[ed. note: Michael Jorrin, who I like to call “Doc Gumshoe,” is a medical writer (not a doctor) who shares his thoughts with our readers a couple times a month. He does not generally cover investing topics, but I find his discussions of broader health issues interesting and useful. Enjoy!]

Doc Gumshoe would not be posting a piece about celiac disease if it weren’t for the fact that he (along with just about everybody else alive and breathing, in these parts at least) is daily assailed by offerings of gluten-free this and that. In our own town a cute little shop has sprung up to supply residents with gluten-free treats, and of course the grocery store has lots and lots of gluten-free items.

So what’s going on? Are there really that many people with celiac disease who require a gluten-free diet? Or is it something else?

As a jumping-off place into this potentially tricky quagmire, permit me to stake out my own basic position on this. I am not doing this because I wish to engage the proponents of the gluten-free diet – who are also likely to be partisans of managing health through diet, life-style adjustments, and supplements – in a protracted war of words. I have already, in a previous post, made it as clear as I could that the feud between advocates of mainline medicine and those of alternative health is mostly unnecessary and unproductive. At the same time, it’s also clear that there are fashions and trends in health, and some of them don’t make a whole lot of sense.

Here’s the Doc Gumshoe position in a nutshell:

• Celiac disease is a serious, potentially fatal medical condition, for which there is no known treatment other than the gluten-free diet.

• However, celiac disease is relatively uncommon, and lots of people without celiac disease have adopted the gluten-free diet based on the belief that it is somehow “healthy.” But this diet confers no benefit whatsoever on persons who do not have this condition – in fact, it is likely to bring significant and specific harms.

What, exactly, is celiac disease?

In normal digestion, the contents of the stomach pass into the small intestine, which is where almost all of the nutrient extraction takes place. In the stomach, whatever we ate has been churned up and subjected to an acid bath, and sugars have already been converted into glucose and absorbed into the circulation, and the resulting slurry descends into the small intestine. There, nutrients from this slurry are removed. The agents for this removal are called villi, plural of the Latin villus, meaning “tuft of hair. In effect, the mucosal lining of our small intestine is totally covered with these villi, which extract all manner of nutrients from the matter passing through.

In celiac disease, for reasons that are not totally understood, the villi atrophy. Instead of being covered with villi, the lining of the small intestine in persons with celiac disease are relatively smooth. This has a number of consequences, ranging from deficiencies in a number of nutrients to effects on the quality of the stool, which is now carrying matter that would, in the normal process of digestion, have been removed from the intestinal tract.

The symptoms of celiac disease arising from this can be mild or severe. Some individuals with mild or early stage disease may experience only fatigue or anemia. Diarrhea is common, and the character of the diarrhea is somewhat unusual: it is light-colored, greasy (because lipids have not been absorbed), voluminous, and evil-smelling. Severe pain, stomach cramps, and bloating may occur because of the volume of gas generated in the gut. As the disease progresses, individuals can become severely malnourished. Persons with untreated celiac disease appear to be at a higher risk for non-Hodgkin’s lymphoma and also risk of developing ulcers of the small intestine.

The nutrients in which persons with celiac disease may be deficient include carbohydrates and fats, several minerals (iron, calcium, and others), and several vitamins (A, B12, D, E, K, and folic acid).

And celiac disease symptoms are not limited to the digestive system. Celiac patients have a higher incidence of other autoimmune diseases including Type 1 diabetes mellitus and some skin diseases, as well as liver abnormalities and increased risk of infections.

The term “celiac disease” is singularly imprecise. “Celiac” means nothing more specific than “abdominal.” It is derived from the Greek κοιλιακός (koiliakós), “pertaining to the stomach cavity.” It used to be called “nontropical sprue” or “celiac sprue,” sprue being usually a tropical disease causing some symptoms similar to those in celiac disease.

In other words – to repeat myself – celiac disease is a serious and potentially fatal condition. The question immediately arises, what gives rise to this dadly disease?

How does celiac disease occur?

You notice that I am avoiding the word “cause.” The trigger has been confidently identified as gliadin, which is a gluten protein found in wheat. Some other grains such as barley, rye, and some wheat varieties such as durum and spelt, have similar gluten proteins. These gluten proteins react with an enzyme called tissue transglutaminase (tTG) which modifies the gluten protein such that it sets off an autoimmune reaction. The specific mechanism of this reaction at the cellular or molecular level is exceedingly complex, and there is debate as to which of the actors – the gliadin/gluten protein or the tTG enzyme – is responsible for the several manifestations of celiac disease. The T cells are involved, and it’s thought that these busy reservists in the immune army may be subverted to attack villi. Immunoglobulin A (IgA) is also involved, and along with tTG is considered a celiac disease marker.

