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You are here: Home / Science & Technology / …And It Can Hit The High E In The Star-Spangled Banner

…And It Can Hit The High E In The Star-Spangled Banner

by Tim F|  December 15, 20069:54 am| 31 Comments

This post is in: Science & Technology

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Even crappy science fiction usually shies away from contrived plot devices like the cheap miracle pill that extends your life, prevents disease, makes you smarter, boosts strength and lets you live on glazed donuts, red meat and beer. It’s hard to create a believable future where the world is that nice to us.

So don’t blame me if the latest research on the compound resveratrol, whose effects already include extending lifespan, fighting cancer, resisting infectious disease and mitigating diabetes, sounds a little on the ridiculous side. Eventually the sheer weight of reality and medicine’s often-dashed hopes have to come crashing down. Will it make people sterile? Attract predators? Cause us to look only one way before crossing the street? Maybe, but the fall hasn’t come yet. Instead it gets weirder. In the prestigious research journal Cell editors summarize a new paper as follows:

Now Lagouge et al. find that resveratrol treatment results in improved mitochondrial function, aerobic capacity, and metabolic homeostasis in mice.

This seems like partly a rehash of what we already knew or suspected – resveratrol (RSV) keeps mitochondria, whose degradation people often associate with aging, in a generally healthier state. But notice that last bit. “Metabolic homeostasis” can mean a couple of things, one of which is the connection between what we eat, our blood sugar regulation (e.g. diabetes) and how much fat the body builds up. The article’s abstract says this:

Our data reveal that RSV potently induces mitochondrial activity, through activating PGC-1α, as evidenced by the increase in oxidative type-muscle fibers, enhanced resistance to muscle fatigue, and increased tolerance to cold, all PGC-1α-dependent effects. Importantly, these effects, induced by RSV, rendered the animals resistant to diet-induced obesity and insulin resistance.

In a nutshell, resveratrol lets mice eat the mouse equivalent of a donut diet without getting fat. That ought to go unnoticed; it’s not like diet pills are lucrative business or anything.

Whenever a medically-relevant mouse researcher gives a talk, the first or second question is usually about how confident they are that the same phenomenon happens in people. Lagouge and co-workers clearly saw that coming and wrap the paper with a key finding – in a Finnish population small mutations in the primary resveratrol target, a protein called SirT1, have effects on metabolism that correlate very well with the results that the researchers found by manipulating the protein in mice.

Preliminary doesn’t begin to describe the state of this research. Two or three labs need to repeat the work before science will consider an idea established and human trials aren’t even in the pipeline yet. At this early stage it even feels silly to write about miracle diet pills that prevent cancer and make you live longer. Somebody will no doubt soon discover the major caveat that brings all this back to Earth. And then again, maybe not.

***

For number crunchers out there, the study used a daily dose of 200-400 mg/kg resveratrol. In a 70 kilogram/150-pound person that translates to 14-28 grams of the stuff per day. If you want resveratrol the natural way you’re out of luck if you don’t like red wine, and at 1.5-3 milligrams per liter you had better like it a lot.

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31Comments

  1. 1.

    ImJohnGalt

    December 15, 2006 at 10:24 am

    From what little I read about the stuff after your initial posts, Tim, I was left with the impression that megadosages were recommended as therapy in the case where you were already ill (cancer, diabetes), but less than half of those dosages would have beneficial effects as a preventative.

    Just sayin’. It’s pretty tough to afford resveratrol at the dosages recommended on the bottles, much less at the dosages indicated in your post.

  2. 2.

    srv

    December 15, 2006 at 10:25 am

    If you want resveratrol the natural way you’re out of luck if you don’t like red wine, and you had better like it a lot.

    So if you’re a researcher, why don’t you solve this problem?

    I can’t find those wacky North Carolina wines loaded with the stuff out here in the Bay Area, and you dissuaded me from believing any of the pill claims.

    Can’t you invent a new grape or come up with an unpastuerized grape juice?

  3. 3.

    Tim F.

    December 15, 2006 at 10:34 am

    So if you’re a researcher, why don’t you solve this problem?

    Actually I think that it can potentially be refined the same way aspirin was. Modify the original compound slightly (in the case of aspirin, acetylate it) so that it passes through the gut more easily and stays in the body longer.

  4. 4.

    Steve

    December 15, 2006 at 10:52 am

    This reminds me of a story I read about a guy who consumed large quantities of royal jelly in search of similar results, and ended up slowly turning into a bee. Your mileage may vary.

  5. 5.

    El Cruzado

    December 15, 2006 at 11:04 am

    It actually would need to be far less than 14 grams. Dosage is proportional to metabolism, not body weight. So to calculate human dosage it would make more sense (although still be far from precise) to do the proportion based on daily food intake or a similar measure.

  6. 6.

    mrmobi

    December 15, 2006 at 11:10 am

    Aren’t the “free lunch” and the “magic bullet” related?

    One of the early lessons my departed father taught me was that when something seems too good to be true, it probably is.

    Dad seemed to get smarter and smarter as I got older. (I think that’s Sam Clemens).

