Free radicals are extremely reactive molecules that can damage cell membranes, organelles, and DNA. Their destructive effects within the body make them an obvious target for therapeutic treatments. The most common types are reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, and reactive nitrogen species (RNS), such as peroxynitrite. Free radicals are unstable because they have an unpaired electron. They become stable by stealing an electron from a nearby molecule. That molecule will then grab an electron from another nearby molecule, and a chain reaction ensues. Ideally, a free radical will come in contact with an antioxidant molecule before it can cause any damage. Antioxidants have a spare electron to donate, so they can neutralize free radicals before any harm is done.
Many environmental factors cause oxidative stress — solar or nuclear radiation, toxic chemicals and pollutants, infections, rancid fats, and more. When these stressors occur at levels beyond the body’s tolerance, a variety of health problems can emerge. Inflammatory diseases such as arthritis are linked to oxidative damage. Chronic diseases such as heart disease, cancer, Alzheimer’s, and diabetes are also associated with oxidative stress. The link between metabolic syndrome and ROS is an area of active research, as it is unclear whether oxidative stress is a cause or consequence of these disease states.
Free radicals are not always bad. Our immune system uses them to combat invading microbes. The process is a bit like tossing a grenade, though. The bad microbe gets destroyed, but your own cells take damage, too. Antioxidants can mitigate this collateral damage, but too high a dose interferes with the immune response.
Free radicals are also produced naturally in the body when mitochondria generate energy. Unhealthy mitochondria spew out greater quantities of free radicals, which normally marks them for destruction. Endogenous antioxidants produced by the body are the best defense against the ROS produced by mitochondria. Glutathione and superoxide dismutase are two potent examples.
The Vitamin Craze
Linus Pauling was one of the most renowned chemists of the 20th century. He won the Nobel Prize in two different fields (chemistry and peace) and authored thousands of papers. His work on molecular bonding was groundbreaking, and Francis Crick credited him as the father of molecular biology. In the 1970s, he was a leading proponent of the vitamin healing movement. His work in this area has largely been debunked, which begs the question of how such a brilliant scientist could be led astray.
Richard Feynman said the first rule of science is “you must not fool yourself and you are the easiest person to fool.” Nothing is more convincing than personal experience, even for a trained scientist. When Pauling was diagnosed with Bright’s disease, a condition that inflames the kidneys, he was treated with a low-protein, salt-free diet and some additional vitamin supplements. The treatment appeared to restore his health and sparked his curiosity about the potential role of vitamins in other diseases. He was especially enamored with vitamin C, taking up to 3 grams per day. That’s 30 times the recommended daily allowance for an adult male. It’s alleged he even added vitamin C to his orange juice.
Geniuses are often blinded by the seductiveness of their own ideas. Pauling was convinced that if oxidation is destructive, then antioxidants must be beneficial. Such a simple, elegant idea must be true, right? The modern-day evidence-based medicine movement warns against such reasoning from physiological mechanisms. A treatment must go through randomized clinical trials or other rigorous testing before it is considered validated. It can’t just look good on paper. It must work in the real world, under controlled conditions. Unfortunately for Pauling, when the evidence from trials was inconclusive, it didn’t sway him in the least. He never wavered in his conviction that vitamins, especially lysine and vitamin C, could be used to prevent colds, reverse heart disease, and prolong the life of terminal cancer patients.
One clear win for vitamin C is its prevention of scurvy — a horrific disease that inhibits collagen production. Collagen is the protein that makes up our connective tissues, and our body literally falls apart without it. On long voyages, it was once not uncommon for half or more of a ship’s crew to perish from scurvy. In the mid-1700s, Sir James Lind discovered citrus fruits could eradicate scurvy. The reason why remained unclear until the 1930s, when it was discovered that vitamin C was the mechanism behind the cure. Most animals can synthesize the vitamin, but humans, other higher primates, guinea pigs, and fruit bats cannot. To the extent we need it, it must come from our diet. Although, unlike the animals who can synthesize their own, we can resynthesize vitamin C from its oxidized form. This greatly reduces our need compared to other species who cannot recycle it.
Sources of Antioxidants
In The Anti-Inflammation Zone, Dr. Barry Sears describes three main types of antioxidants:
- Fat-soluble antioxidants are active on cell membranes, protecting them from free radical damage. They include vitamin E, beta carotene, and coenzyme Q10.
