For a long time we’ve heard the benefits of antioxidants touted, to the point where it’s entered conventional wisdom. Yet the supporting evidence has been indirect and surprisingly weak, as dietary evidence generally and often unavoidably is.
Here are three things we do know for sure:
- Exercise is good for you. Very very very good for you.
- A vegetable rich diet based on whole foods is certainly good for you. Though many details on exactly why remain unclear.
- Vitamins are predicted to be good for you, yet study after study fails to show much if any benefit to supplements.
A wonderful study came out today in PNAS. When I say wonderful I’m not talking about the results obtained, but the study itself.
These authors took a direct approach to the question, “how do antioxidants affect physiology and metabolism?” No hand waving, no leaps of logic, statistical inferences or behavioral correlations. Just direct measurements at the physiologic level.
They put two groups of volunteers through a controlled exercise program, half supplemented with vitamins C (1000 mg/day) and E (400 IU/day) and half without supplements. They look at both trained and untrained individuals (though ‘trained’ remains oddly undefined) before and after exercise. They took baseline measurements, blood tests and muscle biopsies. They measured glucose infusion rates during a euglycemic clamp (a direct measure of insulin sensitivity). They measured levels of superoxide dismutases and glutathione peroxidase, proteins directly involved in neutralizing reactive oxygen species. They measured the expression of genes that are sensitive to reactive oxygen species.
The results were jaw dropping. The no supplement group showed all of the known and predicted effects of exercise. The supplement group did not. There is graph after graph after graph in which the vitamin group looks like it didn’t exercise at all. You don’t need to be science literate to interpret these graphs: Vitamin C and E supplements are blocking several physiologic responses to exercise. Most importantly and most ominously, the change in the insulin response is almost completely blocked.
It looks to me like they nailed it. Not even the vitamin council is criticizing this study, they are admitting that this is good (though of course recommending no one make changes yet). This is huge.
Runner’s World
The daily blog on RW mentioned this study today and the writer was exasperated, naturally. What’s the next headline, he wondered, “Smiling Causes Oral Cancer” perhaps?
I’m glad to see your interpretation because you are highly skeptical of so many of the studies we read about.
I’ve never been a vitamin person myself, so it doesn’t affect me, but it’s good info to have!
Oh good!
Can I stop taking my multis now? Hate those suckers but I do it it for the folic acid and calcium, which I still think I need. Maybe just take folic acid and Tums?
Weird!
A question I have is whether the non-supplemented group were already getting a reasonable amount of C and E, or not. In other words, is it an excess of C and E that is the problem, or is it just having supplements at all? What if they had eaten 20 oranges every day instead of taking a C pill? Would you see the same result?
fruits and vegetables
That’s outside of the scope of this paper – they aren’t studying diet. But here’s what they say in the discussion (emphasis mine):
also
The subjects were randomized into 4 groups (paired by exercise history) and everyone was tested before and after exercise. There were enough subjects that an unusual diet shouldn’t throw off the results much. Plus they got the same basic result whether they were looking at high fitness or lower fitness subjects, so the study was internally replicated, and p-values were really extraordinary, many down into the p> 0.0001 range. So it’s highly unlikely to be an artifact of background diet.
Wow.
Full text of the paper is available here:
http://www.pnas.org/…
pretty impressive, isn’t it?
I don’t know when was the last time I read something this good on human subjects; this quality is usually only found in model system research. I found Fig 1 so mind blowing I’m going to be seeing it in my sleep. It raises more questions than it answers, including the question of why we aren’t seeing more work like this?
I haven’t seen discussion of this on science blogs yet, but I’m looking forward to seeing if anyone is able to come up with any flaws or loopholes. But I bet this has more impact in the scientific community than the general public. After all, everybody knows (except the researchers who study this) that vitamins and antioxidants are good for you, just like everybody knows (except the researchers that study this) that diet soda helps you lose weight. I’m sure that manufacturers and advertisers will make sure they don’t lose their antioxidant sales angle.
One of the questions I saw on another board was
How do we know all of these factors are “good” results of exercise and not signs of the body not keeping up with repair? The insulin/diabetes markers excepted – everyone gets those. I’m not familiar enough with all the factors in fig 2. to dismiss that out of hand.
