amount of PQQ for a premium price.

    Take a look: The rats and mice used in this study were fed 20mg of PQQ per kg. of body weight. This undoubtedly translates into much less, but, on the other hand, given that human beings weigh considerably more than a single kilogram, does that not indicate that the dose of your supplement, at 10mg to 20mg suggested per day. is grossly inadequate an amount to achieve any real benefit? Can you show me any in vivo animal/human studies supporting that all the benefits the product purports to impart, can be achieved at this low dose? This concerns me as I don’t want to spend my money on this supplement if the dosage is far too low to impart any real benefit. 20mg per kilogram of body weight translated to an average weight human model would be more in the range of 1500mg to 2000mg of supplemental PQQ necessary per day. I think this merits due consideration and research as well as an erudite, substantive response on the part of LEF and any other manufacturer offering this substance for sale such as MGC in Japan, who seem to be the ones who’ve patented it as “BioPQQ”. I think this should be addressed to these entities by as many sources as possible before people are gulled into shelling out a lot of money for something that might well be ineffectual at the dosage available, not to mention affordable!

    Here is a link to the study:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212345/

    Best,

    Mr. Steven Oddo

    • Steven,

      Thanks for pointing out this issue.

      My initial reaction is that animal studies of supplements and drugs often use much higher quantity per body mass amounts of supplements and drugs than what are used in human studies. There are many reasons for this. Sometimes they are looking for evidence of toxicity at high dosages, other times they are just doing screening to get any idea of whether a compound might have an effect on measurable health parameters. Often these studies are only run for short periods of time (several weeks) and therefore the benefits of low dosages over long time (such as a year or more) could not be seen in a study that lasts only a few weeks if a low dosage was used.

      The particular study you pointed out actually does not clearly word the dosage used:

      Male Wistar rats (3 months old, Japan SLC Co., Hamamatsu, Japan) and rats fed an antioxidant-supplemented diet (3 months old, fed 20 mg of PQQ, 300 mg of Co Q10, 200 mg of R,R,R-α-tocopherol or 20 mg of PQQ + 300 mg of Co Q10/kg·body weight/day for 9 weeks from 4 weeks of age) were used in this study.

      Some questions from this are: How much did the rats weigh? Were all of the supplements used dosed based upon body mass or only the CoQ10?

      If you look very closely at where the “/kg” is placed in the text, it seems the PQQ and alpha tocopherol were not adjusted by the rats’ body mass but in some of the experiments the CoQ10 was.

      There are some academic/research articles that suggest lower dosages of PQQ per body mass do have an effect. The article Potential Physiological Importance of Pyrroloquinoline Quinone points to efficacy much lower dosages than the study you mentioned:

      The growth-related observations are novel in that adding 100-200 μg PQQ/kg to purified diets improves growth, development, and reproductive parameters in rodent models.

      Given a typical person has a mass around 60kg, the 100 microgram/kg dosage of PQQ would be about 6mg per day and the 200 microgram/kg dosage would be about 12mg.

      That paper refers to a couple of studies to make that assertion. One of them is this:

      Dietary pyrroloquinoline quinone: growth and immune response in BALB/c mice.

      Abstract:

      Pyrroloquinoline quinone (PQQ) is proposed as a nutritionally important growth factor, and we provide evidence that PQQ improves reproduction performance in BALB/c mice and stimulates neonatal growth. In the first experiment, weanling female BALB/c mice were adapted to a chemically-defined diet containing 0, 100, 200, 300, 1000, or 5000 ng PQQ/g of diet. The mice were bred and their reproductive performance and surviving offspring were assessed for 20-wk. Reproductive outcome was markedly compromised for the groups most deprived of PQQ. Supplemented groups (> or = 1000 ng PQQ/g diet) had 8 pups/litter compared with 4-5 pups/litter in the PQQ-deprived groups ( or = 300 ng PQQ/g diet) compared with 4 of 10 in the PQQ/deficient group. The apparent requirement for PQQ for optimal growth of surviving neonates was estimated to be > or = 300 ng PQQ/g of diet. Moreover, splenic cell response to the mitogens concanavalin A and lipopolysaccharide, appeared related to PQQ intake. In a second experiment, female BALB/c mice were fed diets containing PQQ added at 0 or 1000 ng/g of diet, and interleukin 1 and 2 production were assessed. In particular, levels of interleukin 2, an autocrine and paracrine growth factor, were reduced in mice fed the deficient diet at a time when T-cell proliferation occurs in neonates. Results suggest that PQQ or similar compounds may play nutritionally important roles at critical stages in development.

      So it looks like they are talking about optimal dosages around 300 nanograms of PQQ per gram of food intake. From the full text of the study, it looks like the 1000 ng/g and 5000 ng/g diets fed to the mice actually decreased newborn mouse survival rate by somehow causing more of the baby mice to be cannibalized. Obviously this is not likely to be a problem in humans considering how rare human cannabalism is. But the other observations about impaired neonatal growth of PQQ deficient mice and their lower survival rates may have relevancy to humans and human babies. Particularly interesting is that PQQ sufficiency in the mother mice during gestation and lactation (mik feeding of young mice) had an effect on the offspring mice that allowed them to grow normally regardless of whether they were fed a PQQ deficiency diet after weaning. This makes me wonder if maternal PQQ deficiency could have adverse effects on human babies, but I am not aware of any studies that have investigated this.

      As to how to scale this to people, consider that if you ate a kilogram (2.2 pounds) of food per day, that would work out to be about 300 micrograms of PQQ per day to get similar effect to what this study claims. That is only about 3% of the 10 mg of PQQ in many of the current supplement products that contain PQQ. So it is plausible that these 10 mg per day dosages could have an effect, especially if they are maintained over time.

      If PQQ is an essential nutrient as it appears, there is was no toxicity detected at human dosages 60mg or less per day (as found in some studies), and most people are not getting very much PQQ in their diets, then it seems plausible that many people may have a long-term deficiency in PQQ and that even small dosages could help reverse this over time. But to be sure of this, more studies are needed in humans. I think you’re also saying similarly that more studies are needed in humans as the rat studies simply may not be generalizable to humans for many reasons.

