Anti-oxidants: A Disappointment or Worse

Oxidative damage was the prevailing theory of aging in the 1990s, and anti-oxidants became the preferred prescription for youthfulness. But in lab animals and in human studies, the cure didn’t pan out – anti-oxidants never did fulfill their potential, and this left the theorists scratching their heads. Then, in recent years the situation became curiouser and curiouser, with hints that oxidative damage might be essential for a kind of stress signal that tells the body to “stay young”.

The Theory

The theory of oxidative damage was known as the “free radical theory” of aging, and it dates to physicist Denham Harman in the 1950’s. The main evidence for it was that damaged molecules – proteins, sugars, and DNA – can be found in the cells of old people, much more so than in young people. The theory is that the cell’s energy-generating machinery (in organelles called mitochondria) is designed around forms of oxygen that are highly reactive, precisely because of their high energy content. In the process of energy generation, inevitably some of these reactive oxygen species (ROS) leak into parts of the cell where they can cause trouble by corroding essential molecules.

From the first, some noted that there were some problems with the theory: One was the pace. You might imagine that these damaged molecules would accumulate gradually over a lifetime, but in fact they are found only in modest quantities until cells become very old, when the damage appears suddenly to be quite severe. And there was a paradox: Muscular activity was known to use energy at a rapid rate, and spurts of exercise generate free radicals far faster than the body can “clean them up”. Yet people (and animals) who exercise live longer, on average than those who don’t. And activity is much higher in youth, when damage seems to be accumulating slowly, than they are in old age, when the damage becomes a catastrophe.

Nobody (except maybe Cynthia Kenyon) stopped to ask: Why should we expect a Mayfly to accumulate as much oxidative damage in one day as a Galapagos tortoise does in 100 years?


The Remedy

If aging was caused by oxidative damage, then medicines that protect against oxidative damage might be able to retard aging. In the 1990s, the race was on to test anti-oxidants for their life extension potential. The body’s own anti-oxidant system sits on a foundation of three substances: glutathione (GSH), superoxide dismutase (SOD), and ubiquinone (also called Coenzyme Q, sold as a supplement called CoQ10). All of them are problematic for oral dosage. Glutathione is produced in the body as-needed, and only lasts a few minutes. There is a supplement, n-acetyl cysteine or NAC, which is a precursor to glutatione, but, once again, no one has been able to demonstrate life extension with NAC supplemention of lab animals. SOD is even more transient, but there is a cantaloupe extract called glisodin that purports to stimulate the body’s production. No life extension has been demonstrated with glisodin supplementation.

The least difficult is CoQ; still, absorption through the stomach is poor, and very little of it gets through to the mitochondria where it is needed*. There is some evidence that CoQ10 lowers risk of heart disease, especially for people taking statin drugs, which knock out the body’s own CoQ10. In lab animals, too, supplementing with CoQ may improve health, but it has failed to extend life span.

Lab scientists like to study aging in roundworms, C. elegans, because they are easy to grow in a petri dish and they have a fixed, short life span. In the 1980s, one of the first discoveries about aging in worms was that many genes affect life span. The capacity to disable individual genes or to snip them entirely out from the chromosome was developed in the 1980s. It was discovered that removing a particular gene made the animals longer than normal worms that had the gene. The gene was dubbed CLK-1, suggesting that it might be a “clock” for aging. Remove one copy of the gene, and the worms live twice as long. Remove both copies and the worm lives 10 times as long!  What does this gene do, such that removing it has such life extension power? It turned out that CLK-1 was an essential step toward making the worm’s version of CoQ!

This was completely unexpected. Disable the worm’s chief mitochondrial anti-oxidant, and the worm lives ten times longer! But the knock-out blow for anti-oxidant supplements came in 1994, with the Finnish “ATBC study”.  It turns out that vitamins A, C and E are also anti-oxidants. 30 thousand Finnish smokers were enrolled in a trial large enough to see even modest improvements in cancer rates and overall mortality. The study did discern a difference – in the wrong direction. People receiving the supplements were slightly more at risk for cancer, and significanctly more likely to die.


Why did anti-oxidant therapy fail to extend life span?

The counter-productive role for anti-oxidants was so unexpected that it was at first dismissed as certainly a statistical fluke. But other studies since ATBC have confirmed the same thing: for extending life span, anti-oxidant vitamins are worse than useless.

Then, ten years later, another line of research offered a possible hint about the meaning of these results – the physiology behind the epidemiology.

Loss of insulin sensitivity is a classic hallmark of aging. As we get older, we poison ourselves with sugar, as I wrote a few weeks ago. Exercise has been known to help preserve insulin sensitivity, but here’s what was found in some lab studies in the mid-2000s: anti-oxidants can block this benefit.

This suggests a hypothesis that is on the edge of geriatric medicine: Free radicals play a vital role in the signaling that controls the rate of aging. It is precisely the chemical damage that is done by vigorous exertion that tells the body to try harder, to dial up the defenses that can slow the aging process.

When the body is stressed, it rises to protect itself. The surprising thing is that frequently the body is able to overcompensate for the stress-induced damage. The body lives longer stressed than un-stressed. This effect is called hormesis, and it has been seen with exercise, with starvation, with many toxins and even with low doses of ionizing radiation.

You may be wondering: if the body is capable of dialing up its defenses even when stressed, why would it not do so all the time? Aren’t we programmed by natural selection to be as strong and as healthy as we are able to be? Isn’t it part of that program to resist the disintegration of old age with whatever resources the body can muster?

This reasoning is right on the money, and it has a profound implication. The body is not doing its best to avoid aging. The body – “willfully” in some genetic sense of the word – allows damage to accumulate. Protective mechanisms are turned off in old age, and aging is permitted to overtake us.

I have promoted a theory that this is done to help stabilize population levels by leveling the death rate. In times of plenty, when stress is minimal, aging provides a measure of population control. But when times are stressful, there are plenty of individuals dying of famine or hardship, and aging steps aside. “Life is tough enough now – slow down the suicide train!”


