Category Archives: Supplements

Various types of “research”

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I wrote about critical thinking in the last post. And while it would seem that most health care professionals should be pretty good at applying this skill in evaluating information, based on my experience that may not be the case.

Obviously a lot of doctors are when it comes to diagnoses and treatment plans, but I am still surprised at times when I hear what competitors have said and wonder how they get away with it. My friend Ryan Perry told me a story about how, when he was training a new rep (who had come to us from a company that’s very long on “story” and very short on real, objective proof to support their products), he asked this person how his former company had told their reps to respond when a doctor wanted to know how a particular product worked. He said “They told us to look the doctor in the eye and say “Doctor, it works GREAT!”

It’s amazing that anyone would try to get away with nothing but a sales person’s assertion, especially when patients’ trust in their doctor’s treatment is part of the equation.
But what constitutes adequate evidence of efficacy? Should a doctor expect to have a battery of double-blind, placebo-controlled randomized trials before telling a patient they should be taking vitamin C for the sniffles? Especially given the known safety of most supplements? And are RCTs (randomized, controlled trials) even the best way to study supplements? That is the gold standard for pharmaceuticals, but those are novel, individual molecules that are most commonly new-to-nature. Virtually all of them have side effects; some profound and even life-threatening. Should supplements be held to that standard, or is there another way to establish efficacy?

I’m going to address that last question in future posts, but first I want to talk a little bit about “research.” I saw a coffee cup in a physician’s office not long ago that had the inscription “Please don’t confuse your Google search with my medical degree.” This is a common complaint: patients find some obscure website full of dubious, over-the-top claims and march into their doctor’s office clutching this “research” asking why the doctor is hiding this information from them, as it obviously holds the answer to all their health woes. Laughable if it weren’t so annoying. We all know (or should know) that not everything one finds on the “Interweb” should be given credence. Or even a second thought. Finding a reputable source of unbiased scientific information is important, and the data are definitely out there; a Google Scholar search for “Vitamin D immunity” just now yielded a little shy of 740,000 hits. Of course all the hits weren’t unique studies, but that’s still a lot of data.

So in my chosen industry, how should we evaluate what we hear?

First, let’s get some clarity around “research.” A personal experience, no matter how compelling or trustworthy the source, cannot be called research. That’s an anecdote. Coincidence, confirmation bias, unrelated causes, and on and on could be contributing to the observed results. We’ve all heard that visits to ERs spike during a full moon (I’ve had nurses tell me they have no doubt about it), but a careful statistical analysis shows that’s not true.

So we’re talking about actual scientific studies, not anecdotal information. But the vast majority of information available on a given nutrient is generic. This is because, unlike a pharmaceutical, individual nutrients are not patentable, so companies are generally not interested in funding expensive research projects when there’s no hope of recouping their costs through a patent. So most of the research on vitamins is funded by government grants to universities. In some ways this is very good because it removes the charge of a biased outcome (as might be the case if the work were done by a company with an economic interest in the results). Also, if the test product is vitamin D for example, any company that distributes a vitamin D supplement can point to that paper in support of their vitamin D. This is called “borrowed” research, in that it wasn’t an individual company’s vitamin D used in the study, but it still supports the function of vitamin D. The downside of course is that any other company with a vitamin D product can refer to that study in support of their product.

Let’s say however that there IS something unique about the vitamin D used in the research; maybe a novel absorption system. The results prove positive, so some other company (not the supplier of the test product) uses that paper in support of their product (which, as I said, is different than what was in the study). In that case, the company using the paper to support their product is implying that their product will perform the same as the test product, without supporting evidence. This, in my opinion, is fraud.