- Water-soluble antioxidants are able to move through the bloodstream and exit the body through urine. Vitamin C is the most common type.
- Surface-active antioxidants are a vital link in the chain because they shuttle free radicals between fat-soluble and water-soluble antioxidants, ultimately allowing the chain reaction to leave your body. Polyphenols are a type of surface-active antioxidant with thousands of known varieties. High concentrations are found in brightly colored plant foods.
It is widely recommended to “eat the rainbow,” because a diverse intake of different-colored plant foods will provide the full spectrum of antioxidants. Research suggests high-dose antioxidant supplements are ineffective or outright dangerous. It is speculated that a diverse intake of antioxidants might be more healthy.
Sears recommends an intake of polyphenols of 500 to 1,500 mg per day. He advises: “To give a sense of what 1,000 mg of polyphenols per day looks like, it could be approximately 5½ cups of broccoli, 1½ cups of blueberries, 2¼ cups of strawberries.” This approximates to 10 servings of fruits and vegetables per day.
Food manufacturers frequently tout the antioxidant levels in their junk food products. Fruit snacks for children often contain 100% of the recommended daily allowance of vitamin C. Livestrong says of Welch’s Fruit Snacks: “The overall nutritional value of Welch’s Fruit Snacks is considerable.” This is in spite of their being more than 40% sugar. Even if you strongly believe in the value of antioxidants, you should not make food choices on that basis alone. Antioxidants can’t beat a bad diet.
Your antioxidant needs are proportional to the amount of oxidative stress you are exposed to. In certain extreme cases, antioxidant supplementation can be helpful. Many antioxidant supplementation success stories are found in malnourished populations subsisting on grain-based diets. Such populations need to supplement with antioxidants to counter the effects of carbohydrate overconsumption and malnutrition. For example, vitamin A deficiency weakens the immune system and is the leading cause of preventable blindness. It’s especially common in poorer countries. About half of the blinded children die within a year. The World Health Organization cites a 23% reduction in overall mortality due to vitamin A supplementation.
Antioxidant Studies
Antioxidants have many benefits. However, when isolated from food products and packed into high-dose supplements, they rarely show any benefit in the human body and are sometimes harmful. Here is what some of the research has to say:
The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise. Regular supplementation trials have shown that vitamin C reduces the duration of colds [by 8% in adults, 12% in children], but this was not replicated in the few therapeutic trials that have been carried out.
In most cases, no effect of intervention was observed on mortality, except in specific subgroup analyses (e.g., sepsis and higher dose intravenous vitamin C). However, there have been few of these studies published to date, and even fewer of high methodological quality. Other commonly assessed outcomes included ICU and hospital length of stay, duration of vasopressor support and mechanical ventilation, and acute kidney injury. Some of the meta-analyses showed decreases in several of these secondary outcomes, while others showed no effect, depending on the selection criteria used for study inclusion.
We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A.
Some studies have shown potential harms associated with vitamin supplementation. One study that focused on smokers showed a 16% increase in lung cancer after beta carotene and vitamin E supplementation, and another showed a 17% increase in death after beta carotene and vitamin A supplementation. Numerous studies have shown increased risk of mortality among people who take multivitamins. These studies are observational and cannot prove cause and effect. Their outcomes may be due to the fact that sicker people are more likely to take vitamins. It’s also possible that low-quality supplements might have incorrect dosages or contain impurities. There is very little regulation or quality control in the supplement industry. Often, what is inside the pill bears little resemblance to the ingredients listed on the package.
In most cases, antioxidant supplementation represents a failed attempt to outsmart Mother Nature. Many would like to believe vitamins are magic pills that allow a person to thrive on a diet of Pop-Tarts and soda. Replacing the nutrients lost during industrial food processing is a band-aid solution to the myriad problems caused by those same highly refined foods.
Comments on Why Antioxidant Supplements Don't Work, Part 1
Dear Tyler,
thanks for your reply. You are totally right and I agree
that there are little to no general advices you can give in respect of taking
supplements. The application of a supplement should always be an individualised
approach, and ideally it should be based on an improved diet and exercise.
Anyway, nowadays you often hear „black or white“ argumentations, which are very
polarizing.
A last remark: the Medium article also mentions effective Vitamin C
doses of 1 or 2g. This is far from a megadose for me, isn´t it?