Oxidation and inflammation

There’s no doubt that oxidative damage to the body’s chemistry accompanies aging, and it accelerates at older ages. But this damage is not inevitable. I suspect that the high rates of damage in old age come not from the body’s everyday energy metabolism, but from chronic inflammation, which is known to rise catastrophically with advanced age. Inflammation is the body’s own front-line defense against microbes, turned against the self in old age as a mechanism of programmed death. Oxidative damage may be self-inflicted.


Bottom line advice for preserving your health

Skip the anti-oxidants. Bring on the anti-inflammatories. I recommend omega-3 oils, turmeric, ginger, and daily aspirin or ibuprofen.

*A renowned Russian biochemist, Vladimir Skulachev invented a form of CoQ with an extra tail on the end of the molecule that is designed to be sucked up by mitochondria. It is known affectionately as SkQ, and it shows promise for life extension in mice, and has been used as eye drops for treatment of macular degeneration and presbyopia.

74 thoughts on “Anti-oxidants: A Disappointment or Worse

  1. A group from Denmark tried to replicate the experiment with anti-oxidant vitamins and exercise, but they found no effect on insulin sensitivity. In fact, none of the benefits of exercise were lost or diminished when vitamins were administered. “Our results indicate that administration of antioxidants during strenuous endurance training has no effect on the training-induced increase in insulin sensitivity in healthy individuals.” (2010)

  2. The 1994 study on antioxidants was done on the cheap. They used synthetic vitamins. What they proved is synthetic vitamins do more harm than good.

    I take 200 mg COq10 from Life Extension daily. My recent blood test showed that my COq10 level was on the high end of the range. I think they have solved the absorbility problem.

    • I take CoQ10 as well. There is good evidence that it protects the heart.
      The form you’re probably talking about is called Ubiquinol, which addresses the issue of absorption through the stomach. But once it gets into the bloodstream, there is still the issue of getting CoQ into the mitochondria, and that process is very inefficient. That’s why the work of Skulachev (see footnote) is so promising. The only anti-oxidant studies that have achieved life extension in mammals involve bringing the anti-oxidant into the mitochondria. In addition to Skulachev, there is a UWashington study where mitochondrial genes were modified to express more of the anti-oxidant catalase.

      • The question I’m sure you’re already asking yourself is — Will mitochondrial stress from a lessening of CoQ10 provide more of a hormetic remodeling that makes it actually better to not consume coq10. It would be interesting to see if the lessening of coq10 over time might actually be slightly advantageous to an aging individual, but there is always tradeoffs (with less energy production). It would be nice to just supplement with hormones as we age, but I believe they also decline for exactly the same reason. And while having less testosterone for men might be disconcerting for some (or other hormones for women), it probably has a net positive effect on longevity as long as your have your body in good working condition. I’m convinced that as long as you can keep a minimum about of strength to starve off Sarcopenia and illness, you probably don’t want an excess of muscle because you don’t actually want to maximize mitochondria (at least in my view) (I also understand maintaining muscle at 90+ is going to be really difficult ). Think of the mitochondrial situation of a baby vs that of a middle aged individual (They have less mitochondria per area I would assume).

  3. Some good reasoning in this article, but. If free radicals contribute to youth, then smokers and sun bathers ought to look youngest no? You could argue that smoking overwhelmes the body as a non natural inhalation of free radicals, but what about sun damage from even averege sun exposure?

        • I choose to utilize the most ‘natural’ of sunblocks; melanin. Melanotan II with sunbed exposure gives me an excellent all-over tan that have prevented the slightest erythema on subsequent sun exposure. M II was developed for this purpose by UArizona to protect state employees from intense sun exposure.

          • There does seem to be many nuances to use of topical vitamin C. Please see:
            A potential problem became apparent to me: vitamin C is said to be best used after sun exposure, not before. But to create a depot of the substance in the dermis, q8h applications are recommended. When could one shoehorn sun exposure into those constraints?
            At least one ascorbic acid ester has been found to block melanogenesis ( This preparation would seem to reduce natural UV protection. Ascorbic acid generally is a depigmenting agent suggesting the mechanism of suppression of melanin production is typical for topical vitamin C.
            Ascorbic acid is generally benign, but melanin has been the substance evolution tricked us out with for the purpose of UV protection.
            Modifying melanocyte activity with melanotan II would seem more ‘natural’ to me. Merely scavenging free radicals after UV exposure seems to me to be too little, too late.

          • Pardon me if this email seems to be a bit boosting. First,I don’t like boosting and second we don’t know what tomorrow might bring. I am age 79 and retired 19 years ago after carrying mail on a foot route fully exposed to the sun for decades. I did have a bit of minor skin cancer removed twelve years ago but with no recurrence. Today I make it a point to get between 30 to 60 minutes of full sun each day over 80% of my body and have done so the last two years. I have NEVER used sun screen. Since I was age 25 I have always taking mega doses of vitamin C daily of at least 10,000 milligrams. Since my 50s I have added other nutrients such as daily flax oil in cottage cheese, vitamin E and other antioxidants. I am on no medication and never have been on a regular basis. I have never been in the hospital. Most serious thing I have had was the flu, perhaps five time in my life. Knock on wood. Good luck to you!

  4. I’m really sorry but your conclusions and advice lack scientific and logic reasons. Noone with deep understanding of the human body would present it the way you did. The lack of scientific sources that are discussed shows that you are picking your sources to fit your opinion and needs. Advices can harm people!
    As it is too strenous to pick out every wrong detail, just a bottom line: Populations in wealthy and stress-free enviroments live definitely longer than elsewhere, they just die from other diseases and causes. Low grade inflammation is definitely a topic nowadays, but the connections and implications remain too unclear, especially for you to say that it is the main cause of aging. Recommending NSAID is dangerous because you don’t know the people you are recommending it to; next there are also negative effects of nsaids, enough studies done, like increasing inflammation in athletes, hindering gains, causing hypertension etc.
    The right amount of antiinflammatories, antioxidants, polyphenols etc, their TIMING and relations to health are not clear! Even fish-oil and vitamin d can have very strong negative effects on your health!

