I’ve been blogging for over three years and Cold-fX, a popular Canadian ginseng supplement, was one of the first topics I tackled. The omnipresent Canadian advertising, huge pharmacy presence, and impressive-sounding efficacy claims made it an ideal case study. Perhaps not surprisingly, when I reviewed the data, the results didn’t hold up:  I concluded that in a best case scenario, you’d need to take Cold-fX for four cold seasons (about 16 months) to prevent a single cold. And while the manufacturer claimed that Cold-fX could actually stop colds once they’d started, I noted that there was no published evidence to back up that claim. I concluded there was was little rationale to justify supplementing with Cold-fX. The published clinical evidence wasn’t persuasive, and the supplement is not inexpensive. The smarter strategy? Washing your hands regularly is clinically proven, and it’s a lot less expensive.

Since my review, the popularity of Cold-fX has continued unabated. And the manufacturer has branched out into all kinds of supplements: Cell -fX (shark cartilage), Cold Sore fX (bee propolis), Remember-fX (also ginseng), Memory-fX (more ginseng), and Immunity-fX (ginseng again, but with with reishi mushroom). Skeptical yet? So was CBC’s Marketplace, which scrutinized Cold-FX in a episode broadcast earlier this month. (I can’t embed the video, so you’ll need to watch the video at the CBC’s site.) For those of you that haven’t seen Marketplace, it’s a consumer affairs/consumer advocacy show that takes on medical topics from time-to-time. Last year it did an excellent investigation of the elaborate placebo system known as homeopathy. The producers are clearly science and consumer advocates, making natural health products low-hanging fruit. So Cold-fX was a fitting topic. Their investigation focused on several issues:

The Marketing, which prominently features Canadian hockey personality Don Cherry. The extended interview with Cherry must be seen to be believed. There are also several segments where consumers are asked about their understanding of how Cold-fX works, and how it should be taken. Clearly, the marketing has been very effective.

The Approval Process, which highlights that Cold-fX is not approved by Health Canada for a large dose to be taken for “immediate relief”, yet it is marketed this way. It is only approved for prevention purposes, at a dose of one capsule twice daily, with the following wording:

Helps reduce the frequency, severity and duration of cold and flu symptoms by boosting the immune system.

(Yes, that’s Health Canada’s Natural Health Products Directorate, endorsing the “boost” your immune system gambit.)

Despite Health Canada’s restrictions, the manufacturer has labelled and promoted Cold-fX for “immediate use” for several years. The manufacturer tells Marketplace that this is a labelling issue – one that the company has been working out on “phasing out”, apparently for the past five years. Can you imagine a pharmaceutical company developing a drug, then ignoring its own marketing approval, and labeling and advertising it for an unapproved use, with an unapproved dose, for five years? It simply would not happen. But when it comes to Health Canada’s Natural Health Products Directorate, which licenses Cold-fX and other natural health products in Canada, there’s clearly a different standard in place – one in which the safety and efficacy requirements for approved products are questionable, and even more disappointingly, seemingly not even enforced.

It’s on this point that I wanted to see Marketplace do some more digging. It is Health Canada’s approval that we are told should give both health professionals and consumers confidence in natural health products. Yet should we have any? If the Natural Health Products Directorate (NHPD) is to serve any purpose it all, it should at a minimum ensure that approved products are manufactured to high quality standards and labelled consistently with what’s approved. Otherwise, what is the point of registering and approving natural health products? Here is what the NHPD promises:

Through the Natural Health Products Directorate, Health Canada assures that all Canadians have ready access to a wide range of natural health products that are safe, effective and of high quality. We assess all natural health products before letting them be sold in Canada. We also check that NHPs are properly manufactured (without contamination or incorrect ingredients). And we do post-market monitoring to make sure that NHP Regulations are being followed.

They also state:

It is Health Canada’s expectation that natural health products are sold in accordance with their Terms of Market Authorization. Any necessary changes to labels are expected within a reasonable period of time (e.g. the lesser of next label run or 12 months) if no risk to the health and safety of Canadians is identified. Product license holders should take the necessary steps to ensure compliance with these expectations.

Yet, that didn’t occur, and it’s still not occurring. With Cold-FX, it’s been 144 months since the product was first marketed. How much longer should we expect to wait to see enforcement of the Regulations?

Pharmacist Recommendations: Pharmacist after pharmacist is secretly filmed stating that Cold-FX should be taken at the onset of a cold, with some pharmacists claiming that  there is evidence to support this use. Here they’re giving the marketing line – not an evaluation of the actual evidence. The Canadian Pharmacists Association’s president, Jody Shkrobot is asked to explain these recommendations. He notes that pharmacists should be recommending the product according to Health Canada’s indications – which clearly states that Cold-Fx is approved for prevention purposes only. While I don’t excuse pharmacists for not knowing the clinical data for the products they recommend, I am somewhat sympathetic here. Cold-fX has been approved for sale, by Health Canada, for several years – yet Health Canada has never enforced proper labelling.  So pharmacists may be assuming that the “immediate relief” dosing regimen on the label has been reviewed and approved – which is a legitimate assumption, given Cold-fX has a natural product number (NPN) also on the label, signifying Health Canada’s regulatory approval. And despite this labelling issue being identified and noted for several years, Health Canada (to my knowledge) has never sent any communication to consumers or health professionals drawing their attention to this fact.

The Evidence: There’s a brief interview with Dr. Andreas Laupacis who notes that there are no published clinical trials that have studied Cold-fX to treat colds in those that notice cold symptoms. CBC then commissioned a meta-analysis by pharmacist Lane Ilersich to combine and analyze four published clinical trials – all for the prevention of infections. Three of these papers I reviewed back in 2009, and one more has been published since that time: Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial. It was published in the open access journal Influenza Research and Treatment, which from what I can see, does not appear to be abstracted in PubMed – not a promising sign. The clinical bottom line of this study is largely consistent with the other studies: No difference between Cold-Fx and placebo for the prevention of laboratory confirmed infections. So my advice to consumers remains the same: There little evidence that Cold-fX, even for its approved use, has any clinically meaningfully effects.  (I’ll try to come back to the meta-analysis at a later date and do a more detailed review.)

The Manufacturing: Cold-fX is labelled as a Canadian product. It is revealed that some parts of the manufacturing process takes place in China, somewhat contrary to the “Proudly Canadian” labelling. It ‘s also revealed that a liquid formulation of the product, never marketed, was found to be contaminated with Enterococcus faecium, which may have meant that fecal matter, or some source of this bacteria, was contaminating the supply. While the new liquid product, all 375,000 bottles, were pulled from marketing, Marketplace says the contaminated powder was still packaged and sold to consumers – in violation of Health Canada’s standards. There’s also mention of an audit of the Chinese plant, warning of manufacturing issues. Marketplace further notes that Health Canada was tipped off and did test seven bottles for contamination. They didn’t find E. faecium but they did find it contaminated with low levels of Escherichia hermannii, yet allowed the product to remain for sale.  The manufacturer disputes these findings. So does the manufacturing process for Cold-fX follow regulations, or not? It’s not clear. Disappointingly, there is no follow-up on Health Canada’s inaction here, either.

