From chemist Derek Lowe’s blog.

The Evidence Piles Up: Antioxidant Supplements Are Bad For You

February 5, 2014

You may remember a study that suggested that antioxidant supplement actually negated the effects of exercise in muscle tissue. (The reactive oxygen species generated are apparently being used by the cells as a signaling mechanism, one that you don’t necessarily want to turn off). That was followed by another paper that showed that cells that should be undergoing apoptosis (programmed cell death) could be kept alive by antioxidant treatment. Some might read that and not realize what a bad idea that is – having cells that ignore apoptosis signals is believed to be a common feature in carcinogenesis, and it’s not something that you want to promote lightly.

Here are two recent publications that back up these conclusions. The BBC reports on this paper from the Journal of Physiology. It looks like a well-run trial demonstrating that antioxidant therapy (Vitamin C and Vitamin E) does indeed keep muscles from showing adaptation to endurance training. The vitamin-supplemented group reached the same performance levels as the placebo group over the 11-week program, but on a cellular level, they did not show the (beneficial) changes in mitochondria, etc. The authors conclude:

Consequently, vitamin C and E supplementation hampered cellular adaptions in the exercised muscles, and although this was not translated to the performance tests applied in this study, we advocate caution when considering antioxidant supplementation combined with endurance exercise.

Then there’s this report in The Scientist, covering this paper in Science Translational Medicine. The title says it all: “Antioxidants Accelerate Lung Cancer Progression in Mice”. In this case, it looks like reactive oxygen species should normally be activating p53, but taking antioxidants disrupts this signaling and allows early-stage tumor cells (before their p53 mutates) to grow much more quickly.

So in short, James Watson appears to be right when he says that reactive oxygen species are your friends. This is all rather frustrating when you consider the nonstop advertising for antioxidant supplements and foods, especially for any role in preventing cancer. It looks more and more as if high levels of extra antioxidants can actually give people cancer, or at the very least, help along any cancerous cells that might arise on their own. Evidence for this has been piling up for years now from multiple sources, but if you wander through a grocery or drug store, you’d never have the faintest idea that there could be anything wrong with scarfing up all the antioxidants you possibly can.

The supplement industry pounces on far less compelling data to sell its products. But here are clear indications that a large part of their business is actually harmful, and nothing is heard except the distant sound of crickets. Or maybe those are cash registers. Even the wildly credulous Dr. Oz reversed course and did a program last year on the possibility that antioxidant supplements might be doing more harm than good, although he still seems to be pitching “good” ones versus “bad”. Every other pronouncement from that show is immediately bannered all over the health food aisles – what happened to this one?

This shouldn’t be taken as a recommendation to go out of the way to avoid taking in antioxidants from food. But going out of your way to add lots of extra Vitamin C, Vitamin E, N-acetylcysteine, etc., to your diet? More and more, that really looks like a bad idea.

Update: from the comments, here’s a look at human mortality data, strongly suggesting no benefit whatsoever from antioxidant supplementation (and quite possibly harm from beta-carotene, Vitamin A, and Vitamin E).

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Please see the original article, since it contains quite a few links, as well as readers’ comments.

On Vitamin C, And On Linus Pauling

February 6, 2014

Well, just after blasting antioxidant supplements for cancer patients (and everyone else) comes this headline: “Vitamin C Injections Ease Ovarian Cancer Treatments”. Here’s the study, in Science Translational Medicine. So what’s going on here?

A closer look shows that this, too, appears to fit into the reactive-oxygen-species framework that I was speaking about:

Drisko and her colleagues, including cancer researcher Qi Chen, who is also at the University of Kansas, decided that the purported effects of the vitamin warranted a closer look. They noticed that earlier trials had partially relied on intravenous administration of high doses of vitamin C, or ascorbate, whereas the larger follow-up studies had used only oral doses of the drug.

This, they reasoned, could be an important difference: ascorbate is processed by the body in different ways when administered orally versus intravenously. Oral doses act as antioxidants, protecting cells from damage caused by reactive compounds that contain oxygen. But vitamin C given intravenously can have the opposite effect by promoting the formation of one of those compounds: hydrogen peroxide. Cancer cells are particularly susceptible to damage by such reactive oxygen-containing compounds.

Drisko, Chen and their colleagues found that high concentrations of vitamin C damaged DNA and promoted cell death in ovarian cancer cells grown in culture. In mice grafted with human ovarian cancer cells, treatment with intravenous vitamin C combined with conventional chemotherapy slowed tumour growth, compared to chemotherapy treatment alone.

