Trials Find More Health Benefits for Coenzyme Q10

October 8, 2019

Most of us are familiar with the important role of coenzyme Q10 (CoQ10) in the body’s production of energy, particularly in the heart muscle. Recent research continues to uncover positive effects for this versatile nutrient in diverse chronic health conditions.

The results of a review and meta-analysis of nine clinical trials that appeared on June 8, 2019, in Pharmacological Research, suggests an effect for CoQ10 against the systemic inflammation that plays a role in all stages of chronic diseases. Trials included a total of 509 chronic disease patients who received CoQ10 or a placebo for 8 to 12 weeks. It was determined that oral CoQ10 supplementation was associated with a significant reduction in blood levels of the inflammation markers tumor necrosis factor-alpha (TNFa) and interleukin-6 (IL6), which suggests that CoQ10 could improve the inflammatory state that contributes to numerous diseases.

On August 7, 2019, the journal Clinical Rheumatology reported the results of a randomized, double-blind trial in which CoQ10 or a placebo were administered to a total of 54 rheumatoid arthritis (RA) patients. While matrix metalloproteinase 3 (an enzyme that is involved in the destruction of bone and cartilage) increased significantly among those who received the placebo, participants who received CoQ10 experienced a reduction in pain, tender joints and disease activity scores by the end of the trial. “It seems that CoQ10 may provide a new complementary approach for RA patients,” authors Seyed Mostafa Nachvak and colleagues remarked.

Like rheumatoid arthritis, fibromyalgia is a chronic, painful condition. In a randomized, crossover trial reported on August 7, 2019 in Free Radical Research, fibromyalgia patients received the drug pregabalin (Lyrica®) plus CoQ10, or pregabalin and a placebo for 40 days, after which the treatments were switched for another 40-day period. While pregabalin alone reduced pain and anxiety, the addition of CoQ10 was associated with greater relief. CoQ10 supplementation was also associated with decreased mitochondrial oxidative stress levels and inflammation, and an increase in the antioxidants glutathione and superoxide dismutase (SOD).

Polycystic ovary syndrome (PCOS) is a hormonal disorder affecting reproductive-aged women. The syndrome may include multiple ovarian cysts, acne, irregular periods, cardiometabolic symptoms and other conditions. In a randomized trial that involved women with PCOS reported in the February 2019 issue of Archives of Medical Research, supplementation with a combination of CoQ10 and vitamin E was associated with a decrease in serum total cholesterol, low-density lipoprotein (LDL) cholesterol and visceral fat, and an increase in high-density lipoprotein (HDL) cholesterol. Both nutrients (alone and in combination) were associated with lower systolic blood pressure.

These recent studies add to an ever-increasing body of evidence in support of the health benefits of CoQ10. Since the coenzyme is essential to the production of energy and made by nearly every cell of the body, future research will undoubtedly uncover even more roles for this ubiquitous compound.

Why my customers buy supplements from me
Through the last 38 years I have accumulated thousands of hours of research on nutrition, supplements, and vitamins. Customers buy from me because I can explain what each supplement does in their body and what is the correct amount to take for their desired outcome. Our company Life Extension can order extensive blood tests for our customers using the same labs like "LabCorp" that your Doctor uses at a much lower price. The results of the blood test are given to our customer and an MD on our staff, most of my customers also request that I get a copy and many times we will have a three way conversation about what the blood test means and what course of action is best for our customer. All of these discussions with our doctors is completely free. When properly analyzed the blood test can tell our customer what supplements they really need, because many supplements are made by our body, if our body is healthy enough and young enough. An example is CoQ10 which is made by the body, usually in an amount that keeps us healthy until we are about 40 which is when body production goes down. When we reach 50 to 60, it can go down by 50% but that reduction is not consistent with everyone. My twins did a comprehensive blood test when they were 19 and we found they were low in CoQ10 at that young age. The purpose of CoQ10 is to be part of the conversion of the food we eat to the fuel our cells need to function. If we had no CoQ10 in our body we would die, people who are in their 70's or 80's usually are operating with less than 30% of what they had when they were young which is part of the reason they don't function like they did when they were young. The blood test is great because it focuses in on the specific supplements you need or don't need but you don't have to take a blood test. A lot can be figured out with some basic logic.

Most people depend on their doctor to tell them about nutrition but most doctors know very little about nutrition, of course, they are great at so many other things. Below are three things written by doctors that substantiate this fact.

