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Forskolin: Here We Go Again

 Sisyphus and his endless task

Sisyphus and his endless task

My BMI is 21, but my e-mail and Facebook accounts must think I’m fat. I am constantly bombarded with messages about miracle weight loss solutions, and most of them are diet supplements featured on the Dr. Oz show. Back in December I wrote an article about Garcinia cambogia, Dr. Oz’s “newest, fastest fat buster.” I made this prediction: “I confidently expect another “miracle” to supplant Garcinia in the Land of Oz in the not-too-distant future.” I was right. The e-mails about Garcinia have recently been outnumbered by e-mails about a new Dr. Oz miracle weight loss supplement, forskolin. Actually, I think he discovered forskolin before he discovered Garcinia, but the forskolin propaganda seems to have reached a critical mass in the last few weeks.

The Land of Oz

A Dr. Oz episode on the “Rapid Belly Melt” aired a month ago, on May 5. He set fire to a paper representation of a fat belly to show how forskolin “works like a furnace inside your body.” The paper ignited, went up in flames, and revealed a non-flammable model of muscle tissue inside to show how forskolin burns fat, not muscle, and to illustrate how quickly it works.

In an earlier episode, in January, he called forskolin “lightning in a bottle,” and a “miracle flower to fight fat.” His guest, a weight loss expert, claimed it had doubled the weight loss of her clients. She said “if your metabolism is sleeping, forskolin is gonna wake it up.” She doesn’t claim that it will work miracles all by itself, but recommends it as an addition to gentle exercise and “cleaning up the diet”.

Dr. Oz says he pulled up all the research and was impressed by the evidence that it “ignites your metabolism.” He illustrates this metaphorically by throwing a white powder into a pot of simmering water, causing it to instantly start boiling vigorously.

The Land of Evidence

Dr. Oz is easy to impress. He cites a randomized placebo-controlled double blind trial of forskolin. It was a small preliminary study of obese or overweight men; there were only 15 men in each group, and the study lasted for 12 weeks. The subjects on forskolin showed favorable changes in body composition: a significant decrease in body fat percentage and fat mass, with a trend (non-significant) toward increased bone mass and lean body mass. Serum free testosterone levels were also significantly increased.

The details of the study are not important. What’s important is that the subjects taking forskolin did not lose weight. Even without weight loss, the changes in body composition are likely beneficial, but the increase in testosterone could be dangerous. Whatever the unresolved questions about benefits and risks, it is obviously misleading to cite this study as evidence that forskolin has been proven to melt belly fat or improve weight loss.

Another double blind study of 23 mildly overweight women, showed that forskolin had no significant effects on body composition and concluded that it “does not appear to promote weight loss but may help mitigate weight gain in overweight females with apparently no clinical significant side effects.”

Those are the only two studies in humans. Supplement Geek has written an analysis of some of the flaws in those studies that I won’t get into here. The only other pertinent research I could find was a study in rats suggesting that it may be effective in preventing diet-induced obesity. In rats.

What is it?

Forskolin is an herbal extract from Coleus forskohlii, a plant belonging to the mint family. Its mechanism of action? It increases the production of cyclic AMP, which increases the contractility of heart muscle. Evidence for other actions is preliminary and inconclusive: there is speculation that it may have effects in other cells of the body such as platelet and thyroid cells, it may prevent platelet aggregation and adhesions, and it might even prevent tumor cell growth and cancer metastasis. So far, there is no evidence that it is clinically useful or safe for those purposes.

The Natural Medicines Comprehensive Database rates forskolin as “possibly effective” as an inhaled powder for asthma, and as an intravenous medication for idiopathic congestive cardiomyopathy. It also mentions that it may decrease intraocular pressure but has not been tested in patients with glaucoma. It doesn’t even mention the possibility of using it for weight loss. The safety rating is “possibly safe,” and it lists potential interactions with prescription drugs and with other herbs and supplements. They say it may increase the risk of bleeding and should be discontinued at least 2 weeks before surgery.

The bottom line

So what do we know?

  1. There is a more-or-less plausible mechanism of action, as speculated by the study authors (see the study for details).
  2. It improved body composition in one study but not in another.
  3. It has not been demonstrated to cause weight loss, except possibly in rodents.
  4. Its clinical efficacy and safety have not been established.
  5. It raises blood levels of testosterone, probably not a good thing.

I am not saying it doesn’t work for weight loss or belly melting; we don’t have good enough evidence to know whether it does or not. I’m not saying people shouldn’t take it, although they shouldn’t assume it’s perfectly safe. I’m only saying there is inadequate evidence for anyone to make the claims Dr. Oz and other proponents have made for it. If we had such limited evidence for a proposed new prescription drug, I doubt if Dr. Oz would want the FDA to approve it for marketing. The double standard is obvious.

Déjà vu all over again

I’m getting really tired of these weight-loss products, ever since I wrote about Akavar 20/50 “Eat all you want and still lose weight!” back in January 2008. I get a strong stink of déjà vu, because they all fit the same pattern: a small grain of plausibility, inadequate research, exaggerated claims, and commercial exploitation. There are always testimonials from people who lost weight, probably because their will to believe in the product encouraged them to try harder to eat less and exercise. But enthusiasms and fads don’t last. A year later, the same people are likely to be on a new bandwagon for a different product. Dr. Oz will never lack for new ideas to bolster his ratings. Enthusiasm for easy solutions and for the next new hope will never flag as long as humans remain human. I guess I’ll just have to keep doing the Sisyphus thing and hope that I can at least help a few people learn to be more skeptical and to question what the evidence really shows.

Posted in: Herbs & Supplements

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159 thoughts on “Forskolin: Here We Go Again

  1. JoeChemler says:

    One of the first things I learned in biochem 101 about cAMP is that high concentrations trigger ATP production and low concentrations slows down ATP production. In other words, if you trick cells into thinking that cAMP concentrations are too high, it will think it needs more ATP by recycling cAMP. (Blocking cAMP recycling is one way to build up cAMP levels up but that’s deadly to the cells!) Many years later, I’ve learned just how incredibly redundant and rebust primary metabolism is. (Aerobic vs anaerobic; take away O2, there’s a back up system). Perturbation to homeostasis is not tolerated lightly. I will put my $50,000 nickel on saying that any drug that attempts to affect primary metabolism will be catastrophic. That’s what poisons do!

    1. Lucario says:

      So, what are some examples of compounds that do affect primary metabolism? You said they were poisons, so maybe if you listed a few noteworthy examples, maybe that might deter people fom looking for an “easy way out”.

  2. BillyJoe says:

    forskolin!…
    …for a moment there I thought we were about to have another one of those interminable arguments about male circumcision.

    1. Windriven says:

      I’m glad you said it. It was all I could do not to pun foreskolin to death.

      1. mouse says:

        I was thinking – Forskölin, isn’t that a cabinet at Ikea?

    2. Catherine says:

      You aren’t the only one.

    3. Sean Duggan says:

      ^_^ Hey… me too. Great minds, eh?

      1. Lytrigian says:

        ^_^ Hey… me too. Great minds, eh?

        Me too. So, no. :D

        1. Seth Katzman says:

          “Great minds think alike and fools seldom differ.”

    4. goodnightirene says:

      And I was thinking we were going to learn about a new Scandinavian toast!

      1. Calli Arcale says:

        I like that! It could be a more energetic alternative to “Skol!” I might try using that at the next family gathering and see if I can get it to catch on. ;-)

        (My non-Scandinavian husband, however, is fond of following “Skol!” with “Kodiak!”)

        1. WilliamLawrenceUtridge says:

          The boots or the bear?

          1. Calli Arcale says:

            Neither. :-D Kodiak and Skoal are chewing tobacco brands. My husband doesn’t use tobacco of any kind, but his grandmother used to.

            1. Andrey Pavlov says:

              are chewing tobacco brands. My husband doesn’t use tobacco of any kind

              Ugh. I grew up with both of my parents as pack-a-day+ smokers. My mother quite a number of times but my father never did. In college I was the “social smoker” who would have a few when drinking with friends. The nicotine buzz was like downing a few shots in rapid succession (with a much faster onset). Then in my early post-grad days I worked as a waiter. The entire waitstaff smoked and I was in a new city and wanted to socialize. I hated bumming every time so I started buying my own. I even had an evening ritual – I would go home, put on my “smoking jacket,” pop in my headphones, go downstairs and make phone calls back home or listen to music while smoking a few. After about a week, I would go through all the motions but just couldn’t stomach having another cig. After 3-4 days I would be able to light up again. Repeat this for 5ish months.

              In my first year of medical school I was still the “social smoker.” But by that time I was getting less and less tolerant of it so I would only inhale 1 or 2 puffs per cig and Clinton the rest of it just to be social.

              By second year of med school I completely stopped and haven’t touched tobacco since. It makes me absolutely nauseated. Which makes going to some of my favorite bars tough since most of them allow smoking.