    • Thanks for your comments. Data is incomplete and interpretations are subjective and often controversial. The advice and opinions here are my own.
      In response to
      > Populations in wealthy and stress-free environments live definitely longer…
      It is generally true that wealthier countries have longer life spans, and there are many reasons for this: better education, better medical care, better hygiene, etc. I wouldn’t equate wealthy with stress-free. Also: “hormesis” works for moderate stress, and how much stress is considered “moderate” varies with different kinds of stress. Low doses of ionizing radiation increase life span, even as they increase the cancer risk. For slightly higher doses, the cancer risk overwhelms any hormetic benefit.

      > there are also negative effects of nsaids
      Yes, there are risks, and the variation among different people’s metabolisms is wide. I believe that most people over 50 can benefit from daily aspirin or ibuprofen, but of course individuals differ, and there are many people for whom this advice will not be right.

    • Jezus, TUR, keep yr shirt on.

      TUR wrote:
      “Recommending NSAID is dangerous because you don’t know the people you are recommending it to.”

      A recommendation is not a prescription. Ad hominem is downright rude, unscholarly, and an eye-sore on an otherwise brilliant forum.

    • I agree with TUR. The article contains logical errors. I use against aging only antioxidants, no antiglycating agents, no telomeres “extension”, no calorie restriction (except hunger), and yet I “getting old” 3 times slower.

      I formulated a number of principles, compliance with which is necessary to you get started quench free radicals.
      I’ll give you half of this principles:

      1) Take only a Supplement, which prolong the life of at least 100%.

      2) Half of the chemicals are antioxidants and half are oxidizing agents, choose only quenchers of free oxygen radicals

      3) Do not use natural antioxidants, but artificial. What already exists in the nature, It will no prolong the life (eg. NAC)

      4) Give priority to the mitochondrial antioxidants such as the most famous of them SKQ1

      People are choosing anti aging products which they will use, completely unscientific manner. They’ll find anywhere on the internet promising substances that can prolong life.
      They take the list from the beginning and try to get googled individual substances.
      They will prefer supplements when the salesman smiled at them, and they do not take supplements, which they failed to find it in google. Thus, though they violate my principles formulated and therefore they age as well as others.

      • For arthritic pain in a knee I’ve used Ibu 400mg TID po.
        It’s intriguing effects on the high-affinity tryptophan transporter was an added point of interest.

        “These findings identify a safe drug that extends the lifespan of divergent organisms and reveal fundamental cellular properties associated with longevity.”

        “We find that ibuprofen extends the replicative lifespan of yeast cells by destabilizing the high-affinity tryptophan transporter. ”

        My doses were high, possibly helpful with arthritic pain but the life extending effects are present in c.elegans at much lower mmolar levels than that dosing regimine provided.

        I still use it occasionally especially on cold rainy days so common here in the Pacific Northwest. I’ve found excellent pain relief with some of our other nifty anti-inflammatory stuffs, nootropics and other substances.

        Ibu is proposed (by me at least) to be useful in hormetic doses.

        • That is interesting. Thanks for the comment. You should try rubbing a little Cortizone 10 cream on your knee before you go to bed at night. You will find the pain is all gone by morning. In fact use it on any joint or muscle that hurts. I don’t know why; but it works. The label says it is an anti-itch cream; but it heals everything that hurts. It is available over the counter at any drug store.

          • I guess it’s worth a try though I’ve never considered topical corticosteriods for joint pain. Orally if it’s rheumatic in nature, but never heard of it being useful for osteoarthritis.

            Pain all gone now with tianeptine TID and occ. senlank BID sq. and other agents too numerous to mention.


    • Yes, that is a proposed mechanism of action whereby statins benefit life expectancy.

      I’m yet to digest this article that seems to have it both ways…

      PLoS One. 2012; 7(6): e39581.
      Published online 2012 Jun 21. doi: 10.1371/journal.pone.0039581
      PMCID: PMC3380867
      Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation

      “Statins do not extend lifespan by reducing endogenous CoQ10”

      “…we investigated whether simvastatin extended lifespan by reducing endogenous ubiquinone levels. Diets supplemented with simvastatin and/or ubiquinone were administered to Drosophila. Supplementation with CoQ10 alone significantly shortened lifespan, while simvastatin alone significantly lengthened it (Figure 4; Table 1). CoQ10 and simvastatin together significantly lengthened lifespan, although not by as much as simvastatin alone”

      A bit puzzling, but it is only 2AM here. MORE COFFEE!!!

  5. Does PQQ add any help for mitochondrial support?
    I guess that again, as with CoQ10, mitochondrial absorbability is paramount, as with lipoic acid, acetyl carnitine, or anything else used, and as there is no way to know.

  6. Here is a major review of anti-oxidant trials, (Bjelakovic et al 2008)

    Sixty-seven randomised trials with 232,550 participants were included. Forty-seven trials including 180,938 participants had low risk of bias. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects meta-analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed-effect model (RR 1.04, 95% CI 1.02 to 1.06). In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08). When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by vitamin A (RR 1.16, 95% CI 1.10 to 1.24), beta-carotene (RR 1.07, 95% CI 1.02 to 1.11), and vitamin E (RR 1.04, 95% CI 1.01 to 1.07), but no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20). Low-bias risk trials on selenium found no significant effect on mortality (RR 0.90, 95% CI 0.80 to 1.01).

    • Well, before you flush all of your antioxidants, mice experiments have shown a 10%-30% increase in mean life expectancy, but no increase in maximum life expectancy when fed the antioxidant BHT (butylated hydroxytoluene), which is a powerful antioxidant. This means that more mice lived to their maximum age; but did not live past the maximum. In other words the survival curve was squared. What might this mean in human terms? If we assumed 100 years was the maximum human lifespan, then more people would live up toward 100; but not past 100. (Although the record human lifespan is 122). BHT is a synthetic molecule, available off the Internet.
      I have used BHT off and on over the last 30 years with no negative reactions.

      • I got such a laugh telling folk I used a tablespoon of BHT in oil a day “to extend my shelf life”.
        Gosh, was it cheap! I got a kilo by mail for about $4 in 1975 or so.
        Later, it didn’t seem worth the effort, antioxidants showing so little clinical evidence of worth for life extension.
        And BHT could mess with my Irish whiskey ration.
        And nothing is permitted that!