However, to call gluten proteins the “cause” of celiac disease, as many commonly available sources do, is a considerable overstatement. I say this confidently, seeing that the great majority of the planet’s population consumes gluten without developing celiac disease. What makes gluten trigger celiac disease in a small minority while having no adverse effect at all on the majority is the question which much research is trying to answer. Favored candidates are a couple of variants of the HLA-DQ protein; most celiac patients have one or the other of those two. However, HLA-DQ cannot be said to be determinative, since up to a third of the general population has those genetic components and most of these people do not have celiac disease. Therefore, some additional factors must be involved.

Identifying the cause of celiac disease is a major part of the puzzle. Another part, perhaps with less impact on treatment, is figuring out why a genetic disposition to celiac disease has persisted in our species, since it is clearly the opposite of a survival characteristic. Consider for a moment the condition of lactose intolerance. This condition emerges gradually as infants are weaned; obviously, newborns cannot be lactose-intolerant or they would not survive. But as a child’s diet moves away from dependence on milk, the capacity to absorb lactose can diminish and disappear, and this happens very commonly in populations where milk products are not part of the normal adult diet. However, in populations, such as those in Europe where milk products early became essential parts of the diet, lactose intolerance was clearly an evolutionary albatross. Thus, in persons of mostly European descent, the prevalence of lactose intolerance is less than 5%, while in parts of Africa and Asia it approaches 100% in adults.

The same evolutionary pressures could apply to celiac disease; after all, humans have been consuming gluten-containing grains for 10,000 years or so. How can this potentially disabling genetic characteristic have been passed on? A possible answer is that celiac disease confers some as yet unidentified evolutionary advantage. An analogy might be the prevalence of sickle-cell anemia in some populations, particularly in central Africa. The explanation for this is that sickle-cell anemia confers protection against malaria; thus, it is a distinct survival advantage in regions where malaria is endemic. (We’ll see whether, as malaria comes increasingly under control, sickle-cell loses its evolutionary benefit and disappears – wait a thousand years or so.)

Is it possible that there is a similar connection between celiac disease and some unsuspected disease or condition that celiac disease protects against?

In any case, I can easily understand why even the remote possibility that eating gluten-containing foods could actually cause celiac disease would be of considerable concern. Whether this is a legitimate concern or not depends on the details, and here are some details.

How common is celiac disease?

In a word, not common at all. Here are some data: First, a rigorous study done by the National Health and Nutrition Examination Survey (NHANES) in 2009-2010. This survey included 7,798 persons, median age 45. All had blood tests for IgA and tTG and were questioned about prior diagnoses of celiac disease and whether they were on a gluten-free diet. Based on this information, the prevalence of celiac disease in the US was estimated to be 0.71%, or 1 in 141 persons, similar to that in most European populations. Most of the individuals in the NHANES cohort who were found to have celiac disease according to these criteria were undiagnosed. However, the number of people on a gluten-free diet exceeded the number of diagnosed celiac disease patients by a factor of 10.

Depending on how celiac disease is defined, prevalence estimates vary. If we’re talking about diagnosed clinical disease, about 1 in 1750 persons are affected. If the marker is IgA / tTG in blood samples, the prevalence may be as much as 1 in 105 persons. Persons of African, Chinese, and Japanese descent rarely have celiac disease, and Hispanics seem to have a significantly lower incidence than people of European descent.

A question that the prevalence data pushes to the forefront is this: considering that the number of people with serologically-confirmed celiac disease is about 10 to 15 times greater than the number of people with clinically-confirmed celiac disease, does this not mean that there should be a focus on managing disease in individuals before clinical symptoms emerge? In other words, should all persons with elevated markers for celiac disease be on a gluten-free diet even if they have no clinical symptoms? And does this suggest that the entire population be screened for celiac disease?

Let’s look at the second question first.

Who should be screened for celiac disease?

