A Tenuous "Alli"ance

It appears that GlaxoSmithKline has recieved approval to market Alli overseas to our European cousins.

This means the product will now be proposed for final approval by the European Commission and marketing authorisation could be granted in the coming months. On licence grant, orlistat 60 mg would be the first licensed weight loss aid available without prescription throughout Europe.

You hear that? An FDA-approved weight-loss supplement! It's a miracle!

Alli was actually released to US markets last summer as one of the more unusual Rx-to-OTC product conversions that we've seen recently. Popular once prescription-only Zyrtec I expected, but Alli was really out of left field. I actually meant to blog about Alli when it was released, but somehow it got away from me. Now I can do so to commemorate its release across the pond.

What is Alli? Alli contains the same active ingredient as a prescription drug that was developed by the Swiss company Roche Pharmaceuticals--the generic name for it is orlistat. It is the first over-the-counter drug approved as a weight loss aid by the FDA, mostly because there's good clinical data that it's actually effective when used properly.

OTC "diet pills" generally contain high doses of stimulants/caffeine, claim to suppress appetite, or somehow purport to "melt fat" or "block calories." Some stimulant weight-loss supplements contain as much caffeine per capsule as three cups of coffee and have "serving sizes" of two or three caps at a time! Clever wording is usually employed to conceal the simplistic nature of these products--Zantrex-3 refers to its caffeine content as "a proprietary xanthine-based stimulant." Caffeine is part of a chemical family called methylxanthines. Other times numerous herbal ingredients or Latin names for botanicals obscure the true content of the supplements except to the most attentive consumers.

Alli, true to its claims, is different. How does it work?

First, a bit of basic biochemistry. There are three major "macronutrients" required for human nutrition--carbohydrates (sugars), lipids (fats), and proteins. All of these are absorbed through the intestine whenever you eat. Macronutrients are then delivered to the liver or various cells of the body that can use them. Carbohydrates are easy; the body breaks them down into smaller units and uses them to produce ATP, a small molecule that is the primary source of energy for the body at the cellular level.

Proteins and fats cannot be used directly by most cells. Instead, the liver processes them into more readily useful forms. Some proteins can be converted into glucose, the most basic (and preferred) form of fuel for body systems, especially neurons. Fat metabolism is more complicated and involves many steps that ultimately culminate in the release of free fatty acids; these are also usable as fuel by many body systems.

If you eat too much of anything, be it proteins, carbohydrates, or fats, the body is remarkably efficient at storing the excess energy produced. The most energy-dense form of stored energy is fat; fats produce the most energy (in calories) per gram. This fat winds up getting stored throughout the body as a reserve for times when food sources are scarce. Each pound of fat on your body represents a total stored reserve of 3,500 calories. Yum!

I've heard it mistakenly stated that you "can't get fat" eating a high-protein diet because "carbs make you fat" or, more obviously, "fat makes you fat," but this is completely false. Your body can (and will) make fat out of anything the liver can get its...um...lobes on.

What does this have to do with Alli?

Alli is not actually absorbed into the bloodstream. Instead, it floats around in the intestines and binds to fat molecules, preventing those from being absorbed. If your body doesn't absorb the fat molecules, it can't process them--in a sense, it's like you never ate them in the first place. Alli binds an average of 25% of consumed dietary fats, potentially reducing caloric intake from a fatty meal significantly.

Problem: Alli is not magic. It cannot break the laws of physics and destroy matter (and I suspect converting fats to energy in your intestine would have odd effects, were it possible). If you don't absorb the fats, they still have to go somewhere. Since they're already 3/4 of the way through your digestive tract, and getting the whole system to flow in reverse is both very unpleasant and very difficult, I'll let you think about it on your own for a second.

A funny aside: The makers of Alli recommend that you not wear light-colored pants while taking it.

I personally like to think of Alli as "negative reinforcement." Operant conditioning is basic psychology. Continuously eat fatty meals on Alli and you're going to suffer chronically oily stools. You're either going to learn to control your dietary fat intake or you're going to throw away your Alli.

This isn't to say that Alli is bad. As part of a comprehensive diet and exercise plan, it will help you lose more weight, even if it's only a few extra pounds. But the reason Alli can get FDA approval, aside from the fact that it's been subjected to more rigorous clinical trials, is that Alli doesn't claim to be magic. "Eat all you want and still lose weight!" "Melt fat away while you sleep!" Due to loose regulations, dietary supplement manufacturers make these kinds of claims all the time. But the makers of Alli had to be realistic about the potential benefits of their drug to get it approved. This isn't a bad thing. It's what we should expect from all drug and supplement manufacturers--indeed, it's what should be legally required.

Anyway. Now Europeans can experience the thrill of Alli without a doctor's prescription!

...just remember to wear dark pants.

Student Finds Classical Reporting on "Holistic" Medicine Still Lacking Critical Rigor

The rise of "alternative medicine," if you can claim that it has risen at all, has mostly been due to word of mouth and unwarranted exposure by an uncritical press. Seeing as how CAM itself never actually changes, it should be no surprise to anyone that neither does reporting on it. We hear the same fallacies, the same appeals to authority and tradition, and the same overweighting of anecdotal evidence over and over again.

So I wasn't even a little shocked at this typical article on the common cold.

ABCNews.com asked four holistically minded doctors what they do when they feel under the weather. Their prevention and treatment advice might help you dodge or short-circuit the next bug that comes your way.

I'm not even entirely sure where to begin. "Holistically-minded doctors?" What does that even mean? Proponents are going to spout some gibberish about doctors that "treat the whole person, not just their symptoms," but let's see what these doctors recommend to "treat the whole person."

Let's start with Dr. David Rakel, MD.

There's no firm evidence that any medication or herb will prevent the common cold, said Rakel.

Hey, cool, he's actually concerned with whether or not there's evidence for the stuff he suggests!

At the first sign of symptoms, the goal is to attack the virus early because it replicates the most within the first 48 hours, pointed out Rakel. He might drink more green tea, which appears to have antiviral and antibacterial properties. And he would also drink three big glasses of orange juice to get more vitamin C...

...besides consuming more liquids, Rakel might take 20 to 30 milligrams of zinc acetate lozenges twice a day to improve his immunity. He takes zinc only for the first two or three days of a cold, when he feels it's most effective. He might add andrographis, an herb that's sometimes called "Indian echinacea." He would take 400 milligrams of this immune-stimulating herb three times a day.

That's why when it comes to his own health he takes a shotgun approach and tries everything that has ever been suggested for treating the common cold. Vitamin C, zinc, green tea (antioxidants), and "Indian echinacea," which must be better than "Western echinacea."

At least Dr. Rakel gets an annual flu shot, but he bemoans the presence of thimerosal in flu shots. I guess the fact that thimerosal-free flu shots is not important to him, or maybe he just thinks the CDC has it all wrong.

Strike one, MD's out. Who's next? Lynne Shinto, ND. You can probably guess where this is going.

She says she thinks that too much sugar can weaken immunity...when she gets a cold, her philosophy is to let it run its course. She'll turn to the usual suspects: bed rest, more fluids and chicken soup -- or because she's Japanese-American -- miso soup with shiitake mushrooms, fungi known for their immune-strengthening compounds.

Go Lynne! You strengthen that immune system! Is that the humoral or cellularly-mediated immune system? What do you mean you don't know? You're just sure it works? Well, as long as you're treating the real cause of disease instead of just addressing symptoms, like a good holistic doctor.

These approaches may make the symptoms feel better, she admits, but they likely won't make a cold go away faster.

Oops. I guess not. So you fail at both science and pseudoscience.

If Shinto's sinuses are congested, she turns to an "old naturopathic therapy" thought to stimulate the immune system. Called hydrotherapy, she might stick her bare feet in hot water for three minutes then in ice-cold water for 30 seconds, and she repeats this hot-cold sequence three times.

This is a fantastically plausible treatment for nasal congestion. Maybe the alternating peripheral vasoconstriction and vasodilation...no, this really is so implausible as to not warrant investigation.

What about another MD's perspective? Surely a second opinion is worthwhile. Dr. Kevin Barrows?