Conclusion

When it comes to scrutinizing the claims and evidence for marketed natural health products in Canada, Marketplace could devote every single episode to Canadian supplements and never run out of topics.  Skeptic North blogger Erik Davis illustrated this point nicely with his series of Health Canada Approves posts. Marketplace did a thorough job of showing that when it comes to Cold-fX, the clinical evidence is lacking, and the regulations in place to protect Canadians aren’t being followed. So why not go to the source of the problem: Health Canada’s Natural Health Products Directorate, which assures us that approved natural health products are “safe, effective, and of high quality”. Given the NHPD also approves indistinguishable sugar pills for therapeutic purposes, perhaps it’s time to start asking the regulator to start looking out for consumers, too.

For another take on the Marketplace episode, check out Kim Hébert’s review at Skeptic North.

Photo from flickr user Chealion used under a CC licence.

I was recently the guest of Desiree Schell on Skeptically Speaking, where we spent an hour discussing the prevention and treatment of the common cold. Here are some of the references and sources I cited or referred to during the discussion. So read along as you listen to the podcast.

What is a cold, why does it make us feel so crappy, and how does it differ from influenza (the flu)? See Medscape, CommonCold.org, and MedlinePlus for general info on the illness.

What is the only preventive strategy that’s both practical and effective: Wash your hands, and use alcohol gel when necessary (but it’s not as effective).

We don’t get colds from being cold – it’s a viral infection, but perhaps it might feel that way. This myth may have roots in the four humors. It’s not clear that stress has an effect – because when we’re exposed to a cold virus, even a slight exposure, can be sufficient for an infection.

“Boosting” you immunity is not possible if you’re healthy, it’s not a muscle you can pump up. However, those that exercise regularly report they have fewer and milder colds.

Treating a Cold

Despite all the products you may see on the shelf, there are only a handful of ingredients. Some antihistamines, and anti-inflammatory drugs, may be effective for pain, sneezing, runny nose, and cough. (Though the data on cough may not be as impressive as previously suspected.)

Decongestants may also provide some benefit, though the topical sprays should not be used for more than a few days.

Some like neti pots, and while they have not been shown to be that effective for colds, some people do prefer them to drug treatments.  Just make sure you use clean water.

Dextromethorphan, which may be on the label as “DM” is a cough suppressant. There is a lack of evidence showing it works for colds though – in adults and children. Codeine is the other cough suppressant you may see in cold medications, but appears to be ineffective as well.

Zinc lozenges have been studied and the effects are inconsistent.  Side effects (nausea) are common, which may have compromised blinding in the trials. Avoid zinc nasal sprays, such as Zicam, which have been associated with permanent loss of the ability to smell.

Honey for cough has been studied, and while the data have been spun as positive, it’s not impressive. Parents of the children who received honey reported greater improvement than those who received DM, but the difference was not statistically significant. You should never give honey to children under 1 year of age because of a small but real risk of botulism.

Vicks Vaporub has been around since the late 1800s. While it’s popular, there’s little research to suggest it relieves cold symptoms and congestion. Here’s a nicely detailed summary of the most recent trial (PDF). The side effect profile isn’t attractive.

Vicks is an example of a “counter irritant” and they still give them that name, even though the idea that you can cure internal problems by creating external irritations has been discarded. The idea was that you’d draw the blood and toxins out by irritating the skin. So while there may be someting to counter irritants when it comes to pain perception, there’s no evidence it has any effect when it comes to infections. However, these remedies live on in the alternative medicine universe. That’s why some still advocate mustard plasters, which can cause chemical burns on the skin and also have a lack of data to support their use.

Buckley’s Mixture contains ammonium carbonate (giving it an ammonia smell),  potassium bicarbonate, menthol and camphor. The ads say “it tastes awful and it works” but would be more accurate if it said “it tastes awful and anecdotal evidence says it works” – there are no published studies that have actually evaluated it. This is despite it being on the market for decades. I don’t recommend products that haven’t been studied, so I don’t recommend Buckley’s Mixture.

What about treating children? There’s little evidence that cough and cold products are effective in children and they are not recommended. Beware the products that are on the shelf, marketed as being safe for children – they may be homeopathy, which is to say, free of both active ingredients and evidence of effectiveness.

Preventing a Cold

The basic rules apply: limit contact with sick people, wash your hands, don’t touch your eyes. The virus can survive for a few hours on surfaces like doorknobs and telephones. Clean these objects regularly, and wash your hands after touching public ones, to reduce the spread of viruses.

Echinacea has been studied extensively, and it does not work for the prevention or treatment of the cold or flu. Products like Flu Shield are not backed by good evidence.

Ginseng is an active ingredient in a popular Canadian product, Cold-fx, and a number of other similar products. To the company’s credit, they’ve done some research. Unfortunately  the results seem unimpressive.

Vitamin C, a favourite of Linus Pauling, is strongly associated with preventing colds. But the data show otherwise – there is no convincing effect in the general population.There is some evidence to suggest those that are in extreme cold conditions, or are extremely physically active, may benefit, but it’s really not clear this is a real effect. And there concerns about supplements like vitamin C blocking some of the beneficial effects of exercise. On the plus side, there’s little evidence of actual harm with routine supplementation.

The data with Vitamin D are evolving. There’s an association between rickets, which is vitamin D deficiency,  and respiratory tract infections, and population-level study associated vitamin D levels with recent respiratory tract infections. However, trials that have randomized patients to vitamin D supplements have not yet shown a benefit with respect to colds. But stay tuned with this vitamin.

Vitamin E has an emerging harm profile that is concerning. The risks look real and there is no evidence of benefit for primary prevention. With specific exceptions, it does not look like an attractive supplement.

Oil of Oregano kills viruses in a test tube. But it hasn’t been studied for colds. I don’t trust anecdotes, I want good evidence – so I don’t recommend oil of oregano.

Garlic is often touted for preventing colds. It could have antiviral properties, but the evidence is still unimpressive. I’d like to see better evidence before recommending supplementing.

Ginger is another herb touted for colds. There’s no evidence to suggest it has any meaningful effects at all.

Elderberry is in a number of commercial products. There’s some preliminary data showing effects on symptoms and duration of illness when treating influenza-like illnesses. Yet we’ve seen this scenario with just about every herbal remedy: Promising preliminary data, followed by less impressive data when better trials are done. It would be nice to see further studies to evaluate its effectiveness.

Eucalyptus may be used for inhalation – it has not been shown to be effective, and is probably unsafe when the undiluted oil is ingested.

