There are only two things I’ve come across which really extend the life of laboratory mice. The first I came across is caloric restriction. If scientists reduce the calorie intake of mice, they can extend their lives by up to 50%. (Although this is in dispute as some scientists feel this is the difference between overfed lab mice and mice who have to scrounge a living in the wild.)
The second method is with a substance called coenzyme Q10 (which I also refer to as CoQ or Q10). Emile G. Bliznakov, M.D. at the New England Institute increased the life of female mice by 50% and more by injecting them with coenzyme Q10.[1] And importantly, if you can tell about the quality of life in mice, it appeared they do well in their old age. They maintained glossy coats and skin, and showed little or none of the expected signs of old age – patchy fur, organ degeneration, and lack of mobility.
Coenzyme Q10 is an enzyme helper, which aids in the creation of ATP, which is the compound the body uses as energy. It is not a vitamin in the sense that vitamins are substances the body does not make for itself, like vitamin C, for example. If a human does not get vitamin C from the food supply, he will succumb to scurvy and die. A horrible fate that many seamen suffered just a few hundred years ago, when as much as a third of a crew might be lost to scurvy, a lack of vitamin C. Reading about that, I wondered how they could get a crew, and it turned out I wasn’t far wrong. Sailors were often impressed, or kidnapped, and dragged off. It was the only way of getting a crew.
It turns out that most of creatures in the animal kingdom make their own vitamin C, usually in the liver or kidneys. And coenzyme Q10 is made by the body, but there are so many steps in its manufacture, that as the machinery of the body ages, the ability to make this substance is reduced over the years. There are 17 steps in the manufacture of CoQ requiring seven vitamins – B2, B3, B6, B12, folic acid, vitamin C, and pantothenic acid. If a vitamin is not present, for example, then manufacture will slow down. And while the liver is young, it can manage all 17 steps with few problems aside from vitamin supply issues, but over time it becomes less effective. It is estimated that by the time the body loses the ability to make 25% of its CoQ needs, that death results. The body does get some CoQ from food, but few people eat hearts, where it is found in its highest concentration. But perhaps it makes sense that this is where the most CoQ is found since CoQ is involved in the manufacture of ATP, the molecule the body uses for energy. There is no greater demand for energy than in the heart, so heart muscle cells have the most CoQ found anywhere in the body.
Karl Folkers (1906-1997)
No discussion of coenzyme Q10 goes very far without mention of Karl Folkers, who determined its structure. He was born in Decator, Illinois on September 1, 1906, from a father who had imigrated from Germany. At an early age he developed an interest in chemistry, augmented by playing with chemistry sets. He acquired a B.S. degree in 1928 at the University of Illinois at Champaign-Urbana under the tutelage of Carl G. Marvel, who pointed him toward University of Wisconsin and Homer Adkins. He got his Ph.D. in 1931, and published 8 papers with Adkins. He then went on to Yale for post-graduate work lasting from 1931 to 1934. In 1934, his interest in pharmaceutical chemistry resulted in an appointment to the labs at Merck.
He was instrumental in the discovery of B-12. This was a long process that began in 1926 when Minot and Murphy showed that beef liver contained something that produced in patients a remission of pernicious anemia. A product called Fraction G had a potency of 10 times that of beef liver, but still the particular substance was still not isolated. In 1942, Folkers began to work on this problem, and he assembled a team at Merck to work on the problem. But these discoveries are not the sole work of one person, and discoveries at Glaxo and by a microbiologist at the Maryland Agricultural Experiment Station helped to push the work along. Finally, his team isolated crystals of vitamin B-12 in 1948.
Interestingly, it is bacteria (Streptomyces grisesus) again which provided commercial quantities of B-12 in a bacterial fermentation.
The Discovery of Coenzyme Q10
The discovery of coenzyme Q10 begins in the intestinal mucosa of horses, where in 1955 a new substance, a quinone was identified by Morton in Liverpool. Because it was widely distributed in animal tissues (ultimately, nearly every single cell), it was named ubiquinone.
In 1957, David Green’s laboratory at the University of Wisconsin observed a novel quinone in the lipid extracts of mitochondria, and named it coenzyme Q10 because of its participation in the electron transport chain. Crane, of the University of Wisconsin team, traveled to Maryland to bring the problem to Folker, whose team was well known in the structural determination of natural substances. A year later, Folker’s team had determined the structure of CoQ. The structure of coenzyme Q10 in humans is 2,3dimethoxy-5-methyl-6-decaprenyl benzoquinone.