      Alison

      • Alison, thanks ever so much for your erudite reply. Yes, clearly more human model studies need to be conducted. It just seemed to me as though the specific study dosage administration amounts were not appointed to assay toxicity, though, they were done so to assess neurological as well as other beneficial mechanisms of action. Given the gray areas, it would still seem as though the dosages as they would be transposed upon a human model would clearly be much larger than 10 to 20mg of PQQ per day. Given all you have weighed and assayed, I am curious what your own stance is upon PQQ supplementation and dosage? Do you personally take it and if so, in what amounts?

        • Steven,

          I’m planning to order some PQQ shortly and have been shopping around for the best price. It looks like there are a few other vendors (Pure Encapsulations and Douglas Laboratories are two that I found) selling it besides Life Extension, but they are nearly all much more expensive from what I have found so far. The only one comparable in per unit price is Quality of Life Vita PQQ 20 Mg 30 Veg Caps for $30 for 30 capsules of 20mg each, just a slight bit more than Life Extension’s basic product per milligram pricing. While that’s from Amazon.com and therefore you’d probably get what you ordered, I have zero idea of whether Quality of Life is a good vendor or not. Hence I plan to order from Life Extension myself since I know they are reputable and their price is slightly better, too.

          I already take alpha lipoic acid, acetyl L-carnitine, and some of the other ingredients in some of the Life Extension formulas with PQQ. So I’ve been debating which to buy of the three Life Extension formulas including it. I might start with just the basic 10mg capsules of PQQ to judge how it works without changing anything else and then decide where to go from there based upon price. I like Life Extension a lot and buy a lot of my supplements during their sales. But often I can find common supplements through other sources that are less expensive and as I am far from rich cost is always a consideration. Somebody who is taking extensive supplements can easily spend more on them they they do on food, especially if they need some of the more expensive and less common newer supplements that competition hasn’t driven down in price yet.

          The cost of supplements is usually a major consideration for anybody using things beyond the dime-a-dozen multivitamins, vitamin D, and calcium supplements you can find anywhere. Often people think drugs are a good solution because their insurance company will pay for most of the cost. But as one of my friends says, sometimes drugs are short-term cheaper than supplements but long-term far more costly. He was referring to his blood clotting problems. He used to take warfarin for it, a very cheap and widely used drug that also didn’t prevent many of his clots. But then he found out how warfarin causes calcium deposits in arteries and depletes calcium in bones. He’s learned to manage his clotting problems with supplements (fish oil, vitamin E, proteolytics such as bromelain, nattokinase, and serrapeptase, etc.) and stopped the warfarin, but it is much more expensive to do it this way. But what price can you put on extra years of life? Say he were to die two years earlier due to cardiovascular diseases or broken bones brought on by the warfarin. Would it have been worth another $500 or $1000 per year for a few decades to avoid that fate? Your insurance company will say no, but what about your family?

          Alison

      • “There are some academic/research articles that suggest lower dosages of PQQ per body mass do have an effect. The article Potential Physiological Importance of Pyrroloquinoline Quinone points to efficacy much lower dosages than the study you mentioned:

        The growth-related observations are novel in that adding 100-200 μg PQQ/kg to purified diets improves growth, development, and reproductive parameters in rodent models.”

        ***Also, Alison, it should be noted that this one research paper you are quoting low dosage efficacy from is financed in part by Mitsubishi Gas in Japan, whom I believe are the ones that patented and are marketing the PQQ ingredient that is being contracted into supplements by various manufacturers.***

        • Steven,

          Good catch, there could be a conflict of interest there.

          There have been many mentions of a study (Nakano M, Ubukata K, Yamamoto T, Yamaguchi H. Effect of pyrroloquinoline quinone (PQQ) on mental status of middle-aged and elderly persons. FOOD Style. 2009;21:13(7):50-3.) using 20mg of PQQ in older adults that showed good effect, but I still have not been able to find it so I can read it. However, Life Extension is quoting that study as one of their reasons for interest in PQQ. I’m a big fan of Life Extension and their work. They have a very long track record of championing new supplements many years before those supplements become widely known for beneficial effects. Therefore that’s part of why I’m leaning towards thinking that there is something significant to PQQ even though it is hard to find human studies on it.

          But I agree fully that it would help to have more human studies, particularly ones that try to elucidate what dosages are required for various effects.

          Interestingly, PQQ is getting a bad rap in diabetes treatment due to its use in some blood glucose tests. Apparently it responds to blood sugars that are unusual and don’t work the same as glucose in humans and could therefore cause somebody with diabetes to conclude more insulin is needed. This excess insulin dosage could send them into hypoglycemic shock and possibly even kill them. See FDA Issues Warning on GDH-PQQ Test Strips for more information.

          Maybe what will happen is that PQQ will be removed from glucose tests and the cost will therefore go down for supplements due to less demand? That would great news if it happens as the cost of PQQ is presently high enough to make trying it questionable for people who are not big users of vitamins. Even Life Extension’s relatively inexpensive BioPQQ 10mg capsules at 10mg per day would cost about $15 per month. While $15 does not sound prohibitive, by comparison that same $15 could instead buy you a year supply of an OK quality multivitamin from Costco. Or it could buy you a year supply of 5000 IU vitamin D3 softgels. This is kind of the challenge with supplements. The common ones are very inexpensive, but anything less common used on a daily basis tends to be expensive enough that most people have to figure out if they can afford to use it for long.