Astragalus is a Chinese herb promoted to prevent colds and flu. But there’s no  evidence that it’s effective for preventing or treating infections.

Oscillococcinum is a homeopathic dilution of duck liver and heart extract. It’s been reviewed extensively and not only is it absurd, even by homeopathic standards, it does not have any meaningful effects.

Probiotics: Here the evidence is limited but looks promising. A Cochrane analysis considered 10 previously published papers.  It concluded that people taking probiotics had 12% fewer colds. If we get 6 colds per year, that’s 1 fewer cold every two years. For that benefit, I don’t think there’s enough evidence to suggest we take probiotic supplements regularly yet. But this is another area where we need more research to confirm the initial effects observed.

Everyone loves chicken soup but there’s no good evidence to show it’s of benefit for treatment of colds. If you like chicken soup and find it comforting, go for it.

Should you “Feed a fever, and starve a cold”? The best advice is likely to eat if you’re hungry. There’s no evidence that either is harmful for the short-term.

What about humidify the air with steam? A 2011 Cochrane review notes the need for evidence of efficacy before steam can be recommended.

Alcohol? Population research suggests that light to moderate consumption of wine, particularly red wine, is associated with fewer colds. But there’s no persuasive evidence that consuming wine will reduce the number of colds you get. And consumption of alcohol in  high doses is associated with the risk of pneumonia. So there is no evidence to suggest that changing or increasing your consumption will affect the cold or its duration.

Should you avoid milk? While milk may look like mucus, milk is fat emulsified in water. The protein in milk is broken down like other proteins to amino acids. Those that drink milk have  no more mucus than non-drinkers. So if you want to drink mik, go for it.

Where can the average consumer look for good evidence-based information?

• I use the paid subscriptions to Up To Date and Natural Medicines Comprehensive Database. Both are excellent summaries of the literature, and good starting points.
• Tim Farley of What’s the Harm? fame created an excellent Google search engine that only searches skeptical sites. I use it all the time.
• I also use the Netting the Evidence custom search engine to search for systematic reviews at reputable sites.
• Finally the National Library of Medicine has reputable health information at MedlinePlus.

Photo from flickr user meeralee used under a CC licence.

Click to Embiggen

From the website Sci-ənce. Nicely done.

Anything missing?

I recently asked a colleague for search advice on a topic I was researching. When I told her it was for a blog post, she was intrigued. “How much do you get paid to blog?” she asked. When I told her that blogging didn’t provide any revenue, she was dumfounded. “Even writing for [big pharmacy trade magazine] will pay you a few hundred dollars per article! Why would you write something, and then just give it away?” I told her I wasn’t interested in writing 5000 words on someone else’s topic, waiting months to see it in print, and then wondering if anyone even read it. “Blogging provides immediate gratification,” I replied, “That model seems hopelessly outdated. If there’s a therapeutic controversy, or pharmacy practice issue, I want to discuss it now – not in six months, or a year.” And blogging provides a level of feedback that’s unheralded compared to traditional publication models. Sure, you may be called a Nazi, a Communist, or a Big Pharma Shill, but that comes with the territory when you criticize quackery and call out pseudoscience.

The audience for those interested in  science-based pharmacy practice is growing. In January 2009 when the blog launched, it had 40 visits for the month. In December 2011, over 20,000 visited, capping a record 240,000 for the year. Total visits since blog launch are closing in on 500,000. Amazing.

Traffic to the blog is not what I expected. Despite being Canadian-based, most visitors come from the United States. Canada, and then the United Kingdom are not far behind. Readers from 183 countries have visited the blog – even Vanuatu, American Samoa, and Malawi! (Only 12 countries to go!) Consequently, the writing focus has changed: Canada is still a big focus, but the blog now covers more international pharmacy topics, like the infamous “Coke and Fries” vitamin promotion from Blackmores that angered the Australian public. These types of events don’t get much international coverage – but they should, because pharmacists worldwide need to know what happens when pharmacies put profits ahead of patient care.

Here are some blog stats for the year:

Most popular posts in 2011

• What happens when vaccination rates fall – May 2011
• Mulberry for Weight Loss: Not just unproven, but implausible – May 2009
• Does Coenzyme Q10 Relieve Statin-Induced Muscle Pain? – February 2010
• Chili Burn: Can Green Tea and Chili Pepper Burn Fat? – April 2010
• Mulberry Zuccarin Side Effects - April 2010

Most popular posts since blog inception

• Mulberry for Weight Loss: Not just unproven, but implausible
• Does Coenzyme Q10 Relieve Statin-Induced Muscle Pain?
• Chili Burn: Can Green Tea and Chili Pepper Burn Fat?
• Cold-fX: More Hype than Hope for Colds and the Flu
• Oil of Oregano: All anecdotes, no science
• Slipping through the Cracks: Health Canada, Traumeel, and Homeopathy
• Your Urine is Not a Window to Your Body: pH Balancing – A Failed Hypothesis
• Apple Cider for weight loss. The seventies are back!
• Blue Berry Eyebright: Claims without Evidence
• The Alternative that Isn’t: Bioidentical Hormones

Top referring sites

• reddit.com (Thanks, redditors, and particulary, /r/skeptic)
• facebook.com
• twitter.com
• sciencebasedmedicine.org (Where I write biweekly)
• nccc.cool3c.com (from this, which translates with the intriguing title, “Addiction Science: a refreshing beverage in the world there is no God, only caffeine”)

Thank you for following, reading, sharing, and commenting at Science-Based Pharmacy. I’m particularly appreciative to those that pass on tips and suggested topics. I’ve been recently alerted about an unbelievable new pseudoscientific pharmacy promotion. Stay tuned, in 2012.

(Email recipients may need to click the links to view.)

via Yoni Freedhoff

With healthcare costs continuing to rise, generic drugs are looking more attractive than ever. The prospect of getting the same drug at a lower cost is tempting to anyone with a large drug bill — patient or insurer alike. The savings are massive: Lipitor lost patent protection in the USA last month — it was a $10 billion drug worldwide, and the generic versions are priced at a fraction of the original cost. In 2012, Plavix and Seroquel, two other blockbusters, will lose patent protection too — that’s another $10 billion in drug costs that will shrink. This “patent cliff” will shrivel about $255 billion in worldwide patented drug sales over the next five years. If you’re taking a prescription drug and not already on a generic, you probably will be soon. And depending on where you live, you may be automatically switched to a generic version of your prescription drug as soon as it’s available.

Pharmacists are responsible for most of the switches from brand to generic drugs. National, state, or provincial regulations may specify which drugs and brands may be automatically substituted — that is, without patient or prescriber consent. Consequently, pharmacists do spend time speaking with patients about generic drugs. Misconceptions are common, ranging from manufacturing standards (“they’re weaker!”) to efficacy (“the drugs don’t work!”). Pharmacists, with exposure to pharmacokinetics and drug design in pharmacy school, generally understand the science of how generics are approved. Patients, consumers, and other health professionals, however, may not understand why pharmacists are so confident substituting between brands.  So today’s post is directed at anyone interested in how generic drugs are evaluated and approved for sale. Specifically, I want to review the concept of bioequivalence, the confirmation of which assures us of the interchangeability of different drugs — that is, one can be substituted for another.