              During all that time I tried chewing tobacco twice. Both times I went from dip to falling on the ground vomiting in less than 60 seconds.

              I tried Phillip-Morris. And I failed. Your product is just too disgusting to get me hooked. I count myself as lucky.

              1. Windriven says:

                I quit when I was 30-ish. The elevators were out at a hospital I was visiting and I had to climb 3 or 4 flights of stairs. I got to my floor and was breathing like an ox. No. Uh-uh. We ain’t havin’ that. So I quit.

                My mother on the other hand didn’t. She was still smoking with a nasal cannula* (!!!) and COPD that had turned her lungs into flower pots. It wasn’t the cigarettes, of course. The goddamned Republicans were pumping poisons into the air.

                *I was certain she would die in an oxygen enriched self-immolation rather than slowly suffocating. I was wrong.

    5. WilliamLawrenceUtridge says:

      I’m disappointed because I was looking forward to quoting Dan Savage at Andrey again :)

      1. CHotel says:

        Inevitably my favourite part of the debate when it arises.

    6. Thor says:

      That immediate association happens every time I see that word.

    7. renoB says:

      I read it phonetically as “force colon” and thought it was going to be about some horrifying laxative.

  3. Windriven says:

    I was struck by the low testosterone levels in the test subjects, even at the end of the test period. These were young men, roughly 18-37, and yet their free testosterone levels were remarkably low The highest reported free testosterone was 29.68 pg/ml while the normal range (according to Quest Diagnostics) is 35-155. Total testosterone was more or less normal.

    I understand that testosterone is lipid soluble but would that account for free testosterone measures this low in young males? “Low T” mills promise, among other claims, weight loss. Is there a significant relationship between free testosterone and, say, metabolic rate?

    What I am really asking, I guess, is whether the changes in testosterone levels were stimulated by foreskolin or were simply a consequence of a -5 or 10kg change in body fat?

    1. Andrey Pavlov says:

      Is there a significant relationship between free testosterone and, say, metabolic rate?

      Absolutely. Increased testosterone will absolutely increase metabolism. Depending one which one specifically (don’t know off the top of my head) it will be specifically more anabolic than catabolic, but in all cases both sides of metabolism will increase.

      I haven’t read the original studies but I doubt they include the necessary data to determine this anyways, but it is at least possible that this would be why body composition but not weight would change. Increased catabolism would drop body fat and increased anabolism would increase muscle. The thing that people just refuse to understand (including those who should know better, like Oz) is that we already have bangup miracle drugs to massively and easily improve weight and body composition. Just ask Lance Armstrong. Why don’t people ever wonder why those idiots like Lance take illegal drugs to dope instead of these amazing supplements that totally do the same thing but are legal?

      The point is that if there is an effect like that it must be messing with larger systems. We don’t yet have nanobot versions of The Terminator running around and selectively sniping off fat cells and then carting off the lipids into your excrement. So it either doesn’t have an effect or you are taking a lesser version of the stuff people like Lance took with a completely unknown side effect profile.

      As for your specific question – I don’t know that we actually know enough to answer it robustly. I do know that the state of testosterone testing and “low T” replacement therapy is pretty… shady. I don’t have any specific knowledge that would help me answer why these young men had low levels. I would expect a change in body composition to be reflected with a change in T, but how much, I have no idea. And I also know that T levels fluctuate not just daily but over longer periods of time and it is not characterized well. There is also significant variation in normal populations.

      Oh yes, and I too was caught off guard by the title of this post. LOL

      1. Windriven says:

        “Why don’t people ever wonder why those idiots like Lance take illegal drugs to dope instead of these amazing supplements that totally do the same thing but are legal?”

        :-))

        ” I do know that the state of testosterone testing and “low T” replacement therapy is pretty… shady.”

        There is an MD named Mixon in Seattle who runs a chain of these ‘clinics’ complete with ‘seminars’ in hotel meeting rooms; the whole shebang. Apparently he does pretty well. Your line about Armstrong snapped it into clear focus for me: the Low T clinics are legally sanctioned versions of the trainers who can give you something to “help you to the next level.”

        But I can never think of steroids without the image of Lyle Alzedo staring at me from the cover of SI. Don’t know if his brain cancer was related to steroid use but Alzedo certainly thought it was. Anecdotes don’t often move me. But any chance of me using anabolic steroids recreationally died with Lyle Alzedo.

        1. Andrey Pavlov says:

          :-))

          I mean seriously! LOL. Look at what people with millions of dollars, a lot to lose, and a serious need for genuine performance do. Somehow it isn’t this Dr. Oz supplement crap.

          There is an MD named Mixon in Seattle who runs a chain of these ‘clinics’ complete with ‘seminars’ in hotel meeting rooms; the whole shebang. Apparently he does pretty well.

          My stepfather works as a critical care physician at a private hospital where they still do (albeit a fair bit less) Pharma luncheons and dinners. In fact, in some of my undergrad research work I got taken to multi-thousand dollar (per person) dinners by Merck and Pfizer. Anyways, my stepfather doesn’t go all that often and when he does it is pretty much just an excuse to treat my mother to a free fancy meal. But when I am back in town, if he has any offers for such things he asks if I want to go. If I have nothing better going on, I do. A free fancy meal for a med student? Sign me up. One of them was a low T dinner in between my first and second year of med school. I had learned just enough at that point to ask the right questions and ended up being the only one to do anything except fluff the presenter. I was finally told that I had “very good questions” and to “trust” them that there was heaps of really good data to answer them and back them up. There was some data and there is some legitimacy, but it was mostly just anecdotes and basically pushing doctors to try and prescribe more of the stuff in the grey area, so long as it exists. In other words, to shift those cases of ambiguity from watchful waiting to doing something. And, of course, that “something” was prescribing their particular formulation.

        2. Sean Duggan says:

          They dip into those as well. Some of them are effective enough to get their own ban, especially since it’s often the case that the chemicals that give the result are banned. Of course, some items, like megadoses of Vitamin C or E, will be used in much the same way as crusty lucky socks, superstition.

          1. Windriven says:

            Deer antler spray? Really? In an effort to get another 4″ on a drive or another .01 seconds on a run? And all illicitly?

            The eager willingness to cheat is part of the reason that I no longer follow any professional sports. Grown adults playing ultimately meaningless games for big money – for the purposes of transient – even ephemeral – entertainment? RAH, Rah, r…

            1. irenegoodnight says:

              Grown adults playing ultimately meaningless games for big money – for the purposes of transient – even ephemeral – entertainment?

              I’ll show this to Mr Goodnight who thinks I am the only one who thinks this way.

          2. Andrey Pavlov says:

            @Sean:

            Yes, sometimes they do happen upon an as-of-yet unregulated and poorly described “supplement.” After all, plant and animal extracts have the highest a priori likelihood of actually doing something. And, of course, some products just hide actual drugs in them and pass them off much like in my post here about DMAA.

            @windriven:

            Yeah. I was never really into sports ever. Since moving to NoLa I’ve become a Saints fan, purely because it is a really fun place to be a Saints fan. An excuse for a BBQ, beer, and some fun rivalry is OK by me. But overall… yeah.

            I heard an interesting report on NPR about it which basically summed it up as a Nash equilibrium. Somebody will dope because the gains are high enough that it will outweigh the risks for at least a couple of people. Then everyone else dopes because otherwise they can’t compete. Not a justification, but a description.

            1. Windriven says:

              “I heard an interesting report on NPR about [sports doping] which basically summed it up as a Nash equilibrium.”

              A sad twist on the output of a beautiful mind.

            2. Windriven says:

              “Since moving to NoLa I’ve become a Saints fan, purely because it is a really fun place to be a Saints fan.”

              It was even fun back in the days when fans went to the Dome wearing paper bags over their heads. In those days 5 nuns and a girl scout troop could give the Saints a run for their money. But the Dome filled every Sunday they were at home.

              My wife and I watched the 2009 Superbowl in our favorite pizza joint* near Portland. Most of the crowd were Colts fans. It started out with lots of trash talk about how the Colts were going to spank Drew Brees and slowly but inexorably quieted into glum but good humored resignation. Like being a Cubs fan in baseball, win or lose, you can’t go wrong being a Saints fan.

              1. Andrey Pavlov says:

                My wife and I watched the 2009 Superbowl in our favorite pizza joint* near Portland. Most of the crowd were Colts fans. It started out with lots of trash talk about how the Colts were going to spank Drew Brees and slowly but inexorably quieted into glum but good humored resignation. Like being a Cubs fan in baseball, win or lose, you can’t go wrong being a Saints fan.

                Agreed!

              2. WilliamLawrenceUtridge says:

                our favorite pizza joint*

                The asterisk presumably denotes a subsequent effort to identify said pizza joint. It is cruel of you to fail to follow-up on this critical piece of information.

              3. Windriven says:

                WLU, the asterisk was going to mention that we can’t watch at home because we don’t have a TV hooked to anything but a DVD player.