          Alison

          • Alison, thanks so much once again for your substantive earnest reply!

            lol….I personally spend more on supplementation than I do upon food! LEF is of a generally high caliber of quality but not infallible, they are a huge moneymaking entity as well and are looking, obviously, to sell as much as they can like any other corporate unit. They are often overpriced as well. For example, they promote very expensive Acetyl-L-Carnitine Arginate as something veritably transcendent of regular ALCAR, citing spurious and scant “in vitro” studies as proof. If one does judicious searching, and moreover, if one can contend with bulk powders, one can make one’s dollar stretch much further regarding arbitrary supplement budgetary allowances. The sad truth is, most raw materials, regardless of manufacturer, are sourced now from China, that is just the cumulative resultant affect industry de-regulations and Clinton era NAFTA and CAFTA passed legislation has had. LEF has not been able to verify whether or not many constituent, secondary, or even source material ingredients are derived from GMO corn, soy, plant material, even dairy which of course means that in such ambiguous instances, it most likely is GMO. Considering LEF’s stance against Monsanto and the FDA, one would imagine that they’d have more ethical and integrity based quality control. I do use and appreciate several LEF products myself though. I think the standalone PQQ product is the best value and taking 10-20mg a day might be a worthwhile endeavor. Perhaps combining PQQ with Idebenone merits investigation, of course, taking prophylactic superoxide scavenging antioxidants to counter any potential resultant pro-oxidative metabolic process resultant effect of the Idebenone, some studies have pointed to this possibility, though it has not been conclusively proven. COQ10 is assuredly pro-oxidative, though, as has been more conclusively proven. Do you take Resveratrol? I have a lot of ambivalence towards it, bioavailability being a factor as well as price and also conflicting study data. I wish LEF offered a standalone Trans-Pterostilbene product as research data is promising and bioavailability seems far superior. They do offer it in a CR Mimetic Formula, a bit pricey as you are paying for Resveratrol, but I guess worthy of consideration all the same. I take a Red Wine Extract for the time being as well as other polyphenolic rich supplements as well as foods comprising my dietary regimen. I think dietary practices are almost more critical than supplementation on many plateaus.

            One can purchase high quality bulk powders here:

            http://purebulk.com/index/rows/10/start/10

            I think dietary, environmental, exercise, hormetic, as well as emotional factors are significant ones affecting health and longevity. Epigenetics is unfurling pathways of much provocative interest here. Genes are hardly fixed, diet and nutrition are environmental influential factors that can assuredly impart influence unto the growth and development, the expression of the nucleus of DNA, but the nucleus is not affixed and rigid, it can be altered and manipulated, it receives information from the cell membrane which itself dies so in accordance with the dictates of external stimuli of biochemical as is established through dietary assimilation, environmental absorption/assimilation, physical exertion/exercise factors, as well as, and maybe even most significantly, field energy and psychoemotional assimilation/absorption, processing, and response dynamics. The cell membranes instruct the nucleic DNA accordingly upon its developmental pathway of expression and replication. This is one of the precepts of Epigenetics and I think this is integrally key in determining any cultural or infra-cultural longevity factors, statistics, etc. which have defined and permeated many controversial, illuminating cross cultural longevity studies conducted in recent years. Belief system alone is probably, on many strata, even more imperative a factor than diet, exercise, and nutrition/supplementation. It would seem that there is more than enough pure (once one has sifted through the plethora of corrupt, junk, and/or biased ‘data’) scientific data supporting that a largely, if not entirely, plant based dietary regime is more than adequate and sustainable to maintain and even optimize physiological and psychological well being in human life forms/models though this must be carefully conceived, measured, and appointed thusly. Let us consider our environment and Epigentic symbiosis of existence within affecting modalities of health, wellness, longevity, etc. The sustainability and rejuvenation of our biosphere and planetary environment is deleteriously affected by large scale industrial agricultural cultivation of meat based food products as well as non-organic chemical based agricultural practices, period. Einstein was admonishing us regarding this very fact regarding large scale human populace carnivorous dietary practices and its damaging effects upon our system, rendering it not sustainable, nearly a century ago. Our relationship with our planet has been very largely of a parasitic rape nature and it has progressed well past major tipping points now to such an extreme that radical measures must be undertaken, despite the contraindicating, purely defensive, deceiving, and baseless, money based interpolation arguments of corrupt special interests who stand to lose a great deal from necessary environmental and industrial reformations. We need to focus more upon environmental sustainability and Symbiosis with our external system in an unprecedented manner. We exist in a world wherein money and money worship and its power and status accolades define nearly everything, including science, most of which is monetarily defined and influenced and hardly ethical, pure, truthful, nor noble in its endeavors. The sad reality is, corporate state special interests (including medical and pharmaceutical as well as large scale industrial food manufacturers) and their paid proponents, our sub-human “politicians”, do comprise our governmental power structure and regulatory agencies and the profit is made upon insuring the propagation of disease states and modalities propagating and expressing themselves to as great an extent as possible, not the reverse. Corruption, not to mention gross, myopic, ineptitude, pervades nearly all aspects of scientific procedure and research data, even and especially heavily lauded and circulated studies. Academics are defined largely by and aligned with insuring the propagation of the special interest groups and industries who the graduate student drones will be serving. It is no shadowy conspiracy that our academics and educational systems were sculpted and defined by wealthy industrialists, such as Carnegie and Rockefeller, as a means of specific social engineering close to a century ago.

            http://www.propublic…plinary-records

            http://www.theatlant…l-science/8269/

            http://foodfreedom.w…ernization-act/

            http://www.naturalne…l#ixzz16pkYVMPX

            Epigenetics is a burgeoning and exciting perspective integrating many aspects of true scientific endeavor, even transcendent ones. We are only just beginning to scratch its surface but I think it is from there that we will excavate the keys and transitions unto much manifold understanding, evolution, transcendence, wellness, higher conscious, longevity, and most paramount, symbiosis and happiness.

            http://www.scientifi…mes-epigenetics

            I’ll attach an html link to this paper, “Epigenetic Factors in Aging and Longevity” for your enjoyment, you can download the pdf as well there.

            http://www.springerlink.com/content/h43537501n75r153/fulltext.html

            This other paper, link below, sounds great, I am not a paid member, so, alas, I cannot download the full pdf, maybe you or someone else can help with this?

            http://www.ncbi.nlm….pubmed/21088573

          • Steven,

            Thanks for yet more of your thoughtful comments.

            No organization is without its faults, and I’m sure that part of why Life Extension operates is to make an income for its founders and employees. But they do seem very intent on pointing out the problems with the FDA, mainstream medicine, and other health-related concerns of which most citizens are dangerously ignorant.

            It seems like you might have suffered a link cut-and-paste problem with your web browser as many of the links you put into your comment don’t work. If you could supply revised versions I’ll update your comment with them.

            I’ve heard good things about Purebulk, also, but did notice that they don’t always have the most competitive prices. It’s good to watch for sales and stock up when you see a good price on amino acid supplements. As you say, most of these supplements are mass-produced by a relatively small number of major ingredient suppliers. So

            I do take Resveratrol. It’s my view that the low bioavailability can be countered somewhat by spreading it out across the day and taking higher doses of it and related substances like pterostilbene and fisetin which are reputed to enhance the effects of resveratrol.