The most highly rated peer-reviewed, primary research journal in nutrition and dietetics, The American Journal of Clinical Nutrition (AJCN) published an article about a survey they conducted with all of the accredited medical schools in the United States. They found that on average, students received 23.9 hours of nutrition instruction during medical school. The schools ranged from 2 hours of nutritional training to 70 hours. A recent Washington Post article stated that 71% of graduating doctors do not even get the minimum 25 hours recommended by the National Academy of Sciences.

As a wholesaler I have realized that most people don't know how critical vitamins and supplements are to the health of their cells which are responsible for everything we do from talking, seeing, catching a ball, making dinner, or thinking.

If we don't get any of these vitamins and supplements, we die, if we don't get enough, our body doesn’t function well, we get sick, we get diseases. A healthy body makes many supplements, which is why it is imperative to have periodic blood tests to measure all the supplements we need to stay healthy. The only doctors that do this kind of blood test are nutritionists. Life Extension offers comprehensive nutritional blood tests at a fraction of the cost of your doctors test using the same labs, nationwide. Our doctors will go over every aspect of the blood test with you for free.

When our cells fall apart, we fall apart and get cancer, heart disease, Alzheimer's, and all the rest.

If I gave you the task of reading about how to nourish your cells and even rebuild them to enable you to live a healthy productive life past 100 and it took you hours to read and understand it all, would you devote a few hours of your life to enable you to live an extra 20 or 30 years in great health?

If this sounds too good to be true realize that I am on the conservative side compared to many successful wealthy people. Larry Ellison has put hundreds of millions of dollars into life extension research, he wants to live forever. In 2014, he was listed by Forbes as the third wealthiest man in America and as the fifth wealthiest person in the world, with a fortune of 56.2 billion dollars. The president of Life Extension, William Faloon, my boss, has donated 150 million dollars to hospital and University research programs pertaining to life extension. There is a movement in recent years by the rich, super rich, and scientists to increase life spans hundreds of years and they are reaching for the possibility to live forever. Google the word “CRISPR” and you can find numerous articles about how people can live indefinitely in great health by changing the DNA of their individual cells.

The good news for us is that all this research is uncovering how to stay healthy in the life we presently have and even to extend it 20 or 30 years, right now.

My goal is to show people how to live well past 100 in great health and to develop a database with all of our results so that we can prove that following this plan and taking the necessary supplements will enable us to extend our lifespan, in great health, that no government or prescription drug company can argue with.


My customer, Barbara, recovers from 4th stage cancer

The letter below is from Barbara, kindly giving me credit for helping in her recovery.

In January 2018, I was rushed into an emergency room because I was having tremendous stomach pain. I had not been able to eat for several weeks and was literally starving to death. They did a scan and found a perforated bowel. I was diagnosed with 4th stage metastatic colon cancer, which had spread to my lungs. They performed lifesaving emergency surgery on my colon and then I met with 5 different oncologists to determine future treatment options. All but one oncologist told me there is no cure for a 4thstage diagnosis. (Needless to say, I chose to work with the doctor who said I had a 20% chance of a cure.) Because chemo and radiation destroy the good with the bad, I was determined to maintain my health while undergoing these conventional treatments. Making diet changes and using supplements is how I’ve always managed my family’s health issues, so I knew that would be my first approach. Unfortunately, because oncologists’ only use chemo, radiation, and surgery when treating cancer, I felt overwhelmed trying to decide on my own what supplements to take.

When I shared my diagnosis with my cousin, he not only insisted I start using the ketogenic diet, he introduced me to his friend, Joe Hammond, a supplement distributor for Life Extension. I contacted Joe and he immediately went to work with Life Extension’s medical team to create a regimen of supplements specific to my health issues. Joe also helped me locate a doctor who could work with my oncologist. I had just relocated to Colorado when I discovered I had cancer and needed to find a doctor that practiced holistic medicine. Joe let me know Life Extension has a directory of Doctors and Health Practitioners, organized geographically, who are open to alternatives to allopathic medicine.

I feel so lucky to have met Joe Hammond - he’s gone above and beyond my expectations helping me get answers. Not only did he select the supplements I needed to help combat the side effects of chemo and to rebuild my immune system, he also saved me a fortune in blood work. It is critical to have a baseline understanding and to follow-up over time to see how well you’re actually doing. The only way to know for sure is to do blood work. Fortunately, Life Extension has numerous blood tests you can purchase and take to any local lab. It is far cheaper than going to your doctor to get the tests run!