    Not that I wouldn’t appreciate a magic bullet in the 12th mile of a 14 mile run, but there is no crying in baseball.

    One last question. If I drank enough wine to get the recommended dosage and died from it, would my corpse be the heathiest ever? Just wondering

  7. 7.

    stickler

    December 15, 2006 at 11:10 am

    Wait. So does this mean I can become young again if only I drink 12 bottles of red wine a day?

    What effect does resveratrol have on aging in the liver? It would kind of suck to be the youngest-looking victim of cirrhosis in the hospice.

  8. 8.

    Zifnab

    December 15, 2006 at 11:14 am

    All I’m saying is, with the way research is going, one day we’re going to create a pair of lab mice so incredibly enhanced, they’ll take over the world.

  9. 9.

    Zifnab

    December 15, 2006 at 11:19 am

    One of the early lessons my departed father taught me was that when something seems too good to be true, it probably is , except when it isn’t.

    My dad was a stockbroker, so he was kinda in the business of “too good to be true” deals.

  10. 10.

    Pb

    December 15, 2006 at 11:38 am

    It actually would need to be far less than 14 grams. Dosage is proportional to metabolism, not body weight.

    And perhaps other factors as well–this is way out of my field, mind you, but I looked up a bit regarding mercury in tuna, because I was curious about the amounts involved–lots of factors at work there.

  11. 11.

    nichevo

    December 15, 2006 at 11:42 am

    Tim F. notes:

    Actually I think that it can potentially be refined the same way aspirin was. Modify the original compound slightly (in the case of aspirin, acetylate it) so that it passes through the gut more easily and stays in the body longer.

    It’s interesting to recall a meme making the rounds that, if aspirin had been invented today instead of predating the FDA (like Crisco and trans fats!), it might not have received approval.

    One also wonders whether, like marijuana used in various medical treatments, the key ingredient is THC or the hundreds of other cannabinoids floating around in that cloud of smoke. Smoke…mmm…

    Ahem…that is to say, is it reservatrol, pure reservatrol, in isolation, or is it better to consume the ingredient as a whole food with other less-well-understood chemicals in tomatoes and grapes? Perhaps to cultivate a super-grape crammed with the stuff?

  12. 12.

    grumpy realist

    December 15, 2006 at 12:02 pm

    Even with cheap plonk that could get pretty expensive.

    Isn’t there some bizarre fruit from China that has a lot of the stuff in it?

    I predict that within 5 years, someone will come out showing that this stuff causes brain cancer.

  13. 13.

    srv

    December 15, 2006 at 12:26 pm

    All I’m saying is, with the way research is going, one day we’re going to create a pair of lab mice so incredibly enhanced, they’ll take over the world.

    When you start seeing them play Brockian Ultra-Cricket, it would be time to worry.

  14. 14.

    fwiffo

    December 15, 2006 at 12:34 pm

    Somebody will no doubt soon discover the major caveat that brings all this back to Earth.

    If it’s anything like other recent pharmacuticals and diet pills, it will make your heart explode in a giant ball of fire visible from space.

  15. 15.

    jg

    December 15, 2006 at 12:42 pm

    Zifnab Says:

    All I’m saying is, with the way research is going, one day we’re going to create a pair of lab mice so incredibly enhanced, they’ll take over the world.

    I thought this planet was commissioned by lab mice? Aren
    t we supposed to be a part of thier experiments?

  16. 16.

    Krista

    December 15, 2006 at 12:49 pm

    Zifnab Says:

    All I’m saying is, with the way research is going, one day we’re going to create a pair of lab mice so incredibly enhanced, they’ll take over the world.

    Just like they’ve been trying to do every night…

  17. 17.

    Darrell

    December 15, 2006 at 1:03 pm

    I predict that within 5 years, someone will come out showing that this stuff causes brain cancer.

    Or shrivels the genitalia or some other undesirable side effect.. just like TimF stated

    It’s hard to create a believable future where the world is that nice to us.

    Mother nature can be a bitch.

  18. 18.

    ihatespam

    December 15, 2006 at 1:08 pm

    stickler,

    No, it’s like 40,000 bottles of red wine a day. One liter has about 2 milligrams so that means 1,000 liters has 2 grams. You need 14-28 grams and one bottle has 0.75 liters. You do the math.

  19. 19.

    jenniebee

    December 15, 2006 at 1:20 pm

    This reminds me of a story I read about a guy who consumed large quantities of royal jelly in search of similar results, and ended up slowly turning into a bee. Your mileage may vary.

    zomg, Roald Dahl is teh roxxorz!

  20. 20.

    ThymeZone

    December 15, 2006 at 2:23 pm

    Mother nature can be a bitch.

    Noted.

  21. 21.

    John S.

    December 15, 2006 at 2:24 pm

    Or shrivels the genitalia or some other undesirable side effect

    The shriveling of genitalia is generally an undesirable side effect, although in some people the notion of sterility seems like a very desirable side effect…

    I kid, of course. At that point we may as well start throwing undesirable infants off of cliffs like the ancient Greeks used to do.

