The Most Promising Antioxidant You Never Heard Of
    By Hank Campbell | May 19th 2014 01:02 PM | 7 comments | Print | E-mail | Track Comments
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    There is a discovery out there that has shown some success with multiple sclerosis, with amyotrophic lateral sclerosis (ALS - Lou Gehrig's Disease), and has even improved the function of aging hearts – but despite all that, you have probably never heard of it.

    No, this is not a story about how a revolutionary breakthrough got bought up by some giant corporation and stuck in a warehouse to protect their profits - it is instead a story about how potentially good products may never see the light of day for lots of reasons. It happens more often than you think.

    In 2013, we covered a study on Science 2.0 which suggested a cure for a mouse version of multiple sclerosis. A few weeks ago a study came out which showed improvements in the arteries of old mice.  This month Elsevier published a study showing improvements in ALS.  Another study last year showed improvement in Inflammatory Bowel Disease (IBD).

    They all had one thing in common – an antioxidant called MitoQ.


    Antioxidants are widely criticized because some companies in the supplements business are correlating all kinds of health benefits without being any more specific than that they contain 'antioxidants'. The $35 billion organic food marketing machine claims locally-grown organic tomatoes have more antioxidants and are therefore superior to regular-priced tomatoes. It's okay to be skeptical of miracle health claims, I know I am. 

    But long before the hype, there was science happening and there still is today.  Antioxidants are intriguing because oxidative phosphorylation, our metabolic pathway, impacts how the energy stored in food can be used within our cells. As we age, mitochondria, an organelle in cells that uses oxygen to turn carbohydrates and into energy, are less able to carry out their core function of making adenosine triphosphate (ATP). When cells age, we age. Obviously, when antioxidants talk about slowing aging it is going to get attention but, as GlaxoSmithKline has discovered with resveratrol, proving it is difficult.

    And some cynicism is warranted. Joe Mercola gushes about antioxidants, which is a red flag for everyone in science, so how can the public separate the salesmanship from the evidence? And if antioxidants impact how cells create energy, why not just take more vitamin E, since antioxidant activity is its most important benefit?  Or vitamin C?   

    Why indeed. But there may be a bigger benefit than selling better health. Under the radar, away from CNN headlines about antioxidants and red wine, scientists think a particular antioxidant may be the key to unlocking answers to a lot of disease problems.  And the company behind it may never see anything for their efforts.

    That takes us back to ALS, MS, heart disease and the MitoQ at the heart of all those studies. It leads to an obvious question; why isn't this in clinical trials? The answer is intriguing.


     MitoQ is appropriately named because it is a mitochondria-targeted antioxidant descended from discoveries of Coenzyme Q that started in 1957. Coenzyme Q, commonly called CoQ10, is a molecule made inside the mitochondria as a component of the electron transport chain, to enable cellular respiration  and ATP. It’s oily and sticky and that is fine inside mitochondria because it doesn't need to exit or enter the membrane but coming from the outside, like with a supplement, it doesn’t penetrate very well. Because the antioxidants didn’t actually get to mitochondria, people who took a CoQ10 supplement didn't get much benefit, just like eating more fruits isn’t enough. It turns out, a CoQ10 supplement only ends up having about 5 percent bioavailability. 

    Credit: MitoQ.

    A decade and a half ago, Professor Michael P. Murphy and Professor Robin A.J. Smith of the University of Otago found a way to change that, by introducing a phosphonium (salt) ion. You are aware that a lot of our bodily functions are electrical in nature. Mitochondria are negatively charged and, as you know from school, opposites attract. By adding a phosphonium group to the Coenzyme Q quinone group they introduced a positive charge and discovered that the antioxidant could still be quickly reduced to active quinol form by cells - but at levels 800-1200 times greater than CoQ10.

    By doing so, Murphy and Smith solved the puzzle as to why just eating more fruits didn't prevent cells from becoming less efficient as we age – and perhaps how to fix that.

    Accumulation of MitoQ10 into cells and mitochondria. MitoQ10 will first pass through the plasma membrane and accumulate in the cytosol driven by the plasma membrane potential (Dyp). From there it will be further accumulated several-hundred fold into the mitochondria, driven by the mitochondrial membrane potential (Dym). There it will be reduced to the active antioxidant ubiquinol. In preventing oxidative damage it will be oxidised to the ubiquinone which will then be re-reduced. ( Murphy, MP, Smith, RAJ, 'Targeting antioxidants to mitochondria by conjugation to lipophilic cations', ANNU REV PHARMACOL TOXICOL Volume: 47 Pages 629-656 2007)

    There are about 200 conditions associated with mitochondria dysfunction and now an antioxidant could be delivered directly into the mitochondria at levels that were really meaningful.