He's a big believer in meditation and has found this mind-body approach helps increase his awareness of subtle body shifts, a tip-off that he may be getting sick. For him, a sore throat is his early warning sign of a cold, his cue to start taking echinacea.

That's great, doc. I'm glad that you can recognize one of the most common symptoms of the common cold as...indicative of the common cold. But he didn't learn that in medical school. No, he figured it out through meditation! Once he determines that his chakras--er, his throat hurts--he knows it's time to start taking echinacea, the herb that a Cochrane review states "shows inconsistent benefit."

Sixteen trials including a total of 22 comparisons of Echinacea preparations and a control group (19 placebo, 2 no treatment, 1 another herbal preparation) met the inclusion criteria. All trials except one were double-blinded. The majority had reasonable to good methodological quality. Three comparisons investigated prevention; 19 comparisons investigated treatment of colds. A variety of different Echinacea preparations were used...

...there is some evidence that preparations based on the aerial parts of E. purpurea might be effective for the early treatment of colds in adults but the results are not fully consistent.

I know that whenever I have a problem, I'm willing to rush out and spend money on things that "might work."

Outside of a mental health context, I know that if I ever had a doctor who suggested "meditation" as a serious method for identifying or treating any illness I'd pull up my pants and walk out the door. Three doctors I'd never want to visit--assuming that their beliefs are being accurately portrayed in this article. Well, what about Dr. David Leopold, our fourth contestant?

At the first sign of a cold, Leopold treats his symptoms extremely aggressively. His goal is to support his immune system so that it helps clear the virus and slows down the spread of symptoms.

He takes zinc gluconate lozenges, drinks plenty of herbal tea and also uses a liquid tincture of echinacea. Despite research that questioned the herbs' benefits, "I'm convinced that most of the well-done studies of echinacea suggest it seems to be effective for reducing the severity and duration of a cold."

Just what I need, a doctor who flunked both statistics and immunology. No thanks.

The thing is, I'm not entirely sure that the blame is entirely on the doctors being quoted here. Now, granted, I don't think that their words (or positions) are being fabricated; I'm sure that, when interviewed about their "holistic medicine" use, all of these doctors (and the naturopath) volunteered honest information.

But here's the problem. This "sound-bite medicine" doesn't actually leave room for--or invite--serious discussion of anything beyond "some doctor said you should try this." And, in the interest of "unbiased journalism," the reporter behind this story didn't bother to fact-check any of the claims made by the doctors. After all, they're just harmless claims; the article isn't about "what is good medicine" but rather opts to provide some opinions by licensed medical practitioners.

Unfortunately, this approach is seriously misguided. Most people think of physicians of all stripes as having a good, solid understanding of medicine, and this implicit trust that doctors know what they're talking about is crucial. If patients think doctors are idiots, why would they ever solicit one for an opinion? The drawback to this is that off-the-cuff "opinions" about vitamin C, echinacea, or other various treatments that don't stand up as effective under serious scrutiny reinforce the misconception that these treatments actually work. Just try telling a patient whose doctor takes vitamin C that vitamin C doesn't treat or prevent colds. "If it doesn't work, why does my doctor do it?" What surprised me about this article is that it didn't even contain the "token skeptic" interview, but then, the article is subtitled "what alternative medicine experts do when they get sick."

Physicians who succumb to non-evidence-based thinking do more than harm themselves. They drag down patients with them, even patients they'll never meet, because their endorsement of unproven remedies assures that these treatments will never die out despite the immense evidence against their efficacy. As long as there are doctors promoting these remedies, no amount of double-blinded, well-controlled, properly randomized research is going to convince the public that they aren't effective--because their doctors, expected to be the gatekeepers of knowledge, are ignoring it.

Like Decaf Coffee, but More Dishonesty

I got a kick out of this article about a "new" dietary supplement that supposedly contains the FDA-banned stimulant ephedra while still being legal through various loopholes:

Garza, a bodybuilder who nearly won the Mr. USA competition in 2004, said XP2G is manufactured for his store by a private lab.

He said his pills are made from the same plants used to make traditional ephedra products but lack the ephedrine alkaloid chemicals named in the bans.

Garza said because XP2G lacks those particular chemicals, it does not present the same risk of side effects as traditional ephedra products, and it is not in violation of the bans.

Hmm. So it contains "ephedra" but it doesn't contain ephedra. Do you follow?

Ephedra is actually the name for a genus of plants. Extracts from the Ephedra sinica plant, known in Chinese medicine as ma huang, contain the stimulants ephedrine and pseudoephedrine (yes, the same stuff that's in Sudafed). The popularity of ephedra stems from its so-called "thermogenic" properties--it increases heart rate and blood pressure and raises blood sugar by stimulating the sympathetic nervous system. Most people know the sympathetic nervous system as the system responsible for the "fight-or-flight" response. Essentially, ephedrine acts on the same cellular receptors that epinephrine does. Epinephrine, if you aren't aware, is the same thing as adrenaline; they're just different names for the same chemical.

So what Garza is claiming that his proprietary formula contains parts from ephedra--the plant--but not the alkaloid stimulants that make ephedra "worth" adding to diet pills in the first place.

Why would you do this? Well, because, as I've previously stated, most people don't read anything beyond the front of the bottle when they're buying drugs or supplements. By being able to put "new and improved! Totally contains ephedra!" on the packaging, Garza will sell more product, especially to consumers who liked the old ephedra products that are now subject to FDA ban. What those consumers probably won't realize is that they're being scammed even worse than they were before; the manufacturer is using some loophole to claim the formulation contains ephedra when it doesn't contain the chemicals that make ephedra desirable. It's a bit like selling "coffee" to caffine junkies on the basis that your product "contains real coffee extracts!" without letting on that your product is actually decaf.

More troubling is the fact that Garza may, as they say in France, be totally full of merde:

University of Maryland professor Dr. Fermin Barrueto said legal ephedra is only a marketing gimmick. He said the only way to remove banned chemicals from ephedra is through a complicated extraction process that manufacturers are unlikely to perform.

Which means one of two things: The manufacturer is lying about including ephedra (and not including it, but listing it on the label anyway), or the manufacturer is lying about lying about including ephedra (including it despite it containing the banned alkaloids).

As they said in Smash TV: Big money! Big prizes! I love it!

Caveat Emptor: Drugs and the Free Market

First reported (within my circle of sources and reading material) by PalMD of denialism blog, the FDA is cracking down on the sale of many unapproved "cancer cures" being sold online and elsewhere. This, in itself, is excellent.

It is also a fantastic example why trusting the free market to solve all problems is a completely bogus idea.

I always come back to healthcare whenever I want to talk about the free market. This is partly because healthcare is what I know; I am much more capable of talking about the prices of drugs (in particular) and medical services than I am talking about the prices of various other products because I'm surrounded by them. But, more importantly, the healthcare "market" is a spectacular example of an area where "natural market forces" are completely insufficient regulation.

The short answer for why this is is that the costs of healthcare services are not always clear up front, so there's no way to "comparison shop." You usually get treated and worry about how much it will cost later, especially in an emergency situation. The capitalist model of self-regulation requires consumers to be able to discern the cost of services in order for it to make any sense. How can you be an informed consumer if you can't evaluate the cost or the utility (worth) of goods?

Sure, this is true on some massive scale when we talk about hospital stays and surgeries, but the problem with those is that the only consumers who actually know what they cost are already bankrupt because of them (everyone else is insulated from the scary truth of the real costs thanks to insurance companies). But those are the big-ticket items of the healthcare world. And you might argue that in some cases that they're often essential to the point where price is no object, because most people would rather pay any amount of money than die. (They might regret this decision later when they're being suffocated by hospital bills, but few rational people are going to say "nah, let me die, saving my life will cost too much.")

So let's talk about small out-of-pocket expenses of non-urgent matters.

Buying drugs is, in many cases, like buying any other good. There exists genuine competition in the market, especially when we're talking about non-prescription items. Should I buy Alavert or Claritin? Benadryl or the "store brand?" Which pain reliever do I choose? The fact of the matter is that 99.9% of the time all of these goods are equal. It doesn't matter, from a medical perspective, whether you buy Claritin or Alavert. They're the same drug. The only reason consumers might prefer one over the other is because of advertising and brand recognition--this is a "Coke or Pepsi" scenario.