I have done amazingly well this year with my health. Thirteen chemo treatments and two major surgeries – tough on my body! However, I did not suffer with neuropathy, hand and foot syndrome, dry mouth and the numerous other side effects that come with chemo treatments. While I had a few days during the week of chemo where I was slightly nauseous, for the most part I felt well and had good energy. The best part of my journey – the tumors in my lungs shrunk to the point where all of them were removed and I am currently cancer free. I’m almost afraid to put that in writing – I was told in January I had two months to one year at best. I attribute how well I’ve done to the ketogenic diet and the supplement program Mr. Hammond helped pull together for me.


PQQ Revitalizes Brain Energy

August 2019

By Kathy Honem

Scientists have documented that PQQ helps grow new mitochondria in aging cells.

This is important because over time, cell energy diminishes as mitochondria weaken and die. The result is accelerated aging throughout the body.1-3

PQQ facilitates production of new mitochondria,4-7 and helps energize existing mitochondria.

As research continues, PQQ promises to play a key role in the fight against the ravages of aging. Studies show that it restores youthful function and, in animal studies, enhances lifespan. 8,9

Of significance to maturing individuals is the ability of PQQ to protect the brain from traumatic injury and stroke-induced damage, in addition to its systemic anti-aging properties.

PQQ is a vitamin-like compound essential for cellular energy functions.

Mitochondria and Aging

outline of brain

Mitochondria act like tiny power plants. They take digested nutrients and convert them into energizing compounds that cells use to do their work.

Most cellular functions rely on a constant supply of energy from mitochondria for essential activity such as growth, repair, and reproduction.

During our lifetime, mitochondria divide on their own to replenish their numbers—a remarkable process known as mitochondrial biogenesis. But with advancing age, this process slows.

Mitochondrial biogenesis is critical to protect cells from premature aging.2,3 As we get older and mitochondrial function diminishes, many health problems manifest, including neurodegeneration.1-3

But mitochondria can continue to grow, repair, and replenish themselves even in later life. They just need a boost—and that’s where PQQ comes in.

PQQ Boosts Mitochondrial Biogenesis

Man and woman smiling

PQQ serves as a cofactor for several energy-generating reactions in the mitochondria.10 Animals raised without any intake of PQQ display many abnormalities of growth and development.11

New research confirms that PQQ is a powerful stimulator of mitochondrial biogenesis.4-7

A study evaluated the effect of a single dose of PQQ in human subjects.12 Each participant was given 0.3 mg of PQQ per kilogram of body weight, which amounts to approximately 20 mgfor an average person.

Within 48 hours of supplementation there was a definitive increase in mitochondrial function as measured by metabolites in the urine.

A side benefit to this single 20 mg dose of PQQ: Markers of inflammation, including C-reactive protein and interleukin-6, decreased, showing evidence that PQQ also has an anti-inflammatory effect that could help ward off a variety of ailments.

Healthy Brain Aging

The brain is one of the most metabolically active organs in the body. Because of PQQ’s ability to stimulate mitochondrial growth, researchers believed that it should have beneficial effects for cognition and brain health.

Mitochondrial biogenesis has been identified as key in protecting against neurodegeneration and cognitive decline.13,14

In one study, 41 healthy, elderly subjects were randomized to receive either 20 mg of PQQ daily for 12 weeks or a placebo. Compared to the placebo, supplementation with PQQ was associated with significant improvements in attention and working memory, and an associated increase in brain blood flow in the frontal lobes.14

In elderly people with forgetfulness (either self-identified or identified by a family member or acquaintance), the same PQQ dose led to improvements in memory-test scores after eight weeks.15

Researchers have also found evidence that PQQ may slow the progression of serious neurodegenerative disorders, including Alzheimer’s and Parkinson’s—or even prevent them altogether. 16-22 That’s because, in addition to boosting mitochondrial function, PQQ has been found to prevent the accumulation of abnormal proteins (such as beta-amyloid and alpha-synuclein) associated with these diseases.16-18

Moreover, PQQ protects against the toxic effects of these abnormal proteins that damage brain function. For example, cells exposed to amyloid normally display oxidative stress and cell death. In one study, treatment with PQQ dramatically reversed these effects, helping to keep brain cells viable and healthy.22 This indicates remarkable potential for PQQ to halt the development of various kinds of dementia.