      • I used 2 teaspoons of BHT daily in 1984. In the first few days I have experienced unpleasant side effects such as decreased performance and weakness. To the diarrhea. After a few months I had to stop. Long-term inflammation of the intestines remained.

  7. Nice concept which deserves of attention. Do you believe that SOD in the form of gliadin complex (gliSODin) might have chance of reaching the mitochondria or other right grounds to act efficiently?
    Also the SKQ substance is only available in eye drops form or other forms also exist i.e. for P.O. administration?
    Thank you for the excellent work and I wish a happy New Year

    • Hi Georgios. Josh does not think much of the free radical theory of aging; but if you study free radicals, you will see that very little good can come from them. There can be very little doubt that most of the cellular damage occurring over time is caused by free radicals. There are a couple of problems with the studies involving antioxidants. First of all as you add antioxidants to the diet, the body down-regulates its own production of antioxidants. Secondly, the inner membrane of the mitochondria is a very tight bacterial type of membrane which restricts the free passage of most compounds, including the body’s natural protein-based antioxidants, as well as probably the common vitamin type antioxidants. On the other hand there is the possibility that C60 and maybe even BHT can penetrate the mitochondria to quench free radicals. Nevertheless, although free radicals probably cause the damage involved in aging, they are not the actual cause of aging. The cause of aging is the fact that the body down-regulates its repair functions as it grows older. This is written into the genetic code. In fact there are at least 3 genes found in animals as well as humans which appear to have no function other than to kill the host. That would include the genes AGE 1 and AGE 2 which produce a kinase which phosphorylates certain signaling proteins which affect such protein complexes as FOXO and FORKHEAD, thereby affecting which genes are turned on or off. As well as the gene for vitellogin, a lipoprotein whose only function appears to be to carry fats around in the body and dump them where they don’t belong, such as in the arteries. As a side note, replacing the AGE 1 gene with a nonsense gene lengthens the lifespan of C. elegans by 10 times. No other intervention in animals even comes close, not even diet restriction. Knocking out the AGE 2 gene adds even more to the lifespan, indicating the 2 genes have different targets. In addition, removing the gene for vitellogenin increases lifespan by 40%.

      • “…if you study free radicals, you will see that very little good can come from them.”

        But that ‘very little good’ is in the crucial matter of redox signalling. Not to be casually screwed with. It is a good illustration of the dose making the poison, the poison that doesn’t kill strengthens, and hormesis in general.

        I’ve stopped using daily microgram doses of Methylene Blue for this reason. The odd superoxide spun from step 3 of the mitochondrial cascade is normal, and stimulating of antioxidant defenses.

  8. PPQ stimulates biogenesis in all mitochondria and works with co-q 10 better than PPQ alone.NAC stimulates glutathione production which is found lacking in all chronic illness.Milk thistle protects the liver and increases glutathione production.Ashwaghanda and rhodiola regulate high cortisol and aid in serotonin production.Resveratrol acts to lengthen life as a similiar effect as mild starvation.Resveratrol is inthe interior of cells as a protective mechanism.Astaxanthin helps destroy free radicals,helps joints and the heart.Hawthorne berry and magnesium protect and aid the heart.You are incorrect in your blanket statement of supplements.

  9. So, for us laymen here who are looking for suggested supplements to improve health, it seems there is no answer but the trusted “diet and exercise” because nobody agrees.

    SQ1 seems to have garnered the most favorable results. I thought taking NAC, PQQ and CoQ10 would be a good start. But now I am more confused than ever.

    I’m wrapping up my PhD so I understand studies and research but my speciation is not physiology. Please help.

    Thank you.

  10. I’ve read many sources saying aspirin is a long term risk for macular degeneration. A very poor trade off. Sigh. Are you “in” with Pharma?

    • Thank you for alerting me to this, Charlie. I’ve read this for the first time. I’ll read more. It is always disconcerting to see that there are tradeoffs and complications. Perhaps we should look at family history of AMD and heart disease before deciding whether to take aspirin. I wonder if ibuprofen has the same issues.

      • Thank you for all the information in this blog. I’m getting older, have a mitra-valve problem along with A-fib. I have had a “healthy” life & prefer natural to synthetics. I’m concern about living to 100 yrs, but I am concerned about the signs of heart attack.

        Like Jerry, I thought taking NAC, PQQ and CoQ10 would be a good start. This is what brought me to this sight. And like Jerry I am very confused. It appears that the foods do not supply enough of what I need. My HDL is on the low side. My last doctor visit show hyperlipidemia.

        I try to avoid aspirin because of what it has done to my mother (Now 93). She also has macular degeneration. I now am curious. Also, I was told by my neurologist that I had become addicted to ibuprofen after taking it for daily for 20 years. I have to really have joint pain for me to take it any more. I’m glad I have a high tolerance to pain. I do use Tylenol for Arthritis, more than ibuprofen, which seems to help me get to sleep.

        Any suggestions on diet or supplements? The only medication I take is Amitriptyline for my tremors not depression. Then I take Vitamin B, B-12, C, D, E & Multi; Antioxidants; Biotin; Calcium; Potassium; and Zeaxanthin with Lutein.
        I eat oats, barley, cashews, almonds, peanut butter, spinach, fresh dried fruits and fresh frozen vegetables, organic tomato soup, eggs once a week, multi-grain flat breads & bran muffins occasionally, yogurt with fresh blueberries, fresh OJ, V-8 & apple cider, and I have a protein drink drink which I make usually once a day.

        • If you have heart disease, and all humans do, try to get your vitamin C intake up to 1000 mgs per day. It will take about a year; but vitamin C can clear up heart disease by cleaning out your arteries. Go read
          google Why animals dont get heart attacks; but people do. Vitamin C is cheap. Buy it at Walmart. $5.00 for 100 tablets of 1000 mgs timed release. That is less than 5 cents per day! Too much C will cause diarrhea, like about 3,000 mgs per day. If it causes diarrhea, just skip C for one day; then continue taking C.

          • Thanks for the encouragement. I have been taking mega doses of vitamin C (always with bioflavonoids) since I was 25. I am now 80. I have occasionally taken over 50,000 mg in a day when not feeling well. I usually average between 10,000 and 20,000 daily. Diarrhea doesn’t come unless bowl tolerance is exceeded, which is usually well in excess of 3,000 mg for anyone who has built up a tolerance to it.