Summarizing, Folker’s team identified include the structure of vitamin B-6 (pyridoxine), pantothenic acid, biotin, mevalonic acid, B-12, as well as coenzyme Q10. Folker was given many awards, including the Priestly Medal, a Certificate of Merit from Harry S. Truman in 1950, and President’s National Medal of Science from George Bush in 1990.[2]
Coenzyme Q10 and Heart Disease
Coenzyme Q10 does its work in the mitochondria. Mitochondria is a weird thing, something like a cell within a cell. In fact, it appears to be almost a bacterium within the cell. It is the same size as a bacterium. It has its own DNA (which was used to trace back to the ancestral Eve), separate from the cell’s principal DNA. And as we count on bacteria to make cellulase, the enzyme that breaks down cellulose, to get energy from the food we eat, the mitochondria appears to be the furnace, or energy source for the cell.
Mitochondria are found in the greatest abundance where energy is needed the most. So, muscle cells may have several mitochondria, whereas a normal cell may have only one, and heart muscles have the most mitochondria found in a cell because the heart does the greatest amount of work. Not surprisingly, heart is the biggest source of coenzyme Q10 in the food supply. Though few people eat heart, it is perhaps understandable that wild animals such as lions go for the internal organs first, where important substances like CoQ are found in the highest supply. And maybe it makes sense that additional Q10 in the diet would fortify hearts, and improve their output.
And early research into CoQ’s properties started with heart disease simply because that’s where they found it in the largest amounts. Researchers discovered that it that it plainly improved two things: it regulated blood pressure, and it increased heart output (the heart pumped more blood).
In the 1960s it was found by Japanese researchers that Q10 was concentrated in the myocardium, the heart muscle. Folkers and Per H. Langsjoen conducted a study of 19 patients who were expected to die from heart failure. They all responded to the Q10, and all showed “extraordinary clinical improvement.”[3]
Apparently, coenzyme Q10 will not solve the supply problem, that is, nothing I have seen in the literature suggests that it will solve the clotting problem, a blocked cardiac vessel.
However, Q10 does improve the characteristics of each individual cardiac muscle cell, so the amount of work done, the cardiac output, increases with CoQ. Proof comes indirectly from the biopsies of 132 heart patients that Folkers did with associate, Tatsuo Watanabe. Fully 75% of these hearts showed a significant deficit of coenzyme Q10.[4] It was also shown that blood levels of CoQ are low in patients suffering heart disease.
Using the technique of impedance cardiography, a non-invasive electronic measure of the work the heart does, he was able to show in a couple of studies that both cardiac output and stroke volume both increase.[5] And if the CoQ is removed, the output goes back down, so it is important to know that removing CoQ from patients with severe heart deficiencies may be risky.
Studies have shown that CoQ is also beneficial in reducing blood pressure. The method by which this happens is not well understood, but it is theorized that CoQ restores cellular energy levels of the cells in the blood vessels, it allows them to flex with the pressure the heart exerts upon those arteries.[6]
The upshot is that in a program to improve an ailing heart, coenzyme Q10 should play a central role.
Coenzyme Q10 and Cancer
There are two cancer studies circulating on the web about coenzyme Q10, one published and one unpublished. Both studies were funded on Folker’s dime. Without drug company funding or government funding, he went out on a limb and funded these mostly by himself. One was for breast cancer, and the other for prostate cancer.
In 1980 Folkers funded a trial of Q10 for breast cancer, which was conducted by Dr. Knud Lockwood in Denmark, a cancer specialist. Thirty-two “high risk” breast cancer patients` were treated with 90 mg. of Q10, but other substances as well – antioxidant vitamins and essential fatty acids. “No patient died and all expressed a feeling of well-being.” Further, Lockwood wrote, “These clinical results are remarkable since about 4 deaths would have been expected. Now, after 24 months, all still survive; about 6 deaths would have been expected.”[7]
But there was improvement beyond survival for some. Six of the 32 showed partial remission, and two on their own recognizance upped their doses. One was a 59 year old woman with a history of breast cancer in the family, who had had a tumor removed from her left breast. The cancer came back, but “stabilized” at about 1.5-2 centimeters (about ½ to ¾ - inches) when she initiated the 90 mg. treatment. One month after increasing her Q10 intake to 390 mg. daily, the tumor disappeared. Mammography confirmed it had gone away.
Another woman of 74 had a small tumor removed from her right breast. She refused a second operation to remove additional growths and began taking 300 mg. of Q10 daily. Three months later, examination and mammography showed no evidence of the tumor or metastases.