I´m a bit confused every time I read articles like that one. It really would be great if everybody just needed to eat the "right" way and the result would be a healthy organism without any deficiencies. I am regularly blood testing me and many of my patients and I often find deficiencies in minerals, trace minerals or vitamins. I know that blood levels are not the whole of the story, but thats what you can measure. By taking supplements you can see changes in blood levels, and often the condition improves. So what is so wrong about it? In addition to this thoughts here is an article on Vitamin C released in Medium (HQ themselves cited another article from Medium a few days ago, so I think it is well accepted as a resource...):
Stay critical
Daniel, it sounds like you have a smart approach to supplementation. I briefly mentioned to Pat B below that getting blood work done is a wise thing to do before you start randomly taking supplements. If you find out you have a deficiency, take a supplement and your health improves- that's great. If not, you might have some underlying condition driving the deficiency. You would obviously want to probe deeper to figure that one out.
The article you posted mentions the benefits of megadoses of vitamin C for someone on a ventilator. This is a specific medical treatment and you can't apply that to a healthy person. After all, you wouldn't give a chemotherapy drug to a healthy person just because it helped someone with cancer.
Tyler is another guy among a myria who, by resorting to disinformation, paints Pauling as a deluded genius and pushes the propaganda that high dose vitamins are very dangerous.
Everyone should know that Pauling's VALID work with high dose vitamin C supplementation has been "falsified" by data distortions and lies, and he as a person (a double Nobel laureate) has been slandered as some deluded idiot by the criminal orthodox medical establishment and its countless quackwatch shills, lackeys, ignoramuses, and trolls for decades and it continues today -- look for the well referenced article "2 Big Lies: No Vitamin Benefits & Supplements Are Very Dangerous" written by a published author of the Orthomolecular Medicine News Service.
But you can't discredit the facts with lies. That only exposes and discredits the liars (see cited article above).
Hey Joe - I love your passion for the topic. I don't think this article addresses the super high doses you're referring to. I assume you're talking about the benefits of Vit C when given intravenously, which is an area of interest, especially in regards to cancer treatment. Dom D'Agostino is a good source for current research on that.
I think Tyler does a nice job of touting Pauling's achievements, but then questions his specific assumptions about antioxidants. I gather there is a different effect when one takes high doses orally versus IV. Because C is water soluble the root of administration is significant. There is also an interesting competition between vitamin C and glucose, which means the diet is an important element to consider too. My reading of this article was that it was talking about the typical ways most people take antioxidants, which is orally. Perhaps another article on high dose, IV administered vitamin C and glutathione would be worthwhile.
For fun, I thought you and Tyler might enjoy this correspondence between Pauling to Feynman.
LINUS PAULING TO RICHARD P. FEYNMAN, JUNE 28, 1978
Dear Dick:
I have learned from Linda that you have had a malignant tumor removed. These abdominal malignancies are serious.The 5-year survival fraction is rather small. Chemotherapy has little value—in Britain it is rarely used for these cancers.
I think that the best thing to do is to begin immediately a high intake of vitamin C—20 g. per day or more. I am corresponding with a man who had extensive abdominal cancer, and who took 60 g. per day for 3 months. He is now much better, and is down to 35 g. per day.
Enclosed are a couple of papers, with references to more. Linda can tell you where to get pure ascorbic acid and sodium ascorbate and how to take it.
Vitamin C works largely by potentiating the body’s immune mechanisms. The cytotoxic drugs destroy them, and probably decrease the effectiveness of the vitamin C. On the other hand, immune stimulants, such as BCG may well be compatible with vitamin C.
It is very important not to stop the intake of vitamin C, once you have started.
We have another paper in press in PNAS. Also, Morishita and Murata in Japan have got similar results.
Best wishes,
Linus
P.S. Also no sugar, little meat, lots of fresh vegetables, vegetable juice & fruit juice.
***
RICHARD P. FEYNMAN TO LINUS PAULING, JULY 7, 1978
Dr. Linus Pauling
Linus Pauling Institute of Science and Medicine
Menlo Park, California
Dear Linus,
It was very good to hear from you.Thank you for your special interest in my problems.
It turns out my cancer is a very unusual kind of abdominal cancer called myxoid liposarcoma—a soft tissue cancer and although it weighed over 2800 grams it still seemed to be nicely encapsulated. It was apparently neatly removed in its totality and the pathological laboratory can’t even find any apparent invasion of the blood vessels by the cancer cells.