There’s another, more murky area of borrowed research. Let’s say I put a product with 6 or 8 ingredients together, for, say, support of connective tissue. Since many doctors give several different supplements at a time to their patients based on their experience, it makes sense for a company to save the patients money and the necessity of opening a half-dozen bottles by this “mixology.” Now, to support my product, I could go to PubMed and find published articles on each of the ingredients. I now have “research” on my product, even though none of the supportive papers specifically studied my product. I am not suggesting this is fraudulent or even inappropriate, because recall that doctors routinely do this in giving several different supplements at the same time to patients. But it is a bit of an assumption to say that adding each of those ingredients into a mixology approach will yield effects as from each of the individual ingredients. It may, but it may also be true that two of the ingredients interfere with one another in some way. In our industry, this is a commonly used strategy and again, I’m not suggesting it’s wrong to do so (in fact we do so ourselves). It’s a lot better than anecdotes or simple assertions, but it’s not really solid research.

The next would be “licensed” research. Let’s say we connect with a researcher who has done original work on a particular extract or unique ingredient. In our case at Metagenics that’s what happened with our product named Estrovera. It is an extract of the Siberian rhubarb plant named ERr731 and is unique to the German company that isolated and studied it. We license that specific extract from this company, and the research that is associated with it (something like 100 published papers) becomes available to use because it is in fact exactly that extract used in the studies. This is much better (and obviously also more expensive) that borrowed research, but if our relationship with the German supplier ends and we attempt to use a different product than what was used in the study, we’re back to fraud.

One step higher up the food chain would be original studies conducted on our specific product. For example we patented an extract of hops and conducted (and published) a number of studies showing its impact of kinases and inflammation. Since we discovered the product and conducted the original research, we obviously own that information and will continue to as long as our patents last. These studies could by RCTs or case studies; if submitted for IRB approval and conducted with appropriate scientific (and ethical) rigor they provide truly solid support of a product.
So while all of these three types of “research” are in fact appropriate to use (Borrowed, licensed and original), clearly the last is the most expensive for a company, but also gives them a significant, long-term advantage over any competitors.

Just to be clear, Metagenics uses all three. Most companies in our industry only have borrowed research; a few license products (and the associated research) but it’s much more rare to find any significant data published in peer-reviewed journals. Metagenics has something over 80 papers published on our products, with nearly 200 patents granted or pending.

I applaud any company that is willing to spend the capital required to support their product. This adds credence to the industry in general and helps to dispel the belief that “supplements don’t have any research to support them.”

But this line of information also shows there really is a difference among brands. “Doctor, it works GREAT!” has no place when you’re dealing with something as critical as the health of patients.

FDA oversight

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One of the most frequent comments I’ve seen in the media about the nutritional supplement industry is that “there is no oversight” over manufacturing processes and supplement claims. We have a full-time regulatory staff who laugh when they hear this, because if that were true they’d be spending a great deal of time and energy for nothing.

In fact of course, FDA has direct oversight over nutritional supplements; FTC has overlapping authority when it comes to the claims that are made (even if a health claim isn’t being made, which would come under FDA authority, it’s possible to run afoul of FTC if the claims are not supportable).

I think a more accurate statement might be that “Nutritional supplements don’t have to meet FDA pharmaceutical product standards.” So what would that difference mean in practical terms?

First of all, a little history. FDA was established in 1906 to protect the American consumer and promote health. Currently the list of things this agency regulates includes both prescription and OTC drugs, nutritional supplements and cosmetics, but also includes food safety, tobacco products, vaccines and others. Historically supplements fell in a grey area, since they were neither foods nor drugs; regulations that made sense for either of those broad categories don’t fit for supplements, so eventually a set of regs for supplements was developed. At first no claims were allowed, but eventually Congress passed DSHEA (the Dietary Supplement Health Education Act), which states that supplements are for generally healthy people, and claims around structure or function could be made (in addition to “prevention of vitamin deficiency” statements). For example, “calcium is important for bones” would be a structural claim, and “vitamin E protects against oxidative damage” would be a functional claim.

Note however that first caveat, that “supplements are for generally healthy people.” FDA regulations state that “supplements cannot be used for the treatment, prevention or amelioration of a disease or condition, or the symptoms of a disease or condition” (somewhat paraphrasing here, but the general sense is the same). So a supplement company couldn’t say, for example, that “vitamin C is to treat the common cold.” (Even though most people who take vitamin C would say that’s exactly what they take it for). Since cold and flu are “diseases or conditions,” that statement would be considered by FDA to be making a drug claim, and would get the company making the claim in trouble.