PQQ and Recovery from Traumatic Injury

The ability of PQQ to protect and keep cells healthy, even in the face of damage, has led to explorations of PQQ as a neuroprotective compound in cases of traumatic injury.

In experimental rodent models of traumatic brain injury, treatment with PQQ successfully prevented cell death.23,24 It did this by preventing the activation of caspases, which are proteins associated with pathways that lead to cell death. This protective effect is linked to improved brain function and cognitive performance—that are otherwise significantly reduced after head injury.

These neuroprotective effects also extend to the peripheral nervous system, that connects the brain and spinal cord to the limbs and organs. The regeneration of peripheral nerves that have been severed is enhanced by treatment with PQQ. 25-28

This important finding has led to the development of nerve repair conduits that are filled with PQQ. The aim is for surgeons to use these in nerve reconstruction procedures to help maximize recovery following nerve injuries. 25,27,28

Head trauma is a major problem for maturing individuals at greater risk for falls. PQQ may protect against excessive damage if one sustains a head injury.

Man and woman reading together

The Benefits of PQQ

  • Pyrroloquinoline quinone (PQQ) is a vitamin-like compound that many scientists believe should be categorized as an essential nutrient.
  • In addition to PQQ being a required cofactor for some enzymes, it is one of the most powerful compounds discovered to stimulate mitochondrial biogenesis.
  • Rejuvenating cells through mitochondrial biogenesis improves health and protects cells from age-related loss of function, and from disease.
  • In tissues like the brain, with high energy requirements, PQQ can boost function and may prevent the progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.
  • PQQ is not produced in the body, so boosting its levels requires increased oral intake. Most human studies of PQQ have utilized doses of around 20 mg per day.

PQQ and Stroke

Stroke remains a leading cause of paralysis, memory loss, nursing home confinement, and premature death.

Emergency medicine technologies such as clot-dissolving drug therapy (tissue plasminogen activator or tPA) are sparing numerous stroke victims from permanent paralysis.

More advanced approaches, such as endovascular thrombectomy (mechanical clot retrieval from occluded cerebral artery), are enabling more stroke victims to avoid paralysis. Thrombectomy has been shown effective up to 24 hours after onset of ischemic stroke symptoms.

PQQ can also play a role in further protecting the brain from the devastation of a stroke.

In lab studies, PQQ reduced ischemic damage, potentially improving the quality of life following a stroke.

This was demonstrated in an animal model of ischemic stroke. When PQQ supplementation was given beforeischemia was induced, it significantly reduced the size of the damaged brain tissue region.

Surprisingly, PQQ had a similar protective effect even when it was administered after the ischemia was induced.29

Another study showed similar neuroprotective effects. It also showed that PQQ led to significantly improved neurobehavioral scores after the stroke. 30 These findings are tremendously exciting for those working in the area of human stroke prevention and treatment. The implication is that stroke patients could be given PQQ in the emergency room to reduce paralyzing brain damage.

PQQ Extends Lifespan

Image of a brain on a computer

The way PQQ boosts mitochondrial growth turns out to have extraordinary side benefits. 6

Supplementation with PQQ turns on a gene expression pathway regulated by PGC-1 a, a well-known activator of mitochondrial biogenesis.

It appears to achieve this through activation of SIRT1, a sirtuin protein. Numerous recent studies have shown that sirtuins help regulate cellular health, protect against disease and age-related loss of function, and play a role in boosting longevity.6,31-38

In other words, not only does PQQ trigger mitochondrial biogenesis, it also activates and supports many other protective mechanisms tied to lifespan extension and health.

In addition to all these effects, PQQ mops up damaging free radicals. Many other nutrients can only quell oxidative stress for a short period of time.

For example, vitamin C can only participate in about four cycles of beneficial redox cycling. In comparison, one molecule of PQQ can undergo an astonishing 20,000 cycles!10,39

As a result of all these abilities, PQQ has shown it can increase lifespan. A type of roundworm, C. elegans, is an animal model commonly used to study longevity, due to its relatively short lifespan. Two different research groups have used this model to evaluate PQQ’s life-extension effects.8,9

In both studies, supplementation with PQQ led to a significant increase in the average lifespan of treated animals. In fact, the studies’ findings were almost identical, with an average increase in lifespan by 30% in one study and 31% in the other.