Lockwood, who has treated roughly 200 patients a year for 35 years (or 7,000 patients) wrote that he had “never seen a spontaneous complete regression of a 1.5-2.0 centimeter breast tumor, and has never seen a comparable regression on any conventional anti-tumor therapy.”
The prostate trial funded by Folkers was conducted by Dr. William Judy of Bradenton, Florida. Typically in its beginning stages, prostate cancer is manageable with hormone blockade. However, after 2 to 5 years it often becomes independent of hormone therapy and no amount of hormone inhibition will help.
The trial involved 30 hormone independent prostate cancer patients. 15 had no metastases, and 15 did. He treated them with 500 mg. of Q10 daily. Of the fifteen patients with no metastases, 14 saw their PSA (prostate specific antigen, a marker of prostate size) score return to normal. Of the fifteen with metastases to bone and lung, 8 saw their PSA return to normal, suggesting improvement.
Coenzyme Q10 and Other Applications
There are no extensive studies of coenzyme Q10, the kind that would convince the most skeptical, drug-oriented physician. However, there are indications that the improved energy output of CoQ could be useful in other conditions, such as Parkinson’s disease, multiple sclerosis, migraines, amyotrophic lateral sclerosis, post-polio syndrome, Alzheimer’s Disease, and strokes.
My Kind of Researcher
When one of Folker’s financial backers came down with small cell carcinoma of the lung with widespread metastases, Folker persuaded him that CoQ would do no harm, and might help. The backer had been advised by his oncologist that he had less than a year to live. Fifteen years later he was free of metastases, and felt well. The only therapy he ever received was CoQ.
What kind of backer ever gets that kind of return on his investment? Mostly, it’s give and give, and some day in the future, when you’re dead many years, we’ll have something for your grandkids.[8]
If You Take a Statin, You Need More Coenzyme Q10
If you are taking a statin (Mevacor, Zocor, Lipitor, Crestor) to reduce LDL cholesterol, then you will probably need to take more CoQ because the statin, which inhibits the biosynthesis of the cholesterol, also inhibits the manufacture of CoQ. And CoQ we have already established is critical for energy production, especially for the heart cells, which have extra mitochondria to augment energy production. So, if CoQ production is inhibited, you may get what physician’s call statin-induced cardiomyopathy, a heart condition caused by taking your cholesterol-inhibiting statin, such as Lipitor, Zocor, Crestor, Mevacor.
Getting Coenzyme Q10 from Food
It is possible to get CoQ from food, but it would take a pound of sardines, two pounds of beef, or two and a half pounds of peanut butter to get 30 mg of CoQ. I don’t have figures for heart tissue, but that might take a little less.
Super-Charging the Mitochondria
Coenzyme Q10 does its work in the mitochondria, so it is natural to wonder if there is anything else we can take to aid the mitochondria with its work, and the answer is: maybe so.
More tests with rats suggest that two molecules may help. Alpha lipoic acid (ALA) and acetyl-L-carnitine (ALC). Elderly rats (24-month-old) and lethargic rats had more energy and did better on memory tests. The decline in overall activity typical of the aged rats reversed to the level of young and middle aged rats, aged 7 to 10 months. The researchers compared this to a group of 80 year-old humans throwing away their walking sticks and acting 35 years younger.
Acetyl L-carnitine carries fatty acids from the cytosol (the main body of a cell) into the mitochondria (the energy furnace of the cell) so that fats can be oxidized for energy. A note for vitamin buyers, L-carnitine also performs this function; however, the acetyl form has greater solubility in water, which it allows it to diffuse across cell membranes more easily, including the inner wall of the mitochondria. And you get an extra benefit from the acetyl L-carnitine version: it is involved in the production of the key brain neurotransmitter acetylcholine, and it is able to donate its acetyl group in other biochemical transactions.
Anyway, the initial idea of the researchers was to use acetyl L-carnitine to improve mitochondrial energy output by increasing fatty acid oxidation and to boost metabolic activity. It seemed to work, but there was a downside. The increased output in the mitochondria also generated more oxidative damages: free radicals. Think oxygen and rust.
So, the researchers thought the solution would be to also add to the mix a powerful antioxidant to mop up the free radicals. Alpha lipoic acid is a sulphur-containing antioxidant, soluble in both water and fat, which allows it to have an antioxidant effect anywhere in the body, including the brain. In the mitochondria, alpha lipoic acid can act both as an antioxidant, able to recycle other antioxidants such as vitamin C and vitamin E after they have donated electrons and are no longer effective. Also, it can increase levels of glutathione, which is a critical antioxidant enzyme against many diseases.