  22. 22.

    rilkefan

    December 15, 2006 at 2:32 pm

    increase in oxidative type-muscle fibers, enhanced resistance to muscle fatigue, and increased tolerance to cold

    Tim, what’s the reason there wasn’t selection pressure for developing these positive traits without RSV? Obesity-related traits are adaptive?

  23. 23.

    Wolfdaughter

    December 15, 2006 at 2:38 pm

    I agree with others. Anything that sounds too good to be true probably IS too good to be true. I can’t think of a single instance of a drug in the past, touted to be a “miracle drug”, which didn’t show up later with significant and deleterious side effects.

    I’m also a little leary of messing with mitochondrial function anyway. That could have MAJOR unexpected consequences. Sterility comes to mind.

    Picking nits: the high note in the Star-Spangled Banner would be an E ONLY if played in the key of A major. I am a singer with perfect pitch, fully capable of singing the high note and sustaining it. In my 60 years of singing and attending various public functions where the Star-Strangled Spanner, as I call it, has been played, I have NEVER heard it played in A. It’s most commonly played in B flat, which makes the high note an F, or less commonly in A flat, making the high note an E flat. Moreover, most brass instruments are more comfortably played in flats rather than sharps, rendering A major an extremely unlikely key for our national anthem.

  24. 24.

    Tim F.

    December 15, 2006 at 2:42 pm

    Tim, what’s the reason there wasn’t selection pressure for developing these positive traits without RSV?

    The fundamental balance here is between spending energy on maintenance and spending it on reproduction. Spending tons of energy on maintenance and quality control saps resources from reproduction, meaning that fifty generations out your neighbors who live to forty and have two dozen kids will own the planet. Having family members survive to grandparent age was absolutely crucial to the origin of civilization but from an evolutionary perspective the development might have happened yesterday.

    I should have mentioned that one side effect of resveratrol and the treatment it is meant to mimic, a severely calorie-restricted diet, is lowered reproductive rate. That isn’t such a big deal since it doesn’t block reproduction and we’re not trying to breed like bunnies, but it helps to explain the evolutionary trade-off.

  25. 25.

    Zifnab

    December 15, 2006 at 2:47 pm

    I can’t think of a single instance of a drug in the past, touted to be a “miracle drug”, which didn’t show up later with significant and deleterious side effects.

    penicillin
    aspirin
    birth control
    viagra

    I mean, those are the four that come to mind first. There’s a reason the pharmaseudical industry brings in the big dough. They’ve got a number of tried and true products that work damn good. Admittedly, when every drug that hits the market gets billed as a “miracle”, whether it lowers cholestoral or cures restless leg, the term loses a bit of the magic.

  26. 26.

    ThymeZone

    December 15, 2006 at 4:02 pm

    the term loses a bit of the magic.

    True. But when I was having heartburn keeping me awake at night for days at a time, and tried Prilosec, the missus asked me how it was working, and I said, “Miracle drug, as far as I’m concerned. From day one, heartburn gone, me happy, sleep all night. Life good!” Followed by some gorilla-like chest thumping and grunting noises. Which are routine for me and not really noticed by people who hang around me much.

  27. 27.

    BlogReeder

    December 15, 2006 at 5:55 pm

    although in some people the notion of sterility seems like a very desirable side effect…

    There are people like that, they usually get their tubes tied anyway.

  28. 28.

    rilkefan

    December 16, 2006 at 12:42 am

    The fundamental balance here is between spending energy on maintenance and spending it on reproduction.

    Don’t see how that’s much relevant for males, and I would guess it wouldn’t be that hard to tie say estrogen into the system.

  29. 29.

    Jay C

    December 17, 2006 at 9:38 am

    ihatespam:

    Unless MY math is way off (always a possiblity): according to Tim’s figures, the amounts of resveratrol in his post have alrady been expressed in milligrams: 200-400 as the test dose(s); with 1.5 – 3 available per liter of red wine.

    So to get that dosage of RSV “naturally”, one would have to consume 133 – 266 liters of vino (100-200 standard bottles) a day – say, on the average, 150 bottles: or 12-1/2 cases.

    Hmmm….. gotta think about it.

    OK: I’ve thought about – where do I sign up?

  30. 30.

    Jay C

    December 17, 2006 at 9:50 am

    Damn!
    I told you my math skills were teh crap….

    A standard bottle of wine is .75L – so to drink 133-266 L of wine a day, one would have to consume 177-355 bottles
    per diem – 15-30 cases – still a sizeable amount; but definitely short of 40,000.

    Sorry for the mixup: and I haven’t even had any wine resveratrol solution yet!!

  31. 31.

    anthony

    January 28, 2007 at 10:04 pm

    You may want to have folks check Resveratrol out in the online encyclopedia, as it has info on foods, supplements, and the science behind it.

    It’s about 500mg for each 50lbs, to get in line with the HArvard studies. There is only 2 companies I know that provide that kind of dose in a capsule.

    http://en.wikipedia.org/wiki/Resveratrol

    thanks
    Anthony

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