Most consumers know that Coke and Pepsi are equivalent products (more or less). Sure, they might have a preference for one over the other, and that preference might even stand up to blind taste-tests. But how many consumers really know that the "store brand" is as good as the brand name when it comes to drugs?

If marketing research is any indication, the answer is not many. In 2005, generic versions of OTC drugs made up only 23.4% of the market share. Conversely, generic prescription drugs made up over 75% of the market share. Hmm. Why might this be?

When filling a prescription, most pharmacies will automatically substitute the generic if one is available as long as the physician has indicated that such a substitution is acceptable. Some states (Massachusetts, for example) actually mandate substitution unless the physician indicates otherwise. It's easy to see why generic prescription drugs predominate the market. Many commonly prescribed drugs are more or less only available as generics; the brand names are no longer made or no longer carried by pharmacies (how many people really care about getting brand name Amoxil?). I think it is safe to say that one major reason generic drugs predominate in the prescription drug market is that patients are not actively involved in the brand versus generic decision. They are leaving the decision to someone who is more educated about the product they are buying. The doctor and the pharmacist both know (and will reassure the patient if necessary) that the generic is just as good as the brand for a fraction of the cost.

Letting your pharmacist substitute a generic to save you money is kind of like getting insider information on stocks or letting your broker decide where to invest your money. You're not stupid for consulting your broker. You're smart. You're using your broker's expertise to your advantage. He probably knows a lot more about the stock market than you do, and you will make more money if you let him help you.

There's also the fact that the price difference between brand and generic in the prescription drug market is pretty large. Consider lisinopril, a drug used to lower blood pressure, prevent recurrent strokes, and protect the kidneys of diabetics. Generic lisinopril costs about 50 cents a tablet. The branded product costs twice as much. Cholesterol-lowering simvastatin's (Zocor) generic is about $2 per dose. The brand is about $5. Does it really make sense to pay twice as much for something if you don't have to? Of course not. Consumers aren't stupid.

The short story is that about 75% of consumers, given what amounts to "expert advice," will pick the cheaper prescription drug product. So why do only 25% of consumers pick the cheaper generic when making an OTC drug purchase?

The same reasons why they would choose a branded drug if there weren't a pharmacist between them and their prescriptions.

Brand reputation. Perception of generics as inferior products--misconceptions about quality, purity, and efficacy. Prior "bad experiences" with a generic drug. Inability to pronounce the generic drug's name (yes, I'm serious). And people are suspicious about the origins of "store brand" drugs. I'm not sure where people think they come from--they're made in the same factories and held to the same manufacturing standards as the brands.

There's limited standardization in naming generic OTC drugs. Because drug chains can't rely on brand recognition the same way ("Claritin is for allergies, I saw it on TV") most generic OTCs have very...generic...names. "Non-drowsy allergy relief." "Non-aspirin pain reliever." "Stomach acid relief." I kid you not when I say that there are probably half a dozen products on a given pharmacy shelf that have some variation on the phrase "cold symptom relief" as their only name, leaving the consumer to decide which product to purchase.

If the consumer does not first consult an "expert" (the pharmacist), they is left using the same reasoning tools that affect their decision about brand-name drugs. Anecdotally, I would say that most consumers don't know the active ingredients in their preferred OTC cocktails. They know the color of the box. They know what the product is called. And, most important to the consumer, they know what worked last time they were sick. They want that again, whatever it was, even if it's the wrong drug for the symptoms they have this time.

(Walgreens is brilliant in this regard by shoving the "Wal-" prefix in front of all their generic names. I get a lot of people who ask me for Wal-itin. I don't work for Walgreens. Our Claritin generic is obviously called something else. Many of them don't even seem to realize that Wal-itin is Walgreen's name for their Claritin generic--they think Wal-itin is its own unique drug, brewed in some secret Walgreens facility.)

The price difference between brand and generic OTC drugs seems smaller, which is another major factor. A box of 50 Tylenol costs $6.50 at Walgreens. A box of the generic costs $4.50, $2 less. Normally, when someone offers you the same product at a lower price, you take it. The generic market should be totally destroying Tylenol sales, but McNeil Consumer Healthcare still sold $129 million worth of their flagship product, "extra-strength Tylenol tablets," in 2003. That doesn't include sales of the popular Tylenol PM, Tylenol Cold, or liquid Children's Tylenol. The sum for all these product lines from 2003 is about $242 million.

Think about that for a second. Consumers spent an average of $2 more per purchase to buy products with the Tylenol brand name so frequently that McNeil made $242 million dollars. And they did it for the reasons I've already mentioned above--or perhaps others. Marketing experts spend their whole careers trying to understand and capitalize on this stuff; my understanding of it is very basic.

This isn't like buying generic foods, where you might get something you don't like as much as the brand product. The generic drug industry is tightly-regulated by the FDA. You can't sell generic drugs that are inferior to the brand names, unless your definition of "inferior" is different from the FDA's. The drugs have to work just as well.

You could argue that consumers might be buying the brands over the generics because of factors other than how well they work as drugs. Sometimes brand name drug tablets have coatings or flavorings that make them taste better than their generic counterparts. Maybe the packaging is easier to open. Some people are legitimately allergic to certain dyes or additives that might be present in the generic that aren't in the brand (but this is extremely rare). But this probably wouldn't account for 75% of consumers choosing brands over generics.

No, the short answer to why consumers choose branded products when buying OTC drugs is that they don't actually have all the knowledge necessary to make an informed purchase.

Man, that was long-winded. Let's come back to the original point of the entry.

If consumers aren't making informed decisions about whether to buy brands or generics when making OTC purchases, who the hell thinks that consumers will be able to make informed decisions about how to treat their own cancer?

I'm not talking about violating patient autonomy here. Patients should never be forced to accept treatments against their will. Patients should talk with their physicians and discuss treatment options, then choose whatever they feel is most acceptable. But it is up to the doctor--who has many more years of education on the subject--to lay out the options. If the patient believes that there is an option that the physician has not mentioned, he or she should certainly bring it up.

But when physicians say "no, I don't think that's a good idea," the answer is not to go ahead and do it anyway. By all means, ask for a second opinion. You're entitled to one. But do not decide that somehow you are more qualified than a trained oncologist to choose your own cancer treatment. You are not. Ignoring the advice of experts to pursue the beat of a different drum to your own detriment isn't individuality. It's idiocy.

This is why holding up "freedom of choice" when talking about unproven (and often highly suspect) treatments for cancer or any other disease is a bullshit move intended to distract from the real issue at hand. Your doctor telling you that herbal tea will not cure your cancer is not oppression. Shutting down salesmen who commit fraud isn't oppression, either.

But in the worldview of the champions of truly deregulated free-market medicine, the consumer is granted a delicious variety false empowerment. You have the right to choose any treatment you want--even those that don't work. And if you choose treatments that don't work instead of those that do, well, caveat emptor. May the buyer beware. All sales are final and non-refundable. The only person you have to blame for getting scammed is yourself. And this is disgusting.

So go ahead. Fight for your freedom to get ripped off. The primary characteristic of the free-market is that it's self-correcting, right? Frauds will eventually be exposed and people will stop buying their products.

But how many people should be allowed to die before we say "enough is enough?"

Bizarro Health Savings Account

So the company I work for automatically lists items as "FSA eligible" if they are commonly covered by a flexible spending account for health purchases, sometimes known as an HSA. An HSA, if you're not familiar with the concept, is essentially a "bank" of money that you pay into (often with each paycheck). This money is tax-free, but you can only use it to pay for your medical expenses. Some plans allow your unspent dollars to roll-over at the end of the year, whereas others do not, leading to a last-minute spending frenzy. Most HSA plans allow you to spend the dollars you have on any health-related purchase, but there are always exceptions. As a general rule, it's safe to assume that standard over-the-counter products are probably covered, so those last-minute spending frenzies usually turn into people buying more aspirin and bandages than they are ever going to use just so that the money doesn't disappear unspent.