            Idebenone looks very promising, too. In 2009, I wrote an article on idebenone as an alternative to CoQ10. But it is unclear if you can actually test your blood to find if you are taking enough idebenone, so CoQ10 (particularly ubiquinol and QGel water-soluble variants) has some advantages as I’ve seen test results from a friend who varied his doses and can see the increases in his CoQ10 blood tests to know they are indeed working. It’s also much harder to find it. Where have you been buying it? Looking around some, one of the better prices I found was about $30 for a bottle of 80 capsules of 180mg each for a brand called PrimaForce. I know of nobody who has used that brand of supplements, so can’t comment on it from anybody’s experience. The only person I know who has used idebenone bought a brand 1Fast400 that was bulk powder that is no longer available to my knowledge. But he gave up on it between the other sources being more expensive and having no way to tell (i.e., blood tests) if he was taking the right amount.

            I’m not sure I’d say that CoQ10 is pro-oxidant in the conventional sense as when that term is used it often is applied to compounds that don’t have much use to them. But CoQ10 certainly does have a use, the problem is that the use comes with the side effect of more oxidative damage. In other words, when CoQ10 enhances mitochondrial function by increasing energy production, it also enables the mitochondria to generate more oxidation damage in the process. So with CoQ10, the cost of enhancing energy output is more oxidation. Apparently idebenone is better at doing this and at the same time quenching much of the oxidative damage potential by mopping up free radicals. But there are also many other antioxidants available and anybody seriously interested in preventing damage from aging and diseases like diabetes and obesity should be loading up on antioxidants such as vitamin C, vitamin E (not just the typical alpha tocopheral form but all eight forms of vitamin E), and others along with CoQ10.

            Your points about epigenetics are very interesting. Almost anybody who knows anything about biology or health is aware of genetically caused diseases. Yet you can have non-defective genes but still get diseases due to which genes are activated and then pass those diseases on to your children and grandchildren. There is a very easy to understand introductory article on how epigenetics can cause inheritance of serious diseases such as obesity and diabetes in the Newsweek article Sins of the Grandfathers.

            When you look at the epidemic of mental illness in this country and how it is related to child abuse, governmental abuse and fraud and corruption, and generations of parents and children being affected by these things, one can’t help but wonder if epigenetics is also playing a role in these areas. A child is abused severely and grows up with a personality disorder and then abuses his or her spouse (often with full help of the local government as they make money off of the abuse via their Title IV-D funding from the US government) and creates an abusive environment for the children, too. Those children grow up with depression, substance abuse and addiction, and often personality disorders themselves. Is it merely environment or are epigenetics at work here, too?

            In any event, the policies of the governments in the US are destroying the health and well-being of the citizens. They block access to treatments that work, try to shove dangerous drugs like statins down tens of millions of people’s throats to funnel an income stream to their big pharma buddies, and then create whole new markets for new drugs to undo the damage they did to their victims.

            Bringing this full circle, it gets back to why Life Extension and their allies are so important. They are calling the government’s crimes into public view, exposing how the government literally kills and badly harms millions of people with its corrupt policies that are against scientific evidence and appear to be based upon nothing more than greed and power lust.

            Alison

          • Strange, I tried posting lengthy replies several times but the site is not accepting/saving them??

          • It tried re-posting but it says, “duplicate reply detected”, but it did not post the “detected” reply….?

          • Steven,

            Figured out what happened. You put a lot of links in your messages and the website software categorized it as spam (most websites get a lot of spam comments send by automated programs trying to advertise UGG boots, Viagra, and all kinds of stuff that has nothing to do with their content) and so the comment wouldn’t appear even though you’ve had past comments appear instantly.

            When you tried to repost the comment, then the website software recognized it as a duplicate of the comment it thought was spam.

            We do check the spam filter every couple of days (there are usually a few dozen obvious spam comments and rarely ever any legitimate ones that get caught in it), so will catch this mistake but not immediately.

            If something like this or some other problem with comments happens, you can also email a comment to [email protected] and mention the article to post the comment.

            Alison

  5. I’ll link another PQQ paper as well which had resultant effects of promise, but in this case, the test animal models were administered the PQQ via intravenous/parenteral injections which is very disparate from oral dosing. This research also called into question the adequacy with which the PQQ could efficaciously pass the blood brain barrier in order to actualize specific actions/mechanisms of therapeutic value, however.

    http://www.springerlink.com/content/mj40n02463104mt5/fulltext.html

    • Steven,

      I took a quick look at this other study you are citing. Basically it looks like a study to understand how PQQ is distributed and persists in the organs in a rat into which the supplement is injected. They used radioisotope labeled PQQ to be able to figure out where it was going and how long it persisted.

      There was theoretical basis for thinking that PQQ would not cross the blood-brain barrier well. In experimentation it seems they did find that some of it does make its way into the brain quickly but the levels do not get as high as in other organs. After an initial uptake surge, then the brain levels of PQQ decreased rapidly, but this may be because it had initial rapid uptake and then the brain was saturated. Given the high blood flow to the brain and their comments about the solubility characteristics of PQQ, this makes sense. Possibly they can improve this by developing a variant of PQQ with improved fat solubility.

      Based on its water solubility and negative charge, PQQ in its free form would not be expected to easily cross the blood–brain barrier. However, it was reported that PQQ was capable of entering the brain following systemic administration, and particularly notable was the work by Smidt et al. [14]. In addition, possible metabolic products such as the oxazole derivative of PQQ cross the blood–brain barrier in order to exert effects on NGF and may be also neuroprotective [2].

      Injection administration is obviously different than absorption via oral administration, so this can’t be directly used to understand what happens in oral administration. However, I do recall reading somewhere that PQQ is relatively well absorbed via the GI tract, unlike some other nutrients, supplements, and drugs.

      A couple of interesting points I noticed was that the injected PQQ was relatively well spread out throughout the organs in about 18 minutes and the level did not decline below that until around 100 minutes after injection. Simplying this, you could probably say something like the injection half-life of PQQ is about 100 minutes. That’s not a really long time, so given that absent other evidence then appears if somebody is going to take multiple PQQ capsules per day then they would want to space them out over time rather than taking them all at once.