Adding alpha lipoic acid seemed to have the desired effect since the combination of the two worked better than either one by itself.
Humans have a lot in common with the chemistry of rats; however, we are not identical. A seven-week test on rats would be equivalent to a 5-year trial in humans. And the levels of these compounds were very high, equal to 50 grams per day of acetyl L-carnitine, and 5 grams of alpha lipoic acid in a human. The happy thing is these products appear to be fairly harmless. And so you will probably be safe enough trying things out while we wait 5 years or more for someone or some organization to fund a 5- year trial. Ten years in all, a long time to wait for confirming studies.
There was one dinky study with 18 healthy sedentary men aged 60-71 at San Francisco State University in 2001. The double-blind, placebo-controlled study lasted 17 weeks. Randomly, they were given either a placebo twice a day or 1,000 mgs of acetyl L-carnitine and 400 mgs. of alpha lipoic acid in two doses. Both groups were asked to perform a demanding sequence of exercises, blood was drawn and tested for signs of exercise-induced oxidative stress. The study looked at nine different biomarkers: ammonia, beta-carotene, glutamine, glutathione, malondialdehyde, total antioxidant status, vitamin C, alpha tocopherol (vitamin E), and gamma tocopherol (another form of vitamin E). For eight of the nine biomarkers, a majority of subjects in the treatment group recorded values indicating that levels of oxidative stress had fallen. The placebo group reported no such benefit.
While these two compounds seem to aid the mitochondria do its work, it has not been shown that these work with CoQ, or that they speed the CoQ in its work. Coenzyme Q10 can take months and months before it kicks in. I would expect the results of studies of these compounds with CoQ to be additive rather than multiplicative. But all the same, I’m taking the stuff now since there doesn’t seem to be any downside to speak of, though I can hardly afford 50 grams a day.
Crummy little dinky studies
If controversy is raised by the issue of coenzyme Q10, then I say hurray! I myself am taking large doses of CoQ based on consistent but slim evidence. I would be happy if public or private funding agencies would do more studies with larger population samples to establish that the findings of these tiny studies are in fact accurate, or not.
Let the cards fall where they will, let’s find out the truth. Of course, let’s not turn off our minds. If a single study comes in that shows CoQ is less effective than some drug in a study funded by a drug company, we can still ask why that was.
How Does It Work Against Cancer?
Unfortunately, as far as how CoQ works against cancer, for example, we stand on the outside looking in. The scientists don’t seem to know. Folkers, a famous peptide chemist, thought there were several possible explanations, which might include CoQ and protein synthesis to the oncogenes involved with the cancers. Dr. William Judy who ran the prostate cancer trial, thought that it was CoQ’s enhancement of the effectiveness of Natural T Killer cells.[9] What we do know even from the outside looking in is that CoQ has rather remarkable properties, which seem to work without harm to humans.
When Taking Coenzyme Q10
It is recommended that the dose of CoQ be increased gradually. It is a fat soluble substance and does best if taken with some fat to improve absorption. And if you have a heart condition, take care when stopping CoQ.
Also, heart patients should not go off CoQ, it could be quite dangerous, especially if it was the CoQ which brought them back to health.
[1] Bliznaknov, M.D., Emile G. and Gerald L Hunt, The Miracle Nutrient Coenzyme Q10, Bantam Books, 1986, p 11
[2] Olson, Robert E., Karl August Folkers (1906-1997), Journal of Nutrition. 2001;131:2227-2230
[3] Folkers, Karl and Per H. Langsjoen, Proceedings of the National Academy of Sciences of the USA (June 1985;82:4240-4)
[4] Bliznaknov, M.D., Emile G. and Gerald L Hunt, The Miracle Nutrient Coenzyme Q10, Bantam Books, 1986, p 70
[5] Bliznaknov, M.D., Emile G. and Gerald L Hunt, The Miracle Nutrient Coenzyme Q10, Bantam Books, 1986, pp 83-90
[6] Bliznaknov, M.D., Emile G. and Gerald L Hunt, The Miracle Nutrient Coenzyme Q10, Bantam Books, 1986, p 110-123
[7] Lockwood, Knud, M.D., Biochemical and Biophysical Research Communications, (March 30, 1994; 199:1504-8)
[8] http://life-enthusiast.com/exula/ingredients/ing_coenzyme_q10.html
[9] http://www.drpasswater.com/nutrition_library/coenzyme_q3.htm