The concentrations attained by the intravenous route are apparently necessary to get these effects, and you can’t reach those by oral dosing. This 2011 review goes into the details – i.v. ascorbate reaches at least 100x the blood concentrations provided by the maximum possible oral dose, and at those levels it serves, weirdly, as a percursor of hydrogen peroxide (and a much safer one than trying to give peroxide directly, as one can well imagine). There’s a good amount of evidence from animal models that this might be a useful adjunct therapy, and I’m glad to see it being tried out in the clinic.

So does this mean that Linus Pauling was right all along? Not exactly. This post at Science-Based Medicine provides an excellent overview of that question. It reviews the earlier work on intravenous Vitamin C, and also Pauling’s earlier advocacy. Unfortunately, Pauling was coming at this from a completely different angle. He believed that oral Vitamin C could prevent up to 75% of cancers (his words, sad to say). His own forays into the clinic with this idea were embarrassing, and more competently run trials (several of them) have failed to turn up any benefit. Pauling had no idea that for Vitamin C to show any efficacy, that it would have to be run up to millimolar concentrations in the blood, and he certainly had no idea that it would work by actually promoting reactive oxygen species. (He had several other mechanisms in mind, such as inhibition of hyaluronidase, which do not seem to be factors in the current studies at all). In fact, Pauling might well have been horrified. Promoting rampaging free radicals throughout the bloodstream was one of the last things he had in mind; he might have seen this as no better than traditional chemotherapy (since it’s also based on a treatment that’s slightly more toxic to tumor cells than it is to normal ones). At the same time, he also showed a remarkable ability to adapt to new data (or to ignore it), so he might well have claimed victory, anyway.

………………………..

This brings up another topic – not Vitamin C, but Pauling himself. As I’ve been writing “The Chemistry Book” (coming along fine, by the way), one of the things I’ve enjoyed is a chance to re-evaluate some of the people and concepts in the field. And I’ve come to have an even greater appreciation of just what an amazing chemist Linus Pauling was. He seems to show up all over the 20th century, and in my judgment could have been awarded a second science Nobel, or part of one, without controversy. I mean, you have The Nature of the Chemical Bond (a tremendous accomplishment by itself), the prediction of noble gas fluorides as possible, the alpha-helix and beta-pleated sheet structures of proteins, the mechanism of sickle cell anemia (and the concept of a “molecular disease”), the suggestion that enzymes work by stabilizing transitions states, and more. Pauling shows up all over the place – encouraging the earliest NMR work (“Don’t listen to the physicists”), taking a good cut at working out the structure of DNA, all sorts of problems. He was the real deal, and accomplished about four or five times as much as anyone would consider a very good career.

But that makes it all the more sad to see what became of him in his later years. I well remember his last hurrah, which was being completely wrong about quasicrystals, from when I was in graduate school. But naturally, I’d also heard of his relentless advocacy for Vitamin C, which gradually (or maybe not so gradually) caused people to think that he had slightly lost his mind. Perhaps he had; there’s no way of knowing. But the way he approached his Vitamin C work was a curious (and sad) mixture of the same boldness that had served him so well in the past, but now with a messianic strain that would probably have proven fatal to much of his own earlier work. Self-confidence is absolutely necessary for a great scientist, but too much of it is toxic. The only way to find out where the line stands is to cross it, but you won’t realize it when you have (although others will).

We remember Isaac Newton for his extraordinary accomplishments in math and physics, not for his alchemical and religious calculations (to which he devoted much time, and which shocked John Maynard Keynes when he read Newton’s manuscripts). Maybe in another century or two, Pauling will be remembered for his accomplishments, rather than for the times he went off the rails.

The latest from the AREDS experiment (using antioxidants for macular degeneration) seems to have only confirmed what the early results said. Supplementing may be some help if you already have some macular degeneration going on, but it ain’t got no legs for prophylaxis.

I could find the ref if anyone is interested.

So which foods are high in reactive oxygen?

interesting work.

You are pretty right with eating foods Bubblecar. It is supplementing that is fairly pointless to possibly detrimental.

Here is the Cochrane take on supplements:

http://summaries.cochrane.org/CD007176/antioxidant-supplements-for-prevention-of-mortality-in-healthy-participants-and-patients-with-various-diseases

There is a link at the bottom to the one about macular degeneration.

Ooh, and look….someone has actually compiled a table for foods:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841576/

My urine changes color when I use supplements

I presume its all being flushed out

when they can make stuff that can stay in and be useful, Ill buy it

but its just a waste a money when it all gets flushed away

>It is supplementing that is fairly pointless to possibly detrimental

Qualifier..

except the cases in which it is not pointless.