      Another point that was interesting is how well the PQQ persists in the liver even after 6 hours. The liver is a high energy usage organ and therefore mitochrondrial nutrition is very important there. This makes me wonder if PQQ will eventually be found to have good effect in helping people with liver disorders recover from their conditions.

      Alison

  6. When my husband goes to the neurologist this week, he will mention the blood tests as well as the CoQ10 levels in a muscle biopsy.He’ had tons of blood tests, but he will ask specifically. My husband’s CK levels are fine but this has still persisted for a year. Also the neurologist checked the electricity in the muscles and said they were fine as well. I forgot to mention that in the smoothies, we are adding Aloe Vera Juice because there is evidence that dolichols can help with muscle cells as well. I purchased The Dark Side of Statins and am wondering if the lack of CoQ10 could have caused oxidative damage to the mitochondria. The job of the dolichols help the CoQ10′s defense. Since there is no supplement for dolichol, I have purchased Aloe Vera juice. The dolichols are supposedly surface sugars which help mitochondrial mutations. I visit the web site Spacedoc.com regularly.
    I will let him know about the natural ways to correct being depressed. But I am sure it is natural to be depressed if you are unable to do anything movement wise for fear of the major payback of pain. Work is suspended, ability to work around the house is gone, concentration is gone because of the pain. So that is why we are trying to work on ridding the pain first. It happened right after taking the statin drug after only about a month or two.Of course he stopped taking it, but the pain did not.We will love to chat via email as well. Also it would be very interesting chatting with someone with similar problems.I would encourage people to check out Spacedoc.com to read how a NASA astronaut has similar problems with statins. Dr. Graveline has written a lot of books about statins and the cause of disabilities i.e. memory. The article about the sugar dolichols is on Kindle by Glyn Wainwright. As far as the dosage goes, I am having my husband take 20 mg per day for 3 weeks, and if there is no improvement increase it by 10 mg. I will tell him about spacing it.
    Once again, thank you for the suggestions.
    Susanne

    • Like your husband, I have some very good reasons to be depressed that anybody would understand. I don’t think any antidepressant will be likely to help me much, from experience they make things worse.

      Your husband should be really careful with SSRI antidepressants. I personally used them and found that the first months of taking them made me think about death many times every day. I never attempted suicide, but those drugs made me think about it a lot when I never really thought about it before despite being very depressed.

      I had a similar experience getting off of them, too, even though I tapered to low dosages over many months before discontinuation. It is really frightening to feel so out of sorts like this because of a drug.

      Nothing I have read explains why this effect happens. But it is so common that the pro-big-pharma FDA even required warnings on these drugs regarding elevated risk of suicide.

      Having tried tryptophan, 5HTP, St. John’s Wort, mega doses of fish oil, phosphatidylserine, high dosage vitamin B6 (mostly pyridoxamine and P5P), B12 (mostly methylcobalamin form) and folate (mix of folic acid and methylfolate forms), I can say that none of these supplements ever made me feel as bad as SSRI drugs did.

      The tryptophan amino acid supplements made a significant boost in my blood level of that amino acid. Since it is used to make serotonin, that’s probably a good thing for my depression.

      I have also had problems with chronic pain, too, but am sure it is not presently from low CoQ10 because I take a lot of CoQ10 supplements and have never used statin drugs. I have used a little red yeast rice, policosanol, plant sterols, and quite a bit of tocotrienols to help my lousy cholesterol and triglycerides. They have helped a lot, but still not quite enough yet, but then I learned about red yeast rice and tocotrienols might also lower CoQ1. So I had it tested and found my CoQ10 levels were very low. Now I take a lot of CoQ10 every day and the blood test results are much better.

      It is hard to know if the increased energy and lack of some pains I used to have (especially the chest pains and shortness of breath) have anything to do with the higher CoQ10 levels. I think maybe so, but I now have other pains that are different than the old ones.

      The pains I have now, and maybe the earlier ones too, seem related to stress stemming from my horrible ex who spends so much effort trying to hurt our children and me. Alison also writes for another website that has articles about such problems. Some people I have chatted with have considered suicide over such problems. Really ashame that society lets such evil people cause so much pain to others that they want to die.

      Some days the pain is so bad I can barely move and cannot sleep due to pain everywhere, every part of my body. I don’t think it is a 10 pain like your husband, maybe a 7. Those days I feel so weak that I have trouble even lifting an empty glass unloading the dishwasher without severe pain. Sometimes I fear my hand will lose grip of even a small glass of water due to the pain and weakness.

      The pain interferes with sleep, and the lack of sleep seems to make the depression and pain worse.

      I have had many tests for inflammation, arthritis, autoimmune diseases, etc. and nothing explains it. Sometimes I wonder about having chronic fatigue syndrome as I am often very tired, too, but most of my doctors have thought CFS is not real. But I read recently that it may be tied to a viral infection and that it is real despite what many doctors think. Unfortunately, there is no way to test for it.

      I used to take benzodiazipine drugs to help sleep as anxiety is a major problem for me for many years now. But those drugs have problems, too, and I used them very sparingly now because of the problems I experienced. I started to get interdose withdrawal which was making me incredibly agitated the next afternoon after taking them at bedtime. There are whole organizations and treatment protocols devoted to helping people get off that class of drugs, for some it takes years to do so. They are very addictive to many, but even so doctors prescribe them without trying safer alternatives.

      I read about glycine (another amino acid) to help sleep and tried it. I find it works very well and is not expensive and not addictive, at least for me. My blood glycine levels used to be on the low end of normal range, now they are around 2/3 of the way into the normal range. I take around 5 grams of it before going to bed and again if I wake up and can’t fall asleep again.

      Some sleep medicines made me unable to function the next day. But glycine doesn’t do that. It just help me feel more calm and less worried and a little drowsy for a couple hours. By the time I wake up it has no obvious aftereffect, I think this is why I sometimes have to take it again in the middle of the night. I take it with other sleep aids including tryptophan, 5HTP, high dosage melatonin, L-theanine, lemon balm, valerian, and sometimes GABA. No one thing seems to work well enough for me.

