Caffeine Buzz

[Kevin Guse]

30 years holy #*** I haven't even been alive that long. Sorry just having a little fun I'm sure I'll catch a shoken in the ribs for that one in Boston.

I never doubted your education or expertise just wanted to know and have ammo if this guys asks.

I sent you an email. Need your address to send the DVD.

[Bill Glasheen]

I never doubted your education or expertise just wanted to know and have ammo if this guys asks.

Not a problem, Kevin. I'm used to it in my world. Credentials are always being checked and re-checked - as they should be.

I'm sure I'll catch a shoken in the ribs for that one in Boston.

No shokens in the rib. I might however hit you with an arthritic knee...

- Bill

[IJ]

"Nowhere am I stating that single vitamins or even multivitamins have miracle antioxidant effects. Quite the contrary... I and the data are suggesting that whole fruits and vegetables - and sometimes standardized extracts thereof - are demonstrating useful antioxidant effects. And the relationship between beneficial effects and character of the substuance from an antioxidant point of view can now be quantified in ORAC units. (Oxygen Radical Absorbance Capacity)."

I know you're a fan of combinations. My point is that what the data suggest is so far from certain the claims on the supplements are essentially lies. As far as the ORAC score, can you explain to me why we should be using a single, total measure of antioxidant activity when one could reach that sum with a single nutrient, or with many supposedly additive or multiplicative ingredients? This is at the level of faith for me. To point out why, we're having a broad discussion of supplements, but our question came in mostly about energy boosting metabolism aids. THOSE aren't antioxidant. They rev up oxidative metabolism, quite the opposite. I know you're aware, Bill, but wanted to make sure everyone is on the same page.

The benefits of the combos you're describing are speculative. There is a rationale, and some epidemiologic data. That proves nothing, and I listed quite a few examples where a rationale and epidemiologic data turned out to prove dead wrong. You yourself have railed against requiring insurance companies to fund bone marrow transplant for breast cancer--appropriately so. The rationale and early data turned out to be wrong. Obviously there is a difference between forcing an insurance company to fund something and an individual deciding to spend their own money on something unproven, but in a larger sense, the issue is whether we should spend billions on unproven therapies.

Some clarification on your list of single agents:

Niacin: is both a vitamin (in low dose) required for life and health and a drug (in high dose) that lowers cholesterol. Use of a niacin supplement will not affect cholesterol.

Lycopene: no proof yet.

Vitamin D: yes recommended for osteoporosis. However, Just calcium and D are not exactly wonder drugs for osteoporosis, although they help and are especially important for certain areas (eg: Boston nursing home resident more than tan San Diego triathlete). More importantly, Vitamin D has strong data for use in muscle strength/falls prevention, and has shown a benefit in overall MORTALITY.

THAT'S a good place to sink some supplement dollars!

[fivedragons]

Disclaimer: I don't like smoking pot anymore. I spent quite a while thinking that chemically induced states were the key to an expanded awareness. I didn't realize that I was just introducing external distortion into my natural state of awareness. Drugs are bad, unless you learn something from the experience, or maybe pot isn't so bad, if it helps a cancer patient consume and retain nutrients. I guess we'll just have to ask our august congressmen about that...

Anyway... any marijuana afficionado can tell you that THC isn't the only active ingredient. I've smoked all kinds of weed, and also tried pure THC capsules. The interesting thing is that each plant has it's own psychoactive "personality".

Don't fool with with mother nature, lest mother nature fools with you.

[fivedragons]

Rant mode is in the "on" position.

Since this thread is all about psychodelic drugs, I thought to mention that the infusion of LSD and other substances were introduced en masse to the American masses by the CIA.

The thought of a bunch of heinous spooks kicking off the sixties with acid parties (some rather shady and "forced" affairs), looking for a truth serum, for people who only deal in lies, makes me realize that there is no need for all this fun hippy crap.

The reality of this world truly is stranger than any fiction.

Oh, the humanity.



rant mode is now on "off".

[IJ]

Wow. I thought the government was just responsible for crack cocaine and for the AIDS epidemic. That needs a REFERENCE.