Dr. Bruce N. Ames is a widely respected professor emeritus of biochemistry at the University of California at Berkeley, who has also worked for the National Institutes of Health. Dr. Ames writes frequently about nutrients that prolong life and improve health.

Dr. Ames puts PQQ on his shortlist of “longevity vitamins,” 8 based on its ability to stimulate mitochondrial biogenesis. He maintains that optimal levels of PQQ, along with a handful of other compounds (like CoQ10), are “necessary for promoting healthy aging.”


PQQ is synthesized in some of the Earth’s simplest and oldest organisms, such as soil bacteria. That has led scientists to believe it may be central to the very formation and existence of life on this planet.

This viewpoint is supported by fascinating findings from outer space. Researchers recently analyzed the chemical makeup of dust from a comet’s tail. They found evidence that PQQ is contained in this material. 40,41

This startling discovery has led to speculation that the Earth may have been seeded with PQQ from space, contributing to the development of early life.


Scientists and physicians are just beginning to recognize the importance of pyrroloquinoline quinone (PQQ). Compelling evidence shows this nutrient is crucial for healthy cellular functions.

Through its ability to activate mitochondrial biogenesis, PQQ supports healthy aging, and helps protect cells from damage that contributes to loss of function in older age.

Increased intake of PQQ has demonstrated the ability to augment healthy brain function and may prevent age-related loss of cognitive function, including dementia due to stroke or Alzheimer’s disease.

Because PQQ is not produced in the body, it must be acquired from the diet or through supplementation. To date, human studies have generally utilized doses of approximately 20 mg of PQQ daily.

If you have any questions on the content of this article, please call Joe Hammond at 1-786-370-8557 or email