      Occasionally not even all of that helps and so then I also use a benzodiazipine drug. But I don’t feel like feel as rested after taking one of those.

      I wonder how many health problems might be caused by imbalanced or too low or high levels of amino acids. I am trying to correct my remaining amino acid imbalances now and hope it will help.

      It would also be interesting to chat with the person who has similar problems and to see what this person has tried. But I think it would be natural to be depressed if you couldn’t do things around the house, go to work, or do exercise or even walk a ways for fear of a pain level 10.

      I will ask to have my email address sent to you so we can talk if you want.

  7. My husband will discuss the blood tests and the CoQ10 test/ with biopsy with the Doctor this week. The neurologist already ruled out the CK levels being elevated. He also checked on the electricity in the muscles and found that that was fine as well. Glyn Wainwright wrote a book on Kindle about statins and suggests that dolichols are also effected when on the statins. He points out that dolichol inhibition may be a cause of statin behavioral side effects including depression. There is not a supplement for this sugar, so we started putting 14 cup of Aloe Vera juice in a smoothie. Dr. Graveline also suggests this. I would suggest that anyone having problems with statin drugs visit Dr. Graveline’s website at Spacedoc.com. So I guess the term are glyconutrients. I think the Aloe Vera is a good source. I noticed that amino acids are abundantly in here as well. It also suggests that cell death is from the Statin drugs. This is the reason I am pursuing the PQQ because it may correct the cell death from this Statin toxin.
    Dr. Graveline is a NASA astronaut and doctor and I would recommend his books.
    As far as the dosage, my husband takes 20 mg per day of PQQ. I would suggest to him that if after a month, there is no improvement to move it up to 30 mg. We will let you know how our own study is going on a human! I guess my husband is the guinea pig. I would love to email you about things that arise if possible. It would also be interesting to chat with the person who has similar problems and to see what this person has tried. But I think it would be natural to be depressed if you couldn’t do things around the house, go to work, or do exercise or even walk a ways for fear of a pain level 10. And so our own research study goes on…. By the way, our information is also apart of Dr.Beatrice Golumb research at UCSD. They should have received it this week to include in her study. She is finding that some people who used statins without an elevated CK level are permanently disabled with myopathy, memory loss, neuropathies etc. Now I was wondering about Stem cell therapies. I heard about a person with a muscle degenerative disease receiving this therapy but I couldn’t show a study because it was on the news. But that is also a thought. Again, we are willing to travel outside our plan. The Mao Clinic sounds good, but I am not sure who has something else to try. Our Medical plan doctors seem to think time will heal, but this is not working!
    Susanne

  8. Wow–What an informative blog! It’s thrilling to read such detailed, comprehensive information on supplements/health issues. Thank you!! I’m taking PQQ and a hundred other supplements in order to treat a diagnosed cancer of unknown primary…so far, I’m feeling fantastic! It’s thanx to this kind of blog that guides me on the most promising substances to take. :D

    • Barbara,

      Thanks for the note. I wish you the best of luck with treating your cancer condition. I suspect you’re on the right track with attempting to keep your mitochondria strong. You didn’t say if you’re using chemotherapy or radiation therapy, but they are really hard on healthy cells, too, and so extra mitochondrial support seems at first glance like it would be very helpful.

      I’ve recently started taking PQQ, also, choosing the Life Extension PQQ Caps with BioPQQ™ to try it out as this was priced the best out of the PQQ products I found. I’m taking two per day, one in the morning and one at bedtime. It’s too early to know the effects yet, but I haven’t noticed any obvious side effects such as digestive discomfort or sleep impairment that occur with some supplements.

      However, I do suggest you do some reading on cancer treatments and mitochondria. There appear to be some treatment attempts and research that suggest targeting cancer cells via their mitochondria is a plausible way to kill off the cancer. Possibly nobody could say for sure yet, but I’d have a concern that some treatments may be at odds with mitochondrial support measures. I found the September 2010 article Targeting bioenergetics to enhance cancer chemotherapy: mitochondria SLP into apoptosis and an older October 2002 article Chemotherapy: targeting the mitochondrial cell death pathway that suggest some treatment approaches may attempt to cause cancer cells to self-destruct (apoptosis) by destroying the mitochondria within them.

      Alison

  9. We have MELAS in our family. My 14 son passed away in 2005 from the cardiomyopathy caused by MELAS. We have two daughters with 5 children between them, one a female, so the reality of the continuation of MELAS is ominous. Are there any clinical trials using PQQ or have any studies / hypothesis been drawn on the use of PQQ in treating this debilitating and rare disorder? We are keen on using Carnitor, CoQ10, DCA (Sodium Dichloroacetate) and its effects on the Kreb cycle and PDH in particular, and the super vitamin cocktails, but I have not found an abstract on the use of PQQ for treatment thereof. Just curious.

    • Douglas,

      I’m really sorry to hear of your situation. For readers who are not familiar with MELAS (which stands for Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke syndrome), it is generally thought to be connected to mutations in the mtDNA (mitochondrial DNA) that is inherited entirely from a child’s mother. Unlike nuclear DNA of which half comes from each parent, the mtDNA comes entirely from the mother. That explains your concern directed about inheritance of MELAS via the females in your family.

      I did a little bit of looking around for any mention of PQQ being used to treat MELAS and came up empty-handed. I suspect that it could help in theory because research to date in aging people (but not with MELAS) suggests that PQQ helps improve the health and quantity of mitochondria which provide about 95% of the energy used in the human body.

      I’d guess that you have done a lot of reading on the net about MELAS, so you might have already seen this. I came across a Medscape article http://emedicine.medscape.com/article/946864-treatment discussing treatment for MELAS that mentioned many of the supplements you mentioned.

      Two things that I’d suggest further investigating are idebenone and niacinamide. It’s my understanding that idebenone is superior to CoQ10 (ubiquinone and ubiquinol) by being able to get through the blood-brain barrier and being much more able to resist oxidative damage that is especially intense inside the mitochondria. It may also be more cost-effective than the CoQ10 ubiquinol form that is generally regarded as being a few times more effective at raising CoQ10 levels in blood tests than the inexpensive ubiquinone form.