                That said, our favorite pizza joint is Blind Onion. There are several in the area. Many local pizzerias are a carnivore’s wet dream of flabby crust topped with a mound of various cured meats. We prefer a thinner crust and a more balanced array of toppings. We always order ours with anchovies on the good half ;-)

              4. Andrey Pavlov says:

                We prefer a thinner crust and a more balanced array of toppings. We always order ours with anchovies on the good half

                This may make up for your uncouth denigration of hops! :-P

              5. WilliamLawrenceUtridge says:

                I’m way worse than WD, I not only hate hops, I hate beer, period.

                And now Dr. Crislip isn’t going to answer my questions anymore :(

              6. Windriven says:

                “This may make up for your uncouth denigration of hops! :-P

                It is not hops that I denigrate – what would beer be without hops? It is hops creep that I bemoan. Our local brewers hop pale ales as if they were IPAs. They’re brewmasters. Shouldn’t they understand the flavor profile of a pale ale? The hop IPAs as if they were double IPAs. Same question.

                It has gotten to the point where, when I want a pale ale that tastes like a pale ale I have to buy Bass – a mediocre pale ale. Bridgeport, an outstanding local brewery makes a wonderful pale ale called Blue Heron. But the locals have so damaged their palates that Blue Heron is only available at the brewery; they no longer bottle it.

                Luckily, Bridgeport has stayed true to the IPA profile. When I crave an IPA – mostly all summer long – the Bridgeport product is outstanding. And they have a variety of malted turpentines for those who are all hopped up ;-P

              7. Andrey Pavlov says:

                I’m way worse than WD, I not only hate hops, I hate beer, period.

                And now Dr. Crislip isn’t going to answer my questions anymore

                I’ll still grudgingly answer ;-)

            3. Andrey Pavlov says:

              It is not hops that I denigrate – what would beer be without hops? It is hops creep that I bemoan.

              Oh, fine. Fair enough.

            4. WilliamLawrenceUtridge says:

              As I often say when discussing meat with vegetarians, pork with Muslims or beef with Hindus – it means we don’t have to share.

        3. nyudds says:

          @windriven: This is an excerpt from Lyle Alzado’s obituary which confirms his steroid usage and addiction:
          “Although there is no medical evidence that links steroid use to brain cancer, Mr. Alzado, who said he had begun using steroids in college and had become so addicted to them that he continued to use them after his retirement in 1986, never had any doubt.” The entire obit is interesting:

          http://www.nytimes.com/1992/05/15/sports/lyle-alzado-43-fierce-lineman-who-turned-steroid-foe-is-dead.html

          But there are always two sides to the story. This is another opinion by an MD involved in the area of steroids, concussions and brain damage in football and other sports:
          http://www.steroidlaw.com/2012/03/the-real-danger-steroids-in-footballor-football-itself/

          1. Windriven says:

            @nyudds

            Thank you so much for those links, especially the NYT obit. Alzado was a star back in the days when I could still scrape up 2 sh!ts about pro sports. I appreciated his aggressive style of play back in those days.

            But the SteroidLaw piece was the real meat. I’ve always been agnostic as to whether or not Alzado’s cancer was caused by steroids. But I have no doubt that traumatic brain injuries have damaged untold lives of athletes, professional and not. Seems an awfully high price.

      2. WilliamLawrenceUtridge says:

        We don’t yet have nanobot versions of The Terminator running around and selectively sniping off fat cells and then carting off the lipids into your excrement.

        And if we did, the consequences on your social life would be rather catastrophic. There’s a reason olestra didn’t do well.

        I read the words “increases the production of cyclic AMP, which increases the contractility of heart muscle” and thought “well this can’t possibly induce sudden cardiac death, can it?”

        I don’t know enough to say – but am surprised Dr. Oz, a cardiologist, who apparently read the literature, didn’t see this and freak out.

        But that would require ethics I suppose.

        1. Andrey Pavlov says:

          And if we did, the consequences on your social life would be rather catastrophic. There’s a reason olestra didn’t do well.

          True enough. I’m sure I’ve told the story before but when I lost a bunch of weight people who knew me asked the same thing, “What’s your secret?” in those exact words. Secret. When I said that I did nothing except eat less and work out more they were both surprised and disappointed at the same time. Surprised that “all” I did was eat less and work out more. Disappointed that I couldn’t tell them some miracle new pill to take and that they would also have to eat less and work out more to lose their unwanted pounds.

          I read the words “increases the production of cyclic AMP, which increases the contractility of heart muscle” and thought “well this can’t possibly induce sudden cardiac death, can it?”

          Funny that. Seems you don’t even have to be a doctor to think the same things as one. Let’s take my overweight, sedentary, NYHA class II heart failure patient who I have been trying to coach into better lifestyle choices and habits to lose weight and have him watch Dr. Oz. Decides he likes foreskin (unlike Dan Savage) and buys some. He loses weight! Huzzah! And in the process does the precise opposite of what the actual treatment for heart failure is (beta blockade to reduce the contractility and workload of the heart) and goes to NYHA class III or IV. Or absolutely nothing happens.

          I don’t know enough to say – but am surprised Dr. Oz, a cardiologist, who apparently read the literature, didn’t see this and freak out.

          Well, once again, he is not a cardiologist. He is a cardiothoracic surgeon. There is a big difference. And to boot, he is a CT surgeon who his own mentor and the guy who hired him at Columbia has gone on record saying he would not get surgery from because he doesn’t do enough of it anymore.

          And Oz has gone on record (in the same article, can dig it up if you like) saying that science is like religion: you have your science and he has his. Everything is fair game and equal. If you can string together facts to support your science it is valid.

          1. Frederick says:

            WOW, just WOW, Thank Andrey for describing that guy a little more.
            I did not know he was THAT bad. I have totally no respect for people who think science is just another belief system, or religion. Because it just show how much those people do not understand what it is, or don’t want to understand, because it will destroy their comfortable belief. Relativism, “all opinions are valid” is really something made up by scamers to justified them screwing people.

            1. Andrey Pavlov says:

              Frederick:

              Here is the full article. It is long, but a worthy read. Please spread it around. I find it is an excellent knock down source for people who can’t fathom why Dr. Oz is not worth listening to. I sent it to my fiance because her office was constantly talking about how wonderful he is. She knew from me that was not the case but could not articulate why. She said this article left them speechless… and now there is a lot less Dr. Oz talk at the office.

              1. Windriven says:

                OMG, Andrey. I’m only about 200 words in and I have the dry heaves. What a horse’s ass this guy is!

                “Oz squeezed her shoulder and stared into her eyes. “I’ll see you inside,” he said. “We are going to get through this, and we will do it together.”

              2. Frederick says:

                I’ll read it and I’ll spread around, I have to debunked stupid news on my facebook feed from time to time, I’ll find a place for this on :-)

              3. Andrey Pavlov says:

                OMG, Andrey. I’m only about 200 words in and I have the dry heaves. What a horse’s ass this guy is!

                Oh you haven’t even gotten to the best part. He is so sanctimonious it is painful. But the really telling parts are a little past the halfway point. Quotes from Oz himself, showing what he really thinks.

                I’ll read it and I’ll spread around, I have to debunked stupid news on my facebook feed from time to time, I’ll find a place for this on

                Thanks Frederick.

                And I’ll second what Dr. Hall said about your English and your comments. Keep up the strong work.

            2. Mike says:

              Also check out the videos of the time Dr. Novella paid a visit to Dr. Oz.

          2. Lytrigian says:

            Eat less and work out more? Sorry, but no one’s ever gonna get rich on THAT plan.

            1. Andrey Pavlov says:

              Weight watchers? Jenny Craig?

              1. Lytrigian says:

                Jenny Craig and Weight Watchers would sell very little of their products/services/consultancies/etc. if it was clearly understood how simple it all is.

              2. Andrey Pavlov says:

                enny Craig and Weight Watchers would sell very little of their products/services/consultancies/etc. if it was clearly understood how simple it all is.

                No doubt. But it is indeed possible to get rich off of simple advice like eat less and workout more. LOL.

              3. Calli Arcale says:

                The reason groups like Jenny Craig, Weight Watchers, and most of the gyms in the country are successful is because although the advice *sounds* simple, it’s very difficult to actually follow it. You’re basically hiring a coach to urge you along.

              4. mouse says:

                Calli Arcale “The reason groups like Jenny Craig, Weight Watchers, and most of the gyms in the country are successful is because although the advice *sounds* simple, it’s very difficult to actually follow it. You’re basically hiring a coach to urge you along.”

                Good point. “Eat less, workout more.” is a bit like telling an athlete that the way to win races is to run faster. True, but how? Thus, coaching can be helpful.

          3. WilliamLawrenceUtridge says:

            Well, once again, he is not a cardiologist. He is a cardiothoracic surgeon. There is a big difference.

            Ah, thanks for that nuance and correction!