Anyhow, back to regulatory oversight. FDA does in fact regulate the nutritional supplement company pretty closely, given their available resources. Since cGMPs (current Good Manufacturing Practices) were instituted in 2012 (when the law went into full effect), FDA has been conducting inspections of supplement manufacturing companies, and has issued a number of Regulatory Letters warning companies that they needed to clean up their procedures or face pretty stiff penalties, up to getting shut down. (This usually happens only after several warnings have been ignored or not acted upon appropriately, but it has happened on more than one or two occasions.)

So the next time you hear someone say that the supplement industry is unregulated, you’ll be better prepared to correct the misinformed speaker!

Critical thinking

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Critical thinking is defined by Google as “the objective analysis and evaluation of an issue in order to form a judgment.” Note that the level of intelligence of the thinker is not one of the variables.

My observation of how that plays out is that it is entirely possible for smart people to not exercise critical thinking skills. I am of the opinion (based on my own non-statistical observations) that, in practice there is no correlation between the use of critical thinking skills and one’s intellect. My experience has been that most physicians are very sharp people and my purpose is not to denigrate anyone, but I also find that frequently physicians are willing to suspend their critical thinking skills when it comes to some of the claims that are made about supplements.

I remember an incident a number of years ago where I was having lunch with a well-regarded MD in the Midwest. We were talking about immune response and ways to support immune function, and he mentioned a product being sold by a competitor that was labeled as “human interferon.” As I said, this was several decades ago when interferon was just being isolated and before anyone was mass-producing it; I think the worldwide supply at the time could be measured in grams, and valued at hundreds of thousands of dollars. So when I saw on the bottle that they were claiming 10 mg per tablet and selling a month’s supply for around $15.00, I was, to say the least, a bit skeptical. And it surprised me that my doctor friend wasn’t. So I asked him where he understood the “human” interferon came from, given those facts (with which he was also familiar). He said that the rep for this company said that it was “extracted from the foreskins of circumcised babies in New York hospitals.”

Huh. Seriously??

I asked him if he thought that was reasonable. He said “Well, I do know that foreskins are high in interferon, so at first I didn’t question it, but now that you made me think a bit deeper, no, that doesn’t make sense to me. I guess I’ll have to ask my rep for more detail.”

Anyhow, I tell this story to encourage everyone to remember their critical thinking skills, and to apply them to what they hear about products. When I was involved in Metagenics’ training of our new reps, we regularly stressed the importance of accuracy to our newbies, but I must say my experience is that not all of my competitor colleagues are, shall we say, fully informed or completely candid.

Let me use a couple of examples. Metagenics produces both “medical foods” and “functional foods.” I’ll go into more detail about what constitutes each in a later posting (they are not the same), but in short, medical foods are a special category established by FDA and regulated differently than nutritional supplements (which include functional foods). Our medical food products meet the requirements to be labeled as such, one of which is that they have to be based on clinical evidence. This means that we conduct case studies and/or clinical trials to demonstrate that they accomplish what they’re developed to do.

So when a competitor tells one of our customers that their functional food works just as well as one of our medical foods, the practitioner’s first question should be “How do you know?” I find that, all too often, a doctor is willing to accept the assertions of a sales rep without any real proof. And when they are providing these products to their patients, it seems to me they should be asking for more evidence than a simple assertion by a sales person, however well-intentioned. If in fact they do work “just as well,” the rep should be able to demonstrate proof in the form of clinical trials, case studies or some other rigorous method. And telling anecdotal stories doesn’t suffice.

And by the way, our reps should be challenged to support what we say as well. No one should be able to make a simple assertion without evidence, particularly when a patient’s health is at stake.