      Niacinamide is much more readily and efficiently converted into NADH than niacin or tryptophan are. NADH is important for creating ATP in the body. You can read a bit more about it at http://www.antiaging-systems.com/ARTICLE-563/nadh-body-and-mind-energizer.htm . That article discusses NADH supplements which are expensive, but niacinamide itself is very inexpensive. Note that it is also often called nicotinamide. Either name denotes the same compound, an amide variant of vitamin B3 commonly called niacin or nicotinic acid. Niacinamide has some reputation for helping with conditions involving pain, fatigue, depression, and anxiety including fibromyalgia and various anxiety and sleep disorders. Although niacin in any form can be used to make NADH, the niacinamide form is best for this purpose.

      Life Extension has also been promoting findings on a substance called shilajit (sold under the brand name PrimaVie) which is supposed to help boost CoQ10 levels and activity. They are including it in some of their ubiquinol and chromium formulations such as
      Super Ubiquinol CoQ10 with Enhanced Mitochondrial Support
      and
      Chromium Ultra
      . I was finally able to find a couple of the research studies on shilajit via an Indian university and will post them soon.

      Alison

  10. Your conversations and research are very interesting and I wonder if any of you might comment on the problems associated with the lack of REM periods when taking Ambien, which I have been taking for many years.

    Because of increasing irritability and even bursts of rage, I am stopping Ambien to see if Ambien has been among the contributing factors. Now without Ambien, I am experiencing horrific nightmares.

    Any thoughts? Thx.

    • Sandance,

      Ambien is reputed to interfere with REM sleep, in some people eliminating it entirely. Sleep expert Matt Walker mentions the impact on REM sleep as well as many other interesting observations about REM vs. non-REM sleep in an article on the PBS NOVA website.

      REM sleep is tied to a number of biological processes. For instance, there is substantial evidence that it is connected with LH (Luteinizing Hormone) and testosterone release in men. The connection seems to be that LH release peaks with REM sleep and this drives increased release of testosterone, but some studies (such as Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men) note the connection between REM sleep and testosterone but don’t see the correlation with LH release being as strong as others do.

      Either way, guys who get little REM sleep may suffer from lower levels of testosterone which can cause or influence other health problems including obesity, poor blood lipid profiles, depression, anxiety, etc. The sleep architecture connection with testosterone might even be related to sleep apnea as sleep apnea degrades sleep quality, impairs REM sleep, and thereby lowers testosterone which could cause deconditioning of muscle and tissues that result in a higher likelihood of the airway being obstructed during sleep.

      Benzodiazepine drugs widely prescribed for anxiety also are reputed to adversely impact REM sleep. They work on GABA receptors in the brain somewhat like Ambien does. They also alter sleep architecture and have problems with creating dependency like Ambien can do.

      Your nightmares and irritability when you don’t take Ambien might be related to the sudden change in the GABA receptor activation in your brain due to going from a full dose of Ambien to no dose. Have you tried cutting the dosage and weaning yourself off of it? Ambien has potential for chemical dependency and suddenly stopping it may not allow for your body to gradually and comfortably adjust to the change.

      Note that a lot of people think that testosterone and aggression are connected. That’s an oversimplification in my opinion. There are studies in animals that point to estradiol (a form of estrogen) being tied to aggression. It is possible that any disruption in the normal preferential hormone balance for testosterone and estrogen could introduce psychological effects such as increased anxiety and irritability that could appear to be aggression.

      Do you suffer from depression? Anxiety? Both are often related to sleep disorders, both as causes and effects. You may need to treat all three problems rather than just one or two.

      If you can explain your situation and what you’ve tried and how it has worked, I might be able to give you some additional suggestions on things to investigate to help your situation.

      Alison

  11. Hi, Alison, I was just wondering, when a cell divides and reproduces itself repetitively over someones life, their DNA gets progressively more and more damaged until the cell just dies right? So, like, shouldn’t the mitochondrial DNA get progressively more damaged, in the same way, the more times it divides? Could vitamin pqq speed up the aging process of the mitochondria then? Kind of burning them out in like a blaze of glory or something? Thanks

    • Daimon,

      The mtDNA in the mitochondria is not the same as the nuclear DNA. Keep that in mind for clarity about how the effects of DNA damage may vary between the types of DNA. Both nuclear DNA and mtDNA can be damaged, but damage to mtDNA is far more likely if for no other reason that the mtDNA is attached inside the mitochondria without a protective membrane like the nuclear DNA has and that the mtDNA is in such close proximity to rapid redox reactions which throw off large quantities of reactive oxygen species (ROS).

      Not all DNA damage results in the death of cells. Some DNA damage may trigger other malfunctions such as cancer.

      Every human cell has many mitochondria, typically hundreds of them but depending upon the cell type it varies from about 2 to around 1500 per cell. The higher energy usage cells in organs like the brain, heart, liver, and kidney tend to have more of them. Mitochondria can and do replicate even if their host cells are not doing so.

      Both nuclear DNA and mtDNA replication can result in mutations or damage, but it is generally more likely such damage will come from oxidation, glycation, radiation, and other similar processes than from replication itself. Interestingly, the damage from radiation is probably more from the resulting widespread oxidation than from anything else.

      There are DNA repair mechanisms that can fix a lot of these problems. But mtDNA is particularly susceptible to oxidative damage, as is discussed in this article. Such damage is particularly likely to be mtDNA deletions caused by the intense oxidative stress inside the mitochondria.

      PQQ can help reduce the oxidative damage resulting from normal functioning of the mitochondria. It is reported to be a far more powerful antioxidant than CoQ10. There is reason to believe this antioxidant activity may benefit not just the mitochondria but the entire cell and its nuclear DNA, also, as discussed in a research paper of which I’m quoting an abstract below:

      DNA damage in telomeres and mitochondria during cellular senescence: is there a connection?