          4. mouse says:

            Andrey Pavlov “when I lost a bunch of weight people who knew me asked the same thing, “What’s your secret?” ”

            I have asked similar questions of people I know who are looking newly fit. I guess it’s all in how the conversation goes, but sometimes there is some useful information, beyond less calories more exercise. One friend replied that she had been working out on her elliptical trainer most evenings. I said, “Wow that’s great! I get so tired in the evening, I just want to lay on the sofa.” She said “Yeah, I thought the same thing, but then I realized I was mentally exhausted but I still had the physical energy to exercise, so I watch mindless TV while I exercise. ” I thought that was a brilliant observation and very helpful at times. The “secret”is not nessacarily a pill or easy fix (although many folks might be looking for that) it can be an inspiration or mental strategy too.

            1. Andrey Pavlov says:

              The “secret”is not nessacarily a pill or easy fix (although many folks might be looking for that) it can be an inspiration or mental strategy too.

              Oh absolutely. Which is why I followed it up by stressing “secret” and saying:

              When I said that I did nothing except eat less and work out more they were both surprised and disappointed at the same time. Surprised that “all” I did was eat less and work out more. Disappointed that I couldn’t tell them some miracle new pill to take and that they would also have to eat less and work out more to lose their unwanted pounds.

              Certainly, some people were wondering what my new exercise regime was, what had actually changed, etc. But so many – most of them nurses in the ER where I worked at the time – were really just interested in that “one weird trick to lose belly fat” sidebar ad BS.

              I am reminded of a few times when the nurses would go up to the attending ER docs and ask them if they thought [x] supplement or extract worked and could help them do [y] (including weight loss). At the time I didn’t know too much better and wasn’t as interested in the topic as I am now, so I just observed. Almost invariably the response was literally a shrug and something like “Well, sure it could work. Why not?” and the occasional “Sure, I’ll give it a try.”

              1. mouse says:

                Hm. I think this may have been one of those times that I used a comment as a jumping off point to share some thoughts and it came across like I was disagreeing.

              2. Andrey Pavlov says:

                I think this may have been one of those times that I used a comment as a jumping off point to share some thoughts and it came across like I was disagreeing.

                Indeed. It happens. And I do agree with your thoughts.

  4. dh says:

    Why do all my patients keep talking about things they see on Dr Oz? Clearly they have no idea about the crass commercialism and quackery practiced by this physician. I have nothing against a practicing MD having a talk show but at least limit it to evidence-based medicine. Unfortunately, weight loss is far too simple – calories in, calories out – simple, but difficult to do. Does not make for an exciting episode of a talk show! Having lost 50 lbs myself, I can say that only by radical dietary change, sustained by exercise, will work. No herbals, no pills, no potions, no eye of newt, or meatus of foreskin…

    1. Windriven says:

      ” I have nothing against a practicing MD having a talk show ”

      Where is Dean Edell when we need him?

      1. Bill says:

        They are probably both trying to figure out a way to get their clinical efficiencies above that of Prozac, which is statistically insignificant when compared with placebo.

        1. Lytrigian says:

          Dr. Edell is an ophthalmologist, not a psychiatrist.

      2. Lytrigian says:

        Retired. :( He’s laying down on the job!

    2. irenegoodnight says:

      I lost 45 lbs (I’m 5′ 2″) and I did only some brisk walking and don’t even do that anymore–although I garden and do other active things. It’s mostly about the food.

      @Andrey

      I had exactly the same response when I lost weight. I finally started telling people (in a jokey way) that I had some magic pills and could pass them on for $200/ bottle. Most of them bit. I was sorely tempted to get a lot of homeopathic sugar pill blanks and get a nifty label done up to “brand” my “miracle”.

      P.s.
      When are you going to marry that “fiancée? Strictly speaking, being fiancéd means that there is a ring and THE DATE IS SET. :-)

      Pass

      Thanks very much for the link. I have a couple of immediate recipients in mind.

      1. Andrey Pavlov says:

        I was sorely tempted to get a lot of homeopathic sugar pill blanks and get a nifty label done up to “brand” my “miracle”.

        Yeah, I believe it was Phil Plait who said (perhaps not the first, but the first I recall) that if we (skeptics) had no scruples we could laugh our ways to the bank with all that we know about how people get fooled into believing ludicrous garbage. I myself did pharmacognosy on anti-aging herbals that showed very serious promise in my fruit flies. Chuck an MD after my self-branded version and throw in a few of the tricks we know and I could pay off my student loans. Just not in good conscience.

        When are you going to marry that “fiancée? Strictly speaking, being fiancéd means that there is a ring and THE DATE IS SET. :-)

        Hmmm. I was not aware of the “date is set” convention. I thought I just had to trick her into saying yes :-P

        But the TL:DR is that we were supposed to have been married (a couple weeks ago) but last year we got into an argument about timing (she thought it was not enough time to plan) and then her cousin set a date for exactly when we were going to do it. So we opted to go to his wedding in Costa Rica instead. We’ve now decided on August of 2015, with August 15 being the preferred date. I am just waiting to hear back from my venue of choice about availability and details. The 15th is our preferred but any weekend in August will do.

  5. chris hickie says:

    I saw this title and thought “forskolin–isnt that just for basic science lab use? Who would ingest that?” Well, never underestimate human stupidity. Of course biochemistry memories of years ago returned and I thought “well, at least no one is using dinitrophenol (DNP), which uncouples most of a cell’s ATP production, leading to unregulated hyperthermia and death”. But wait…you can buy it online (as something called “DNPX”. Apparently body builders got bored with enduring only the damage of anabolic steroids, so now they use this stuff as well.

    I don’t think Oz deserves to have a medical license anymore for some of the things he’s done and said. If he thought there was $$$ to be made in endorsing DNP, he’d probably do it.

  6. Tom Lang says:

    Dr. Oz and fad weight-loss supplements aside, there is interesting research using forskolin extract in topical form to induce tanning in the skin: http://www.ncbi.nlm.nih.gov/pubmed/19087231. This all only for rats, of course, but intriguing for sun-damaged gingers like me.

  7. Angora Rabbit says:

    Exactly my thoughts, Chris. And about DNP as well. Apparently if it is in a plant it is perfectly safe to ingest but if it is instead in a drug or from Sigma/Aldrich it is transmogrified into evil. I saw “forskolin” and immediately reached for Lehninger. Unfrakkinbelievable. My second thought was also “sudden heart attack death”, just like Andrey and William. Alas, Merck Index doesn’t list an LD50 probably because who would be stupid enough to willingly ingest this? Elsewhere the given LD50 is 2.5g/kg rats and 3.1 g/kg in mice. So I suppose no Darwin Awards here. Sigh.

    From Calbiochem’s Signal Transduction (one of my bible’s): “At low doses, it acts as a positive inotropic agent. At higher doses, it serves as a hypotensive and vasodilatory agent due to its actions as a smooth muscle relaxant. No major side effects are observed at effective doses. (Me; thank frikkin’ heavens for that! Though note they aren’t providing the effective dose.) Forskolin’s pharmacological activities are due to its activation of adenylate cyclase (EC50=4 uM), resulting in increased cAMP levels.”

    Which means I predict a similar story as Ephedra, amphetamine, or high-dose caffeine. The poor trusting, desperate folks take it, and the ones who have impaired heart function (and remember these folks are more likely to be obese) or have an undiagnosed cardiac problem are the ones who will pay the price in sudden heart attack death.

    But this, of course, is okay because it’s “natural.” (sarcasm off)

  8. Frederick says:

    Thank Harriet for yet a other great article.

    The wizard always get new stuff, every couple of weeks, always new miracle things, If they are so miraculous, why you need so much of them? if they work so well, why a lot of people, who watch the Wizard show, are still fat? . This guy Is a joke, I personnally cannot call him Dr, anymore, Maybe is still good as a cardiologist, I think that I cn be doubtful pf that, he show too much often how He cannot understand how science works.

    We have a couple of Medical doctor around here, His this guy like a water-coolers joke around your offices ? Do you use it as a Friendly taunt between doctors?

    This is a Easy one, But yes he his the real Wizard of Oz, there is some much magical stuff on his show, not only weight lost, touch healing, all sort of debunked myth raise back from the dead there ( or maybe He his the Necromancer of Oz).
    it is unfortunate that Excellent writer have to continuously debunked his junk, but people still believe him, so I guess that is a public service to do It. Well it’s good thing we have SBM!

  9. Frederick says:

    I wish we could edit or entry. Just so you know, English is not that easy to write correctly, not more/less than french, it is just different ( for me at least). Well, I’m sorry for all those errors

    1. Harriet Hall says:

      You may not be able to edit your comments, but you can proofread and correct them before posting them. You needn’t apologize for your faulty English; it is much better than my faulty French would be, and your ideas come through quite clearly. I appreciate your contributions.