          • Do not eat vitamin C, or you will be as old as any. I do not eat vitamin C and I’m shifting my age to “every 3 years in 2 years” down for 16 years. I lie to people that I’m 44 years old, but I have not been here for so many years.


            I’m starting to have a problem with the doctor, the authorities where they start to suspect I have a false date of birth.

        • be careful with oats and legumes. They are extremely high in glyphosate—-Roundup—– which now is being touted as a carcinogen. Educate yourself. Peanuts and cashews are not touted as healthy. Again educate yourself. Legumes are high in lectins which are natural poisons and do damage to your body which negates a lot of the good you are trying to do with supplements. Again, educate yourself. Opinions are like rectums….everybody has one. Educate, educate, educate…..

          • Agreed, most gmo grains and beans are embedded with glyphosate … and according to wikipedia some toxicity is shown in humans … but much less than people make it out to be.

            “It is important to remember that eating foods with a high amount of active lectins is rare. One reason is that lectins are most potent in their raw state, and foods containing them are not typically eaten raw. Cooking, especially with wet high-heat methods like boiling or stewing, or soaking in water for several hours, can inactivate most lectins. Lectins are water-soluble and typically found on the outer surface of a food, so exposure to water removes them.” … always learn …

  11. Let’s start with aspirin. I don’t really want to bad-mouth aspirin; except that it does have its drawbacks, especially with young athletes who take aspirin before each game to avoid pain: Aspirin blocks COX 1 and down regulates COX 2. These are the enzymes that we feel as pain. If we block pain, that’s good right? Well, maybe not. If you feel the pain, then your body is healing. No pain, no healing. COX activates the prostaglandins which are responsible for the healing and growth of muscles. So when a athlete takes aspirin, it blocks muscle repair and growth; or as weightlifters say, “No pain, no gain!” Nevertheless, aspirin may be good for older people who are trying to block inflammation, and are not trying to grow stronger. As for myself, I only take aspirin if the pain is intense.

    • As a person with fibromyalgia / chronic pain, it’s important to remember that pain is a signal that can become deranged in the CNS and hence become a disease in and of itself. Pain is not always indicative of tissue damage nor tissue healing. No pain, no gain is true if limited to acute, hormetic processes. Unfortunately, far too many people find themselves in a state where this connection is lost.

  12. Let’s consider heart disease in its various forms: heart attacks, strokes, and atherosclerosis, the leading cause of death in old age. We are looking for supplements which extend the lifespan of animals; but this may not be the best plan; because humans are not regular animals. With few exceptions, animals produce their own vitamin C in their livers in copious amounts. Therefore, it should not be surprising to find that mouse studies do not always transfer to humans. A better lab animal for lifespan studies would be the guinea pig, which like humans does not produce its own vitamin C. It should be obvious than any vitamin C lifespan studies in mice would be completely meaningless. If we look at an animal the size of a human, we find that the animal produces about 1,000 to 3,000 mgs of vitamin C per day, and up to 20,000 mgs when sick. This should be a wake-up call to those of us who believe the RDA of 60 mgs per day is adequate. This is barely more than the 46 mgs per day that is required to prevent scurvy, an often fatal disease among sailors prior to about 1800. Scurvy causes the blood vessels to break down, and the individual basically bleeds to death. The blood vessels are held together by collagen protein triple helix fibers which are stronger than steel of the same size. In order for the collagen protein to work properly, it must be hydroxylated; so that it can properly form its triple helix fibers. Vitamin C acts as a co-enzyme to hydroxylate collagen. When there is NOT enough vitamin C, the collagen is not fully hydroxylated and the collagen fibers are weak. When there is no Vitamin C, collagen does not get hydroxylated, and it does not form triple helix fibers. The result is the blood vessels fall apart. Sub-optimal vitamin C leads to weak collagen fibers which allow weak spots in the arteries, in places where they are stressed, like in branches, and in the coronary arteries which are filled and then flattened every time the heart beats. The body then compensates by patching the weak spots inside arteries with cholesterol and calcium deposits. Eventually this atherosclerosis can grow too big and block the artery, causing a heart attack or stroke, or the artery may just break, causing a bleeding stroke. We know from studying animals that they could get atherosclerosis, but if they produce their own vitamin C in their livers, they don’t get atherosclerosis. We ought to take a cue from animals, and bring our vitamin C up to about 1,000 mgs per day or more. The problem is that a large amount of vitamin C tends to cause diarrhea; so it is best to use the “timed release” tablets. Start slowly with a half tab of 1000 mgs of vitamin C and work up to at least 1,000. If you can prevent heart disease, you will eliminate the leading cause of death in old people. It is never too late to start vitamin C, since atherosclerotic deposits will slowly dissolve after about a year of high vitamin C intake, as shown on X-rays. If you can only afford one supplement, take a 1,000 mgs of vitamin C! It is far cheaper than open-heart surgery to replace coronary arteries. If you already have heart disease, by all means take vitamin C. It should be noted that vitamin C thins the blood; so if you are already on a blood thinner, check with your doctor before taking vitamin C; you made need to reduce the amount of rat poison that the doctor as prescribed for you, as shown by a laboratory blood test.

  13. Let us now consider Cancer, the second leading cause of death in old people: I have not found any good explanation for the cause of cancer, except that it may be caused by a mutation. I say this because the Ames test used to test chemicals for carcinogenesis is testing for mutations in bacteria. We know that free-radials can cause cancer as in radiation; and I suspect that free radicals maybe the usual cause. Naturally one would expect antioxidants to help prevent cancer. However, the only supplement I have found in the science literature that seems to prevent cancer is Bucky Balls, commonly called C60. Rats usually die from cancer; but none of the rats in the C60 experiment died of cancer; and yet the rats lived almost twice as long, which in itself should have led to more cancer. Hopefully, some lab is redoing the rat experiment with more rats and a more consistent dosing of C60; but it may be years before such a study is published. In the meantime for the last 2 years I have been doing my own study of C60, feeding my experimental 65Kg rat a full pipette full every day. So far this 2 year study has shown no cancer or other bad side effects from C60. If you study C60 and free radical reactions you will find that C60 makes an excellent antioxidant. It’s small oily structure indicates it probably locates in the oily center of cell membranes, including the the mitochondrial membranes. I am 75 years old; so if I come down with cancer, I will inform you of such a disease; and then we can figure C60 does not work. Cheers!