What is a generic drug?

What is referred to as a “generic” drug may vary by country, and be influenced by both medical practice and by regulatory requirements. The most common definition is that used by the World Health Organization:

A generic drug is a pharmaceutical product, usually intended to be interchangeable with an innovator product, that is manufactured without a licence from the innovator company and marketed after the expiry date of the patent or other exclusive rights.

Generic products may also be called “multisource” products. And you’ll often see a drug’s chemical name referred to as the “generic name” or the “non-proprietary” name, which I’ve described can lead to confusion among consumers who may only know their prescription by the brand name alone.

The Active Pharmaceutical Ingredient

To understand the scientific basis of generic drug evaluations, it’s necessary to understand some key concepts. The first one is the active pharmaceutical ingredient or API. In Lipitor, for example, the API is atorvastatin, or to use its full chemical name, (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate. The API is the chemical that has the desired biological effect. There may be a dozen ingredients in a tablet, for example, but the API is the ingredient we’re interested in. It’s the API that will allow us to generalize data and studies with the drug, linking the original bench science and preclinical research, to the tablet dispensed by the pharmacy — it’s the same chemical. The fact that drugs have an API allows generic drugs to be marketed, because when we compare generics, the API is the same. In contrast, consider the scenario of an herbal remedy. A single tablet of 100mg of a raw herb might contain hundreds of different chemicals. If there is no known API or standardized active ingredient, we cannot compare between brands, or assume that clinical trials with one brand are relevant to any other product, because we have no idea which ingredient is actually having an effect, and if any other version has that same ingredient (or combination of ingredients.)

Bioavailability

Most dosage forms (e.g., tablets and capsules) are designed to deliver the API to the site of action. Unless it’s a drug that acts directly on the lining of the gastrointestinal tract, we rely on the circulatory system to carry the drug to the site of action in the body. Bioavailability refers to the amount of drug that, once ingested, reaches the bloodstream. Bioavailability is evaluated based on two measures — the rate of absorption, and the extent of absorption:

Blood plasma level curve for a typical single dose of an oral drug

(source)

Look at this graph carefully. Let’s assume a dose of a drug is taken by mouth at time=0. A dosage form, such as a tablet, needs to disintegrate, and then the API needs to dissolve. It then must be absorbed through the gastrointestinal tract, where it will move into in the blood. Sequential blood samples are taken (say, every 30 minutes) and measured for the concentration of the drug. The point measurements are then connected, resulting in the smooth line you see. At first, the drug is absorbed rapidly, peaking at concentration Cmax at time tmax. The drug then starts to be eliminated from the blood — it could be metabolized, perhaps by the liver, and/or be filtered out of the circulation, by the kidneys. We’re then able to calculate the rate of absorption, described by Cmax/tmax, and the total extent of absorption, which is the area under the curve (AUC), calculated using integral calculus.

Studying the physiological actions of the API, and relating it to the concentration time profile allows us to understand if there is a maximum tolerated concentration (MTC) and if there’s a certain blood concentration where the drug’s action seems to start and wear off, termed the minimum effective concentration (MEC). These values are estimates, based on the understanding that there is a relationship between the drug’s concentration in the bloodstream, and the amount of that same drug at the site of action in the body. These measures will guide how the drug is eventually manufactured: We want each dose to predictably and reliably follow the same curve. That means standard production methods, and the use of fillers, diluents and other excipients, all of which serve to ensure that there is little to no variation tablet-to-tablet or dose-to-dose. This is done with the intention of also minimizing interpatient variability, which is the variation seen between different patients given the same dosage form.

There may be other ways that the formulation can be varied. When the MEC is very close to the MTC, greater precision in per-tablet accuracy may be necessary. Further, we can vary shape of the curve, by doing things like enteric-coating the tablet, or making a sustained-release version that releases the API more slowly. The final absorption curve of any pharmaceutical preparation will be a product of both the physical characteristics of the drug (i.e., the intrinsic chemical properties) and the dosage form (i.e., the pharmaceutical properties).

Generic manufacturers that want to duplicate a drug coming off patent then have a few challenges. First, manufacture the complicate chemical structure that is the API (or find someone else who can make it for you). Second, package it in a dosage form that resembles the patented drug. Third, show that the new generic shares the same absorption curve as the branded version. That is, they must show that two product are bioequivalent.

Bioequivalence

We now want to compare a branded drug, one that’s been on the market for years, with a new generic. There is a single fundamental assumption that underlies the comparison:

Two products are considered equivalent when the rate and extent of absorption of the generic drug does not show a significant different from the rate and extent of absorption of the brand drug, when administered at the same dose under similar experimental conditions.

So let’s unpack this. We don’t need to know if the tablets look alike, or have different fillers. We also don’t need to do clinical trials with the generic drug. If we can demonstrate that the API is absorbed at the same rate and extent as the brand drug, then we can declare two products to be bioequivalent. That is, taking one or the other results in the same “body exposure” to the same drug. Assume we want to compare Drug A and Drug B. We will take a group of normal, healthy adults and put them in standardized conditions — usually fasting overnight and then giving a drug on a empty stomach or with a standardized meal. We’ll give Drug A to a patient, take serial blood samples, and then calculate Cmax/tmax and AUC. Later, after the drug has been fully eliminated from the body, we’ll repeat the process in the same patient, under the same conditions, with drug B. This may be done in 20+ patients. We’ll get a graph that looks like this:

Typical concentration-time graph for two drug products

(source)

Are the two curves super-imposable? Not quite, in this example. There are slight differences in the extent of absorption. Are these two drugs bioequivalent? Here’s where the statistics come in. We apply statistics to evaluate if the curves are meaningfully different. To do this, we need to make some assumptions about what we will accept as a meaningful difference. Does a slight difference in the rate or extent of absorption make a clinical difference? Most regulators worldwide have decided that a 20% variation is generally not clinically significant.

Two versions of a drug are generally said to be bioequivalent if the 90% confidence intervals for the ratios of the geometric means (brand vs. generic) of the AUC and Cmax fall within 80% and 125%. The tmax (brand vs. generic) must also be comparable — and there should not be any significant differences between different patients.

For practical purposes, generic versions of branded drugs have AUC and Cmax ratios that are very close to one. With significant variation in either value, it would be unlikely for the confidence intervals to lie withing the 80% to 125% range. For the sake of keeping this post short I’ll leave a more detailed discussion of the statistics to the interested reader.