    2. Calli Arcale says:

      Don’t apologize for your English; I think it’s English that owes an apology to any of the poor saps trying to learn it. ;-) The grammar is one of the simplest around, but the vocabulary is a bastard (and I’m not speaking metaphorically) and the rules of phonetics are “more honored in the breach than the observance”. (I’m looking at you two, I and E.)

      1. Frederick says:

        Well, wow, Thank for the compliments, Coming from someone as accomplish as you, it’s a honour :-). Thank To Andrey Too, you guys are so great,

        My biggest problem is the verb tenses, English verbs do not have that much “form” they can take, overall, ( verb are complicatie in french a lot more) but the way you use tense are different than in french and there’s a lot of little detail, like Possessive case, that are not intuitive for a frenchmen. Also Questions, how to build them properly. In english you also you capital little a little too much, lol, like, right there in English.
        So yeah I Do my best, I always have a French/English dictionnaries not far away.
        I do have the advantage of 95% undertstanding all i hear and read, Of course The exception of some accents, like some people from England or deep South,

        1. Andrey Pavlov says:

          ( verb are complicatie in french a lot more)

          Ha! That’s an understatement!

          I learned to speak French before I was 8. I studied it for 4 years in high school. I lived in France for a month and have traveled back there (and other French speaking countries) a number of times. My good friend in medicine speaks French. My sister and her husband are completely fluent*. And yet I still stumble and have difficulties these days. Especially in written French. I can speak it much better than I can write it.

          You are doing extremely well Frederick. Keep up the strong work.

          *Besides the fact that my sister and her husband (whom she hadn’t met yet) studied French for 4 years in high school, they met in French class in college. They studied French in college for another 3 years, including 1 year where they both lived in Grenoble together. Her husband also did an extra 4 months in Paris studying business and finance. And then he ultimately became Vice President of the European and Asian division of Societe Generale. They have also been back to France many more times than I have, even after leaving SG. So their French is still pretty much perfectly fluent.

          1. Frederick says:

            Nice, I myself have problems with french lol, There’s a lot of thing going on in written french, Language is not my strong suit, I more of a science nerd and computer nerds. But this year I was to college ( at 35 with people between 17-20 that weird lol) and I had to do french literature class, I really mange to improve my written french quality by a lot. I also had a English class, it did help me with verbs.

            just to test your french, I might write a whole comment in french at least once in the future :-)

            1. Andrey Pavlov says:

              just to test your french, I might write a whole comment in french at least once in the future :-)

              By all means!

              I will venture to guess that I will be able to understand it almost entirely just from reading it, filling in a few gaps by looking up a word or two. However, if you use idioms or deeply nuanced sentences, I will most likely not pick up on those.

              1. Frederick says:

                Ok so no sarcasm or french Idioms :-) deal. I’ll check the article next week and write a comment on one of them just for you.

              2. Andrey Pavlov says:

                Ok so no sarcasm or french Idioms :-) deal. I’ll check the article next week and write a comment on one of them just for you.</blockquote!

                D'accord!

              3. Harriet Hall says:

                I read French too. I’m looking forward to it.

  10. Alia says:

    And don’t forget the influence on platelet aggregation and increased risk of bleeding. Something like that could be very dangerous for someone like me (I have platelet count in lower ranges, it’s genetic, half of my family has it and was warned by my doc to stay off aspirin for that reason).

  11. Bill says:

    Maybe if humans would stop emulating lab rats by eschewing excitotoxins they would develop an equally obesity-resistant genotype.

    1. Lytrigian says:

      Or just stop eating so goddamn much and stop sitting on our fat butts all day.

      1. irenegoodnight says:

        I lost 45 lbs (I’m 5′ 2″) and I did only some brisk walking and don’t even do that anymore–although I garden and do other active things. It’s mostly about the food.

        @Andrey

        I had exactly the same response when I lost weight. I finally started telling people (in a jokey way) that I had some magic pills and could pass them on for $200/ bottle. Most of them bit. I was sorely tempted to get a lot of homeopathic sugar pill blanks and get a nifty label done up to “brand” my “miracle”.

        P.s.
        When are you going to marry that “fiancée? Strictly speaking, being fiancéd means that there is a ring and THE DATE IS SET. :-)

        Pass

        Thanks very much for the link. I have a couple of immediate recipients in mind.

        1. mouse says:

          irenegoodnight “When are you going to marry that “fiancée? Strictly speaking, being fiancéd means that there is a ring and THE DATE IS SET. :-)”

          He won’t tell us when he’s getting married because we might crash the wedding. ;)

          1. Andrey Pavlov says:

            He won’t tell us when he’s getting married because we might crash the wedding.

            I could have sworn I answered this already but I don’t see the comment anywhere. I am on a weekend holiday in Chicago at the moment on a friend’s laptop so I may have missed it.

            The short answer is it was originally thought of for this past May. But it proved a bit overwhelming in terms of planning and then a cousin decided to get married at that exact time in Costa Rica and we decided that would be more fun than planning a wedding. So now we are in the stages of finalizing a date and confirming it with the venue. Ideally August 15 of 2015, but it may be September because of ever changing availabilities and some delays in getting follow up.

      2. agitato says:

        “Or just stop eating so goddamn much and stop sitting on our fat butts all day.”

        Yes! You’re describing the amazing H.A.M-G.O.Y.A diet. (Half as much and get off your a$$.) Very effective.

    2. Windriven says:

      I’m just a poor physicist. Wtf is an excitotoxin? I don’t know what it is but I’m pretty sure I want one (some?).

      1. Windriven says:

        OK, I looked it up. Never mind. I don’t want any.

        1. Andrey Pavlov says:

          LOL!

        2. Lytrigian says:

          My impression is he got the definition of “eschew” somehow inverted. Either way it’s very tangled syntax.

          1. WilliamLawrenceUtridge says:

            My impression is he got the definition of “eschew” somehow inverted. Either way it’s very tangled syntax.

            As a major contributor of tangled syntax, may I suggest it can be read in two ways?

            Maybe if humans would stop emulating lab rats by eschewing excitotoxins they would develop an equally obesity-resistant genotype.

            The use of “they” could be interpreted as referring to both humans and rats; I would read this as “Maybe if humans would stop emulating lab rats, who are forced to consume excitotoxins, by the humans eschewing excitotoxins, then they, the humans, would develop an equally obesity-resistant genotype.”

            But perhaps I’m wrong.

            1. WilliamLawrenceUtridge says:

              Heh, and ironically my own statement is ambiguous. The italicized “and” should really be an…or? Or the whole sentence needs to be reworked.

              OK, I’m not going to “help” anymore.

          2. Windriven says:

            WLU, I’m going with Lytrigian on this one. Eschew doesn’t mean what Bill (Oh no, Mr. Bill!!!) thinks it means.

            1. WilliamLawrenceUtridge says:

              Eschew – to deliberately abstain from. As in “if humans would eschew excitotoxins, they would not get fat”.

              “If humans eschewed excitotoxins, by which they would cease emaluating lab rats who are unable to eschew said excitotoxins, they would not get fat.” Though he does use “genotype”, which is probably incorrect, phenotype would be appropriate I believe.

              But I’ve been wrong at least twice so far today, so I should probably quit while I’m ahead. But let it be noted – there is nothing so trivial I won’t argue about it.

              1. Windriven says:

                ” But let it be noted – there is nothing so trivial I won’t argue about it.”

                Yeah, me too :-)

                What Mr. Bill said was: ” Maybe if humans would stop emulating lab rats by eschewing excitotoxins…” suggesting that rats avoid excitotoxins. I’m guessing here but I think rats probably don’t avoid them. I suspect that what Mr. Bill meant was along the lines of, “Maybe if humans would stop emulating lab rats and eschew excitotoxins …”

                But then again, my ability to cold read the mind of a dummass is probably questionable. Nonetheless, Mr. Bill has hit that pigeonhole in my roll-top desk until better evidence appears.

              2. Andrey Pavlov says:

                ” But let it be noted – there is nothing so trivial I won’t argue about it.”

                Yeah, me too :-)

                Me three.

                Which is part of why I spent a good portion of my day trying to educate a couple of proper gun totin’ ‘Murricans (one of whom I know from high school and another is his friend) about the science and data on guns and why they are really racists even though they claim science backs up their claims.

                Le sigh.

              3. Lytrigian says:

                Hmm. Yes, perhaps we’ve had conjunction/preposition problems.

              4. Windriven says:

                “about the science and data on guns and why they are really racists even though they claim science backs up their claims.”

                .380 Walther PPK
                .22 Taurus pistol for armadillo control
                .223 Ruger Ranch Rifle for general stuff that needs killin’
                12 gauge long barrel Browning BPS for goose and duck
                20 gauge Browning Citori for upland game birds

                Andrey, I have nothing scientific to say about guns other than the empirical observation that a .223 in the hands of a couple of teenaged boys can take down a pretty fair sized pine tree over time*. And I’m pretty sure I’m not a racist.