So my oncologist (Dr. Thomas C. Hall, a man introduced to me by Benzer) suggests even no chemotherapy at all but of course a very careful periodic thorough search with x-ray for metastases. At any rate, I have given him your letter to be sure he is thoroughly familiar with the results given in your references.
Linda has already offered the information, etc., that you mentioned in a very kind and lovely note. One of your great accomplishments, Linus, has been to help to produce such a lovely daughter.
Thanks again for your interest.
Sincerely,
Richard P. Feynman
Hi Joe,
I ran across the orthomolecular medicine outfit about 15 years ago and they seemed a bit sketchy to me. I see they still have the same website. They’re already promoting the idea that you can cure coronavirus with vitamins...
Linus Pauling was brilliant. I said so in the article. But his work on antioxidants has been refuted by a large body of evidence. There is still research being done on Vitamin C and cancer. The proposed mechanism behind it is that supraphysiological doses (only achievable through injection) might have a pro-oxidant effect inside tumor cells. The hypothesis is that vitamin C can react with metal ions and generate hydrogen peroxide. It’s believed this will preferentially occur within cancer cells vs healthy cells. You can read a study here if you’re interested in the mechanisms.
Intravenous use for cancer patients was beyond the scope of my article. There are sources of info out there covering this topic better than the orthomolecular crowd, and there are RCTs underway. If vitamin C ends up being a potent cancer therapy or useful adjunct, that would be great. But it wouldn’t imply that high doses of vitamin C would benefit healthy people. Most likely, they would experience bad diarrhea. The question addressed in this article is whether the average healthy person stands to benefit from antioxidant supplements. My conclusion is that the pills often do more harm than good and are no replacement for a healthy diet.
Thanks Emily, you're spot on. Great idea, in regards to the article on IV administered antioxidants. Maybe one of the docs will take it on. I love the exchange of letters between Pauling and Feynman!
Tyler, you (and Emily) are intellectually dishonest.
Joe was not referring, as you both falsely implied, to IV vitamin C therapy. Neither was the article Joe referred us to because Pauling advocated high dose ORAL vitamin therapy generally and not just IV vitamin C for specific conditions
or cases.
You didn't just say that “Linus Pauling was brilliant” you also alleged that he's a “blind” genius and had been “led astray” and that his work with high dose supplements “has largely been debunked” without providing any real substantiation for your allegation. But you do cite much bogus evidence that supposedly debunks him. It's the type of junk evidence
of corporate medicine that is revealed as such in the article Joe was referring us to.
But it's clear that you (nor Emily) have read it because you also make new false statements such as that for the average healthy person vitamin pills “often do more harm than good” as in that article many study references are cited in solid support of high dose supplements for average healthy people (unlike your numerous empty wrong statements, ie lies).
You also point out, right after stating that "the pills often do more harm than good" that they “are no replacement for a healthy diet” as if proponents of high dose vitamins make such a silly claim as a matter of routine. Presumably it's another disingenuous way of yours to "discredit" those type of people.
Bottom line, Joe was right when he said that you are pushing disinformation. You are here to push a political agenda but certainly not real science.
Pat,
I brought up the intravenous vitamin C (IVC) treatment for cancer simply to show that I am open minded to the idea that there are potentially valid uses for it. Several trials are underway. Dr. Seyfried, who has written here at CrossFit, mentions using IVC alongside hyberbaric oxygen therapy and a ketogenic diet as a cancer treatment method in his press-pulse paper. Linus Pauling could have been close to being right on this. If so, it's a pity others didn't carry on his research until relatively recently.
I don't know if you have followed CrossFit Health much, but there has been extensive writing here about "the Mess"- the collusion between big pharma, government regulators, medical journals and even doctors. The article Joe recommended goes over some of the same material. However, I personally don't think supplements are the solution to the mess. Intense exercise and a clean low-carb diet are the two highest impact methods to improve one's health. After that, fine tuning levels of various micro nutrients could be beneficial. First, get blood work done to see which interventions you actually need.
Here is some information from the Linus Pauling Institute at Oregon State University on Vitamin C:
"The pooled effect of vitamin C supplementation was a 14% reduction in cold duration in children and an 8% reduction in adults. Finally, no significant effect of vitamin C supplementation (1-8 g/day) was observed in therapeutic trials in which vitamin C was administered after cold symptoms occurred."