Anyway, at my store, both the register and the customer's receipt specifically note items that are eligible purchases; the customer can keep the receipt in the event that there is a dispute with the insurance company. This also allows the customer to just swipe their HSA card and have eligible items paid for while ineligible items remain unpaid. This saves the cashier from having to ring the items up separately if the customer wants to pay for some items that are eligible and some that are not.

There used to be an occasional problem where ineligible items would get rung up with an HSA debit card by mistake. Ultimately the consumer would get an audit from their insurance company bitching at them about trying to use their HSA to pay for bread and greeting cards. A recent update to the system actually prevents the register from accepting an HSA card for items that the register does not recognize as eligible; the cashier will get an error message saying that the customer needs to use a different form of payment.

So imagine my surprise today when Mucinex and Benadryl didn't ring up as FSA-eligible items. That was odd, and potentially noteworthy, but not that strange. It was conceivable that recent policies had changed to prohibit consumers from buying OTC items without a prescription.

Then Oscillococcinum rang up as FSA-eligible and I stared at the register screen in disbelief.

To make a long story short, "Oscillo" is a homeopathically-prepared dilution of the organs of a muscovy duck. It is a "200C" dilution, which is impressive even by homeopathic standards; the original formula has been successively diluted in a 1/100 ratio 200 times, meaning that the ultimate concentration of duck organ solution is 1 with 400 zeroes following it. This is four times the estimated number of molecules in the known universe, so the probability that the resulting solution contains any of the original "duck molecules" is basically nil unless somehow we have an entire universe filled with "Oscillo." Not that that's a problem for devoted believers in homeopathy. The preparation is touted by its manufacturer as a remedy for "the flu." You know, an illness that actually kills people from time to time.

So let's get this straight. According to the computer system at work, your insurance company is more likely to let you spend your tax-free savings on fake medicine than real medicine. In fact, the register would not let me charge a box of Benadryl to this guy's HSA because it considered the drug "an ineligible purchase."

See why I used the word "bizarro" in the post title?

Thank You, Orac, or: A Little Knowledge

This is what happens when people who know absolutely nothing about how to do science get their hands on a little bit of scientific data. An excerpt from Orac's post:

According to Mrs. Janak, less than one milligram of histidine is going to cause nausea, vomiting, and irritable bowel syndrome. Mrs. Janak needs to learn some units before she embarrasses herself by posting such burning stupid to the web. But she's just getting warmed up. She fixates on an observation that histidine is involved in the regulation of of trace minerals and concludes that getting all that histidine (remember, 0.78 mg worth, to be precise!) must somehow mess up the body's metabolism of heavy metals and cause heavy metal poisoning.

Orac, know that if I could, I would have your children. You've probably already found someone else to do that by now, assuming you want them, and I lack the essential plumbing, but the offer stands in some sort of metaphysical context.

The Future of Automotive Engineering

I couldn't resist sharing this comic I found:

Alternative mechanics ahoy?

Advertising in Bizarro World

The other day I picked up a new copy of everyone's favorite pharmacy publication, DrugTopics. I generally like DrugTopics, except when they're running Zicam ads or otherwise uncritically promoting unproven treatments because the manufacturers were willing to pay for a page. The Zicam ads are annoying because they attempt to lend legitimacy to a product that has done everything conceivable to skirt FDA regulation--like calling itself homeopathic when in fact it contains measurable amounts of zinc. At a "1X" and "2X" dilution, a "recommended daily dose" of oral Zicam "cold remedy" tablets contains 80 mg of zinc. That's nearly eight times the typical dietary intake, and your average multivitamin contains about 10 mg as well. In essence, Zicam is about as homeopathic as Prozac, except that Prozac required FDA approval and Zicam didn't. Way to go, guys.

But this post isn't about Zicam. No, another advertisement caught my eye this time around--it was an ad for Luvox CR.

Luvox CR is a new formulation of fluvoxamine, a drug used to treat depression and obsessive-compulsive disorder. It's in the same general family as all the other SSRIs--Prozac, Zoloft, Paxil, Lexapro, et cetera. Granted, there are subtle differences between all of these drugs, but it's fair to say that fluxovamine (more or less) doesn't do anything spectacular by comparison; it is, in fact, one of the oldest SSRIs on the market.

Luvox CR, like many other drugs, is a follow-on drug intended to extend the patent life of a drug entity. Of course, follow-on drugs typically tend to come out a few years before a patent expires as opposed to a decade later, so Luvox CR is kinda missing the boat, but they're trying. All of this is acceptable, if shady, given the tendency of drug reps to push follow-on drugs like they're the greatest thing since sliced bread (and, of course, are totally worth paying $5 a dose for as opposed to the 50 cents the generic version of the old drug might cost).

Here's why I'm making the bizarro world reference. The advertisement's tagline was, and I quote: "NEW LUVOX CR: AN ANTIDEPRESSANT WITH NO GENERIC EQUIVALENT!"

I blinked in curiosity after reading these words. Was this supposed to be a good thing? Are reps supposed to approach psychiatrists, talk them up about the wonders of their new product, and wow them at the end with a concluding "best of all, this drug is going to cost your patients a fortune?" Who is this supposed to impress? I'm pretty sure the only people who think that "no generic equivalent" is a merit are the drug companies.

Or maybe these sorts of advertisements aren't ads at all--they're a warning to uppity pharmacists not to try doing stuff like "saving patients money" by "requesting lower-cost alternatives" and "cutting into pharma's profits."

Did I publish that where it was publicly viewable? Oooops.

Seriously. This is my biggest gripe about the pharmaceutical companies and their method of advertising. I can deal with them buying filet mignon for doctors. I can tolerate the magazine ads and even the occasional television spot, even if I think direct-to-consumer advertising does a lot more harm than good (no statistics, just impressions). What I can't stand is pharma advertising flaws as merits. "Our product costs ten times as much as our competitor's!" is something you would never hear touted as a positive in any other industry.

But hey, I'd much rather pharma play fast and loose with patent laws to try to squeeze a few more good years out of drugs that the FDA has thoroughly reviewed than "big woo" (sometimes the same companies, for that matter) play the get-out-of-jail-free "it's alternative medicine" card. After all, big woo has to slap the quack Miranda warning on all their products.

It's a strange day and age when "costs more!" and "isn't proven to work!" are somehow twisted to be signs of a good product.

Really Delayed Ambulance Chasing

A few months ago I was in a minor vehicular accident when traffic ahead of me slowed to a complete stop on the highway. A pickup truck swerved across three lanes and cut in front of me; my eye still on the truck, I failed to notice that the cars ahead had stopped, so I wound up rear-ending a fellow motorist at about five miles per hour as I failed to come to a complete stop. The total damage done was a slight scratch on my front bumper and a tiny imprint the shape of my car in the poor guy's fender. Neither party was injured, so the police didn't even file a full report, just a non-investigated accident form for the both of us as a way of formally exchanging information.

Fast-forward to today, nearly four months later.

When I got home from class, I was told that someone had called about my insurance. Since the other driver had (about a month after the accident) apparently smelled money and tried to claim an injury, I figured that this was about the resolution to that case.

Nope. It was a chiropractor's office.

They were trying to convince me to schedule an appointment in the event that I was having "headaches, backaches, or other pain problems" as a result of the "accident." "It can take several weeks or months for problems to develop," noted the woman on the phone. "This is because at the time of the accident your body is full of all kinds of chemicals."

Right. It still is, as a matter of fact, and I bet I know more about them than she did. Moving on.

I was polite to her; there was no reason to be otherwise, and I declined her offer to make me an appointment for a chiropractic evaluation.

This is all just a story--an anecdote. But I've never seen any other "doctors" having to resort to cold-calling patients from accident records to solicit them as patients. Chiropractors have more in common with ambulance-chasing lawyers than with physicians; the only way most of them are going to get any business is with colorful advertising or by dubious phone-farming.

In retrospect, it might've been somewhat humorous to suggest that I had developed allergies or diabetes since the accident. I wonder what the representative on the phone would've told me if I asked what they could do about it at the office?

Abused Vocabulary #2: Chemicals? In My Child's Hair?