    For obvious reasons, they got patents on it, and research continued. Clinical trials began. Optimism was high.


    Clinical trials are almost as old as society itself. There is a clinical trial in The Bible (the Book of Daniel) but a more famous example is recent, when James Lind used a clinical trial to show that citrus fruit cured scurvy - a disease that leads to open wounds, rotting teeth and lethargy, primarily in sailors - in 1747. Since then, clinical trials have become the norm. 
    We hear a lot about Phase II and Phase III and other terms when it comes to clinical trials so here is a short primer. Research is often done on animal models and, if the results are promising, they will go to a clinical trial. All clinical trials share a few traits in common - informed consent, statistical power and a placebo group. A Phase I trial is looking for side effects that haven't been found in animal tests and to figure out dosing. If things look promising, as in it could be a commercial product, a Phase II trial recruits larger numbers to really see that it works, that there are no side effects, and that it is better than a placebo.

    Phase III is where things get really exciting because it compares the new treatment with the best currently available treatment. In today’s drawn out regulatory environment, a Phase III trial will often be an exit for a small company because conducting it requires a lot of money and a larger company may be confident enough in its potential that they are willing to pay for the product right now.

    Trials are absolutely required to get government approval and what many people do not realize is that, while the government makes the rules about how trials are conducted, companies have to pay for them. "Industry-funded" is the biggest misnomer among critics of science - all studies are industry-funded by law. You can't sell your drug unless you first prove it is safe and does something useful, the local pharmacy cannot be your lab and taxpayers shouldn't have to pay to find out if something is safe.

    Trials are expensive and so no company undertakes them unless they are convinced they have a winner. The risk/reward ratio is lopsided but someone has to be adventurous enough take a chance.

    That’s where venture capital comes in.

    MitoQ was exciting and so a company named Antipodean Pharmaceuticals raised money and bought up the patents. The investors were intrigued by its possible benefits for Parkinson's Disease. It did well in studies, until the Phase II results didn't show the outcome they were looking for.

    Venture capitalists immediately lost interest. 

    That's not a knock on VCs - VCs see a lot of losses before they see any wins and they are a huge boon to society and especially drug discovery. But when an investment doesn't work they check out, for one reason that makes sense to everyone - the clock is still ticking on the patent.

    A company that has a product that doesn't meet expectations in a Phase II trial may have a great thing on their hands somewhere else - but they are not going to own the patent for long to be able to start over. Expecting venture capitalists to spend a lot of money proving the worth of a compound only to lose it and then reset, start all over and pay for new trials is unrealistic.

    But sometimes products fail in a clinical trial and then have other benefits.   Viagra is a good example of a product that didn’t succeed with its original target but was found to have a benefit elsewhere. MitoQ had that too - it actually seemed to work for aging and all those studies had shown MitoQ was safe. Murphy and Smith got a patent for a "Lipophilic cation-mitochondrially targeted antioxidant compositions for skin care" in 2009.

    Today, the MitoQ compound is being marketed by a company fittingly called MitoQ. They sell supplements and skin care and avoid any discussion of medical uses because regulatory bodies frown on that sort of thing when there are no clinical trial results. But the animal model research is right there, it’s hard to miss. They have to be at least a little excited about that.

    I contacted MitoQ CEO Greg Macpherson to ask the obvious questions about how so much research is still finding results - and if MitoQ is ever going to see any money from it.

    He says they are thrilled that it’s still being studied extensively. " I also think the research coming out from various sources on issues relating to “broad spectrum” antioxidants is very interesting. We now know that free radicals have beneficial effects as well - like helping the body identify and remove cells that are infected or unhealthy or to capture the benefits of exercise in terms of breaking down and rebuilding new muscle. Broad spectrum antioxidants appear to negate these positive “pro-oxidant” signaling mechanisms. Something a targeted antioxidant like MitoQ, that goes into the mitochondria within minutes, avoids."

    I asked him if, given the volume of studies coming out showing positive results in animal models, if perhaps creative people were self-experimenting and using the supplements off-label for conditions they read about in studies. He wasn't biting on that but if you search the Internet, people with MS claim it helps, people with heart disease say it helps. And the clinical trials showed it can't hurt.

    No matter what results happen in animal models this year or next, with only 10 years of patent life remaining and such a lopsided risk/reward landscape for drug development, the window is too small to turn MitoQ into another Glaxo. But Macpherson is surprisingly upbeat regardless of that. 