Myths, Misconceptions, and Controversies

Generic drugs are manufactured differently from branded drugs, and branded drug manufacturers use better processes

If the dosage form releases the same drug with the same concentration/time profile, then any minor manufacturing differences are irrelevant to the pharmacological activity. Regulators have established standardized manufacturing practices and standards, termed good manufacturing practices, that all manufacturers, brand or generic, must adhere to. Final products must meet the same product quality standards as well.

Biosimilars are bioequivalent

Biosimilars refers to follow-on versions of antibodies, proteins and other patented biological drugs, like growth hormones. Biological drugs are very large molecules that are structurally more complex that the relatively simple, smaller molecules in most tablets and injections. Their complexity means that a simple bioequivalence evaluations may be insufficient to fully describe a drug’s action. Manufacturing processes may involve recombinant DNA technology, and can take place inside living cells, leading to a final dosage form which cannot be fully characterized as a single defined API. As some of the biologic drugs approved over the past few decades have lost patent protection, the challenge of verifying both pharmaceutical but also clinical equivalence of “generic” biologicals has become an evaluation challenge for regulators. So if they’re not completely bioequivalent, do they have the same effects in patients? That is, are they clinically and therapeutically equivalent? While approaches between countries may vary, many are being cautious and requiring more detailed comparisons, including clinical safety and efficacy trials to adequately demonstrate that “generic” versions of biologic drugs have the same end effects. As regulators gain more experience evaluating these products, expect the testing standards to evolve.

Bioequivalence studies are always necessary to establish interchangeability

For some dosage forms, bioequivalence studies may be inappropriate or impractical. Consider ophthalmic eyedrops. These products are administered at the site of action, and don’t rely on systemic absorption. It may be more appropriate to verify equivalence by comparing physicochemical properties including pH, viscosity, and osmolarity/osmolality. Where all relevant parameters are evaluated to be comparable, regulators will deem generic versions interchangeable based on these parameter alone.

Generics need to be tested in sick patients, not healthy volunteers

The intent of a bioequivalence comparison is to determine the differences in formulation between two drug products. Healthy standardized volunteers are used in bioequivalence studies to control for patient differences, meaning that any differences in bioavailability will be the result of drug formulation issues, not patient issues. In order to isolate drug formulation effects, it is necessary to hold everything else as constant as possible. If formulations are consistent, the rate and extent of drug absorption will not differ, and consequently there should be no differences in the pharmacologic effects of the drugs.

I absolutely can’t take a generic version of my prescription

Patented drug manufacturers usually aren’t willing to sacrifice their entire market share to generic competitors. Some will start producing “generic” versions of their own drug, selling them to a partner or subsidiary who will sell them as an “ultrageneric”. So in many cases, at least one of the generic versions that’s marketed will be truly identical (except perhaps for markings) to the branded products. Now if you think this means people won’t occasionally identify the switch as the source of efficacy issues or side effects, my anecdotal experience says otherwise.

I had a negative reaction (e.g., more side effects) to the generic

There are no requirements for generic drugs to contain the same non-medicinal ingredients as the brand-name drug, so allergic reactions are not impossible. Most of the excipients are generally inert but there have been suggestions that serious allergies may rarely affect some patients. However, complaints about intolerance in the absence of a true allergic response or documented allergy could also be nocebo effects, negative symptoms elicited by negative expectations from the patient.

Bioequivalence testing isn’t an accepted evaluation method

It’s not just generic companies that must do bioequivalence studies. The company that owns the patent may need to do the same studies. Any changes to the dosage form either during development, or after marketing the product, may necessitate bioequivalence studies to demonstrate that changes do not meaningfully alter the concentration-time curve. So if the clinical trial was with a capsule, and the final marketed product is a tablet, a bioequivalence study comparing the two may be necessary. This reassures regulators that the clinical trials continue to be relevant and applicable to the new dosage form.

I don’t care what you say, the drugs are not equivalent in the real world

The Medical Letter recently summarized some studies that have evaluated the clinical effects of generic substitution:

• A systematic review of 47 studies that compared cardiovascular drugs found no evidence that brand-name drugs were superior with respect to clinical outcomes.
• An RCT comparing a brand antibiotic vs. a generic antibiotic found no differences in clinical effects.
• The FDA conducted its own evaluation of proton pump inhibitors (e.g., Prilosec/Losec). All five generics met dissolution standards.
• Levothyroxine as an API is unstable, and the FDA recently tightened manufacturing standards for all versions. There are no well-documented cases of therapeutic inequivalence between brands deemed to be bioequivalent. Most health professionals still recommend using a consistent brand, however.
• Retrospective case-control studies with anti-epileptic drugs have yielded some data suggestive of therapeutic inequivalence. Given the limits of these studies (patients who have switched brands may differ in some way from those that did not switch), the data are not conclusive. Clinically, most health professionals are cautious when switching to generic antiepileptic drugs.

Conclusion

The science of bioequivalence evaluations for generics has been in place in most countries for more that 20 years with an established track record of therapeutic equivalence. These evaluation methods have been so successful in establishing generic drug standards that they are largely consistent between all of the major drug regulators worldwide. Consumers and health professionals alike can be reassured that generic drugs approved under these regulatory frameworks are indeed bioequivalent, and therefore, interchangeable with brand name products.

Retail pharmacy is a competitive business, and these are tough economic times. And as I’ve pointed out before, retail pharmacies are increasingly selling ethically questionable products like homeopathy, positioning them as alternatives to real medicine. So I guess I should not have been surprised when a blog reader, (who is also a very prominent Canadian pharmacy leader) passed on the following to me from Pharmacy Development Services – a program to profile and promote products recommended by Dr. Oz:

In a nutshell, we highlight and create marketing templates and sales-training sheets for specific Dr. Oz recommended products on a weekly basis.

Why Dr. Oz recommended products? Well, have you ever heard or experienced the Oprah Effect? In general, when products are recommended on TV shows such as Dr. Oz, Oprah and The Doctors, viewer’s drive directly to the retail stores with the goal of purchasing these products.

How the program works: Each week, our staff creates detailed product sheets, including sales training information and target questions for your staff. In the packet, we also include marketing templates to display in your Dr. Oz section. Pharmacy owners have seen great results by stocking their shelves with relevant items and using the sales sheets to arm their staff with the knowledge they need to comfortably speak about the products. Once a new supplement is recommended on the show, we aim to create new templates within the week, which shortcuts your process and keeps your pharmacy current and interesting.

Why is this a bad idea? Dr. Oz is a leading, if not the leading proponent of pseudoscience on daytime television. In addition to promoting homeopathy, he’s hosted supplement marketer Joe Mercola several times to promote unproven supplements. He has been called out for  promoting ridiculous diet plans, and giving bad advice to diabetics. So while occasionally he can give more reasonable advice, it’s more typically highly questionable from a science-based perspective. Always, always verify the evidence supporting anything that Dr. Oz profiles or endorses.