                All that said, I favor reasonable gun control measures, licensing, registration, background checks, and the right of commie government types to pry my guns from my cold, dead fingers ;-)

                * A target was affixed to it.

              5. Andrey Pavlov says:

                Andrey, I have nothing scientific to say about guns other than the empirical observation that a .223 in the hands of a couple of teenaged boys can take down a pretty fair sized pine tree over time*. And I’m pretty sure I’m not a racist.

                There is a difference between responsible gun ownership and use and ‘Murrica, fuck yeah! I’m dealing more with the latter. I’ll add that this year I built from parts, sighted in, and had fun on the range with, and sold an AR-15.

                That said, I agree with your thoughts in general with the additional caveat that I would like to see a progression towards a society where gun use and ownership is an anachronism and no longer necessary or wanted.

                The science is sparse, in very large part because the NRA successfully lobbied to have it literally shut down for well over a decade. But what data there is give strong indication that guns are more trouble than they are worth.

  12. Young CC Prof says:

    Weight-loss ads are hilarious. I can find plenty of anecdotes of women who lost 20 pounds or even more in just one week with the help of Pitocin. Does that mean I can start pushing it as a weight-loss drug?

    1. Windriven says:

      My wife has an employee who dropped a huge (>30 pounds as I recall) bunch of weight on one of the diet deals where you buy food from the diet company. Then she put it back more quickly than she lost it. And … wait for it … she’s still buying the food!

      What I really need is somebody like FBA to tell me how to anesthetize – or better still euthanize – any sense of ethics and just cash in by fleecing people while I humiliate them.

      1. WilliamLawrenceUtridge says:

        I just finished Yoni Freedoff’s The Diet Fix (reviewed here by Scott, but too lazy to link) and he hammers, again and again, that it’s not about losing the weight – it’s about changing the lifestyle so the weight stays off.

        Good book, I’m glad Scott brought it to my attention.

        1. Andrey Pavlov says:

          it’s about changing the lifestyle so the weight stays off.

          Bingo!

          1. irenegoodnight says:

            It can be difficult to maintain lifestyle changes. I started having the odd beer again ( which has slowly escaped to about one a day) after years of weight loss maintenance and sure enough, I’ve started to gain weight. :-(

            Sadly, I think the beer has to go.

            1. Andrey Pavlov says:

              Sadly, I think the beer has to go.

              Now that is truly sad. I’d rather go for extra laps around the park than totally give up beer.

              1. Windriven says:

                “I’d rather go for extra laps around the park than totally give up beer.”

                And if that didn’t work, I’d rather get fat.

    2. Calli Arcale says:

      BWAHAHAHAHHA!

      Hey, I can be an anecdote for you! I was severely overweight — nearly 190 pounds, and I’m only 5’2″. Admittedly, this weight gain had come rather rapidly over a period of nine months, most of it in the last three, but the doctors checked me in to the hospital and put me on a Pitocin drip. Oh sure, there were complications and I needed surgery, but it all worked out okay and I was indeed 20 pounds lighter by the time I was able to get on a scale again. More weight melted off over the next couple of months. I lost 45 pounds by the time I returned . . .

      . . . from maternity leave.

      :-D

      (Yeah, I got the joke, and I’m kind of amused nobody else seemed to.)

      1. Young CC Prof says:

        YES! Someone else figured it out!

        There aren’t a whole lot of ways a person can lose 20 pounds or more in one week. Giving birth is the most common one.

        1. WilliamLawrenceUtridge says:

          Amputation is another. I keep telling people “You don’t want to lose weight – you want to change shape. The easiest way to lose weight is an accident involving a chain saw and a severed leg.”

          Though in retrospect, a haircut would work as well but you miss out on the fun gore factor.

          1. CHotel says:

            What remains my favourite conversation I’ve ever had at work, asking a nurse if she knew what a patient weighed:

            “Well, he was 170ish on admission, but not anymore”
            “Oh did he get some fluid drained or something?”
            “No, not that, he’s uh, slightly less leg’d than he was before”

            I mean, unfortunate situation, but just the way she said it was priceless.

            1. Windriven says:

              Gotta love it! I hope I’d have the humor after something like that to quip that I’m shorter on one side than I once was.

              1. CHotel says:

                “Well, I now have twice as many socks as I used to!”

          2. Calli Arcale says:

            I’ve been growing my hair out; it’s to my waist now if I take it out of the braid. Eventually I’ll get sick of it and donate it to Locks of Love, and as it’s now longer than I’ve ever had it before, I’m sort of curious how much weight I’ll lose. ;-) (It’s hard to weigh the braid while it’s still attached to my head, after all.) I have noticed that getting it wet during my morning shower has a measurable impact on the bathroom scale; my hair is very absorbent, to the frustration of many hairdressers who I guess don’t see many Scandinavians. (In Minnesota? Really?)

            1. Andrey Pavlov says:

              Eventually I’ll get sick of it and donate it to Locks of Love, and as it’s now longer than I’ve ever had it before, I’m sort of curious how much weight I’ll lose

              I only have the vaguest of information from once, many years ago, learning that there was significant controversy surrounding LoL. It seems that there have been multiple accusations that they take some of the donated hair and sell it for profit under the table. According to this Forbes article to the tune of $6 million per annum.

              I’m not saying don’t donate to them. I honestly don’t know enough to say how credible the accusations are. But it seems worthwhile to do a little legwork for yourself and see if you are comfortable donating to them and if not what other options there are (there are others, I just don’t know them off the top of my head).

            2. CHotel says:

              In high school I had my hair about halfway down my back at it’s longest before finally cutting it to donate for wigs (I wanted to get it to my waist, but cut it early for a variety of reasons, not limited to my mixed doubles partner in badminton getting mad when people confused us when only seeing the backs of our heads, and being really tired of my more moronic peers calling me a faggot). My scale read in intervals of 0.5 lbs, and it did not change from before and after the fateful day.

              I share your absorbancy issues though. Half Icelandic. I felt like my hair was perpetually wet.

  13. Angora Rabbit says:

    For the past two days I’ve been muttering “forskolin…forskolin…” And then I remembered.

    HOLY MOTHER OF PEARL!!!!! People are TAKING this?????!!!!! (Yeah, I’m shouting.)

    Consider this article (ah, crap, I don’t know how to do links). It is just one a good couple dozen examples of how we like to use forskolin in the lab. So you will have to plug this link into your web browser yourself, sorry. And it’s probably behind a paywall (so see if you can get the free word version – look at the pictures).

    http://www.ncbi.nlm.nih.gov/pubmed/17647295
    http://onlinelibrary.wiley.com/doi/10.1002/bdra.20387/full

    We use forskolin to induce cyclopia. It works really, really good. Really good. 50 uM will beautifully eliminate your facial midline. The susceptible period for that is about 14 to 18days post-fertilization, meaning a woman won’t know she’s pregnant yet. A little later and you can wipe out limb buds, jaws, kidneys.

    This stuff should have a black box warning, and FDA should be coming after them. This is my professional opinion. Any woman who takes this supplement and has a child with a birth defect should sue their fur off.

    Just when you think that supplement greed and stupidity can’t hit a new low, here we are. Why on earth are you people (you know who you are) still bleating that supplements should be unregulated?

    1. Bill says:

      Wow! That is scary.

      Why would one want to induce cyclopia?

      1. Andrey Pavlov says:

        Why would one want to induce cyclopia?

        Because that way we can better understand the processes of embryology and cellular differentiation. Essentially if we want to figure out how cell signaling works in order to create a bilaterally symmetric midline, we find something to short circuit that process. And then identify where the short circuit is and what exactly is being shorted. We look for multiple different ways to do this so that we can identify each of the steps involved and reconstruct them.

        There may be other reasons, but from my old evo (with some devo) days that’s the one that comes to mind off the top of my head.

      2. WilliamLawrenceUtridge says:

        Why would one want to induce cyclopia?

        Because most of science is really about being cruel to rats :)

        1. Windriven says:

          !!!

      3. Angora Rabbit says:

        Why would anyone want to study cyclopia? Great question! It turns out that cyclopia is just the severe end of a range of spectrum disorders called Holoprosencephaly. Basically, the gene sonic hedgehog (yea!) tells early embryonic structures to expand. This includes your hand plate (five fingers not three like a chicken) and your face. HPE disorders are more common than people appreciate. For example, fetal alcohol exposure can cause HPE. People can also be heterozygotic for HPE, meaning they can be a partial carrier (one altered copy, not two). If you see someone with a single, middle incisor, that’s on the mild end of HPE.

        On the other end, you can also have too much sonic. In that case, the midline is wider than normal. Take a look at Dave Letterman’s grinning face. See that gap between his teeth? He’s a little hyperteleoremic, meaning a bit more sonic than usual. The eyes would be a little wider, too. This is more common and there are multiple people reading this who have the condition. We typically don’t worry about it.

        One can have a vast excess of sonic. This is where you get the two-headed calves or pigs (google Xerox the pig) or kittens.