I cringed today during one of my lectures.

The instructor was discussing pediculosis, otherwise known as lice infestation. Lice are a recurring nightmare for public places where children gather in large numbers--daycares and schools come to mind. I have vivid memories of the school faculty lining us up in the hallways outside the nurse's office for occasional lice inspections.

She went on to mention--but not necessarily recommend--"natural" treatments for head lice. Apparently, olive oil, tea tree oil, and mayonnaise, and various other products are occasionally used as alternatives to "chemical pesticides."

What threw me was the professor's specific quote: "Well, some parents are going to use these because they don't want to put chemicals on their children."

Huh. I don't know. I would be terribly concerned about rubbing oleic acid, palmitic acid, stearic acid, and lineoleic acid into my child's scalp, wouldn't you? I mean, they're acids. Acids are corrosive, dangerous substances that can dissolve rocks and metals!

Except that they're fatty acids. There's a big difference between hydrofluoric acid and oleic acid, especially considering that the latter is the major component of olive oil.

The point is that anything can sound scary if you describe it the right way--consider the dihydrogen monoxide issue. (For those who don't immediately get the joke, dihydrogen monoxide is water). And it drives me nuts when people who are supposed to be scientists--or worse, educators--haphazardly use the word "chemicals," apparently validating the public's irrational fear of the very word, a word associated with harmful, "unnatural" things like benzene and turpentine instead of water, salt, and sugar.

Of course, the joke is on them. The active ingredient in RID is made from crysanthemums.

A Remarkable Lack of Self-awareness

A tragic story released today by the Chicago Tribune really makes you wonder about people's abilities to critically examine their own point of view--even when lives are on the line.

Police are investigating an 11-year-old girl's death from an undiagnosed, treatable form of diabetes after her parents chose to pray for her rather than take her to a doctor...

...the girl's mother, Leilani Neumann, said that she and her family believe in the Bible and that healing comes from God, but that they do not belong to an organized religion or faith, are not fanatics and have nothing against doctors. [emphasis mine]

Are you sure about that?

According to the article, the girl had not been to a doctor since she was three (at least she got routine immunizations). Relatives, including an aunt, called the authorities to report that the little girl's life was in danger because her parents were refusing to take her to a hospital and were instead trying to heal her with prayer.

The interesting thing about the case is that, like so many others in the same vein, the legal route of investigation is whether or not the parents were negligent in caring for their daughter. The authorities (and most sensible people) will most likely conclude that not taking a comatose girl to a hospital qualifies as negligence.

The parents, on the other hand, are going to argue that "they did everything they could." They wanted their little girl to live; this was not negligence in the sense that they were unconcerned whether she lived or died. The father attempted to perform CPR. If the family's statements are to be believed, they did not want to see her die.

If the parents truly believe that they did everything they could, one of two things is the case. They were incompetent or they were brainwashed.

I'll leave which one up to the reader to decide.

Abused Vocabulary #1: "Sensitive"

Sometimes, people gratuitously misuse or overuse words in the context of medicine or pharmacy that drive me up the wall. Inspired by The Bronze Blog's doggerel section, I bring you a new feature for S.A.: Abused vocabulary. In these entries, we will explore words that tend to get flung around in such a way as to make them completely meaningless.

Today's word is sensitive.

Dictionary definitions are a poor basis for an argument. The purpose of a dictionary is to catalogue how people use words, not prescribe their meanings. I may have lifted that phrasing from Overcoming Bias, and if so, hat tip to them. Anyway, I'm not going to quote the dictionary at you. What I am going to tell you is how the word is commonly used in a medical context.

One of the classic examples of an adverse drug reaction is a hypersensitivity reaction. There are two major classes of hypersensitivity; immune and non-immune. Immune hypersensitivity includes anaphylaxis. In essence, immune hypersensitivity involves some part of the immune system "overreacting" to the presence of a foreign drug product. Immune hypersensitivity is generally dramatic and hard to overlook, depending on its severity. If your throat swells to the point where you're suffocating when you take penicillin, it's pretty clear that you should avoid penicillin in the future. Immunogenic hypersensitivity is highly unambiguous.

Non-immune sensitivity, on the other hand, is highly ambiguous. Which leads to people claiming "diseases" like multiple chemical sensitivity to be the source of life's ills. MCS is a non-specific diagnosis of a non-existent illness that is more likely a manifestation of a psychiatric problem than a problem with an environmental cause. But I digress. Luckily, few people I encounter on a daily basis claim to have MCS (although one did). But a lot of them do claim "sensitivity" to this or that drug--or just to "drugs."

If you want to annoy your pharmacist, tell them that "there are very few drugs that you can take."

It's true that some patients are more susceptible to particular side-effects due to age, gender, or other preexisting diseases. Drug interactions are another potential culprit. In the field, we call a patient's unwillingness to take a drug due to side-effects (real or imagined) intolerance. Some drugs have noteworthy (and common) side-effects that almost everyone experiences. High doses of niacin, for example, dilate blood vessels and produce a characteristic facial flushing reaction. A huge percentage of patients taking niacin experience flushing--it is an expected reaction, totally predictable based on the drug's pharmacologic profile.

But when patients pull "side-effects" out of seemingly nowhere, claiming that their sleeping pills make them itchy or that they've been jittery and nervous ever since they were switched from brand to generic on their antidepressant--one has to wonder what's going on. Part of the problem is likely "nocebo" effect--the fact that even patients administered an inert tablet containing no drug will report side-effects and associate them with taking the "drug." Sometimes these complaints can be explained by the pharmacology of the drug. Other times they cannot. Frequently reported adverse effects are collected and sent to the FDA for evaluation, and some of them do turn out to be related to the drug in question. But many more are in no way related to the drug, which is why most pharmacists--and doctors, for that matter--don't jump three feet every time a patient complains of "drug side effects." The signal to noise ratio is poor.

When a patient says "I'm very sensitive to drugs," what he or she really means is "I have no tolerance for the same side-effects that everyone else deals with without complaining." The vast majority of the time, the problem is not that these patients are affected by drugs "worse" than other people are. The problem is that the patients are picky. They have unrealistic expectations. They are frequently overly preoccupied with minor aches, pains, or sneezes. These are the patients who call the pharmacy to complain every time they get diarrhea during antibiotic therapy--a common side-effect that is frequently mentioned during patient counseling. They think that they are "informed" patients--that they keep close tabs on their body. They want to know every side-effect that might be caused by their medications. They are the hypervigilant patients of the pharmacy world.

This is all very annoying for your pharmacist. But these people aren't necessarily at fault. What can we do?

For starters, we can make sure to convey realistic expectations to patients. We should do our best to make sure that they receive information about side-effects in context, or they end up like this guy who was convinced he was growing breasts as a side-effect of his antacid. Drugs are not magical cures. They alter the way the body works to achieve a desired outcome, and drugs do not "know" what to alter and what to avoid, which is why most side-effects happen.

Some of these patients are legitimately concerned. But many others frequently seem like they're just seeking attention, hypochondriac-style. Claiming to be "sensitive" to all kinds of things makes them feel special. It's a common altie claim, actually, that they're "sensitive" to "drugs and chemicals," so they avoid them altogether and drink hyperdiluted nux vomica, because natural is safe. Nevermind that most of the world's deadliest poisons are made by plants and animals--not labs.

"Sensitive" doesn't mean anything in a clinical context. Be specific. State the name of the drug you took and what happened when you took it. If your pharmacist or physician seems skeptical that the drug was to blame, it isn't because he or she is an insensitive prick. It's because people are very bad at accurately establishing cause-and-effect, and the drug may not have been responsible at all.

Quote of the Day

"Medicine used to be simple, ineffective, and relatively safe. Now medicine is complex, effective, and relatively dangerous."

From a lecture I attended today.

Blog Plug: Why We Can't Solve "The Mysteries"

Overcoming Bias is rapidly becoming one of my favorite blogs. In particular, I'd like to point to a relatively new post:

If you demand magic, magic won't help.