So just what products is this program ready to promote? It seems Dr. Oz has been busy:

•     Artichoke Extract
•     Konjac Root
•     Astaxathin
•     L-Carnitine
•     Seabuckthorn Seed Oil
•     White Kidney Bean Extract
•     Vitamin D
•     Cocoa
•     Milk Thistle
•     Brown Seaweed Extract
•     Melatonin & Magnesium
•     Rhodiola & Ashwaghanda

The marketing materials are behind a password, so I can’t verify what they’re saying, and compare it to what Dr. Oz really said. But what’s relevant here is what this program is suggesting you, the pharmacist, tell your customers. It’s not Dr. Oz’s recommendation they need – this is your opportunity to provide your professional opinion on the merits of his featured supplement. Here’s the suggested signage for white kidney bean extract:

Hmm. I wonder what obesity and dietary experts think of white kidney bean extract? The Natural Medicines Comprehensive Database says that there is “Insufficient Evidence to Rate” kidney bean for the treatment of obesity. Data are conflicting and its effectiveness is not established. So suggesting that kidney bean supplements mean you can eat chocolate cake without caloric consequences isn’t a statement backed by robust scientific evidence. The sample and detail documents, go even further:

Bottom Line: Protecting your body on  cheat days, this secret ingredient is a known carb blocker and is perfect for those days when your eyes are bigger than your stomach. Taken along with a high-carb or high-fat meal, White Kidney Bean Extract will block those unwanted calories from being stored in your body and will also keep your blood sugar balanced.

And here are some suggested messages pharmacists can use with their patients:

Smoking Cessation – As you may know, many people who stop smoking are often faced with the risk of weight gain. Would you be interested in taking a supplement that has shown to help prevent weight gain? We want to make sure there isn’t any reason for you to start smoking again.

Patients who are subject to weight gain – Some people are more prone to gaining weight than others. Based on what you’re telling me, would you like me to tell you about a supplement that will help keep off unwanted weight?

Patients who are trying to lose weight – I know you are trying to lose weight. We are so excited about your goals and progress. Would you like me to tell you about a supplement that will insure you keep off the weight throughout the holidays?

I won’t comment further – these messages go well beyond any credible interpretation of the scientific evidence. Selling unproven supplements to patients with real medical needs? It sounds a lot like the “Coke and Fries” supplement promotion that shamed Australian pharmacy practice and created a national uproar. Pharmacists would do well to heed the lessons learned in Australia – put patients, not profits, first.

I see promotions like this and I ask my pharmacist colleagues: Is this where retail pharmacy is going? Is there no way that a pharmacy can survive, if not prosper, based on the provision of medication, products, and advice that are backed by good scientific evidence? Promotions like these will do nothing for the credibility of pharmacists, or for the long-term viability of pharmacy practice.  Pharmacy practice must be science-based, not marketing-based.  This approach, where the pharmacy is just a platform to sell implausible, unproven and ineffective products, is the wrong path for the profession. Pharmacists, don’t let the profession take that path.

For more reading

If you’re looking for more about Dr. Oz’s questionable judgment and dubious recommendations, here’s a summary list compiled at Science-Based Medicine:

From Science-Based Medicine:

• Dr. Oz Embraces Joseph Mercola
• For shame, Dr. Oz, for promoting Joseph Mercola on your show!
• Dr. Mehmet Oz completes his journey to the Dark Side
• Dr. Oz, you’re not helping diabetics
• Dr. Oz and John Edward: Just when I thought Dr. Oz couldn’t go any lower, he proves me wrong
• Dr. Oz promotes homeopathy

From other sources:

• Dr. Oz: America’s doctor and the abdication of professional responsibility
• Dr. Oz and John Edwards = Bad Medicine
• Dr. Oz asks who can we trust when it comes to Genetically Engineered Crops?
• Dr. Oz – so corrupted by fame he even sells himself out
• Emmys, don’t be led down Dr. Oz’s yellow brick road: Oprah’s favorite doctor promotes quackery
• The 5 Worst Promoters of Nonsense
• The Irresponsible Dr. Oz, Softening The Public Up for Charlatans
• Just in time for April Fools’ Day…Dr. Oz and the Pigasus Awards! (in which Dr. Oz also promotes homeopathy)
• More health tips from Dr. Oz
• Oz: The great and gullible
• Questioning Dr. Oz

From the  Nightingale Collaboration, a UK-based group that is challenging misleading claims in healthcare advertising:

We know from what our supporters tell us that there are more than a few pharmacists up and down the country who still either aren’t sure what homeopathy is and even recommend it to some of their customers in the mistaken belief that it is a proven, efficacious alternative medicine.  We thought we’d seize the opportunity of this time of year to try to raise awareness among high street pharmacists and their staff about homeopathy. We have sent greetings cards to the pharmacists and staff of nearly 2,000 Boots pharmacy stores up and down the country.

You can download and send your own homeopathic greeting to pharmacists here.

The campaign highlights an important difference in homeopathy regulation between countries. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) recently ordered pharmacies to stop providing point-of-sale information on homeopathy products. That is, the regulator is prohibiting medical claims for products with no active ingredients.  The opposite occurs in Canada, where Health Canada approves homeopathic products, many with specific “recommended uses”, and also deems these products to be “safe and effective”.

Homeopathy in pharmacies is an embarrassment to the profession of pharmacy, and an abuse of the trust our patients place in us. Kudos to the Nightingale Collaboration for politely asking the profession to do the right thing for patient care.

As glands go, we don’t give the butterfly-shaped thyroid that straddles our trachea too much thought — until it stops working properly. The thyroid is a bit like your home’s thermostat: turn it high, and you’re hyperthyroid: heat intolerant, a high heart rate, and maybe some diarrhea. Turn it down, and you’re hypothyroid: cold, tired, constipated, and possibly even depressed. Both conditions are associated with a long list of more serious health consequences. Between the two however, hypothyroidism is far more prevalent. The mainstay drug that treats it, levothyroxine (Synthroid), is one of the most prescribed in the world.

One of my more memorable pharmacy experiences involved levothyroxine. The store had recently changed its prescription labelling standards: It switched from listing the brand name, to only including the generic name (with the manufacturer in parentheses). Few patients noticed. But one elderly patient, taking Synthroid, was furious, and accused me of making a dispensing error. I assured her that levothyroxine was the active ingredient in Synthroid, and she was getting the exact same product as her last visit — but she would have none of it. Her symptoms had worsened, she said, because the medication wasn’t the same. “I want Synthroid — this levothyroxine stuff does not work,” she screamed at me across the counter. No amount of reassurance would satisfy her — I think we eventually resorted to custom, typewritten labels.