There is no doubt that there are multiple active agents in the natural world. And no guarantee of what is getting from nature into your capsules. There is also no guarantee that the cocktail you've purchased doesn't contain some other natural, earthy substances such as aflatoxins in contaminated plant products:

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

If not contaminated, that mixture might have some good chemicals and some bad ones. Until the combo is standardized and studied or you deal with something purified that's studied, you're just doing a little bit of gambling.

Pot is a good example. Marinol (THC pill) isn't the same as smoking weed. Everyone will tell you. Same as vanillin is similar to, but not the same as, real vanilla with all the aromatics the natural plant produces. However, at least you can look up what Marinol does and know what it'll do to you (or more precisely, you'll have a gmable with known odds, since there are more unhelped patients than helped patients in most clinical studies, sometimes by a factor of hundreds).

People should go in informed... and they're welcome to buy what they believe is beneficial if they want. *I* would remove all unproven claims from the bottles, personally. My general concern is the preference for "natural" over "medical" just based on vibe. This is how you get cancer patients skipping proven medicines to go take toxic extracts from fruit pits instead. Or, how about the woman I met who had a large, rotting, bleeding tumor on her breast she was smearing herbs on? Yikes.

[Glenn]

Part of the problem is that most people don't think of herbals the same way they do medicine. "It's not medicine, it is a natural herb so it is safer and better for me than medicine." (Just like some of Mother Nature's other all-natural creations such as hemlock, poison ivy, snake venom, and uranium.) And of course the herbals are promoted that way. Never mind that they do cause effects on the body, both intended and unintended, and thus can have potential harmful side effects just like medicine can. Herbals do not have to come with warning labels like medicines do, warning of potential side effects...how many users realize that the ever popular ginseng is a blood thinner and should not be taken with other blood thinners like aspirin or before surgery, nor by pregnant women? You won't find those warnings on the bottles of ginseng sold at the local grocery/drug store.

The other aspect at play here is that we have incomplete cultural knowledge transfer. A lot of these herbals have been part of medical traditions for millennia and likely have some positive effect to have lasted so long, however in those traditions they are used in specific ways, at specific times, and often to treat specific conditions. They are not necessarily taken as a supplement twice daily. Does having ginseng added to a lot of bottled drinks so that it can be consumed a few times a day (assuming there is actually enough in those drinks to have an effect, which is reportedly questionable) correspond to how it has traditionally been used in China? I truly doubt it. What we are seeing is a diffusion of one aspect of a medical tradition, the medicine in the case of many of these herbals, with large-scale mass production but without the native knowledge base on how it should be used. Does that automatically mean there cannot be changes to or improvements on use? No, but we need an appropriate knowledge base first to build on. It's like trying to reinvent the wheel...or a closer analogy, buying some rubber trees after you hear they can be used to make tires. It's going to be a while before you perfect making tires with them, if you ever figure it out.

And I kinda doubt most sellers of mass-produced herbals in the U.S. are truly trying to improve their utility rather than just trying to create a market. Speaking of markets, I find it interesting that Appalachian folk have been harvesting and using a wild native ginseng for centuries (as the Native Americans did before them) without it catching on as a fad in the rest of the country. It wasn't until Traditional Chinese Medicine became popular that a market arose for ginseng, and of course people only want the Chinese ginseng rather than the native one.

[NEB]

Rant mode is in the "on" position.

Since this thread is all about psychedelic drugs, I thought to mention that the infusion of LSD and other substances were introduced en masse to the American masses by the CIA.

Actually, this thread is, or at least started out all about caffeine, not psychedelics, but its all good.

Bill, et al:

Thanks for the great responses, I would have checked back sooner but my email alert seems to be turned off so I thought there hadn't been any replies as of yet. You mention theophylline as another dimethylxanthine found in tea. I was under the incorrect assumption that it only existed in the body as a caffeine metabolite. Turns out that's paraxanthine. Anyway, you mentioned that theobromine makes us feel good, while theophylline act as a stimulant. After checking it out on Wiki, I see that its affect on adenosine re-uptake is diminished (theobromine), but may be the ingredient in chocolate that is said to have qualities of an aphrodisiac. Very interesting. So, perhaps these two alkaloids are what is responsible for the "buzz" of tea being slightly different from that of coffee.