Supplementation in the presence of an adequate diet is not necessary.

>Supplementation in the presence of an adequate diet is not necessary.

That tidies up the generalization quite well.

There may be some conditions in which ratios of minerals are not regulated optimally by the body, so supplements may help. A ratio problem (if any exist) is not quite the same as a deficiency.

buffy said:

Supplementation in the presence of an adequate diet is not necessary.

Yes, my diet is adequately varied and wholesome in quality (but still in need of more disciplined quantity control).

buffy said:

Supplementation in the presence of an adequate diet is not necessary.

I view them as cheap insurance. Plus I have been told to take vitamin D anyway. Plus my diet can be lacking, but even so, its a couple of cents a day.

There are also certain conditions, and situations (some medical treatments) that tend to come with absorption problems.

Bubblecar said:

buffy said:

Supplementation in the presence of an adequate diet is not necessary.

Yes, my diet is adequately varied and wholesome in quality (but still in need of more disciplined quantity control).

I suspect that it contains more than the recommended amount of fat (which is <~1g per kg ideal body weight).

and what if the food is crap?

I’ve worked at plenty of places where the food was being grown on fertiliser alone unless the plants started wilting (add iron)

great looking food – no real nutritional value

the whole idea of the industrialised society is that everything becomes industrialised including the people and the food they eat. a society based on the industrialised way of doing things also doesn’t need people to last very long – ideally everyone should die before they take the pension.

>I suspect that it contains more than the recommended amount of fat (which is <~1g per kg ideal body weight).

Probably, but I’m going to plan this year’s apple season around low-fat recipes. And add just a tiny drop of olive oil to my beans rather than a knob of butter.

>ideally everyone should die before they take the pension.

Wook mate, you could get a job with Centrelink.

Bubblecar said:

>I suspect that it contains more than the recommended amount of fat (which is <~1g per kg ideal body weight).

Probably, but I’m going to plan this year’s apple season around low-fat recipes. And add just a tiny drop of olive oil to my beans rather than a knob of butter.

Why have either? Beans don’t need butter or oil. They work well with rice though.

A bit of butter helps you to assimilate the Vitamin C from your veggies. OK, beans are not really Vitamin C sources, but they taste better with a bit of butter. You don’t need much. OK, it’s just the oil really. Doesn’t have to be butter.

:)

Phew, lucky I don’t exercise too much.

Taking antioxidant supplements increases mortality. Why would anyone take them outside of doctor’s advice?

>you’d never have the faintest idea that there could be anything wrong with scarfing up all the antioxidants you possibly can.

And is this what people generally do. Even if you narrowed that proposition down to people that tend to buy supplements, would it be true.

And as for that small minority that are ‘scarfing up all the antioxidants you possibly can’, and if they are doing it regularly or all the time, well, please step forward and identify your selves, you antioxidant scoffing maniacs.

here is an overview (and information about where to find the actual paper) for nut’s comment:

http://www.webmd.com/news/20070227/antioxidant-supplements-up-death-risk

buffy said:

here is an overview (and information about where to find the actual paper) for nut’s comment:

http://www.webmd.com/news/20070227/antioxidant-supplements-up-death-risk

Taking vitamin A supplements increased the risk of death by 16%. Taking beta-carotene supplements increased the risk of death by 7%. Taking vitamin E supplements increased the risk of death by 4%. Taking vitamin C supplements did not have any effect on risk of death.

16% is quite significant.

ideally everyone should die before they take the pension.
——————————————————————————

lol

Well thats easy… just increase the age limit.

Thats why they (The people that get to keep their jobs, and their family and friends) are so needed in Aust.

They save us so much money.

Mr Ironic said:

ideally everyone should die before they take the pension.
——————————————————————————

lol

Well thats easy… just increase the age limit.

Thats why they (The people that get to keep their jobs, and their family and friends) are so needed in Aust.

They save us so much money.

I’ll never collect the pension anyway. I’ll work my arse off to keep the country afloat like so many of us do yet we still have to put up with uninformed bullshit .

I’ll never collect the pension anyway
—————————————————

I know this will be hard to believe…

But the post wasn’t about you.

Mr Ironic said:

I’ll never collect the pension anyway
—————————————————

I know this will be hard to believe…

But the post wasn’t about you.

it is OK.. but if you include anyone.. you must also include me and I do speak for a large percentage of us.