  1. Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest. 2013 Mar;123(3):951-7.
  2. Srivastava S. The Mitochondrial Basis of Aging and Age-Related Disorders. Genes (Basel). 2017 Dec 19;8(12).
  3. Valero T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des. 2014;20(35):5507-9.
  4. Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression. J Biol Chem. 2010 Jan 1;285(1):142-52.
  5. Hwang P, Willoughby DS. Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise. J Am Coll Nutr. 2018 May 1:1-11.
  6. Saihara K, Kamikubo R, Ikemoto K, et al. Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1/PGC-1alpha Signaling Pathway. Biochemistry. 2017 Dec 19;56(50):6615-25.
  7. Stites T, Storms D, Bauerly K, et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J Nutr. 2006 Feb;136(2):390-6.
  8. Sasakura H, Moribe H, Nakano M, et al. Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans. J Cell Sci. 2017 Aug 1;130(15):2631-43.
  9. Wu JZ, Huang JH, Khanabdali R, et al. Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans. Exp Gerontol. 2016 Jul;80:43-50.
  10. Rucker R, Chowanadisai W, Nakano M. Potential physiological importance of pyrroloquinoline quinone. Altern Med Rev. 2009 Sep;14(3):268-77.
  11. Akagawa M, Nakano M, Ikemoto K. Recent progress in studies on the health benefits of pyrroloquinoline quinone. Biosci Biotechnol Biochem. 2016;80(1):13-22.
  12. Harris CB, Chowanadisai W, Mishchuk DO, et al. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects. J Nutr Biochem. 2013Dec;24(12):2076-84.
  13. Li PA, Hou X, Hao S. Mitochondrial biogenesis in neurodegeneration. J Neurosci Res. 2017Oct;95(10):2025-9.
  14. Itoh Y, Hine K, Miura H, et al. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ) on Cognitive Functions. Adv Exp Med Biol. 2016;876:319-25.
  15. Koikeda T, Nakano M, Masuda K. Pyrroloquinoline quinone disodium salt improves higher brain function. Med Consult New Remedies. 2011;48:519-27.
  16. Kim J, Harada R, Kobayashi M, et al. The inhibitory effect of pyrroloquinoline quinone on the amyloid formation and cytotoxicity of truncated alpha-synuclein. Mol Neurodegener. 2010 May 20;5:20.
  17. Kim J, Kobayashi M, Fukuda M, et al. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins. Prion. 2010 Jan-Mar;4(1):26-31.
  18. Kobayashi M, Kim J, Kobayashi N, et al. Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein. Biochem Biophys Res Commun. 2006 Oct 27;349(3):1139-44.
  19. Lu J, Chen S, Shen M, et al. Mitochondrial regulation by pyrroloquinoline quinone prevents rotenone-induced neurotoxicity in Parkinson’s disease models. Neurosci Lett. 2018 Nov 20;687:104-10.
  20. Martino Adami PV, Quijano C, Magnani N, et al. Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer’s disease. J Cereb Blood Flow Metab. 2017 Jan;37(1):69-84.
  21. Sawmiller D, Li S, Mori T, et al. Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer’s disease. Heliyon. 2017 Apr;3(4):e00279.
  22. Zhang JJ, Zhang RF, Meng XK. Protective effect of pyrroloquinoline quinone against Abeta-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Neurosci Lett. 2009 Oct 30;464(3):165-9.
  23. Zhang L, Liu J, Cheng C, et al. The neuroprotective effect of pyrroloquinoline quinone on traumatic brain injury. J Neurotrauma. 2012 Mar 20;29(5):851-64.
  24. Zhang P, Ye Y, Qian Y, et al. The Effect of Pyrroloquinoline Quinone on Apoptosis and Autophagy in Traumatic Brain Injury. CNS Neurol Disord Drug Targets. 2017;16(6):724-36.
  25. Azizi A, Azizi S, Heshmatian B, et al. Improvement of functional recovery of transected peripheral nerve by means of chitosan grafts filled with vitamin E, pyrroloquinoline quinone and their combination. Int J Surg. 2014;12(5):76-82.
  26. Li HH, Liu SQ, Peng H, et al. Pyrroloquinoline quinone enhances regeneration of transected sciatic nerve in rats. Chin J Traumatol. 2005 Aug;8(4):225-9.
  27. Liu S, Li H, Ou Yang J, et al. Enhanced rat sciatic nerve regeneration through silicon tubes filled with pyrroloquinoline quinone. Microsurgery. 2005;25(4):329-37.
  28. Luo L, Gan L, Liu Y, et al. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect. Biochem Biophys Res Commun. 2015 Feb 20;457(4):507-13.
  29. Jensen FE, Gardner GJ, Williams AP, et al. The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury. Neuroscience. 1994 Sep;62(2):399-406.
  30. Zhang Y, Feustel PJ, Kimelberg HK. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat. Brain Res. 2006 Jun 13;1094(1):200-6.
  31. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71.
  32. Johnson S, Imai SI. NAD (+) biosynthesis, aging, and disease. F1000Res. 2018;7:132.
  33. Zhang C, Wen C, Lin J, et al. Protective effect of pyrroloquinoline quinine on ultraviolet A irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway. Mol Med Rep. 2015 Sep;12(3):
  34. Zhang J, Meruvu S, Bedi YS, et al. Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells. Nutr Res. 2015 Sep;35(9):844-9.
  35. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253-95.
  36. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-47.
  37. Satoh A, Stein L, Imai S. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol. 2011;206:125-62.
  38. Watroba M, Dudek I, Skoda M, et al. Sirtuins, epigenetics and longevity. Ageing Res Rev. 2017 Nov;40:11-9.
  39. Ames BN. Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):
  40. Krueger FR, Werther W, Kissel J, et al. Assignment of quinone derivatives as the main compound class composing ‘interstellar’ grains based on both polarity ions detected by the ‘Cometary and Interstellar Dust Analyser’ (CIDA) onboard the spacecraft STARDUST. Rapid Commun Mass Spectrom. 2004;18(1):103-11.
  41. Available at: Accessed May 23, 2019.


Reducing Nighttime Urinary Frequency in Men

July 2019

By Stephen Harrington

Waking up multiple times during the night to urinate is more than an inconvenience.

It’s one of the most common lower urinary tract symptoms in older men.

The medical term for this is nocturia.

It disrupts sleep patterns, which can lead to a host of health problems, and it’s a frequent cause of falls and resulting fractures. 1,2

Current medical therapies offer limited improvements. 3

A recently conducted pilot trial evaluated the effect of four nutrient compounds plus melatonin on mild, lower urinary tract symptoms, especially nocturia in healthy, older men.4

The primary study outcome was a decrease in nighttime urination. 4

By the end of the study, the number of people suffering from nocturia at all was reduced by 64%. And not a single participant was left waking up more than one time a night.4

This finding can potentially help millions of men who suffer from an overactive bladder to improve their sleep health, while reducing risk for falls and injuries.