    • I have read that 1.7 mg / kg daily should be used to slow down aging, that is 200 mg per day. I’m afraid the C60 in olive oil is a scam since it’s 10 mg / 10 ml, so you’d have to drink 2 deciliters of oil a day.

      Does anyone have experience with C60? They wrote that C60 with a purity of 99.5% also contains carbon 70 and C76. How does C70 work on the human body?

    • I have found that fullerenes are toxic

      Fulleren is almost non-dissolved in the oil, and therefore the c60 with olive oil may contain only a few micrograms.

  14. Speech by Dr. Rath: Heart Disease is an early form of the sailor’s disease scurvy. In my presentation I can only focus on the most compelling evidence. For more details I encourage you to visit our research website (

    All existing hypotheses of atherogenesis have one problem in common – they defy human logic. The theory that high cholesterol levels, oxidized LDL or bacteria damage the vascular wall would lead to the formation of atherosclerotic plaques along theentire vascular pipeline. Inevitably, peripheral vascular disease would be the primary manifestation of cardiovascular disease. This is clearly not the case.
    It doesn’t require a degree from Stanford or any other medical school – any lay person can solve the Plumber’s riddle. The arteries, veins and capillaries in our body are a pipeline that is 60,000 miles long. But this pipeline fails in 90% of the cases at one specific spot: The coronary arteries, with the length of only one billionth of the total vascular pipeline. If bad water quality – e.g. high cholesterol – would cause damage to this pipeline, it would clog everywhere, not just at one spot. Obviously, elevated cholesterol can not be the cause of coronary artery disease.

    The solution to the puzzle of cardiovascular disease, therefore, must lie in the explanation of coronary artery plaques as the predominant manifestation of cardiovascular disease.

    To solve this puzzle we need to refocus our attention away from the blood stream and its constituents towards the one and only relevant target: the stability of the vascular wall.

    This animation (requires RealVideoPlayer) shows the connection between cardiovascular disease and the sailor’s disease scurvy. As opposed to animals, the human body cannot synthesize vitamin C. Ascorbate deficiency results in two distinct morphological changes of the vascular wall: Impaired vascular stability due to decreased collagen synthesis and loss of the endothelial barrier function.

    The sailors of earlier centuries died within a few months from hemorrhagic blood loss due to lack of endogenous ascorbate synthesis combined with a vitamin deficient diet aboard. When the Indians gave those sailors tea from tree barks and other vitamin rich nutrition, blood loss was stopped and the vascular wall healed naturally.
    Today, everyone gets some vitamin C and open scurvy is rare. But almost everyone suffers from chronic vitamin deficiency. Over decades, micro lesions develop in the vascular wall, especially in areas of high mechanical stress such as the coronary arteries.

    Just as in the sailor’s disease scurvy, so does vitamin C induce the natural repair of the blood vessel wall in cardiovascular disease leading to a halt in progression and even to natural regression of vascular lesions.

    In contrast to current models of atherogenesis, the Scurvy / Heart Disease Connection can answer all key questions in clinical cardiology today.

    Why do we get infarctions of the heart and not the nose or ears? The answer can be reduced to two factors: Structural impairment of the vascular wall due to vitamin deficiency combined with the mechanical stress from pulsatile blood flow in the coronary arteries. It is at this unique spot where the underlying structural impairment is exposed first.

    Why do we get arteriosclerosis, but not venosclerosis? The cholesterol and the infection theory would inevitably lead to clogging of veins and capillaries. The scurvy heart disease connection provides the only logical answer to this phenomenon.
    Why animals don�t get heart attacks, but people do? Why do bears and other hibernators with cholesterol levels of 600 mg/dl are not extinct from an epidemic of heart attacks? The answer: Animals produce their own vitamin C in amounts between 1 gram and 20 grams each day, compared to the human body weight. These amounts of ascorbate are obviously sufficient to optimize the stability of their vascular walls � without any necessity for Statins.
    Why are all important risk factors for CVD closely connected to ascorbate deficiency, including, diabetes, hyperlipdemia, homocysteinuria and others. The common denominator of these metabolic disorders is to provide compensatory stability for the vitamin deficient vascular wall. This is also the reason, why ascorbate deficiency increases fibrinogen and thromboxane levels while decreasing endothelial derived relaxing factor (NO) and prostacyclin.
    Lets turn to key evidence for the scurvy / heart disease connection. The guinea pig, like man, cannot synthesize ascorbate endogenously. In our published research we demonstrated that, when guinea pigs are fed vitamin C only at the level of the human RDA they develop atherosclerosis. These vascular lesions are histologically indistinguishable from human atherosclerotic plaques. In contrast, the control animals receiving Vitamin C levels of one teaspoon vitamin C per day have clean arteries.

    These experiments were confirmed by Meade et al. in an ascorbate “knock out” animal model. The first manifestation in these animals was the deterioration of the vascular wall, resembling early atherosclerosis in man.
    We confirmed these results in a clinical study in patients with preexisting coronary artery deposits measured by Ultrafast Computed Tomography. Following a defined vitamin program, the progression of calcification significantly decreased and in some cases the disappearance of lesions was documented, as you can see in this X-ray CT pictures. Copies of the publication of this clinical study are available at this meeting or online.
    The scurvy heart disease connection means a paradigm shift in medicine from symptom-orientation to the only relevant preventive and therapeutic target: The stability of the vascular wall. With the discovery of the scurvy / heart disease connection, the “world of heart disease” has ceased to be a plate and has become a globe.
    Now that we have identified the true nature of cardiovascular disease, its eradication is only a question of time. Already in ten years from now the headlines of the leading newspapers may read: “WHO proclaims heart disease as eradicated / The pharmaceutical market of statins and other symptom-oriented drugs have collapsed on Wall Street / and the cardiology departments at Stanford and other Medical Schools are closing”.
    On behalf of millions of patients with heart diseases I call upon Stanford University and other medical institutions to accept their responsibility and join us in the eradication of cardiovascular disease.