One of the occasional complaints against a rationalist/materialist worldview is that choosing to use empiricism as a standard for beliefs destroys some notion of "wonder" or "imagination." Eliezer Yudkowsky argues that the people who are most drawn to the "wonder" of magic would not, in fact, pursue magic if we lived in a fantasy world like those commonly depicted in literature. If magic were real--more importantly, if magic were commonplace--the people chastising scientists for being too preoccupied with testable reality would be just as disappointed with magic in that hypothetical world simply because of its common nature.

In fact, the people who would study magic and become its most skilled practitioners are likely the people who in this world are scientists; those driven to explore the world through observation and experiment and willing to spend years of their lives studying, especially if magic required any significant amount of work to master.

This, in some sense, can be generalized to medicine, but not in the sense of the end-user. The victims of this "love of fantasy" are the practitioners of faith-based medicine systems.

Let's face it. Medicine is hard. It takes years of rigorous study to become a professional at any level of the trade--nurse practitioner, pharmacist, physician, whatever. By comparison, chiropractic is easy. At the most basic level, a chiropractor only needs to know how to do one thing--crack spines. Being a homeopath is easy because there's no reason to believe that you can make mistakes; the worst thing that will happen is your patients aren't satisfied. No one can accidentally overdose their child on homeopathic teething tablets. Sure, people can die during alternative medicine treatments. Yes, there are risks. But the draw, both for practitioners and for patients, is that alternative medicine is easy. "All diseases can be traced to a nutritional deficiency."

The draw to fantasy, like the draw to alternative medicine, is the fact that it is a shortcut around lots of effort.

Filling the Void

I really, really hate seeing pseudoscience in pharmacist-targeted publications. Granted, I'm sure that physicians and other healthcare professionals feel the same way, as evidenced by Orac's feelings about woo in medical schools.

Let it be known that I just flat-out don't like Drug Store News. Drug Store News is a publication that is at least 50% about stuff I totally don't care about. They have some occasional clinical information, or a little bit here and there about how to improve your outpatient practice (say, how to talk to patients with diabetes). The rest of Drug Store News is about how to sell more lip balm and whether or not your drug store should stock chunky peanut butter. It's not a science-oriented publication; it's a business-oriented publication. Because I have absolutely no interest in the "business end" (har har) of pharmacy, all of this seems like a huge step backward to me. If pharmacists are going to spend all their time fighting to be recognized as clinicians instead of shopkeepers, their right hand clearly doesn't have any idea what the left is doing. The left is still very concerned with keeping profit margins high by knowing which Burt's Bees products that the public prefers.

However, I have reason for my annoyance with the publication above and beyond the fact that they don't focus on things that I care about. They, perhaps in the "printing all the news that's fit to print" vein, have no qualms publishing articles about such ridiculous and unproven woo as homeopathy. They regularly advertise homeopathic products, often with several ads per issue, and announce their introduction to the market with the same fanfare that they give to real medications. And I'm not just talking about "homeopathic" products like zinc lozenges, which are marketed as being homeopathic to avoid FDA regulations despite containing comparably large amounts of zinc.

What stunned me was that a recent column was promoting homeopathy as a substitute for drug therapy in children under two due to the recent OTC cough-and-cold withdrawals. Much to my annoyance, I can't find the column replicated on their web site, preventing me from simply linking it, but the highlights of the column were more or less what you might expect from proponents of homeopathy pushing the products as a replacement for the pulled children's medicines.

"Homeopathy is safe," they assert, first and foremost. A definite reassurance needed in a time of uncertainty. The shifting guidelines and need for further research (which will probably never be done) mean that parents are struggling with the idea that they can no longer simply give their children medicine when they're not feeling well. Homeopathy can fill the void for concerned parents--giving them a way to feel like they're helping, even if they aren't. It's certainly easier to give children homeopathic tablets, which are mostly lactose, than it is to try to use a rubber suction bulb to reduce nasal congestion in an infant. But parents will feel better either way. What a seductive marketing promise.

Treating a teething child with homeopathy isn't exactly child abuse, but it is a waste of money. And providing parents with false alternatives to medical treatment is likely to delay the time until children see a physician. You might think that reasonable parents will take the time to go see a doctor, but I've talked to my share of parents who just want to give their poor babies some medicine and avoid a doctor's visit--or worse, the parents who can't afford to take their children to see a doctor, so they really want you to recommend some liquid Tylenol and send them on their way. Which really means that the decision to include homeopathic products on the shelves preys on the poorest and most desperate of parents, those trying to find a way to comfort their children when all other ready alternatives have been removed from their grasp.

It's easy to see why a "drug store" would market homeopathic products. They make money. But is it ethical to market homeopathic "cures"--especially when the tendency is to place them right next to the "real" medicine, where consumers can't tell the difference? In a world where patients tend to choose products based on what's on the front of the box--instead of the back, where the real information is--current marketing practices are nothing but a cleverly designed deception. And that's why a pharmacy shouldn't be doing it.

Nothing I Can Say Will Top This

Orac's Friday Dose of Woo for the week has left me so jaw-droppingly stupefied that I can say absolutely nothing that will top his post.

Someone claims to have discovered the Philospher's Stone.

Not only that, but it will give you god-like powers. In fact, the only ability you don't get, as far as I can discern, is the ability to turn undead, which would arguably be useless unless somebody discovers a way to create zombies over the weekend. Maybe Big Pharma will unleash the T-virus and we'll all be totally screwed. Who knows.

That makes me wonder. Would "zombies" created by the T-virus actually be affected by turn undead? After all, they're technically living, just infected with a pathogen that alters their physiology, kind of like the zombies in 28 Days Later. This is going to be on my mind for the rest of the day.

Lose Weight--Naturally!

I'd like to plug an entertaining (and short, this time) entry by Pharmacy Girl.

In Arizona, naturopathic doctors can legally prescribe any legend drug or controlled substance (except IV medications, chemo drugs, and antipsychotics). The only prescriptions I see from naturopaths are for phentermine and metformin. Usually for the same patient.

This is why licensing naturopaths doesn't help. No, I don't have statistics that this is true, just one pharmacist's observations. I would like to get detailed statistics. And sure, you could argue that without licensing they would be doing something less savory than handing out amphetamines to any yuppie who wants to lose ten pounds before swimsuit season. But you give them legal power to prescribe medications and this is what they do.

This isn't even me saying that naturopaths are irresponsible or incompetent at treating illnesses. There is always the possibility that there are some naturopaths that actually know their anatomy, physiology, and pharmacognosy. What annoys me about this is that they are hypocrites. Aren't proponents of so-called natural medicine always advocating things like diet and exercise instead of drugs? You know, letting the body work itself out "naturally" as opposed to dumping in synthetic compounds that speed up the central nervous system? Wouldn't a real naturopath prefer you get on a treadmill to raise your heart rate than take speed? Hell, prescribe bitter orange or guarana extract. Those, at least, are derived from plants--even if they are just sources of caffeine or ephedra.

There are a lot of physicians with questionable motives and practices out there, too. They aren't blameless by any means. Look at the plastic surgeons who put up phony "board certified" credentials and operate on patients in their offices. But if becoming a naturopath is quantitatively easier in terms of time and money investment, and you can get your naturopathic license and rake in the cash by seeing patients for five minutes and throwing phentermine at them, isn't that a bad system? You simply can't expect me to believe that getting a degree from Bastyr takes the same amount of work and time as going to Johns Hopkins. Why should we give people a short-cut to opening crooked practices?

Why Bioavailability and Drug Delivery Make the "Simple" Complicated

A co-worker, colleague, and fellow student of mine approached me a long time ago saying she had a story that I absolutely had to hear. While home for the Christmas holidays, she wound up talking with some in-laws and family friends. One of these people turned out to be some sort of naturopathic practitioner. There was some disagreement about the value of statins, as could be expected (apparently someone suggested that everyone on statins should just take high-dose vitamin E instead). But the part that interested me was the fact that my colleague wound up having to explain the dopamine hypothesis of ADHD.

In short, the naturopath didn't understand why hyperactivity was commonly treated with stimulants. This is a reasonable question if you don't understand how amphetamines work. Most ADHD drugs are prescription amphetamines, essentially "Speed" used for a legitimate medical purpose. The same drugs are also sometimes used for narcolepsy. On the surface, it really does seem like a massive contradiction. Why give children who are having trouble focusing because they can't sit still stimulants?