      Cellular senescence is the ultimate and irreversible loss of replicative capacity occurring in primary somatic cell culture. It is triggered as a stereotypic response to unrepaired nuclear DNA damage or to uncapped telomeres. In addition to a direct role of nuclear DNA double-strand breaks as inducer of a DNA damage response, two more subtle types of DNA damage induced by physiological levels of reactive oxygen species (ROS) can have a significant impact on cellular senescence: Firstly, it has been established that telomere shortening, which is the major contributor to telomere uncapping, is stress dependent and largely caused by a telomere-specific DNA single-strand break repair inefficiency. Secondly, mitochondrial DNA (mtDNA) damage is closely interrelated with mitochondrial ROS production, and this might also play a causal role for cellular senescence. Improvement of mitochondrial function results in less telomeric damage and slower telomere shortening, while telomere-dependent growth arrest is associated with increased mitochondrial dysfunction. Moreover, telomerase, the enzyme complex that is known to re-elongate shortened telomeres, also appears to have functions independent of telomeres that protect against oxidative stress. Together, these data suggest a self-amplifying cycle between mitochondrial and telomeric DNA damage during cellular senescence.

      Cells that have badly damaged mitochondria are more likely to self-destruct (such as via apoptosis) or be unable to replicate than cells without badly damaged mitochondria. Either result should help reduce the spread of damaged mtDNA throughout the body. In my view, PQQ probably won’t change that.

      But PQQ may help cells with healthier mitochondria function better, replenish their mitochondia, and replicate longer. There’s a good chance that PQQ may reduce the oxidative damage that is probably contributing to some of the telomere shortening in cells, somewhat like other antioxidants are reported to do. However, I’d speculate that the effect of PQQ in this manner may be more significant because PQQ antioxidant activity appears to be focused in the mitochondria and the mitochondria are such a big source of ROS (reactive oxygen species) throughout the body.

      In case readers interested in telomerase activators (such as TA-65 and cycloastragenol) run across this comment, I’d like to be clear that PQQ doesn’t appear to be a telomerase activator that directly repairs or directly affects the nuclear DNA telomeres. But there is reason to believe that it may reduce the natural rate of damage to telomeres and therefore would probably help enhance the benefits of any supplements and drugs that lengthen telomeres.

      Alison

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  14. I started taking PQQ a few months ago. I’m using the Life Extension 10mg capsules, two per day with one on the morning and one at bedtime. One big difference in my test results that I’ve noticed is that my cholesterol problems are vastly improved. I am not sure this is due to the PQQ, but it and acetyl L-carnitine are the two supplements I’ve added during the time between my blood tests that seem like they might have something to do with the change.

    I have tried many supplements for years to get my LDL cholesterol down including high dosage niacin, plant sterols, red yeast rice, Sytrinol, tocotrienols, fiber, and more. I think they helped and the tests showed they did, but I was still left with lots of small dense LDL and low HDL. What is weird about this change is that because I’ve been so sick, tired, and pained I have had trouble taking my supplements at the usual levels and have had to drop out most of the fiber supplements, half the dosage of niacin, and cut the plant sterols by about half. Yet my cholesterol improved! So I suspect it is the PQQ and/or acetyl L-carnitine making the improvements, but am not sure.

    It is not just my LDL cholesterol that dropped a lot. The VAP tests I have had done in the past always showed I had small dense LDL and probable metabolic syndrome. I also have had high triglycerides for many years, too. Both of those have improved dramatically in the about three months I’ve been taking the PQQ and acetyl L-carnitine. I was already taking ALA (alpha lipoic acid) and read that the acetyl L-carnitine is supposed to help it work better and that the PQQ is supposed to help the CoQ10 I take work better, too.

    I don’t think this was just a one-time fluke as I’ve had two regular CBC tests and one VAP test since adding the PQQ and acetyl L-carnitine and all these tests showed consistent improvements.

    Has anybody else noticed big changes in blood lipids from using PQQ or acetyl L-carnitine?

    • Tired and Pained,

      I read your comment and decided to investigate. I did not find anything substantial about PQQ helping to lower cholesterol levels, but there is definitely a lot of information on carnitine supplements having this effect. Please see my article L-Carnitine Helps Reduce LDL Cholesterol, Triglycerides, Blood Glucose, and Insulin in Fatty Liver Disease and Diabetes Patients for more information on carnitine and how it can help with abnormal blood lipids, high glucose, and many other related health problems.

      There’s reason to believe that PQQ could work synergistically with carnitine supplements to boost their effect. Unfortunately, so far as I can determine from a bit of searching, nobody has done any studies on this possibility as of yet.

      I did find some discussion that PQQ activates a gene that can help break down cholesterol and triglycerides.

      See these links for more details:

      Generate Fresh Mitochondria with PQQ

      PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). PCG-1α is a “master regulator” that mobilizes your cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.26

      Short-term inhibition of peroxisome proliferator-activated receptor-γ coactivator-1α expression reverses diet-induced diabetes mellitus and hepatic steatosis in mice

      Peroxisome proliferator-activated receptor gamma coactivator 1 alpha promoter polymorphisms are associated with early-onset type 2 diabetes mellitus in the Korean population

      I suspect that PQQ could further help carnitine supplements boost their effects on blood lipids and glucose because PQQ helps keep mitochondria healthy from oxidative damage and helps them replicate more mitochondria. When there is enough carnitine to help shuttle fatty acids into the more healthy and numerous mitochondria that research suggests should result from using PQQ, it seems reasonably likely that these mitochondria would then be able to more rapidly burn off the fatty acids to produce usable energy for cells while each mitochondria has to do a little less work and thereby accumulates less damage as the overall number produce the energy needed by each cell. In the process, they in theory should thereby help maintain healthier blood lipid levels while reducing the need to dump glucose into the bloodstream to fuel the mitochondria. It’s possible that it may also reduce the overall energy and nutrient load needed to maintain the mitochondria in a healthy state, too, as they don’t have to drive their oxidation reactions as intensely and therefore there is more time to repair damage they experience during less intensive operation.

      Hence your guess that the improvements you’ve seen could be due to the mix of PQQ and acetyl L-carnitine seems sensible for these reasons. But it would be nice to have some more definitive confirmation from one or more studies examining this possibility.

      Alison

      • Thanks, that was interesting. I think I am going to try taking more carnitine supplements and dropping the small amount of red yeast rice I have been using. Wish I could find more answers about how much of this improved blood lipids effect is due to PQQ. Also, I should have mentioned I lost about 10 pounds weight while I’ve been taking PQQ and acetyl L-carnitine. This must be connected to the lower LDL cholesterol and triglycerides?

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