[Bill Glasheen]

Lycopene: no proof yet.

Lycopene in the prevention of prostate cancer.
Dahan K, Fennal M, Kumar NB.

Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, FL 33612-9416, USA.

Based on the evidence from epidemiologic, animal, and in vitro data and human clinical trials, it is evident that lycopene, a non-provitamin A carotenoid, is a promising agent for prostate cancer chemoprevention. It is also clear that the form of lycopene used (purified versus food sources), dose of lycopene and concomitant use with other carotenoids and antioxidants, duration of exposure, specific target populations, and stage of disease appear to play a major role in determining agonistic or antagonistic effects. Based on our review, there is enough evidence to warrant use of lycopene in phase I and II clinical trials to examine its safety and efficacy as a potential chemopreventive agent for prostate cancer. The objective of this article is to review this evidence from epidemiologic, animal, in vitro, and clinical trials and provide the need and rationale to examine further the role of lycopene for prostate cancer prevention.

Don't even get me started on the idiots who are trying to use lycopene to treat people who ALREADY HAVE cancer. If you're trying to indict this phytonutrient via that "evidence" (or lack thereof), then you're barking up the wrong tree. Researchers decades ago showed that vitamin and phytonutrient therapy generally makes cancer cells grow faster. Duh!!

Also... Don't expect Pharma to be funding nutrient therapy studies, since there's no money in it for them. That's one major reason why the literature is lacking in the kinds of expensive RCT studies that the purists want. But if they can get a patent on it and sell it via prescription, well that's another story. As history as shown, there's a lot of money to be made when your talking about saving a man's weenie. Viva Viagra!

- Bill

[IJ]

Let me clarify what I meant by "no proof yet," and the evidence you've posted.

When some epidemiologic data and lab data accumulates that something may work for some condition, it's time to study it in a phase one trial.

If that phase one trial goes well, you get yourself a phase II trial.

If that goes well, you get yourself a phase III study.

At this point the drug is often approved for the indication in question, if the phase III study is positive.

Phase IV research occurs post-marketing and may identify new toxicities (as with trovafloxacin, Vioxx, troglitazone, erythropoeitin, etc)

http://en.wikipedia.org/wiki/Clinical_trial#Phase_IV for an overview of the process.

When multiple randomized controlled trials have been done, evidence can be overwhelmingly strong, such that no new trial could be ethical, or can be quite confusing if the data is conflicting. Case in point: trials on N-acetylcysteine (NAC) for the prevention of kidney injury are cheap and easy to do, but many have been done with small samples and conflicting results. I searched for RCTs on NAC limited to full text english articles in core clinical journals and found 66 hits for adults alone. And yet, many meta-analyses conflict on NAC's benefits.

My point?

All of the debunked therapies I listed previously had as much or more data going for them than lycopene does. Lycopene may be wonderful, it may do nothing (and have been a only marker for a healthy diet or certain other patient behaviors), and it may actually be harmful. This is why the abstract Bill cited recommends that we start studying it rigorously. As Sagan put it, "I don't want to believe, I want to know." I'd happily enroll in a trial!

As for pharma sponsorship, yeah, that's a problem. IF people couldn't make unsubstantiated claims about their products, and pharma had a chance to sell lyopene (once proven) to men, this problem would go away. If they're lucky, they can turn all lycopene into a drug, just as the evidence that red yeast extract actually does something has become an issue with it remaining a "supplement" for sale without a prescription, like the ones required for its active ingredient, pravastatin.

[Bill Glasheen]

The abstract I cited was (I thought) particularly good at summing "the problem" of nutrient therapy.

• What dose is relevant? Is the dose/response curve linear? Nonlinear? Unimodal? Multimodal?
• What is/are the effect(s) in question?
• Are there toxicities involved? Important nutrient-nutrient or nutrient-drug interactions to consider?
• Is "the effect" due to a single agent or a family of agents? Is "the effect" achievable with a single isolated agent, or relevant only in the food source?
• Is the health/disease process multidimensional? (Heart disease is a good example)
• What is the time window of treatment vs. outcome?
• Does anyone with the resources care to make a stronger case for the substances in question? What motivations/biases come into play here?