        It’s not that we like causing cyclopia. Rats are some of our best friends (except when they go into politics). It’s that, if we understand the rules of how the embryo gets put together, then we can make change to reduce that risk and prevent birth defects. HPE can be pretty devastating, so it’s good news when we can help those kids and families.

        1. Windriven says:

          “except when they go into politics”

          Take the rats out of politics and there would be 11 members of the House of Representatives.

        2. Motherofmany says:

          My youngest daughter has (lobar) holoprosencephaly, along with Goldenhar, cleft lip/palate, heterotaxy and a whole host of other associated issues. We have done all the genetic testing for HPE, including testing for SHH. (and let me tell you, the first time I heard about sonic hedgehog, I thought “it sounds like the video game”…..sure enough, it WAS named after the video game. I guess when you find it, you can name it what ever you want!)

          All of her genetic testing has come back normal, including the testing for heterotaxy specific genes. Some of her issues, like goldenhar, are usually considered environmental, not genetic, so we have no idea. There was a fascinating article about the tilt of cilia in the node early on in embryonic development that determining the differentiation of left/right asymmetry, and when disrupted, situs inversus or heterotaxy results.

          All that to say, my daughter is involved in several NIH research studies, and I very much appreciate those medical researchers and scientists who dedicate themselves to unlocking the unknowns behind diseases and disorders that may be rare, but have profound consequences for the children who live with them.

        3. Motherofmany says:

          My youngest daughter has (lobar) holoprosencephaly, along with Goldenhar, cleft lip/palate, heterotaxy and a whole host of other associated issues. We have done all the genetic testing for HPE, including testing for SHH. (and let me tell you, the first time I heard about sonic hedgehog, I thought “it sounds like the video game”…..sure enough, it WAS named after the video game. I guess when you find it, you can name it what ever you want!)

          All of her genetic testing has come back normal, including the testing for heterotaxy specific genes. Some of her issues, like goldenhar, are usually considered environmental, not genetic, so we have no idea. There was a fascinating article about the tilt of cilia in a node within the developing embryo determine left/right asymmetry, and disruption of that tilt causing situs inversus or heterotaxy,

          At any rate, my daughter is in several NIH research studies, and I just want to say to you that yes, what you are doing does indeed matter, and I am extremely appreciative of the doctors and researchers who dedicate themselves to increasing our understanding of birth defects that have such profound implications for the children who are born (and the many who sadly die) with them.

          1. mouse says:

            Hear, hear!

          2. Angora Rabbit says:

            Motherofmany, I am sorry to learn of your daughter’s challenge. I have several relatives with similar conditions; for one it took decades to identify the deletion. It didn’t alter the treatment plan, but not knowing created challenges for their families. For both children (separate families), it ended up being primary mutations. I hope your daughter is doing well. I am guessing you may be working with Dr. Max Muenke at NIH? I hope so – he’s terrific.

            “I thought “it sounds like the video game”…..sure enough, it WAS named after the video game.”

            So I have to share the story because Cliff Tabin (part of the teams that discovered these) is an old friend. The original gene in Drosophila was named hedgehog because the mutation produced little bumps all over the Drosophila larva integument. When Hh was cloned in vertebrates, they discovered there were three genes, not one. As Cliff tells it, the teams decided to name them after the three hedgehog species. So we have Indian Hh, Desert Hh. But Cliff and all couldn’t bear to call it “Common European.” So they opted for “Sonic.” And if you knew those involved, you’d know that name makes sense. There’s also a different Hh gene in, I think, Xenopus that was originally called “Tiggywinkle” but, sadly, I understand that name has since been dropped. Too bad, as I really like Beatrix Potter and her work.

    2. n brownlee says:

      I love that you comment here, Angora. I learn so much that I wouldn’t ordinarily have a chance to read.

      1. WilliamLawrenceUtridge says:

        (mashing imaginary “Like” button)

        Guest post! Guest post!!!

    3. mouse says:

      Eeek!

      1. Angora Rabbit says:

        Oops, sorry Mouse. We love our little mice here. :)

        Actually, apropos of nothing, a colleague once mutated a gene that created angora mice. I thought it was the coolest thing.

  14. Bill says:

    Thank you so much for taking the time to explain–and thanks to all of you who blog and post. This is a very informative site.

  15. Bill says:

    What units are “M”s, as in uM? Micro…

    1. CHotel says:

      Molar concentration. So a 4 uM solution has 4 umol/L of a given solute.

  16. Bill says:

    Ah, moles. That seems like a tough way to think to me (an engineer with a pretty basic chemistry background). Why are molar measurements preferred over mass or mass/volume?

    Thanks for your time and patience.

    1. Angora Rabbit says:

      Great question. Mass is meaningless because it doesn’t indicate concentration. Biology is all about life in liquids, so we (pretty much) always think in concentrations. Molarity IS mass/volume. But if you say, 4g NH4Cl in a liter, this is a problem because your 4gthat you just weighed out may contain water or other impurities. So it is most precise to state concentrations based upon atom concentrations. 6.02 x E-23 is a mole, so, voila, it is easy to determine what your true concentration is. When we make solutions, we always read the bottle and then calculate based on the true molarity, because salts can be complexed with water, even though they look “dry.”

      Also, problems can arise because volume and therefore concentration changes with temperature, which adds another layer of complexity. It seems like people don’t pay much attention to that anymore (old geezer speaking) but for buffers and enzyme reactions, it is actually pretty darn important. DNA doesn’t care so much. It’s such a uniform structure that even my mom can isolate it. :)

  17. Bill says:

    Angora Rabbit: I am a newbie here, but I’m already in support of those who believe you should do a guest post. I am SO appreciative that you have taken the time to respond–in detail–to my questions!

    I am still missing something. If we have a solution of a given strength. it still seems that the “total exposure” is what matters. Do we float an embryo in the solution? Do we administer a “shot” to the mother? Do we inject the embryo itself? In my simple mind, I could drink a “whatever” molar solution containing the botulism organism, and I may or may not die depending how much of the solution I drank (probably not correct to speak of molarity with respect to a living organism). I hope you can see my difficulties in spite of my ignorance.

    Thanks again.

    Another Geezer.

    1. Andrey Pavlov says:

      Hi Bill.

      Firstly, Angora is amazing. We are all better off for her spending some time here.

      But I can also help clarify I believe. Of course Angora was correct in her explanation of molar concentrations but left off one specific thing I think is important to understand – it tells us how many molecules are in a solution. If I get 4 grams of NaOH (sodium hydroxide) and 4 grams of HCl (hydrochloric acid) they will weigh the same amount but the number of molecules will be different. When we do chemical reactions we “balance” them like this:

      NaOH + HCl –> NaCl + H2O

      So we need 1 molecule of each to react completely and turn sodium hydroxide and hydrochloric acid into 1 molecule each of table salt and water.

      So I know that if I have precisely 1 mole of NaOH I will need precisely 1 mole of HCl to fully react. If I put in 1.5 moles of HCl, I know I will have exactly 0.5 moles left over. If I know I have a 10 molar solution, that is 10 moles / liter, which means I will need 100mL to have exactly 1 mole of the compound.

      So it makes doing chemical reactions and knowing concentrations very, very easy.

      The other thing to bear in mind is that all chemical reactions are reversible. Some are so hard to reverse that for all practical purposes they go to completion and there is no more reactants (on the left side of the equation) and maximum amounts of products (right side). The NaOH and HCl would be an example of that. But some happen to have an equilibrium point where some of the reactants will always be present. That is because the products are turning back into the reactants at a certain rate. When the rate of the backwards reaction equals the forwards, you are at equilibrium. That has a constant associated with it called the Km (from Michaelis and Menten who came up with the equations for it). There are other things like Ka which is the dissociation constant for acids (so our HCl has a Ka). And so on.

      The actual rate is not the Km, but is determined from it. Things like temperature and the solvent used as well as presence of enzymes change that actual rate and we do math using these to determine that rate and the actual equilibrium concentrations. One thing that affects the rate is the concentration of the molecular species. As the reaction starts with all reactants and no products it goes at max speed (Vmax) towards products. As products build they do the reverse reaction thus “slowing down” the reaction overall. As it approaches equilibrium the net reaction speed slows until zero at equilibrium.

      Most organic reactions (like what happens in the body) are actually “tough” and have a high “activation energy” – the amount of energy that needs to be in each molecule in order for the reaction to occur. Basically, how hard they have to slam into each other in order to change conformation by breaking and making new bonds (which release and require energy respectively). That is why heat increases the speed of a reaction – more of the molecules are likely to have enough energy to react. Enzymes lower this activation energy, making it more likely for the reaction to occur. But, the same rules apply – as products get produced they start going backwards and the reaction reverses. This is handled in the body with enzymes, making one direction a LOT more favorable and by compartmentalizing – removing the products from where the reaction is happening to keep the reaction rate moving forward.