The current hypothesis supposes that ADHD is at least in part caused by an insufficient quantity of the neurotransmitter dopamine in the brain and central nervous system. Dopamine is associated with pleasure and reward; in fact, all addictive drugs, directly or indirectly, have some effect on dopamine pathways in the brain. In ADHD, insufficient dopamine results in "lack of satisfaction," resulting in children and adults with ADHD being unable to focus on tasks. In essence, their brains are not programmed to acknowledge task completion as worthwhile, making it difficult to concentrate; the brain is too busy trying to find something else to do that is worthwhile. Many stimulants, amphetamines included, increase the concentration of dopamine in the brain. Appropriate stimulation of the brain and central nervous system increases "satisfaction" in patients with ADHD and allows them to focus more effectively.

Unfortunately, amphetamines have other side-effects. They speed up the heart, increase blood pressure, and, if the dose is too high, may cause insomnia, jitteriness, and anxiety. So the naturopath's next question was reasonable. "If dopamine is low, why can't you just give kids with ADHD dopamine?"

I don't expect laymen to know the answer to that question. I do expect anyone with an understanding of pharmacology to know. Naturopaths claim they understand the workings of the human body. Clearly, drug bioavailability is beyond their expertise.

There are a whole slew of reasons why you can't just take dopamine tablets. Some of them are specific to dopamine; others are general drug issues. Bioavailability sounds like a tough word, but its meaning is actually fairly simple. Essentially, bioavailability is a measure of how much of a drug the body can use after the drug is given. In order for a drug to have an effect, it has to reach its site of action. An anaesthetic has to diffuse into nerves before it can produce a numbing effect. Drugs designed to lower blood pressure have to be able to access the heart, arteries, and veins.

When you swallow a tablet, it goes to the stomach and is broken down to release its contents. In order to get into the bloodstream, the active drug must cross body membranes; otherwise, it will proceed through the intestines and be expelled unchanged. Luckily, your intestines have a large surface area and are good at absorbing things--otherwise, eating would be rather pointless, because you wouldn't be able to get any of the nutritional value from your food. However, there are limits to what is allowed to cross the intestinal membrane. Some drugs or chemicals can't cross it at all. In fact, some drugs are designed not to cross the membrane; they stay in the intestine and do their work right there. Alli is a good example. It doesn't need to be absorbed into the body. It stays in the intestine and binds fat molecules, preventing them from being absorbed.

Once a drug is across the intestine and in the bloodstream, the first stop is the liver. The liver is responsible for removing poisons from the body; it would be irresponsible for your body to deliver absorbed substances directly to organs like the heart and brain without filtering the contents first!

The liver is responsible for breaking down many drugs introduced to the body, usually by adding or removing a chemical group to inactivate the drug or make it water-soluble so that it can be excreted more readily. The liver does this to substances your body makes naturally, too; when red blood cells die (they only live about 120 days), the liver modifies the remnants, recycles them, and converts the waste products to a form your body can easily get rid of.

There's an enzyme called COMT (or catechol-O-methyl transferase) that's responsible for breaking down neurotransmitters like epinephrine (also called adrenaline, depending on which side of the pond you're on), norepinephrine, and dopamine. If we gave dopamine by mouth, COMT in the liver would rapidly inactivate most of the dose, assuming it were absorbed across the intestinal membrane.

So give a higher dose, you say. Or give it by some other route. You can bypass the liver in a lot of different ways; inhalation, injection, tablets absorbed through the cheek or under the tongue, skin patches or creams...

Let's go for broke and say we inject ADHD patients with dopamine shots like we give insulin to diabetics. What's going to happen?

Increased heart rate, first of all. Dopamine acts directly on the heart. It has different functions in different parts of the body, though dopamine isn't the primary regulator of heart rate (that would be due to the combined efforts of epinephrine and acetylcholine, which is also the neurotransmitter that is responsible for muscle contractions). It will increase blood pressure, too. Same side-effects as amphetamines, more or less. In fact, dopamine is sometimes used in emergency situations to raise patient BP and heart rate (though a synthetic alternative, dobutamine, is actually better for the task). But isn't it a more natural way to deal with dopamine insufficiency in the brain?

Nope. Here's why.

The blood-brain barrier is essentially the brain's defensive perimeter. It is composed of tightly-jammed cells that are designed to keep out miscellaneous poisons and waste products to prevent damage to the central nervous system. In order for a drug to affect the brain, it has to cross the BBB. Lots of drugs do. But dopamine doesn't. The brain would like to keep the dopamine it has...in the brain. The BBB prevents dopamine from escaping or entering.

Let's summarize. Extensive metabolism will break down an oral dose of dopamine very quickly. And even if we bypass the liver, the dopamine will never enter the brain. We'd have to inject the dopamine directly into the brain with a long needle. Try to get your kid to hold still while you do that. Even if we could get dopamine directly into the brain, neurons are good at recycling or re-absorbing stray neurotransmitters. The best case scenario is that we'd get a very brief improvement. The worst case scenario is that we'd go overboard on the dopamine level and the kid would have hallucinations.

Dopamine, in short, is a crappy drug. The solution is to give other substances (amphetamines) that indirectly increase dopamine levels to push the brain in the right direction. And you know what? It works. Sometimes the chemical your body would use to naturally regulate a function isn't something we can easily replace or modify directly.

So that's why we give hyperactive kids uppers to chill them out. It seems counterintuitive at first, but there is a good explanation. And the theory behind the dopamine hypothesis holds up in clinical trials; kids (and adults) treated with amphetamine do get better.

Isn't pharmacology fascinating?

Oops, I Patented Your Natural Product

What are good ways to lower your cholesterol? You could eat less cholesterol. That helps, but the human liver is great at making cholesterol. In fact, it tends to do so pretty much constantly--but entertainingly enough, the liver works the hardest at producing LDL cholesterol (the "bad" cholesterol) while you're sleeping. No, you shouldn't give up sleep. But what's worth recognizing is that diet isn't the only source of cholesterol, and in fact, the liver probably contributes more bad cholesterol than diet. In fact, removing part of the liver reduced circulating LDL concentrations in animal studies. You could also exercise, drink less alcohol, and give up smoking. All of these things work. But what if they aren't enough?

Statins are a popular target for proponents of "alternative medicine." You don't need statins, they say, you can just take vitamins and eat healthy. Sometimes they promote other unproven supplements or "treatments." Statins are dangerous. Statins are worthless. The lipid hypothesis is false; scientists are lying to you and cholesterol has nothing to do with cardiovascular disease. Here, drink this Kool-aid.

Pigs fed high-cholesterol diets are more likely to develop cardiovascular disease (CVD). And Watanabe rabbits lack a specific gene that prevents them from manufacturing receptors for LDL cholesterol in the liver. Normally, the liver's LDL receptors sense circulating cholesterol levels as a regulatory mechanism; if there's a lot of cholesterol floating around, the liver will react by making less cholesterol. Since the rabbits' livers are unable to compensate for high levels of LDL, they develop arterial plaques with astounding frequency. If fed a high-cholesterol diet, the rate and probability of plaque formation increases. And if animal studies aren't good enough, check out the Framingham heart study, which involves an entire town in Massachusetts that's been followed for three generations to learn more about CVD risk factors. Scientists didn't just pull the lipid hypothesis of atherosclerosis out of thin air. There's a lot of very thorough research and credible data that's been taken into consideration.

All the attempts to "debunk" the lipid hypothesis and the value of statins are crackpottery. Are they miracle drugs or cure-alls? Of course not; no one says they are.

Anyway. "Natural" methods for treating illness are popular with a lot of patients. There's something wholesome-sounding about the word, like your mother would want you to take natural products. Nevermind that natural does not mean safe; botulinum toxin is one of the most dangerous substances in the world, and it's made by bacteria. All-natural! Maybe that's why people are willing to inject it into their faces to get rid of wrinkles.

Here's a secret. Statins are natural.