Here are the recommendations, from the American College of Gastroenterology, as of May 2013:

Recommendations

1. Patients with symptoms, signs, or laboratory evidence suggestive of malabsorption, such as chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating, should be tested for CD. (Strong recommendation, high level of evidence)
2. Patients with symptoms, signs, or laboratory evidence for which CD is a treatable cause should be considered for testing for CD. (Strong recommendation, moderate level of evidence)
3. Patients with a first-degree family member who has a confirmed diagnosis of CD should be tested if they show possible signs or symptoms or laboratory evidence of CD. (Strong recommendation, high level of evidence)
4. Consider testing of asymptomatic relatives with a first-degree family member who has a confirmed diagnosis of CD. (Conditional recommendation, high level of evidence)
5. CD should be sought among the explanations for elevated serum aminotransferase levels when no other etiology is found. (Strong recommendation, high level of evidence)
6. Patients with Type I diabetes mellitus (DM) should be tested for CD if there are any digestive symptoms, or signs, or laboratory evidence suggestive of CD. (Strong recommendation, high level of evidence)

The emphasis here is clearly on signs and symptoms, followed by laboratory evidence. The symptoms mentioned are the same as the ones we described earlier (steatorrhea is the technical term for the type of diarrhea mentioned above). The laboratory evidence is the presence of IgA and tTG in blood samples. Because of the possibility that first-degree relatives may be susceptible, they too are potentially candidates for screening. And, because of possible links with liver disorders, persons with elevated liver enzymes may be candidates for screening, as are persons with T1DM with suggestive symptoms. Testing for celiac disease includes upper endoscopy with biopsy of the duodenum, which is a tube connecting the stomach with the rest of the small intestine. This is not a routine procedure, and there has to be good reason for doing it; thus, the American College of Gastroenterology has stated its recommendations in such as way as to make it clear that there has to be reasonable suspicion of celiac disease before carrying out this procedure.

We should point out here that there is an immense difference between screening for celiac disease and screening for a number of cancers. The basic and essential difference is that if a patient with celiac disease symptoms initiates the gluten-free diet, the symptoms will resolve, and, what’s more important, the villi in the small intestine will re-grow. Celiac disease is not like cancer; it will not metastasize. There are certainly advantages is detecting it sooner rather than later and bringing it under control, but it’s not a race against the clock as it is with some cancers.

And as for the first question …

Should everyone with markers for celiac disease be on a gluten-free diet?

This is a hard question, no doubt about it. The gluten-free diet will almost certainly prevent the individual with markers for celiac disease from progressing to frank, symptomatic celiac disease. But if recommendations are followed, and this individual is diagnosed with celiac disease based on serologic screening and biopsies demonstrating changes in the villi lining the upper intestine, the gluten-free diet can be instituted and the individual will be restored to health. And that means not only the absence of symptoms, but also the absence of celiac markers from the blood.

In short, there should be no rush to put an asymptomatic person on a gluten-free diet.

The downside of the gluten-free diet

The question is, what do we consume instead of gluten? The usual substitute for wheat flour in food products is rice flour, and there are at least a couple of potential harms in swapping rice flour for wheat flour. One is that there is much less inherent flavor in foods made with rice flour (don’t get me wrong, I love rice, but it needs a good-tasting something served over it). So gluten-free products tend to have other stuff in them to enhance the flavor – most often sugar, but also fats and salt. Usually the gluten-free product will have more calories than the product it’s aiming to replace.

Another factor is that rice flour tends to contain traces of arsenic – not much, but enough so that if food products made with rice flour are a mainstay of your diet, you may be consuming too much arsenic. A 2014 study in Spain, reported in Consumer Reports in January, 2015, estimated that if a 165-pound man was on a diet in which rice-flour products regularly substituted for wheat-flour products, he would take in 247 micrograms of arsenic per week – about 10 times the maximum safe level. Is this cause for alarm? Probably not for most people, at least in the short term. In fact, fashionable ladies in past times used to take tiny amounts of arsenic because it was good for the complexion. We excrete arsenic extremely slowly, through the skin, hair, and fingernails, which (in the meantime) look terrific. So maybe the gluten-free diet will be attractive to girls seeking to be supermodels. But prolonged exposure even to low levels of arsenic can be harmful, and, on balance should be avoided.

“Gluten-free” has become one of those cheerful little phrases that I suspect manufacturers of food products attach to anything that they can think of in order to catch the attention of the health-conscious, whose numbers are legion. Of course, all the products that normally contain wheat flour – bread, pasta, cookies and crackers and muffins and bagels and and and … are now available in gluten-free versions. But one also sees all manner of products that would normally have no reason to contain gluten now being labelled as gluten-free – tomato sauce, salad dressing, potato chips, laundry detergent, makeup. “Gluten-free” has now, in the view of lots of people, become nothing more than a synonym for “healthy.” And, as such, it’s being employed by the marketing contingent in the same way that they use the word “green” whenever they mean to imply that whatever they’re pushing on us is energy efficient, environmentally sustainable, and morally admirable.