ITA
That’s the one I was thinking of too. We can’t say that all of these are positive goals in and of themselves, and we can’t really be sure they’re all positive signs. PPAR-gamma, for example, correlates with an improvement in diabetes markers and is an intervention target itself. But it’s way downstream in the pathway and is affected by a whole slew of different things.
GST and the SODs are directly involved in the reduction of reactive oxygen species, and based on these authors’ publication history I’m guesssing ROS is their real interest. If you raise the level of GST you directly affect ROS, but I’m not sure you can assign good/bad to that. In fact the authors argue that we may have this somewhat backward.
But at some level, rating these changes as good or bad somewhat misses the point. The logic stream is: exercise is beneficial, exercise induces a large number of changes at the cellular/molecular level, and antioxidant doses of C and E block at least a subset of these changes, including the all important change in insulin sensitivity. The leap all the way to “vitamins are bad” is not supported, but the leap to “uh-oh” certainly is. The correct conclusion to this paper is “Holy sh*t!
I think the question was
if exercise is always beneficial. The place I saw that comment was a horse board, where people are all too aware of how quickly too much work leads to arthritic changes.
the exercise regimen doesn’t look too bad
The subjects were selected to all be young and healthy. The exercise looks like it could be a lot for the couch potato group, but might be less than what the ‘trained’ group was accustomed to. If the exercise were too stressful you’d expect a difference between the trained and the untrained group.
I think I’m gonna stick my fingers in my ears
and say “la la la, I didn’t hear this.”
And the way I’ll justify it is that the study only looked at a small group of healthy young men.
I’m not a healthy young man.
So this doesn’t apply to me at all, right?
La la la! :P
lol
You must really enjoy taking your vitamins!
Not so much that…
as I really hate changing my routine! Specially for the latest study-of-the-month, even a high-quality study-of-the-month. :-)
On the other hand, I might could just not buy another bottle of Vit. C when the current one runs out. And chalk it up to frugality. Hmmm.
Amen!
Glad to hear that someone is feeling the same as me. I don’t take multivitamins (I’m surprised to hear that they do anything at all), unless I’m pregnant or breastfeeding. But changing anything based on one tiny sample size study that didn’t actually show anything all that relevant (though it’s still interesting and certainly bears further research), is fairly reactive, in my opinion.
Wow…
Good to know. It sounds like supplements with vitamins C and E are the issue? If that’s the case, I will probably switch to a calcium-only vitamin as I exercise a lot. But my doctor told me to take 1,200 mg of calcium a day to avoid bone loss, which starts in your 30s.
vitamin D
The most recent data suggests that vitamin D is far more important to bone maintenance than calcium. Most people take them together, of course. But when you look at the benefit of vitamin D, the presence or absence of calcium doesn’t seem to matter much. On the other hand when you look at the benefit of calcium, the vitamin D intake is critical – no benefit is seen at less than 800 IU/day vit D.
magnesium also, no?
I thought magnesium is also important for absorption of calcium. A friend who is a midwife also recommends magnesium (as part of a calcium supplement) for women with some hormonal issues in the postpartum months.
I get a lot of sun in CA…
does that mean I should take a vitamin D supplement as well?
In the winter, maybe
You’re a little far north to get much decent UV in the winter – it’s not just amount of sun, it’s also the angle. Most researchers say if you live north of chicago you need supplements no matter what, even if you sunbathe all day in the nude. But others take things like clothing and typical outdoor time into account and place the dividing line as far south as LA. There’s really far too many variables to generalize, including cloud cover, angle of the sun, occupation, sunscreen use, skin color, etc, etc.
I live in your area and spend a fair amount of time outdoors but I have osteopenia (a fancy name for ‘watch out you’re getting close to osteoporosis’), so I take 1000 IU despite my white white skin and my resistance to sunscreen. I’ve gotten a little too casual about chewing my tums, though, and really should be more diligent.
I’m thinking if you sunbathe
all day in the nude, you probably need a little more than a supplement.
in a chicago winter?
anti-psychotics?