    • Today I want to again discus atherosclerosis; a disease that kills over half of the people on Earth, sometime between the ages of 30 to 100 years old. The only reason it does not kill everyone; is because something else kills the rest of the people before Atherosclerosis can kill them. Atherosclerosis is a mild form of scurvy. Scurvy used to kill over half of the sailors on Earth, before they discovered it was caused by a lack of vitamin C, and could be prevented by eating a lime, some other citrus fruit, or even vegetables or meat containing a little bit of vitamin C.
      Since then our government has recommended everyone eat about 50 milligrams of vitamin C per day. Obviously 50 mgs of C per day does not prevent atherosclerosis; since half of the GI’s killed in Korea and Vietnam showed atherosclerotic deposits in their arteries, even though most of them were less than 25 years old.
      Holding everything together in the body are molecules of collagen consisting of a long chain of some 1000 amino acids. Three of these collagen molecules are woven together to form a fiber, which is stronger than steel for its size. (That is why weightlifters can put a steel barbell weighing 500 pounds over their heads, without collapsing into a puddle of Jello on the gym floor.) Vitamin C is required as a co-enzyme to hydroxylate these collagen molecules as they are formed. If there is not enough vitamin C, then the collagen molecules do not get completely hydroxylated, and are therefor weaker.
      Certain places in the arterial system are more stressed than others. This occurs mainly in the coronary arteries surrounding the heart. As the heart beats, the coronary arteries collapse and then expand as the heart relaxes for a second. This goes on all day and all night, stressing the coronary arteries. If these arteries don’t get enough vitamin C, then the collagen molecules start to fail, causing tiny cracks and tears in the artery walls. This damage is repaired by pasting over the damage with cholesterol and some calcium to hold it all together. Eventually after years and years, these plaques grow too big and almost close, causing the blood to quit flowing and therefor clot, shutting off the artery and depriving part of the heart of oxygen, causing that part of the heart to die. The dead part of the heart is subject to failure itself, and can blow out later causing instant death, even if the original blockage is cleared and the blood is allowed to flow once again.
      Because of the calcium, these atherosclerotic plaques can be seen on Cat scans. The good news is that this atherosclerotic process can be slowed, stopped and reversed by supplying sufficient vitamin C, a minimum of 500 mgs or more per day, preferably more, over a year’s time for the rest of your life. I recommend a 1000 mgs per day, 500 mgs in the morning and 500 at night, at a cost of 5 cents per day, which is considerably less than the cost of heart surgery at $100,000 and up. Walmart usually carries it in 1000 mg tablets, timed release. Break the tablet in half to split it between morning and evening. Unless you have been getting 500 mgs per day of vitamin C most of your life, it is almost a dead certainty that you have atherosclerosis, whether you know it or not; and unless you promptly increase your vitamin C intake, you will eventually die from a heart attack or stroke, probably sooner rather than later, unless something else kills you first! If you are wondering whether or not you are getting enough vitamin C? If you ever have “pink tooth brush” from bleeding gums, bruises on your legs or arms where they got bumped, or chest pains when the weather is cold, or you exert yourself, then you are deficient in vitamin C, and atherosclerosis is forming in your coronary arteries.
      I must caution you that too much vitamin C causes diarrhea. When I first learned about the need for mega doses of vitamin C, I took too much and came down with diarrhea. I decided that the doctor recommending a mega dose did not know what he was talking about; so I quit taking a mega dose and went back to my little 200 mgs capsules. Eventually that mistake nearly killed me in 2013, when I ended up in the hospital with my chest wide open and my heart disconnected. It took me 5 weeks to recover and get out of the hospital; but I still could not walk; because I had no sense of balance. Besides that I looked like a reject from a Nazi concentration camp in WWII; you have seen the WWII pictures!
      While I am on this subject of heart disease I need to explain strokes. There are two types of strokes; the ones caused by a blockage, like a heart attack; and the kind when the wall of the artery simply blows out like a flat tire. Either one can kill a person. Naturally the arteries in the brain are not being stressed like a coronary artery; but nevertheless, there is stress in the areas where the arteries branch in a “Y”. Once again the cause is a lack of vitamin C, causing weak collagen fibers, which are not completely hydroxylated, and therefor eventually break. This can cause the artery to break in a bleeding stroke; or the damage may be patched up with cholesterol and calcium; but eventually fail do to blockage with a blood clot.
      You notice I am not blaming cholesterol for these problems. Cholesterol is just a secondary factor. If Cholesterol were the cause of these problems, then the entire arterial system would eventually plug up, not just the coronary arteries and places in the arteries where they branch. Also, if cholesterol were the problem, then we would also have our veins plugging up; but that does not happen. In fact, my doctor used a vein from my leg to replace my coronary arteries.
      We also have to understand why most animals do not have heart attacks. Animals produce their own vitamin C in their livers in whatever amount their bodies need. An animal the size of a human produces about 1,000 to 20,000 mgs of vitamin C per day. Since it is made in its liver, the animal does not get diarrhea. Of course some animal lovers will try to tell me that animals do have heart attacks. Well, some of them may die suddenly; but is is not from atherosclerosis plugging up their coronary arteries. It is probably from the animal being scared to death and his heart just quits beating. Of course, if a scientist somehow deprives an animal of vitamin C, like they have done experimentally with mice, then the mice do get atherosclerosis and eventually die from it; which proves the point. Another animal that is subject to heart attacks is the guinea pig. Of course the guinea pig is not a wild animal, and does not produce its own vitamin C in its liver. Also, most of the higher primates do not make vitamin C; but most of the wild ones get barely enough C from fruits and vegetables, and don’t live as long as humans do; but I suppose they do have an accumulation of atherosclerosis; and some of them probably do die from heart attacks.
      I should also mention that the amino acids proline and serine are used in making collagen; so therefor adding some to your diet can help; but a person may get enough from the diet. Also, some vitamins such as vitamin E, beta carotene, and other antioxidants help protect vitamin C; so they also can help. Vitamins are also used for other purposes in the body; so it is always a good idea to take a multivitamin tablet every day.
      Read more from the Internet at “Why animals don’t get heart attacks; but people do.”