    "MitoQ has incredible potential to help with lots of conditions associated with oxidative stress imbalances and mitochondrial dysfunction, be it primary or secondary to another condition. When we optimize mitochondrial function we are improving the energy production in a cell and more energy means that the cell is able to function optimally. Because our bodies are essentially self repairing machines, when we get optimal cellular function we are providing the energy a cell needs to repair itself. MitoQ also slows the oxidative stress related damage that occurs slowly to our cells over the years. This includes damage to DNA, telomeres and other cellular machinery.”

    And if things do change in the regulatory future?

    "Someone in the future is going to make a killing going back through all these compounds and cross checking their activity vs the various genotypes to assess function and toxicity profiles."

    In the meantime, researchers continue to study MitoQ. Macpherson is happy about that, obviously they believe in it, and a page on their site even carries links to the latest research.

     The science is very strong and safety is well established so we are regularly approached by research scientists and universities around the world who want to investigate it’s effects in the various disease models they are studying.  We have made MitoQ available for this research and there is some amazing research being undertaken by leading scientists that will surface over the next few years.”

    So Mitoq was a loss for VCs but may still end up being a win for society.


    Martin Vlaskamp
    I want to do an experiment with this. Where do I get it?
    'Who can give up essential liberty to obtain a little temporary safety, deserve neither liberty nor safety' Benjamin Franklin
    I think if they are going to take you seriously enough to approve you in the experimenter requests they curate, it might help if they know you read the article first.
    Hank provided a link where supplements can be bought.

    One might wonder whether there would be any need for 'mitochondrial permeating supplemental antioxidants' if one were to control the amount of iron allowed to accumulate in the mitochondria.
    "Lipofuscin-bound iron is a major intracellular source of oxidants: role in senescent cells"
    Thereby allowing food bound quinols and phosphates, vitamin E and chaff as examples, to naturally accomplish what supplemental MitoQ is ntendd to accomplish?
    "Mitochondria as Possible Pharmaceutical Targets for the Effects of Vitamin E and its Homologues in Oxidative Stress-Related Diseases"

    "It is suggested that pulse doses of iron chelators that easily penetrate membranes could be used to diminish lipofuscinogenesis"

    Bonny Bonobo alias Brat
    Very interesting article Hank. I have been taking a daily supplement of Coenzyme Q10 for over 30 years ever since I read a newspaper article when I was about 20 years old in which thousands of white coat laboratory technicians were interviewed about what supplements if any they were taking after them often being in a unique position of being able to observe first hand the effects of the many drugs and supplements they were testing on thousands of laboratory animals. At the time it was claimed that coenzyme Q10 had been seen to double the life expectancy of some laboratory mice and as a result of this and maybe their own observations quite a high percentage of these lab technicians were found to be taking Coenzyme Q10 supplements daily but nothing much else of any significance, like aspirin for example. 

    Occasionally I forget to take my Coenzyme Q10 but then I usually notice a mild craving to take it later on in the day which may be just a psychological craving not a physical one, I'm not sure. 

    Last month I went for a pap smear and a relatively young lady doctor who was not my normal doctor performed this test because my regular doctor is a man and I felt a bit uncomfortable about him doing it. She took the sample and then filled out the details ready to send it off for analysis. When she asked me my birth date for the form she acted very amazed and said she thought I was more than 10 years younger and kept asking me 'what's the secret?' I told her that a lot of people say I look 10 years younger than I am and ask me that same question and often I just think they are being polite but that if its true then maybe the daily Coenzyme Q10 is having some sort of anti-aging effect on me and also maybe causing me to have a late menopause? I guess I will never know but one thing is for sure I am going to keep taking the coenzyme Q10 ;)
    My article about researchers identifying a potential blue green algae cause & L-Serine treatment for Lou Gehrig's ALS, MND, Parkinsons & Alzheimers is at
    The little known amino acid L-ergothioneine found in mushrooms is a natural mitochondrial antioxidant. I'd love to see it tested against MitoQ. L-erg meets the definition for a vitamin but hasn't yet been recognized as such. Still while MitoQ passively enters mitochondria L-erg is actively transferred into mitochondria since it has specific transporters as is common with vitamins. So I predict L-erg outperforms MitoQ.

    Greetings All,

    If you think MitoQ is "interesting" then you will love SKQ1.
    Google: SKQ1 Skulchev

    " It's the Mitochondria ! Stupid"
    Albert Thompson III circa 1990