Or something a little stronger? LOL
well i do take the happy pill
and just recently joined that crowd. i must say i feel much much better and i am not inclined to stop any time soon
but, do
you sunbathe all day? LOL
i would if i could
the happy pill has put my high drive into a lower gear, so sunbathing all day might just be what i do
i really love you. nt
lyn help me please
i exercise and i eat like a health freak. but i also take supplements; multi vit and calcium. i also take fish oil, cumin and restravol. argh…what do you suggest based on this study? my diet is heavy on fruit and veggies, rarely red meat.
help me
one more..
i checked my vitamin d level in last blood test…it was just dandy. and lots of sunshine her in ca.
Great questions, Melinda!
I am tempted to e-mail my doctor to ask what I should do. I am a health nut, but as this study pointed out, I may be overdoing it.
lol
What do I recommend? How about Michael Pollan’s In Defense of Food – it might help you relax. :-) Seriously, I’m not qualified to dispense nutrition advice. Neither is Pollan, I suppose, but he’s awesome.
Classmates of mine in the nutrition dept claim that ‘everyone knows’ (in their department at least) that supplements aren’t equivalent to nutrients. If you’ve got a great diet and exercising you’re already doing the very best thing you could be doing, so you probably don’t need the pills. But I found this paper incredibly convincing, so I would personally lay off the C and E. Which have absolutely no data in their favor in the first place, despite decades of dedicated effort. Fish oil and resveratol, on the other hand . . .
That’s what’s so frustrating about vit D
I’ve never been a supplementing kind of gal so the vitamin D research bothers me a bit. I want there to be a fix where I go outside and it’s all okay…. In the meantime my kids get a Gummi Vitamin with 100% of the RDA of vitamin D (which may be low, I know) and a ridiculous amount of vitamin D fortified milk (their choice).
Lyn, what do you give your kids for vitamin D?
nothing much
They get a gummi vitamin with 200 IU of vit D, which isn’t enough really. In fact that’s the only reason I gave them the vitamin in the first place – I’d figured the rest of it was harmless, though now I’m not so sure. But we’re not a sunscreen family (DS1 could never tolerate lotions on his lizard hide) and we live in CA so even though they have dark skin I count on the sun to provide enough.
yes i laid off
C and E a long time ago. but fish oil? and restravol( sp?) and cumin? i do eat a ton of blueberries and pomegranite seeds so i feel like i have that covered. i guess i will drop the multi vitamin. i also take glucosmine (sp again?) as i swear it helps my joints. great info lyn..really appreciate the heads up. i admit i have always been a health nut but with common sense
and you’re asking me?
It sounds like you’re way out ahead of me in health and nutrition. I felt compelled to diary this paper out of admiration for the sheer beauty of the science. I love seeing wobbly conventional wisdom tested by researchers who ask the right questions and design the right tests. And of course it touches on my old field of insulin signaling and metabolic disease, and I’ve never seen anything do what these supplements did.
Fish oil and resveratrol (I can’t spell it either) are fascinating, aren’t they? I continue to keep an eye on these. I don’t know anything about cumin, though.
sorry lyn
i promise not to make you my MT nutritionist
appreciate the scientific scoping you provide.
quantities
The levels of supplementation in the study are very high. I guess some people really do take that much, but I just checked my multi, and it only contains 60 mg of C and 30 IU of E (versus 1000 and 400, respectively, in the study). I have always been suspicious of megadoses of vitamins, so I take a multi that only provides 100% of RDA (with 200% of D, so I’m meeting the 800 mg recommendation). The study says nothing about this level of supplementation, so it’s anybody’s guess whether the damage is from supplementation per se or from overdosing on C and E.
yes but
I believe the amounts they used are common doses for people who are taking these vitamins specifically for their antioxidant properties. My mom was a vitamin E fan (no idea why) and I know she took 400 IU, and I believe Linus Pauling followers take way more than 1000 mg of C. But you make a good point – a multi with the RDA is probably not doing much harm.
“not doing much harm”
I disagree with your wording here. The study cannot say whether they are doing any harm at all at RDA levels, and it does not nullify the possibility that they are doing quite a lot of good. Any drug works at the correct dosage and is toxic at high dosages. I’m feeling increasingly strongly that that is what is going on here. It has long been known that high doses of vitamin A are toxic. This is the first indication that that is the case with C and E. But that says absolutely nothing about their effect at lower levels.