When a nutritive substance is involved, the fastest way to answer many of these questions and get people interested is through a well-run epidemiologic study. The many studies of nurses volunteering to be life guinea pigs is a good example. (Salad consumption vs. hip fractures showed us the importance of Vitamin K.) We wouldn't be where we are today with heart disease, effects of smoking, etc. if it weren't for those important studies.

The extremely expensive, sometimes unethical, phased Randomized Controlled Trials come much, much later. And they take a very long time.

Meanwhile...

Rational, pragmatic people can sit somewhere in-between "I believe!" and "There is no proof!"

...... "I believe that no-touch knockouts work!"

...... "There is no proof that smoking causes cancer."

If a CEO - or a normal human for that matter - needed "proof" before any choice was made, we'd be paralyzed. Humans are extremely elegant pattern recognition machines and yes, they sometimes make mistakes.

Sometimes carefully run RCTs come up with "the wrong" results. There is often a lot of randomness that happens outside the confines of bench research.

What I'm trying to say is that with nutrition, it makes sense to start paying attention to the epidemiologic data. If I'm getting fat or my sister got breast cancer or my dad died of prostate cancer, it SHOULD give pause. And measuring my BMI, getting a breast exam, PSA test, or digital rectal exam is not prevention (to give a few examples).

At the very least, I'm going to seek out my sources of cooked tomatoes. And If my multi has some lycopene in it, I'm not complaining. The evidence is... compelling. And it is my prostate.

And frankly, I'm not a fan of digital rectal exams.

- Bill

[IJ]

"The extremely expensive, sometimes unethical, phased Randomized Controlled Trials come much, much later. And they take a very long time."

They have their downsides. I wouldn't hit them with the "sometimes unethical" label though, lest it give the impression an observational study is exempt (Tuskeegee, anyone?) or that NOT doing the study might be more ethical (eg, vytorin lowers cholesterol, so allow us to assume it reuces heart disease and make another 5 billion in sales, many due to siphoning off $ that used to go to proven therapy!).

"Rational, pragmatic people can sit somewhere in-between "I believe!" and "There is no proof!""

That's probably the best bet with something unlikely to harm, but everyone has to go in knowing there is a real likelihood of none benefit and money might well be better spent elsewhere.

"...... " There is no proof that smoking causes cancer. ""

Now that's getting a little unfair If you mean to suggest that only an RCT will satisfy me, you're wrong. There is overwhelming evidence that smoking is harmful, as the magnitude of the effect far exceeds that which might be concealed by a lack of perfect controlling for confounders. Also, there is no way to do the RCT outside of Nazi Germany. There's a similar situation with antiretrovirals after HIV exposure. We THINK they work, but there's no RCT because of the low conversion rate and the inability to sign people up. Then, you HAVE to give advice based on limited data, even when the agents in question are toxic and costly.

"Sometimes carefully run RCTs come up with "the wrong" results. There is often a lot of randomness that happens outside the confines of bench research."

This is where it helps to read the statistical methods section and the peer review and figure out WHAT might have been missed. How much of an effect could be hiding within the error bars? Do we need another study? Should we accept a "trend?" Should a trend to harm scare us? It is complex, but its no reason to downplay the best tool we have.

"And frankly, I'm not a fan of digital rectal exams."

You realize, of course, that taking lycopene won't alter your need for these, yes?

[Bill Glasheen]

"And frankly, I'm not a fan of digital rectal exams."

You realize, of course, that taking lycopene won't alter your need for these, yes?

- Bill

[fivedragons]

Posted by Ian:

"Wow. I thought the government was just responsible for crack cocaine and for the AIDS epidemic. That needs a REFERENCE."

That's funny, the link I was going to direct you to doesn't seem to work right now. Here's another one. If we hold hands, maybe we can jump into the deep end of the pool. Maybe we can find out how the world really works.

Or maybe not.

Maybe we can't handle the truth.

[Jason Rees]

Truth is a bitter pill to swallow.