  15. I have a theory that says rather than trying to take antioxidants as a pill or as an injection, you should eat things that causes your body to create its own antioxidants such as avocado will help your body produce it’s own glutathione. If I am wrong please tell me and tell me why hurry up if I am correct then please tell me so that I can start that type of a regimen.

    • First, I’d say that glutathione is an exception to my thesis about antioxidants. I’ve never heard anything but good effects from glutathione. Second, about ingested vs body-produced antioxidants, what you say makes sense to me, but there’s no data I’m aware of one way or the other.

    • That’s right, there are weak antioxidants and strong antioxidants. In order for the experiment to show that antioxidants do not work, it is enough to “skillfully” choose a quantity of antioxidant to produce a pro-oxidative effect and a “tolerance” effect that will reduce the effect to zero.
      The average cost of antioxidant treatment that slows aging by 60% is +/- 500 dollars per month. And add the Gerontologist’s reward for the $ 1000-2000 entrance exam.

      • This is not credible. “Slowing aging by 60%” means living 2.5 times as long, or a life expectancy of about 200 years. If this is available for $500/mo then this is the first I’m hearing about it.

        • When you use antioxidants stronger than SKQ1, it’s real. A long-term study has been done with SKQ1 to prove that it extends the life of experimental rodents by 100% to 200%. It’s like a man lived 170 to 255 years. If you take this antioxidant for 100 years, you will live 60 years more. It depends on everyone if he wants to pay $ 6,000 for 100 years.

          • Do you have a reference for that study Omasta?

            From what I’ve read, the danger with antioxidant studies is that the antioxidants either do not reach where they’re needed (I.e. mitochondria), or they down regulate endogenous production, so are counter productive. Similarly, slightly toxic substances can increase endogenous production of anti oxidants, and so prove on balance to be ‘beneficial’.

          • You are still looking for one anti-aging medicine. But that’s not the case. Imagine aging as a leaky hose that doesn’t leak water, but your youth. When you clog 1 hole, another 9 holes will drain your youth. When you block 9 holes, the tenth hole will run more water.
            It was enough for me to study the pharmacokinetics, a professional publication on antioxidants (about 700 pages) and read the work of Denham Harman. Denhan Harman invented aging accelerating foods in 1956. Presently, all of America eats food to accelerate aging and the best-selling food supplements are speed up aging supplements.

          • I should add by way of example and in partial support of your statement,

            Methylene Blue reduces the production of ROS by mitochondria in IMR90 cells by 28%, and guess what? It extends their number of population doublings by…28%.

            See’ Combined activation of the energy and cellular-defense pathways may
            explain the potent anti-senescence activity of methyleneblue’

          • As you do Josh, I subscribe to the theory that aging is a programmatic process that is part of the standard developmental program and antioxidants are not extending life span beyond our species specific maximal life span. I do however think that antioxidants can increase the probability that an individual can attain this maximal life span. For this reason I am on a whole food plant based diet and I take, Fisetin, Methylene blue, sulforaphane, and carnosine, and I exercise and sauna. ( One positive result from this regimen is my hair grows faster and has become very thick, but I feel that I am still aging.)

            If we are to make real progress on halting and reversing aging, we need to find a way to intervene in the actions of the part of the developmental program that is controlling aging. Considering that there are no outliers, no one lives past 123, extending maximum human lifespan could prove difficult considering that aging and death seen to be under strong homeostatic control.

          • Who among you does not eat food accelerating aging? I praise the eating of aging accelerating food and supplements. These have a beneficial effect on health. For example, they reduce the time spent on sick leave and total hospitalization.
            For me it was very hard to give up the eating of aging accelerating food. All the known and the doctors tapped their forehead and one doctor even forbade me to skip aging foods.

          • Age accelerating food? I take it you mean food with added anti-oxidants as preservatives?

          • Aging foods are foods with a naturally high content of aging accelerators without added stabilizers and preservatives. Plants synthesize these chemicals against browsing and nibbling. Google it out!

          • So you don’t eat easily oxidised foods without lots of anti-oxidants?

            There must be more to life and healthspan extension than that…

  16. Well guys, unlike some of you, I’m no expert when it comes to the science of all this. All I Know is that I am 82 and have been taking mega doses of vitamin C (10,000mg plus) daily for the past 57 years. About 30 years ago I started taking the other anti-oxidents like vitamin E, Coq10, and recently NAC and astaxanthin. Today I can walk three miles at the same pace and time that I could 40 years ago. I walk at least 2 miles daily .I take no medication and, unlike my seven siblings, have never been in the hospital nor been operated on, except for the removal of a tiny bit of skin cancer 15 years ago. They say that “the proof is in the pudding.” Don’t mean to boast. Just passing along these facts while knocking on wood. I might add a quote here from two time Noble prize winner Linus Pauling: “Every disease, every ailment can be traced to a mineral deficiency.” Get your minerals. Good luck to all!

  17. Michael Reardon,

    I agree completely with what you are saying about vitamin C being a cure for atherosclerosis. However if you have an autoimmune disease such as hyperthyroid or Hashimoto’s , then the vitamin C is going to stimulate your immune system and cause you to be inflamed and cause your body to be attacked even more. I am trying to figure out what can be done 2 stop the autoimmune attack on your body from the vitamin C. Do you need to fix the thyroid first or do you need to use something other than vitamin C or do you need to take high doses of vitamin A and selenium along with vitamin C to prevent the flare-ups?

    • Thank you for your information of which I was not aware. If I remember correctly, I started to take mega doses of vitamin C due to the research done by Linus Pauling. Dr. Pauling, as I understand, himself took about 18,000 mg of vitamin C daily, and he worked 16 hours a day, seven days a week, right up to his dying at age 93. And I believe he didn’t start taking it until he was in his 60s. As I understand it, if human beings were able to produce their own vitamin C at the rate that animals do, they would produce about 12,000mg a day. That was my guide on the amount to take. What you write is highly interesting, and I will research it further. I do have some inflammation, nothing debilitating, but what you write is worth looking into. Overall, I think taking mega doses of vitamin C has been a plus, but anything can be overdone. Thank you.!

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