I disagree that “any drug
works at the correct dosage.” There have been all sorts of drugs over the years that people take that not only do no good but even a great deal of harm at the “correct” dosage. (Radium pills come to mind.)
I believe lyn said there have been no studies at all showing benefits that supplements of vitamins C and E “work” at any dosage. I’m sure she’ll be along to correct me if I’m wrong.
Well, you certainly don’t want to get scurvy
so there’s some optimal point, but part of the concern is that what we consider vitamins is only a small part of the profile of a whole food.
But we still don’t know
if vitamin supplements work.
I mean, we know our bodies need certain nutrients, to be sure, and as you say there’s an optimal point.
The question is whether it’s even possible to see benefits from vitamin supplements (which is what I was thinking when I saw the word “drug,” as opposed to vitamins from food).
It depends on the supplement
I think there are known things and unknown things. For example it is definitely been demonstrated that folic acid prevents neural tube defects if taken preconceptually. And there have been studies demonstrating positive impacts of prenatal vitamins on birth outcomes (e.g. this one). I think it would be an overstatement to say that absolutely no benefits of any supplements have been shown. I can’t speak for C and E in large quantities though.
badly worded
Clearly, not all drugs work. I meant that any drug that works at the correct dosage will be toxic above some level, which varies with the drug.
Right.
But (if I’m understanding lyn correctly) we don’t know that vitamin C or E supplements do work at the correct dosage. All we know is that (1) dietary vitamins C and E are necessary and (2) the supplements don’t work (in fact, are harmful) at a higher dosage.
no info on RDA levels
Perhaps “little if any harm” would have been a better phrasing. When I said “probably not doing much harm” I meant there is nothing in this study to raise concerns about low doses. Maybe they’re doing harm, maybe not – you can’t say anything at all about the RDA doses based on this study, good or ill.
I don’t really know this field well. However I get the impression that the balance of evidence seeems to be tilting toward weakly negative on most vitamin supplements. Most careful and well designed studies seem to turn out inconclusive, but there have several that have correlated supplement use with small increases in the risk they expected to lower.
Remember that the RDA is the recommended daily allowance of the nutrient. Nobody is recommending that you take that amount of a supplement in pill form on top of your normal diet. In fact a few years ago I read a long feature length article (NYT magazine, maybe?) on the FDA and the RDA. The journalist had the bright idea to ask each of the scientists on the panel responsible for setting the recommendations what he or she personally takes. IIRC one scientist confessed to taking a children’s multivitamin daily, the rest said “nothing”.
here’s a couple of recent articles
From the NYT well blog, last year. The first article lists a bunch of recent studies correlating vitamins with health outcomes, the second provides a good discussion and perspective on one study.
News Keeps Getting Worse for Vitamins
Disappointing News on Vitamin E and Selenium
And the RDA itself
was done so long ago that I don’t know that those numbers are really “it” any more.
Fairly highly qualified….
The media will run with a headline of “multivitamins are bad for your health”. A better headline would be “In men, the benefits of exercise on insulin sensitivity are reduced by high levels of antioxidants”.
But that’s not exciting enough…
actually
The media is doing better than I expected. About half of the headlines on a google news search were reasonable and included qualifiers – ‘may block benefits’, ‘blunt some benefits’, ‘may reduce effects’, ‘may nullify positive effects’, etc. The other half were as expected, with headers either overstated or jazzed up to entice (‘wait – now vitamins are bad?’). But the articles I clicked on were ok. Of course there is always the just plain wrong: ’Study Warns Against Taking Vitamin C, E After Workout’. What? No it doesn’t; not even close.
thank you- just the push I needed
to get me out of my slump and get moving. I have been taking a prenatal vitamin because that’s what I thought was recommended for breastfeeding mothers. But it may be too much. I’m going to cut back on that, keep taking fish oil, have a little red wine, and–
– thank you Elisa for pushing that Tracy Anderson DVD–
getting my butt back in gear.