      The point of all this being it is total exposure that matters but only if reaction you are referring to will have a very high Km – meaning it will go to products very strongly. If it doesn’t, and the conditions are right, then even though in one sense there enough total molecules to have a specific outcome, they cannot react quickly enough in order to stay reacted and thus have the effect. For example, botulism is something with a very high Km. Those molecules bind acetylcholine receptors very tightly and produce massive muscle contractions as a result. So every molecule that is available binds. That is why it is so toxic in such extremely low doses. The backwards reaction is almost non-existent. On the other hand methanol (wood alcohol) poisoning is different. It reacts with the molecule that breaks down ethanol (the stuff we drink, sometimes too much of) and it is that breakdown product that harms you. However, you also just pee it out. But the reaction is not so favored and certainly not as much as ethanol. So if you have a very low concentration of methanol you are much more likely to pee it out than get harmed from it. But if you have a high enough one, the treatment is giving lots and lots of ethanol. Basically, we get the patient even more drunk. The reason is that the ethanol competes for the reaction with methanol and since the activation energy favors ethanol, it happens faster, soaking up all the available enzyme (alcohol dehydrogenase) and doesn’t create the by product that will kill you and is peed out instead.

      So it isn’t quite as simple as just total exposure, though sometimes it is because the reaction kinetics (which is the general term for this topic in chemistry) make the extra things to consider such a small part of the equation that you won’t be very wrong if you ignore them. But in most cases of biology, you can’t ignore those factors or you will get a very wrong answer.

      Hopefully that clears things up more than muddies them. I’ll be around to explain further tomorrow if need be and Angora doesn’t beat me to it.

    2. Angora Rabbit says:

      Hi Bill! When we express in uM, we are usually thinking blood concentrations when dealing with a whole organism. The “effective dose” is calculated off the blood level because that’s what we can measure. So when I think whether forskolin enhances PKA and thereby shuts off sonic, I would do a test to see what intake (and that would be weight of drug per weight of animal, ie mg forskolin per kg body weight). Then I would sample forskolin in the blood (because you won’t get a “true” intracellular level) and then plot the mg/kg values vs. the uM values to figure out the dose-response curve.

      You’re absolutely right that there’s other measures that we would want to consider, including first-pass effect of liver, volume of dose, size of animal, metabolic rate, etc. The value I tossed out was based on floating zebrafish embryos in forskolin, hence their exposure was in liquid. What was in the embryo was likely quite lower, since the forskolin would still have to cross the chorion and embryo integument. So actually that 50uM value scares me even more, especially since zfish embryos don’t have livers to dispose of the forskolin. For humans, I’d be looking at blood forskolin.

      Thanks, Andrey, for stepping up to the plate! I wasn’t going to get into osmolarity and molecule count due to time and pedantry risk (was actually banging out my answer on the way out to dinner), so your answer was perfect.

      1. Andrey Pavlov says:

        Thanks, Andrey, for stepping up to the plate! I wasn’t going to get into osmolarity and molecule count due to time and pedantry risk (was actually banging out my answer on the way out to dinner), so your answer was perfect.

        My pleasure. I got the sense that Bill was genuinely interested in learning more about the topic and at least understanding that there are many things to consider that most people don’t realize would be helpful, even if it did ultimately prove a little more detailed and pedantic than necessary. Often I find that people don’t necessarily need to understand the nitty gritty of such topics, just merely see an example that they exist in the first place to better put into context the parts that they do want to understand more deeply and fully.

        I also appreciate your comments as I had not considered the idea that vitamin supplementation could possibly lead to deficiency by inducing higher levels of catabolism of the vitamins. I’ll definitely keep that one in the back of my mind for future discussions on the topic.

  18. Bill says:

    Thanks Andrey and Angora! I am now much down my path to a Nobel in chemistry.

    1. Andrey Pavlov says:

      Glad to be of help. I loved my chem classes. Particularly ochem. I don’t have cause to use it as much these days, but I have been able to from time to time and it is always a crowd pleaser :-D

  19. Thank you so much for your input…I have tried some of Dr. OZ recommendations on other products that will help you lose weight without exercise like the mango pills which didn’t work. So now he has Forskolin which will do the same (really???). I don’t like taking anything into my body that may or may not upset my chemical balance. Everything goes to the liver first, our chemical factory so when you bring foreign object into it not really knowing how it would effect you for the good or the bad you are taking a risk.. It’s difficult for me to exercise do to my work schedule, but I watch what I eat, (fruits, veg, small meals and drink water). I am 67 years old but people think I am in my med 50′s when they meet me. All I need to do is get to the gym. Everything you have said is right on. More people should read what you say instead of wasting there money. eat an apple…

    1. WilliamLawrenceUtridge says:

      The nice thing is, for the most part Dr. Oz’s recommendations are problably chemically inert; they’re just food. There’s usually little chance to actually hurt yourself with them. Of course, any nonsense he recommends with an actual effect would be likely to have side effects as well, a concept he never seems to entertain.

  20. sally says:

    I found this article while looking for info on forskolin. Very helpful.

    As for Dr. Oz, here is my non-scientific take on him. After seeing his face seemingly every week on the cover of various magazine at the grocery check out I noticed that each cover was Dr. Oz proclaiming some new weight loss miracle. My untested hypothesis is that what Oz has found, and all that he has found, is his own miracle money-making scheme. Tout anything and everything that will make him more money.

    1. Chris says:

      Welcome to our small community that dares to question advertisements!

      Please stick around, since you are actually willing to do the work to find actual answers. It is a sign that you apply critical thinking. Plus we don’t bite… much. ;-)

    2. WilliamLawrenceUtridge says:

      I don’t really think Oz is in it for the money, I think he is a pious fraud. I think he’s mostly in it for the ego, and the misplaced assumption that his SCAM crap gives people the hope to stick to a diet and maintain their effort to lose weight. I believe he’s even on record as saying this, and I’m inclined to think he actually believes his paternalistic nonsense.

      1. Windriven says:

        I’m in complete agreement up to the last sentence. A person educated in medicine would have to be a complete moron to believe this stuff. I have many negative perceptions of Oz but I don’t believe him to be a moron.

  21. Jim says:

    I am agree with you Windriven ,There is no such thing as “weight loss miracle” as Dr. Oz proclaiming.

  22. Forskolin says:

    Thank you for that information, it triggered me to do more research about forskolin, so here are some glimpse of my research about forskolin.

    i found out that forskolin dates as back as Ayurvedic medical practice of India, it is an extract found on the roots of an herb that belongs to the mint family. This herbal medicine is instrumental for curing a number of medical conditions such as heart failure, asthma, cancer, glaucoma, and obesity.

    1. Windriven says:

      “This herbal medicine is instrumental for curing a number of medical conditions such as heart failure, asthma, cancer, glaucoma, and obesity.”

      This herbal medicine is instrumental in separating morons from their money, nothing more. Your “research” is bullsh!t, Ayurvedic medicine is bullsh!t, and anyone who believes one magic herb can cure ailments ranging from asthma to cancer is delusional.

    2. WilliamLawrenceUtridge says:

      i found out that forskolin dates as back as Ayurvedic medical practice of India, it is an extract found on the roots of an herb that belongs to the mint family

      How is that an endorsement? Ayurvedic medicine existed for milennia, right? What was the life expectancy in India before the advent of scientific medicine? In other words, despite having access to forskolin, why did people die younger and more frequently of diseases that are now trivial to prevent and treat?

      Sounds like your research is worthless, but then again – since you appear to be just an asshole shilling for your asshole supplement company out to make a quick buck – none of this is surprising.

      Also, if mint cured heart failure, asthma, cancer, glaucoma and obesity (how does one “cure” obesity by the way?) why did we need to develop real medicine at all? Why didn’t India explode out of the subcontinent, unhampered as it apparently is by these diseases?

      1. MadisonMD says:

        Eat mint chutney and live forever.

        1. Windriven says:

          “Eat mint chutney and live forever.”

          But keep it off my leg of lamb. Whoever came up with the idea of marrying lamb with mint jelly/chutney/anything should have their tongue cauterized.

          1. n brownlee says:

            Yes. Personally, I marry it with lots of garlic. And ouzo.

            1. Windriven says:

              Me too. Garlic, rosemary, salt and pepper. I haven’t used ouzo during the roasting process (other than roasting myself). Do you use it as a baste? Braising liquid? Chef lubricant?

              1. n brownlee says:

                The last mentioned optioned- and judiciously, because of falling down.

                My little home town (Fort Worth) has a sizeable and venerable Greek community- that’s where I learned to cook lamb, and to drink ouzo. I have no idea how ‘authentic’ the lamb method might be, but it’s very good.

  23. Nicola says:

    Would you like to put some forskinia in your mouth?

    Forskolin and Garcinia blends are featured as a big seller over on the forskolin guru website. (www.forskolin.guru)

    Someone should add some Raspberry Keytones so that slipping some forskinia in your mouth is even more delightful.

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