A Common Aging Problem

Man sleeping

The male urinary tract is prone to problems that worsen with age.

Lower urinary tract symptoms (LUTS) are a broad spectrum of clinical manifestations related to the bladder, urethra, and prostate gland. LUTS affect as many as 70% of men over 80 years of age.5

Besides nocturia, these symptoms can include increased urinary frequency, urgency, incontinence, incomplete bladder emptying, hesitancy, prolonged micturition, dribbling and a weak urine stream. 6

The worsening of LUTS as men get older is due to various factors that cause dysfunction of the urinary system.7 An overactive bladder, enlargement of the prostate gland, and damage to the urethra can all contribute to urinary symptoms.

Compounds that incite chronic inflammation in the urinary tract can contribute to the development of LUTS and prostate enlargement.8,9 Men with LUTS have increased levels of plasma pro-inflammatory biomarkers.8

The aging process increases the risk for all of these problems. Obesity, diabetes, high blood pressure, smoking, some medications, nervous system disorders, and others can also contribute to LUTS.10

The Dangers of Nocturia

The most common LUTS, and the one which can lead to the most serious problems, is nocturia, the need to get up to urinate during the night, often more than once.1,2

Nocturia can occur in at least half of all men over 50 years of age.11 Clinically relevant nocturia, defined as having to get up to urinate two or more times each night, increases significantly with advancing age, affecting as many as 62% of those aged 70-80.1

Aside from being annoying, nocturia is also a serious health condition that should not be trivialized. Nighttime urinary frequency has the greatest impact of any of the LUTS on quality of life. 1,2,11,12

By disturbing sleep, nocturia can contribute to poor health, lower energy, depression, and increased overall mortality.1,13-16

Frequent nocturia can result in falls. Particularly in older individuals who may suffer from frailty, poor balance, and bad vision, navigating the way to the bathroom multiple times in the middle of the night can be treacherous.

Very tired man


  • Lower urinary tract symptoms (LUTS) is a constellation of symptoms that affect urinary function in men, caused in part by an overactive bladder, enlargement of the prostate gland, and/or injury to the urethra.
  • With advancing age, LUTS is increasingly common, affecting up to 70% of all men over 80 years of age.
  • The most common symptom of LUTS is nocturia , the need to wake one or more times during the night to urinate.
  • Untreated nocturia is associated with risk for falls and related injuries, poor sleep, and diminishing physical and mental health.
  • Five compounds—beta-sitosterol, pygeum bark extract, lycopene, boron, and melatonin—have been shown to reduce LUTS and nighttime urination frequency.
  • A pilot clinical trial of these ingredients showed a significant reduction in nocturia in older men suffering from mild LUTS.

Remedies for Nocturia

Most pharmaceutical approaches to treating LUTS focus on controlling bladder overactivity and obstruction of urine flow. These drugs are far more effective in treating the daytime symptoms of LUTS, but have little impact on nocturia.17

But research has shown that several compounds have beneficial effects on the aging urinary system and can potentially reduce nocturia. A study showed that the following five compounds work together to maximize the relief from nighttime urinary problems.


Beta-sitosterol is a plant sterol isolated from the oils of certain vegetables and nuts. A study in an animal model established this compound is an inhibitor of an enzyme in the prostate gland, called 5a-reductase, which converts testosterone to dihydrotestosterone.18

By reducing the levels of dihydrotestosterone, beta-sitosterol helps reduce age-related prostate enlargement. When the prostate is enlarged, it blocks the flow of urine through the urethra. This contributes to nocturia and other LUTS. Reducing prostate enlargement supports healthy urine flow.19-22

Clinical studies in men with prostate enlargement show beta-sitosterol improves urinary symptoms. In a randomized, double-blind, placebo-controlled study, scoring of LUTS severity was reduced by 50% and measures of quality of life improved by 42%.20

Experimental evidence also points to anti-inflammatory activities of beta-sitosterol. 23-25

Pygeum bark extract

Pygeum africanum is the scientific name for the African cherry tree. The bark of this tree has been used in Africa to improve urinary symptoms and bladder discomfort for centuries. Modern science has revealed that this extract works through several mechanisms. In addition to anti-inflammatory effects, it helps control bladder overactivity and reduces prostate enlargement.26,27

Clinical trials of pygeum bark extract have shown a reduction in frequency of nighttime urination. Two meta-analyses of existing studies found an average 19% reduction in nocturia,26,27 and one trial found as much as a32% reduction in the frequency of nocturnal urination.28

