On February 13th of 2013, I published a post entitled Fibromyalgia, Irritable Bowel Syndrome and Endotoxemia. I made the case that the high prevalence of bowel dysfunction and fibromyalgia was no mere coincidence. In today’s post, I’ll present evidence from a preliminary study out of Spain implicating non-celiac gluten sensitivity (NCGS) as a possible trigger for this disease. (1)
NCGS has received a lot of press lately, with many in the medical and nutritional communities dismissing it as a phantom disorder. Nevertheless, many researchers have come to the conclusion that NCGS is not a figment of a hypochondriac’s overactive imagination.
Commonly accepted clinical indicators of NCGS include:
- absence of tissue transglutaminase antibodies
- absence of villous atrophy in the intestinal brush border
- presence of mood and behavioral disturbances
- bone and/or joint pain
- muscle cramps
- IBS, GERD, and other gastrointestinal complaints
- leg numbness
- loss of weight
- chronic fatigue
- brain fog
- anemia and other vitamin and mineral deficiencies
- psoriasis, acne, or other skin outbreaks
- canker sores
The list is far longer than this, but that will do for now.
The researchers in the study I’m highlighting today are following 246 fibromyalgia patients who have all tested negative for celiac disease, confirmed both by an anti-tissue transglutaminase test and endoscopy. All patients have consented to try a gluten-free diet to see if doing so would improve their condition.
Of the 246 patients under study, significant clinical responses have been noted in 90 patients as of this writing. For the purposes of this study, a significant response was defined as meeting at least one of the following criteria:
- remission of pain
- a return to work
- return to a normal life as defined by the patient
- discontinuation of opioid therapy
These criteria are unusual as far as trials of this type go. Most studies rely on questionnaires where points are assigned to various subjective responses given by the patient. When utilizing such methods, it can be easy for researchers to fool themselves that something significant is happening even though the patient is far from being cured.
As fibromyalgia is a very debilitating disorder, choosing the above criteria as measures of clinical success means these patients didn’t just subjectively feel better, they actually regained a life they had lost. In other words, these criteria are more objective and harder to fudge.
In addition to going gluten-free, all participants were instructed to take iron, vitamin D and multivitamins to compensate for nutritional deficiencies. Those with a history of lactose intolerance were also encouraged to eliminate dairy from their diet.
Today’s post, like this preliminary paper, concentrates on the characteristics of twenty of these patients who responded positively to this elimination diet.
All twenty subjects are female, with a mean age of 46. These women had been suffering with this disorder anywhere from three to twenty years.
Prior to remission, eight of the twenty were also diagnosed with chronic fatigue syndrome. Seventeen were diagnosed with various gastrointestinal complaints: irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), indigestion, constipation, hiatal hernia, lactose intolerance and/or generalized colitis. There is no indication that any were screened for small intestinal fungal or bacterial overgrowth (SIFBO).
Eight patients complained of depression and migraines, while others complained of low thyroid function even after supplementation with replacement hormone. Five of these women also suffered from spondyloarthritis.
Spondyloarthritis is arthritis of the spinal column. While there are other symptoms of this arthritis non-specific to the spine, the most common symptom is lower-back pain.
Of the twenty women, eighteen carried one form or another of either the HLA-DQ2 or HLA-DQ8 genetic predisposition for celiac disease, although as I said earlier, none of these women tested positive for this autoimmune disorder. The two remaining patients carried neither marker.
Again, let me remind all of you that in North America incidence of these genetic markers in the general population is estimated to be about 50%. I say estimated because there is no systematic study to determine true prevalence.
Apart from being genetically susceptible to developing celiac disease, those who carry these genes experience prolonged periods of increased intestinal permeability whenever they ingest any amount of gluten. That said, two of these women carried neither gene so in their cases gluten’s ability to contribute to disease was not mediated by genetics.
Medical follow-up after commencement of the diet was anywhere from between five to 31 months. Eight of these women were also on a lactose-free diet.
All twenty patients experienced great improvement in pain relief. Fifteen out of the twenty experienced complete remission of their fibromyalgia. They either returned to work or to a normal life. Three patients who had been receiving opioid pain medications were able to discontinue them.
Along with reduction of pain, gastrointestinal symptoms abated. Fatigue, depression and migraines went away. Two patients who had suffered from recurring canker sores experienced remission from this as well as their psoriasis and arthritis.
Some patients experienced dramatic improvement after five months on a gluten-free diet, while others took much longer to note any results. In eight patients, reintroduction of gluten was immediately followed by a complete relapse that ceased once gluten was again removed from the diet.
Interestingly, this was one of the few studies concerning NCGS that showed elevations in immune lymphocytes (white blood cells) in the small intestine of patients prior to commencing a gluten-free diet:
Here we see intestinal stains from two of these patients at the beginning of the study. Those protrusions are villi, or hair-like fingers that compose the digestive brush border of the small intestine.
It’s apparent that there is no damage to these structures as would be the case with celiac disease. However, note the many reddish-brown dots. Those are white blood cells in a state of chronic immune activation.
Now, I suspect these immune cells were not just reacting to gluten, but to bacterial and perhaps fungal pathogens coming into contact with gut epithelial cells. Recall that inflammation on its own is entirely capable of displacing beneficial intestinal organisms and replacing them with bacterial pathogens, especially of the gram-negative variety.
It is therefore all the more remarkable that just cutting out gluten led to such dramatic results in 90 of these women without treating underlying dysbiosis. I predict that as this trial goes on, those numbers will continue to increase.