Have you heard of red yeast rice? It's an interesting product. Monascus purpureus, a fungus that grows on rice, produces a wide variety of chemical compounds, including a group called mevinic acids. Naturally fermented red rice yeast is about 0.4% mevinic acids by weight. Red yeast rice supplements are not always what they claim to be on the label, but there's presumably some statin-equivalent content in there.

How about mevastatin? Mevastatin was isolated from Penicillium citrinum mold. Man, mold is great stuff. We play with mold long enough and we have this interesting tendency to serendipitiously find antibiotics and anti-cancer compounds.

Like penicillin, statins were originally isolated as naturally-occuring substances. The major mevinic acid compound in red yeast rice was named lovastatin. And guess what? It got patented. It's called Mevacor. Huh. I thought the natural medicine folks were always saying that the reason Big Pharma isn't willing to seriously investigate "natural remedies" is because they can't be patented?

That claim, of course, is a load of Penicillium fungus. Sure, you can't patent vitamin C, but you can patent unique compounds that you discover, no matter where they come from. Statins are some of the top money-makers for Pharma today (for better or for worse), and they got their start in yeast and mold colonies. Pharma would have to be incredibly to stupid to ignore nature as a potential source for useful drug compounds. It's true that most of the statins prescribed are synthetic compounds like simvastatin (Zocor). But simvastatin was made by modifying lovastatin to increase its effectiveness. Inspired by nature, proven by science. Saying Zocor is unnatural is like saying cutting trees into two-by-fours to build houses instead of just using felled logs is unnatural. By altering a naturally-occuring substance, we can make it a better drug than it would be otherwise.

If something proves to be useful, medicine will use it, whether it's "natural" or not--a false dichotomy to begin with. And if it isn't, medicine will discard it. Scientific analysis is the only way to tell the difference. And anyone who tries to tell you differently needs to go read about penicillin.

Rx Essentials: Are They Really?

You may have seen a product line on the shelves recently called RxEssentials. The marketing for these new vitamin supplements is actually pretty slick; Nature Made is a big company, and they do produce some quality products. A lot of their supplements are USP Verified, which means that the United States Pharmacopoeia has verified that what's on the label is what's in the bottle. Always a good thing. I have to commend them for going the extra mile to meet those standards.

RxEssentials, on the other hand, is a clever way to get you to pay more for your vitamins than you would otherwise.

The basic claim behind RxEssentials is that each formulation supplies key nutrients for people taking specific medications. Sometimes this is the case because the drug blocks or reduces nutrient absorption; in other cases, the manufacturers seem to be taking a page out of Pauling's orthomolecular medicine, which posits that nutritional deficiencies (or, for extra woo flavoring, "imbalances") are the root cause of basically every disease ever. There's a little bit of truth to some of this reasoning. Some drugs do reduce absorption of specific vitamins or minerals. Isoniazid, which is used to treat tuberculosis, can reduce vitamin B6 levels to the point where patients may actually suffer neurological problems if they fail to supplement. And methotrexate, an immune system modifying drug, is usually given with folic acid to prevent deficiency--methotrexate actually works by inhibiting the conversion of folic acid to its active form, tetrahydrofolate.

So let's look closely at RxEssentials. What do they offer that your basic multivitamin might not? They cost, on average, about $10 a bottle for 60 tablets, a two-month supply.

The arthritis formula is recommended for anyone taking ibuprofen, naproxen, or aspirin to relieve arthritis pain. It contains vitamin C, vitamin D, and folic acid. Fail. None of these drugs are going to significantly impair absorption of these nutrients, and most of that 500 mg of vitamin C is going to end up excreted in the urine. Vitamin C is abundant in the diet, and vitamin C tablets are dirt cheap ($6 for 250 tablets is pretty common). The most valuable component of the formula might be the vitamin D; most people with arthritis are older, and most older people get insufficient vitamin D. But vitamin D isn't expensive, either. An inexpensive multivitamin a day is going to cover everything.

The cholesterol formula is designed for patients on statin drugs--Lipitor, Zocor, or their close cousins. As expected, it contains CoQ10. Oh, and B-vitamins, but those are in everything, including bread. CoQ10, or coenzyme Q10, is commenly touted as a means of preventing muscle damage due to statin use. Unfortunately, the evidence doesn't hold up. Some studies show benefit; others don't. One study using 200 mg of CoQ10 daily showed no benefit but noted that patients might respond due to the placebo effect. Another showed some benefit with a 100 mg dose. The evidence is inconclusive. CoQ10 is also kind of expensive, as much as $20 for a bottle of 30 softgels containing 100 mg each. RxEssentials might actually be the better buy if you're dying to try CoQ10, but that's not saying much.

I have to admit that I find the depression formula particularly lacking. B-vitamins, folic acid (maybe for pregnant, depressed women?) and vitamin D. Yes, it's the old "depression is caused by vitamin deficiencies" gambit, except that they're telling you to stay on your Zoloft or Prozac and "supplement." More orthomolecular medicine at work. B-vitamins are important cofactors in energy production; the idea is that a lack of B-vitamins results in "decreased energy," which somehow translates into "depressed mood," "sleep disturbances," "loss of pleasure in daily activities," and, my personal favorite, "suicidal ideations." There is no evidence whatsoever that nutrient deficiency is a primary cause of depression; B-vitamin deficiencies can cause neurological problems, but B-vitamins are so prevalent in the diet that hardly anyone has a problem meeting their needs. You're going to get all this stuff in your (much cheaper) multivitamin. Vitamin D is great for bone health, but store brands are generally cheaper. The manufacturers are clearly assuming depressed people don't get enough sun.

I was really hoping that they'd get their heartburn formula right. An acidic environment is important for the absorption of iron, and chronic acid-suppression therapy coupled with low iron intake creates a situation where deficiency is a very real possibility. Except that there's no iron in the supplement! None! Instead, they're pushing B-vitamins again. B-vitamins are a very necessary component of nutrition. They aren't worth paying a lot of money for; they're in everything, including enriched flour, grains, vegetables, bananas, and even beer (although alcoholic beverages are not a good source of nutrients and chronic alcohol consumption, in excess, can cause other problems). Oh, and they throw in some calcium, but only 120 mg per dose. For reference, most people need 1200 to 1500 mg of calcium per day in divided doses (you can only absorb 500 mg "at a time"). It would've been easy to formulate an iron-replacement regimen for patients with acid reflux; I can't believe they blew this one.

Finally, we have the diabetes formula. In case you hadn't guessed by now, their supplement for diabetics includes--yeah, it really should've been obvious--B-vitamins! Oh, and folic acid. We wouldn't want anyone giving birth to babies with neural tube defects. Except that, of course, that's not why the manufacturers chose to include folic acid in the supplement; it's to "maintain energy." Argh! Yes, patients with diabetes have problems with "energy" metabolism; they can't properly utilize glucose to fuel cells because they produce insufficient insulin. But taking extra B-vitamins doesn't help the body utilize glucose any better, unlike oral diabetes medications or insulin injections.

To summarize, RxEssentials gets the big thumbs-down. The manufacturers claim that RxEssentials "provide specially selected nutrients." But as you can see, most of the products contain the same ingredients: B-vitamins and folic acid. At least they're being responsible and telling people that RxEssentials are not a replacement for their prescription drugs.

There are therapeutic precedents for taking specific nutrient supplements for various conditions or with particular medications. I already mentioned a few. But any responsible physician is going to prescribe those nutrients alongside the medication--especially if serious harm will result from not having them. Note that none of these products are for people on methotrexate! Arbitrarily deciding you need to supplement is a waste of time and money.

So what should you do if you think you have a nutritional deficiency? Talk to your doctor. Evaluate your diet with information from appropriate food guides. Nutritional deficiencies have a set of clear diagnostic criteria; less-specific concerns like "I feel tired sometimes" or "I get a lot of colds" are generally not indicative of a problem. Everyone feels tired sometimes. B-vitamins are not effective in reducing the effects of "stress" or a replacement for a good night's sleep. You probably don't need RxEssentials. And even if you did, a cheaper multivitamin would offer the same benefits.

Like most dietary supplements, RxEssentials relies on good marketing to make sales. It's too bad that marketing is all they have.