It also has anti-inflammatory properties relevant to prostate enlargement and LUTS. 29


Scientist looking into a microphone

Found in tomatoes and some other red or pink fruits and vegetables, lycopene is a carotenoid pigment with anti-inflammatory properties.30 Lycopene naturally tends to concentrate in the prostate gland,31 making it ideal for reducing the inflammation that can contribute to frequent nighttime urination.32

Like beta-sitosterol, lycopene also has the ability to reduce the production of dihydrotestosterone in the prostate, removing one of the major drivers of prostate enlargement. 33,34

Lycopene has anti-proliferative properties, which means it helps prevent the abnormal growth of cells. In studies of prostate cells, lycopene blocks cell division, which may help prevent enlargement.35

Lycopene was shown to inhibit pro-inflammatory cytokines such as IL-6 and IL-8, further supporting benefits on LUTS. 32,36


In further support of inflammation management relevant to LUTS, the mineral boron has been shown to reduce several markers of inflammation, such as TNF-a, IL-6, and C-reactive protein.37

Boron has effects on other signaling compounds in the body that are associated with development of LUTS and nocturia. It modulates sex hormone function and ameliorates the impact of growth factors, such as IGF-1, which may contribute to prostate enlargement.37,38


Melatonin is a hormone produced by the pineal gland that is involved in the regulation of sleep-wake cycles. Supplemental melatonin can help induce better sleep.

But beyond sleep support, melatonin has been shown to be helpful in treating nocturia. A randomized controlled trial published in the Journal of Urology evaluated its use in men suffering from significant nocturia, waking on average three times each night to urinate.39 In these men, 2 mg of melatonin before bed was superior to a placebo in reducing the frequency of nocturia.

Another human study of melatonin found similar effects. Men receiving the same dose of melatonin reduced the frequency of nighttime urination from an average of 3.4 times per night to 2.6 times per night.40

Successful Pilot Human Trial

Man laying down smiling.

A pilot trial studied a group of men with mild nighttime (LUTS) urinary issues to analyze the effects of a formula containing:

  • Beta-sitosterol 180 mg
  • Pygeum extract (bark) 100 mg
  • Lycopene [LycoBeads® from 15 mg natural tomato extract (fruit)]
  • Boron (as Albion® bororganic glycine) 10 mg
  • Melatonin 2 mg

Healthy men with mild LUTS, aged 45 to 72 years, were recruited for the trial. 4 Baseline urinary symptoms including the frequency of nocturia were assessed before treatment began. Subjects were then instructed to take one capsule of the bladder control supplement formula daily, just before bedtime. At the end of the 60-day trial period, urinary symptoms were again evaluated.

At the start of the trial, 87% of men reported some degree of nighttime urination. This included roughly 50% of men who had to get up one time at night, and 37% who reported waking two to three times each night to urinate at the beginning of the study.

At the end of the 60 days, the researchers observed a remarkable improvement in nighttime urination frequency. Those suffering from nocturia declined from 87% at the start of the trial to only 23% by the trial conclusion—a 64% reduction!

Particularly notable was the reduction in the most severe cases of nocturia. While 37% of the men originally complained of waking two or more times each night to urinate, none suffered from this degree of nocturia at the end of the study. The 23% who continued to report nocturia by the study’s end were all a single awakening per night.

This means that those who suffered the most extreme nocturia, and were at highest risk for falls, loss of sleep, and diminished quality of life, all had a significant positive impact on their symptoms. Some of these men went from two or three nightly wakings to none—a major impact for those at greatest risk.


Lower urinary tract symptoms (LUTS) are very common in men as they get older. The most prevalent and potentially dangerous of these symptoms is nocturia, the need to get up one or more times during the night to urinate.

Conventional medical treatments for urinary disorders mostly address daytime symptoms. They do relatively little to remedy nocturia, which can increase risk of falls and related injuries, and can lead to diminishing physical and mental health and increased rate of mortality.

In a pilot clinical study, five compounds that included beta-sitosterol, pygeum bark extract, lycopene, boron, and melatonin were shown to improve LUTS, and reduce the frequency of nighttime urination in men.

These findings can potentially improve quality-of-life in men who suffer urinary symptoms.

If you have any questions on the content of this article, please call Joe Hammond at 1-786-370-8557 or email


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