What makes this even more incredible is that this population has high rates of non-steroidal anti-inflammatory (NSAID) and opioid drug use to control pain. NSAIDs are notorious for increasing intestinal permeability, and opioids predispose to SIFBO by paralyzing gut motility.
Of course, elimination of gluten would also mean elimination of the five different gluten-opioid peptides formed during its digestion. (2) Those peptides cause everyone’s gut to slow down to some extent, and contribute greatly to constipation, fecal impaction and development of SIFBO.
Moreover, none of these women underwent antibiotic and/or anti-fungal therapy to attack the pathogens that were clearly present in their small intestine. Nor were these women instructed to make other dietary changes that would have accelerated their recovery. Among those would have been severely limiting the intake of pro-inflammatory polyunsaturated omega 6 vegetable oils, curtailment of refined sugar intake, avoidance of insoluble fiber and omega 3 supplements and refraining from binge drinking alcohol.
The results of this preliminary trial is a testament to how destructive gluten can be for certain vulnerable groups. To counter the argument that these results were nothing more than the placebo effect, they note:
“The spectrum of symptoms of our patients is wide and complex, as is typical for FM [fibromyalgia] and described in non-celiac gluten sensitivity. The reduction in the level of pain was accompanied by improvements in asthenia [lack of strength, dizziness, fatigue] and gastrointestinal and neurological symptoms, suggesting a common underlying cause related to gluten. The clinical response definition for this report was decided upon after the initial observations of impressive improvement in some patients after starting the gluten-free diet. We chose demanding outcome measures, such as the remission of FM or return to normal life, rather than changes reflected by questionnaires. To our knowledge, this degree of improvement has not been reported previously for FM. It is unlikely that our results were caused by a placebo effect. The majority of patients had severe distress and disability and were unable to cope normally with daily activities or on sick leave, despite having been treated with many different regimens for years. In FM clinical trials, the placebo effect has been very modest and transient, in contrast to the great long-term improvement of our patients. Lactose-free diet and the addition of vitamins could be confounders, but the majority of the patients with lactose-free diet had tried it before without improvement of FM, and in our experience FM does not have relevant clinical improvement [sic] just adding vitamins and minerals. Furthermore, the reintroduction of gluten, for 7 patients, was followed by FM relapse; when re-introduced, the strict gluten-free diet led to clinical improvement.”
Of course, that probably won’t convince the naysayers out there who continue to warn of the supposed dire consequences of going on a gluten-free diet. What those consequences are have never been clear to me unless an inability to eat pizza chased down by beer is the dietary equivalent of the holocaust.
Once again, I warn all my readers that ingesting this grass protein on a regular basis is not the wisest thing to do for your digestive or overall health, especially if you are a carrier of either the HLA-DQ2 or HLA-DQ8 haplotype. If you suffer from fibromyalgia, an autoimmune disorder, chronic inflammation, metabolic syndrome, psychiatric distress or gastrointestinal upset, the first piece of advice I always give to those who ask for it is to eliminate these grains from your diet. It isn’t the only dietary modification I recommend, but it’s foundational.
Trying to treat any inflammatory disease while simultaneously eating a grain protein that adds fuel to that fire is an astoundingly self-defeating strategy. I don’t deny there are those who get better in spite of refusing to make this dietary change, but the road to recovery would be far less of a struggle without eating foods known to disassemble intestinal tight junction proteins and increase endotoxemia. (3) (4)
One last thought. In their summation, these researchers point out that vitamin and mineral supplements have never been proven effective at curing this condition, and they are absolutely correct. Whatever nutritional deficiencies these people suffer from is a symptom of a small intestine incapable of properly absorbing nutrients from food. While short-term supplementation certainly has a role to play in those with confirmed vitamin and mineral deficits, it is incapable on its own of strengthening the gut wall to a level necessary to prevent translocating gut pathogens.
So I agree that vitamin and mineral supplementation is not a confounder worthy of consideration for explaining the positive results reported in this trial. The same cannot be said about any prebiotic soluble fibers these women may have eaten while on their gluten-free diet.
Prebiotics have in many animal and human studies been consistently shown to increase levels of beneficial bacteria in the colon, especially of the bifidobacteria variety. As I wrote in this post, the addition of inulin to a diet containing wheat pasta mitigated gut leakiness caused by eating gluten.
Fermentation of these soluble fibers by beneficial colonic bacteria produces, as many of you already know, short-chain saturated fatty acids. One of these fatty acids, butyrate, is used by all cells lining the digestive tract for repair and maintenance. This fatty acid is also essential for ensuring integrity of the gut wall. This is no minor benefit in those suffering from a disorder caused by endotoxins.
Apart from short-chain fatty acid production, an increase in beneficial lactobacillus and bifidobacteria simultaneously means a reduction in gut pathogens via competitive advantage. And it’s awfully difficult for a pathogen to attach itself to the gut wall and provoke a chronic inflammatory immune response if that same gut wall is populated by friendly organisms.
So could the improvements seen in some of these women be confounded by prebiotic intake? I have no idea, but it’s a question certainly worth exploring.
Finally, ingesting probiotics, either via supplements or by eating fermented foods, would also be highly recommended for these patients. As I’ve repeatedly written, replenishment of friendly bacteria and their feeding by prebiotic fibers are essential steps for sealing and healing a gut, including one damaged by prior gluten ingestion.