EPI

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I was watching TV the other day and saw one of those commercials from a drug company trying to get people to ask their doctor for whatever was being flogged in the ad.

The question of how ethical it is to try to get TV viewers to coerce healthcare providers into prescribing one drug over another aside, this one caught my attention for its topic. It was for a condition called “EPI,” which stands for exocrine pancreatic insufficiency. It listed the symptoms (gas and bloating following a meal, undigested food in the stool) some of the causes (disease, alcohol abuse, and interestingly, simply the aging process) and presented their solution, without naming exactly what their solution contained. Turns out it’s a standardized pancreatic enzyme product; something Metagenics has sold (as AzeoPangen) since the beginning of the company in 1983. In fact, I had sold it back in the mists of time prior to Metagenics; Nutri-Dyn had a product called Pan-5-Plus, which was processed for us by VioBin corporation in Monticello, Illinois. As I recall VioBin sold the same product under the name Viokase, as a treatment for…wait for it…exocrine pancreatic insufficiency.

It’s a porcine pancreatic enzyme, which means it’s derived from the pancreas of pigs, dried through a physical process and made into a tablet. Turns out that pigs can eat the same things we do, and thus have a digestive system that almost exactly matches our own, right down to the profile of enzymes that are produced in the pig’s pancreas. When properly prepared, these digestive enzymes from pigs work just like those we produce; for all intents and purposes they are identical. Thus the enzymes that we may not be manufacturing in adequate quantities (for the reasons listed in the commercial described above), can be taken as an oral supplement, preventing our digestion from being compromised. The original uses for Viokase were for cystic fibrosis patients, where their digestive function is compromised, or in patients with total pancreatectomy, where there is obviously no pancreatic function at all. In our application at Nutri-Dyn (and now at Metagenics), it was recommended for patients with ‘pancreatic insufficiency.” This sounds remarkably like the claim for the TV ads of “exocrine pancreatic insufficiency.”

One reason this caught my attention is the shift in medicine it represents. While we’ve been carrying a pancreatic enzyme product for many years, the “conventional wisdom” (at least in the sense that “conventional” healthcare providers held this position) was that, short of a known disease state such as cystic fibrosis or a total pancreatectomy, there was no such thing as “exocrine pancreatic insufficiency.” If you had a functioning pancreas then you were producing enzymes adequate to digest your meals. We always maintained that enzymes (and for that matter, most of the compounds that support metabolic processes) are produced in very differing amounts from person to person. In his book “Biochemical Individuality” Roger Williams observes that there may be a thousand-fold difference in the amount and activity of any enzyme from person to person. This would imply that any given person may not be producing adequate amounts of digestive enzymes (for example), even in the absence of overt pathology. Thus, supplementing with exogenous enzymes could help support digestion, and my personal experience with healthcare providers over the years has supported this contention.

Of course, pancreatic digestive function is only one piece of the puzzle; digestion is a complex process and a number of different steps are required in the breaking down and absorption of food, and enzymes for digestion are produced not just in the pancreas but also in the cells that line the upper part of the digestive tract, but without a healthy pancreas producing enzymes as required, our digestion is going to be compromised. So taking an oral pancreatic supplement may be in important part of staying healthy. And as the ad alludes to, it’s entirely possible that people may not be making enough of these enzymes and their ability to extract nutrients and energy from food may be suboptimal.

Years ago before HealthComm merged with Metagenics, the clinicians there developed a support program for people with compromised digestion and called it the 4R program, for “Remove, Replace, Repair and Reinocculate.” The Replace part referred to replacing enzymes and other digestive juices that the patient wasn’t producing in adequate amounts. (In the current iterations of this program being taught by IFM, a fifth “R” has been added, for “Rebalance” and including relaxation and stress reduction techniques, as stressful conditions are well known to interfere with digestion.)

At any rate, it’s nice to see that the conventional medical approach now recognizes the value of supporting digestion through the use of exogenous pancreatic enzymes. Like everything else however, the outcome is influenced by the quality and potency of the product used; I’ll discuss that in more depth in another post.