So, given the average duration of a cold is about a week, taking vitamin C year round would shorten it 13 hours.
Much of the other information in that article correlates low serum vitamin C levels to various health outcomes. The question is: what causes the low serum levels? My money would be on excessive carbohydrate intake. Some of the other studies correlate high dietary vitamin C levels to various health outcomes. In this case, they might be tracking several other variables under the guise of vitamin C. My personal opinion is that a low-carb diet with plenty of unprocessed vegetables and some fruit provides plenty of vitamin C and also reduces your need for it, thanks to overall lower oxidative stress.
From the info provided by the Linus Pauling Institute (hopefully credible enough for you), I don't see a compelling reason for healthy people to supplement with vitamin C. There are potential medical situations where it might be useful, though. And I don't think Linus Pauling was a quack. Many great scientists have been proven wrong. In Pauling's case, I don't think he's so wrong that his reputation deserves to be ruined. And by the way, James Watson, who beat Pauling in the race to describe the structure of DNA, wrote this paper a while back absolutely slamming antioxidants.
This is a great round up, lots of important information. Thank you Tyler! I particularly liked:
“Geniuses are often blinded by the seductiveness of their own ideas. Pauling was convinced that if oxidation is destructive, then antioxidants must be beneficial. Such a simple, elegant idea must be true, right?”
Excellent writing and so much to consider in this question. For one, there is a dangerous hubris inherent in the idea that we can identify good v bad, which leads us to assume ramping up the “good” will mitigate the “bad.” As if there is no natural balance at play, no other variables to consider. The whole fascination with antioxidants extends to the modern notion that we can extract some specific part of a well balanced (because nature is very good at homeostasis) product and then amplify it to increase our health. This kind of pill popping model is often flawed. It shows our ignorance with regard to how well designed natural foods are when taken as a whole. We routinely believe we can improve, extract, amplify that which is actually optimal in its natural packaging.
Can’t wait for the rest of the series!
Love this - especially the last paragraph!!!
I enjoyed this entire piece, however, a couple of quotes really jumped out at me...
"Richard Feynman said the first rule of science is “you must not fool yourself and you are the easiest person to fool.”"
and...
"Unfortunately for Pauling, when the evidence from trials was inconclusive, it didn’t sway him in the least."
Sadly, I feel this is very common.
I see this is "Part 1" of the series, and I look forward to the next installments. One topic of potential significant interest to this audience is the interference of antioxidant supplementation with exercise adaptations. A highly impactful 2009 study showed that Vitamin C & E supplements inhibited exercise-induced improvements in insulin sensitivity: https://www.ncbi.nlm.nih.gov/pubmed/19433800
My team has some data on this topic as well. We found that supplementation with a mitochondria-targeted antioxidant didn't do anything to enhance muscle or whole body aerobic capacity. https://www.ncbi.nlm.nih.gov/pubmed/27501153
Just two studies from a fairly sizable evidence base... my takeaway is that these supplements are at best a waste of money, but at worst they are a potential source of harm!
PS it wasn't until after I read the article and posted the comment that I saw that this article was credited to Tyler. Great job as usual sir! Again, very excited for this series. You, and Clarke, and everyone writing for the site are creating some first rate educational content. I learn more on crossfit.com than pretty much anywhere else these days!
Nathan, first, thanks for the compliment. I'm glad you're enjoying the work being done here. There's an amazing team behind it and I'm only a small part.
Secondly, thanks for posting a major spoiler on part 2! haha
Eating meats, vegetables, nuts & seeds, some fruit-little starch (or vice versa for some), and no sugar, seems to still remain the greatest approach to feeding due to the nutrient synergy and density offered by this simple prescription of plants and animals. The human being will always be tempted to find the pill, powder, or potion that holds the secret to eternal life. Additionally, the subconcious of a person who DOES eat a variety of natural foods seems to often ignore the ingestion, inhalation, and exposure to the toxic as well. Abstinence from processed food and unnecessary drugs seems to be harder than the addition of regular exercise and real food. Supplement companies know this, and they will present the low-hanging-fruit (pun intended) to all potential seekers.
Thanks for sharing this article with the general public. Supplements are great health options, however, many have abused the items, making it at the expense of natural processes.
Why Antioxidant Supplements Don't Work, Part 1
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