I mention this anecdote not to dismiss the symptoms of hypothyroidism as sensitive to placebo effects — hypothyroidism is a real condition with objective monitoring criteria. But this episode was one of my earliest lessons in understanding how perceptions can shape expectations of effectiveness — something that I’ll come back to, when we look at the controversies of this common condition. Any the treatment of hypothyroidism is not without its controversies – most of which occur outside the realm of medicine, and can more accurately be labelled pseudoscience.

Hypothyroidism is the consequence of the thyroid gland failing to produce enough thyroid hormone. The body produces two thyroid hormones: thyroxine (T4) and liothyronine (T3). Primary hypothyroidism is the result of insufficient production of T4 by the thyroid gland. (Secondary hypothyroidism is a consequence of pituitary or hypothylamic disorder.) The overwhelming majority of cases of hypothyroidism are primary, and the major cause of primary hypothyroidism is autoimmune thyroid disease (Hashimoto thyroiditis). Iodine deficiency can cause primary hypothyroidism too, but it’s rare in developed countries. There are other causes of hypothyroidism, including drug therapies. But to keep this post to a reasonable length, I’ll restrict my focus to primary hypothyroidism, which seems to attract the most treatment controversy.

The prevalence of hypothyroidism varies with gender, age, the population surveyed, and the definition of hypothyroidism used. A recently completed large survey suggested an overall prevalence in America at 3.7% — presumably this will be similar in other countries where iodine deficiency is equally rare. Hypothyroidism is much more common in women compared to men., and increased in prevalence with age.

The presentation of hypothyroidism varies based on severity, from no symptoms at all, to severe cases with coma and organ failure. Patients with untreated primary hypothyroidism may describe weight gain, cold intolerance, dry skin/hair, constipation and hair loss. While the assessment and treatment of hypothyroidism is based around patient-relevant symptoms, the diagnosis of hypothyroidism must be based on lab tests, owing to the non-specific nature of the symptoms. Three laboratory measurements evaluate thyroid function and are used to diagnose hypothyroidism:

• Thyroid Stimulating Hormone (TSH), secreted by the pituitary, is the primary screening measure in most situations. The normal range is usually reported to be 0.3-5.5 mIU/L, and a diagnosis of hypothyroidism is likely when the TSH is elevated above 10. The less functional the thyroid, the higher the TSH. (Values will vary for what is a “normal” TSH depending on the lab.)
• Free T4 (FT4) is evaluated when the TSH is abnormal. The usual range is 9-19 pmol/L and will be reduced in hypothroidism.
• Free T3 (FT3) has a usual range of 2.6-5.7 pmol/L. It may be reduced in hypothyroidism, but its value is not useful for diagnosis.

The Treatments

The standard therapy for hypothyroidism is synthetic levothyroxine (LT4) alone, which supplies FT4 to the body. The body converts FT4 to FT3 as required. LT4 is effective for the vast majority of patients and is the mainstay of treatment guidelines. Many patients need to take nothing else; once their dose is determined, they take one dose a day, forever. LT4 is lifetime therapy. Benefits of LT4 include very accurate tablet standards, stable absorbtion and steady blood levels, and good tolerability.

Liothyronine (LT3) (Cytomel) is uncommonly used for thyroid dysfunction. The active form of thyroid, administration can cause wide fluctuations in FT3 levels, increasing the risk of cardiovascular harms compared with LT4. If LT4 is like gradually turning up your home’s thermostat, LT3 is akin to big fire in the fireplace – it can work quickly, but it’s difficult to maintain a consistent effect. With a less desirable risk/benefit profile, LT3 is generally used only in patients intolerant to LT4, or in those who are unable to successfully achieve treatment success and symptom resolution on LT4 alone.

Combination therapy (LT4 + LT3) occurs, but isn’t supported by good evidence, despite what you might expect from the testimonials. Trials comparing LT4 to LT4 + LT3 have shown no benefit over LT4 alone — and sometimes LT4 alone comes out on top.

Some physicians, patients and particularly alternative medicine purveyors advocate that dessicated thyroid (ground up pork thyroid) has advantages over LT4. This may be based in part on the naturalistic fallacy: the idea that using a “natural” thyroid source is better than “synthetic” levothyroxine. The evidence doesn’t support such a conclusion. In fact, judging by the evidence with LT4 + LT3, the evidence points the other direction. Dessicated thyroid contains a mix of T4 and T3. The lack of any randomized head-to-head comparisons make any comparison difficult, and renders claims of superiority unproven. While some patients seem to prefer it to T4 alone, the unpredictable stability, and potential for batch-to-batch variation make it less attractive from a patient perspective, and consequently treatment guidelines generally advise against its use. If combination therapy is felt to be necessary, using synthetic LT4 and LT3 together allows more precise and consistent dosing. Yet there exists a vast network of websites dedicated to locating sources of dessicated thyroid and shipping it to countries where it’s not available.

Treatment Goals and Monitoring
The assessment and treatment of hypothyroidism is based on symptoms, and is guided by laboratory monitoring. Monitoring includes measurements of TSH and more rarely FT4, with the goal of putting both into the “normal” range. And improvement can be rapid, usually starting within a few weeks, with significant improvement as levels normalize.

The Controversies

Normal Ranges
Laboratory monitoring is a critical component of evaluating thyroid function. Redefine what’s considered “normal” and you redefine what it means to by hypothyroid. While the upper limit of “normal” TSH is generally accepted to be around 5.5 mIU/L (it will depend in part on the lab standard), lowering the upper limit will move millions from “normal’ to “subclinical hypothyroidism”. There’s a debate as to whether the upper limit of a “normal” TSH should be dropped to 2.5 mIU/L. Confounding its critics, the medical “establishment” that is criticized online doesn’t yet seem convinced that revising the definition is necessary – which would create (on paper) millions of new patients. . Perhaps it’s because there’s no clear evidence of adverse consequences for not treating TSH values in the 2.5-5mIU/L range. So narrowing the range may do little for patient outcomes. Still, this is an area of continued controversy.

Subclinical Hypothyroidism
Subclinical hypothyroidism is generally defined as a “normal” T4 and a slightly elevated TSH: That is, some laboratory signs of a thyroid dysfunction, but not sufficient enough to warrant a diagnosis. Symptoms are not always present, and can be vague and nonspecific: dry skin, constipation, depression, poor memory, etc. Subclinical hypothyroidism can only be diagnosed based on test results. The clinical significance of the condition is unclear. A recent Cochrane Review suggested that treating subclinical hypothyroidism doesn’t seem to result in meaningful differences in symptoms or quality of life, nor does it decrease cardiovascular morbidity. Given the risk/benefit perspective seems unclear, treatment decisions need to consider the long term consequences of treatment in the context of individual patient factors, and preferences.

Screening
Routinely screening thyroid function in adults is controversial. Screening may be more reasonable in higher-risk patients (advanced age, family history, those with signs/symptoms, etc.). Screening would be expected to increase the likelihood of treatment and over treatment, and consequently exposure to the potential risks (not well understood) of long-term thyroid treatment. Given the uncertainty about the benefits of treatment of subclinical hypothyroidism, screening may not be necessary in those at low risk and free of typical symptoms.