But how should the person with celiac disease go about following a gluten-free diet?

Ordinary common sense will steer him or her in the right direction, perhaps supplemented by the advice of a nutritionist. There are lots and lots of foods in the supermarket that are absolutely gluten free – the entire produce section, the fish counter, the meat aisle, the dairy department – none of those will have any gluten. Okay, maybe if you buy fish sticks that have already been breaded, or chicken pot pie, or pizza. But the celiac patient should not simply rely on the food products labelled gluten-free that have been prepared to look just like their non-gluten-free counterparts. More than anything else, it’s a matter of using (in the words of Miss Charlotte Truesdell, my 11th grade math teacher) the brains we were born with.

The “what do we do instead” factor

This applies not only to the gluten-free diet and to diet in general, but to many things we do in life. For example, my grandfather was advised by his wise physician to stop smoking. This was in Cuba (where I was born) and quite a long time ago, so it was perhaps an unusual recommendation. The old man was in the habit of lighting up as a reflex. Just to be doing something with his hands he would reach for a cigarillo and light up. The doctor told him to start carrying a walking stick, and if he had an impulse to fiddle with something, play with his walking stick. It seemed to work pretty well.

But what we do instead isn’t always quite so benign as playing with our walking sticks. The data in the USA these days is discouraging. When our fellow-citizens were advised to cut back on fats, what they ate instead was probably worse for their health than the fats they cut out. Consumption of carbohydrates and sugars has soared, from about a quarter of our total calories to more than a third, and in some groups, up to about 40%, with dire consequences for such diseases as Type 2 diabetes. Cut out sugary soft drinks? That’s a good start, but the data on artificially-sweetened soda pop is not cheerful. And I’ve noticed that when Alcoholics Anonymous meetings break up, a lot of the members light up as soon as they hit the sidewalk.

Fortunately, avoiding gluten, for those relatively few individuals who really must avoid gluten, doesn’t land us in a quandary. There are abundant other non-gluten carbohydrates, and the other food groups are, to adopt the chosen label, gluten-free.

Are there any possible options for celiac patients other than the gluten-free diet?

Not at present, but that doesn’t mean that the pharma outfits are sitting idle. One small biotech, ImmusanT, has completed Phase 1 studies of an agent that – if it proves effective – will permit persons with celiac disease to consume gluten-containing foods. The biotech has raised $12 million for Phase 2 proof-of-concept studies for its agent, which they have tentatively called NexVax2. GlaxoSmithKline and AbbVie are also in the hunt. So, even though celiac disease is relatively uncommon, if we go by a more-or-less 1% prevalence figure, that’s 3.5 million in the US alone, and plenty more elsewhere. Pharma is going to keep looking at ways to manage this disease, and, based on the great success in managing several other autoimmune conditions such as rheumatoid arthritis, I would expect progress.

* * * * * * *

In my last piece, I overlooked the FDA’s approval of Pfizer’s Ibrance (palbociclib), which happened on February 3, 2015, a couple of months ahead the expectations. This drug, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 & CDK6), is now approved to treat post-menopausal women with breast cancers that are estrogen-receptor responsive but not human epidermal growth factor 2 (HER2) responsive. CDK4 and CDK6 are active in promoting cancer cell division, and inhibiting their action is thought to be a promising avenue to the treatment of several other cancers. This is just another sign of the ferment of activity in cancer research that is going on in the pharmaceutical industry.

And Novartis’s panobinostat (Farydak) got FDA approval on February 23rd as treatment for multiple myeloma, a blood plasma disease that affects about 20,000 Americans annually and has a fatality rate of about 50%. The drug blocks some enzymes (histone and non-histone deacytilase enzymes, HDACs and DACs), that can foster the growth of cancer cells, and in a clinical trial in combination with two other drugs, it doubled survival from about 5 to about 10 months in patients who had failed two previous trials. As I said earlier, this hardly looks like great data, especially when considered in the light of the severe side effects that panibinostat can cause. But, as with all cancer clinical trials, modest success in the most difficult patients may be a harbinger of more clear-cut successes to come.