Is Measuring FT4 Enough?
Guidelines recommend routine monitoring of TSH and FT4, but not FT3, as T3 is felt to vary too significantly to normally guide treatment (though it may be useful when LT4 therapy is initiated). The alternative approach discounts the evidence and guidelines and advocates treatment with LT3 alone, or a combination of LT4 and LT3. At the extreme, some groups advise against laboratory monitoring and suggest relying on symptoms alone. It’s the alternative approach that may have driven the continued interest in dessicated thyroid, which persists on the market despite quality control and dosing challenges.

Switching Brands and Using Generics
Some countries carry multiple brands of levothyroxine, and regulators may allow brand substitution – that is, they are deemed to be interchangeable. But even in settings where switching is permitted, health professionals generally try to keep patients on the same brand, to minimize the remote chance of any variation in effects due to formulation. (So the protestations of my customer, if not based in science, were consistent with usual pharmacy standards.) Looking at the data, however, there’s probably more variation in absorption based on food effects than any potential variation between brands. And the FDA recently tightened the quality standards for all brands, reducing the likelihood of variation between tablets or between brands. Still, taking the daily dose at the same time each day is probably equally important to maintaining stable blood values.

The Pseudoscience

Are Lab Measures Enough? Or Even Necessary?
A popular alternative approach to thyroid treatment is body temperature measurements, which are felt to be a proxy for thyroid function. While it sound plausible and could give you the impression of “taking control” of your hypothyroidism, there’s no persuasive data to link the two. Body temperature does not accurately measure thyroid function and should not be used to guide treatment.

Over-the-Counter Supplements
There are several over-the-counter thyroid supplements on the market, some of which contain animal-sourced thyroid gland. A recent study tested these supplements: 9 of the 10 had animal hormones present, some with amounts comparable to prescription drugs. Given the questionable quality control and potential for batch-to-batch variation, OTC supplements are a potentially dangerous choice for treatment.

Beyond the glandular products, there are a host of nutritional products targeted at consumers with hypothyroidism. Some of the common ingredients include:

• Kelp and other products that are sources of iodine; however, iodine deficiency isn’t an issue for most.
• Dong Quai, tyrosine, pantothenic acid (vitamin B5), ashwagandha, bladderwrack, schisandra, ginseng (Siberian and American), astragalus, rhodiola, selenium, zinc, copper and dozens of other ingredients that haven’t been demonstrated to have any meaningful effects — or to actually address the root cause of the condition.

Regulators like Health Canada don’t make it any easier: they approve multivitamins and iodine-containing supplements with “thyroid” in the name, or with recommended uses like, “Helps in the function of the thyroid gland” which, while not entirely incorrect, are misleading, given iodine or vitamin deficiency isn’t a relevant contributor to most cases of hypothyroidism. I could label the same supplements, “Helps in the function of the index finger” and be equally accurate.

You brought this on yourself
Well, that’s what Christine Northrup suggests:

It’s no coincidence that so many more women than men have thyroid problems. Thyroid disease is related to expressing your feelings, something that until relatively recently had been societally blocked for women for thousands of years. In order to have your say—and maintain your thyroid energy—you must take a fearless inventory of every relationship in which you feel you don’t have a say. Ask yourself why you don’t. Are you a silent partner in a relationship? Does your partner make all the major decisions? Is it worth it? Did your mother have her say? In what ways are you like her?

Depending on your answers, I would urge you to skillfully and empathetically begin to say what is on your mind regarding the decisions that affect your life. Make sure that when you say what’s on your mind, you do so at the right time and remain detached from the effects. In other words, try not to force your will on others. For example, it’s okay to tell your best friend that you are worried about the character of her new boyfriend, but be aware that she may not necessarily be ready to hear your remarks. It’s not appropriate to “turn up the volume” as she’s rushing out the door to meet this new man.

OK, Dr. Northrup, I’ll try saying what’s on my mind. This advice is unadulterated magical thinking. Stop blaming women for autoimmune disorders.

It’s the Adrenals
No, hypothyroidism is not adrenal fatigue – a made-up condition without any demonstrable evidence that it actually exists. Given the “symptoms” of adrenal fatigue overlap with those of hypothyroidism, screening for hypothyroidism is an appropriate element of any workup for unexplained fatigue. The same applies to taking hydrocortisone for hypothyroidism – while there are recommendations online, there’s no good evidence to show this is either safe or effective.

A Little boost to help me lose weight
The thyroid is a convenient villain when confronting weight loss. If I can toss in a final anecdote, I had my Labrador Retriever’s thyroid function evaluated when she became sluggish and gained 20lbs over 12 months. It turns out, she actually was quite hypothyroid, and her activity level and weight responded well to levothyroxine, calorie restriction, and more exercise. In the obese, hypothyroidism is rare in the absence of other symptoms. And if there’s no hypothyroidism, manipulating thyroid hormones is inadvisable.

Making Sense of It All
While there’s a lot of dissatisfaction with thyroid treatments online, the vast majority of patients find levothyroxine to be a simple and highly effective daily therapy. There are some true controversies in the treatment of hypothyroidism, but they’re buried in vast amounts of pseudoscience and bad treatment advice. So I advise my newly diagnosed patients against complicating treatment unless it’s necessary, and to start treatment with positive expectations: Synthroid is a top dispensed drug for a reason: It works. And despite the controversies, and the outlier opinions, the medical consensus on the treatment of hypothyroidism is quite strong. That means ignoring the noise, focusing on the relevant outcomes, and taking a stepwise, science-based approach to treatment.

Other References
Desiccated thyroid vs. synthetic thyroid supplementation. Pharmacist’s Letter/Prescriber’s Letter 2008;24(10):241013.

Towards Optimal Practice. Clinical Practice Guideline Working Group. Thyroid Dysfunction.

AACE Medical Guidelines for Clinical Practice for Evaluation and Treatment of Hyperthyroidism and Hypothyroidism. 2002

Disclosure: Scott treats his Labrador Retriever with levothyroxine.

Point of Inquiry is the premier podcast of the Center for Inquiry, drawing on CFI’s relationship with the leading minds of the day including Nobel Prize-winning scientists, public intellectuals, social critics and thinkers, and renowned entertainers. Each episode combines incisive interviews, features and commentary focusing on CFI’s issues: religion, human values and the borderlands of science.

This discussion focused on the role of the pharmacist and the need for science-based pharmacy practice. We touched on a lot of issues including the changing role of the pharmacist, the ethical responsibilities of pharmacists when it comes to products like homeopathy, what compounding pharmacies do, what generic drugs are, what an expiry date means, what pharmacists think about vitamins and other supplements, and more. You can listen to the podcast here.