Gluten-free diet can improve depression and behavioral problems in adolescents

Posted on May 28, 2010 by Dr. Jonathan

As the authors of this study published in the journal BMC Psychiatry observe:

“Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment.”

We are equally concerned with the ‘non-celiac’ aspects of gluten sensitivity. Gluten related inflammation in the brain can manifest as a host of cognitive, emotional and neurodegenerative disorders in the absence of intestinal manifestations. This is often referred to as “silent celiac disease”:

“Coeliac disease is an under-diagnosed autoimmune type of gastrointestinal disorder resulting from gluten ingestion in genetically susceptible individuals. Non-specific symptoms such as fatigue and dyspepsia are common, but the disease may also be clinically silent.”

They further note that:

“”Depressive symptoms and disorders are common among adult patients with coeliac disease, and depressive and disruptive behavioural disorders are highly common also among adolescents, particularly in the phase before diet treatment. Recently 73% of patients with untreated coeliac disease – but only 7% of patients adhering to a gluten-free diet – were reported to have cerebral blood flow abnormalities similar to those among patients with depressive disorders.”

Their data revealed abnormalities in tryptophan assimilation (tryptophan is the amino acid precursor to serotonin) and prolactin levels in adolescents with celiac disease and depression prior to treatment. Consequently…

“A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients’ baseline condition, coinciding with significantly decreased coeliac disease activity…”

They also make a fascinating observation that links gluten sensitivity, inflammation, and the serotonergic aspect of depression unrelated to malabsorption:

“…increased production of interferon-γ (IFN-γ), known to be the predominant cytokine produced by gluten-specific T-cells in active coeliac disease, can suppress serotonin function both directly and indirectly by enhancing tryptophan and serotonin turnover…even without malabsorption.”

To diagnose gluten sensitivity in the absence of celiac disease the gluten gene sensitivity test is the most reliable method for a number of reasons.

Diarrhea without infection or allergy can be due to autoimmune pancreatic insufficiency

Posted on May 9, 2010 by Dr. Jonathan

Clinical Gastroenterology & Hepatology This insightful paper just published in the journal Clinical Gastroenterology and Hepatology sheds light on why some patients may have persistent diarrhea even when they have no infection, are avoiding allergic foods, and not under unusual stress. The authors begin by observing…

“Patients with irritable bowel syndrome (IBS) might have other underlying pathologies. Pancreatic disease can be elusive—especially in the early stages, and some symptoms overlap with those of IBS. We evaluated the prevalence of exocrine pancreatic insufficiency in diarrhea-predominant IBS (D-IBS) and assessed the effects of pancreatic enzyme supplementation.”

Their study compared patients with chronic diarrhea who met the criteria for D-IBS with a control group without diarrhea for stool frequency, stool consistency and fecal elastase-1 (Fel-1, also called pancreatic elastase 1), a definitive metric for the production of pancreatic digestive enzymes. What did their data show?

“Fel-1 levels were less than 100 μg/g in stool from 19 of 314 patients with D-IBS (6.1%)…and none of 95 controls. After enzyme supplementation, improvements in stool frequency and abdominal pain were observed in patients in group 1 (D-IBS, but not in group 2.”

This result shows that pancreatic enzyme insufficiency may not be the most common cause of chronic diarrhea but it is important to not overlook.

“Pancreatic exocrine insufficiency was detected in 6.1% of patients who fulfilled the Rome II criteria for D-IBS. In these patients, pancreatic enzyme therapy might reduce diarrhea and abdominal pain. Pancreatic exocrine insufficiency should be considered in patients with D-IBS.”

How reliable is fecal pancreatic elastase for diagnosing exocrine (secreting directly or through a duct) pancreatic enzyme deficiency? The authors of this study published in the Journal of Gastroenterology asked the same question. Their conclusion:

“Fecal pancreatic elastase is a reproducible marker for severe exocrine pancreatic insufficiency. This test is valuable for longitudinal follow-up of exocrine pancreatic function.”

This is convenient because fecal pancreatic elastase is part of our regular gastrointestinal function profile. But we still have to ask, “What are the underlying causes of the loss of ability for the pancreas to produce adequate digestive enzymes?” Besides well-known conditions including cystic fibrosis and certain malignancies, idiopathic (cause unknown) chronic pancreatitis (ICP) is a big category. How often may this be an autoimmune condition?

Pancreas The authors of another paper published earlier in Clinical Gastroenterology and Hepatology looked into this.

“The proportion of patients with idiopathic chronic pancreatitis (ICP) that have an autoimmune origin is unknown. Three forms of ICP have been described: pseudotumoral, duct-destructive, and usual chronic pancreatitis. The aim of this study was to identify autoimmune stigmata in the 3 forms.”

What did their data show?

“Clinical or biochemical autoimmune stigmata are present in 40% of patients with ICP. Autoimmune mechanisms may be frequent in idiopathic pancreatitis.”

Alimentary Pharmacology & Therapeutics Readers here will not be surprised by this fact considering how common autoimmune conditions have become. Is this a concern for the many people who are sensitive to gluten? Is it possible for people with gluten sensitivity to have persistent diarrhea due to pancreatic insufficiency even after they are no longer eating gluten? The authors of this paper published in the journal Alimentary Pharmacology & Therapeutics asked that question having been compelled by this observation:

“Patients with coeliac disease may have diarrhoea despite being on a gluten-free diet.”

They set about their investigation with this aim:

“To assess whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in coeliac patients with chronic diarrhoea.”

What conclusion did their data lead them to?

“Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.”

Importantly, they also observed that stool frequency reduced from 4 times per day to 1 time per day in 18 of 20 subjects who were given pancreatic enzyme supplementation.

If you’re thinking now that the pancreas is one of the many possible targets for an autoimmune attack with gluten sensitivity, yet another paper published in Clinical Gastroenterology and Hepatology would confirm your suspicion. Elevated pancreatic enzymes in the serum result from destruction of pancreas cells…

“We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD (celiac disease) patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.”

Another paper published in the World Journal of Gastroenterology reviews the various causes of idiopathic pancreatitis and agrees:

“Intriguingly, recurrent pancreatitis can be caused by celiac disease. The mechanism appears to be duodenal inflammation and associated papillary stenosis causing pancreatitis.”

Important: Consuming gluten for years without knowing (or ignoring) that you have a gluten sensitivity can result in the irretrievable loss of tissues subject to autoimmune attack and their function (such as the cells of the pancreas that produce enzymes). The sooner you find out and adhere to avoidance the better.

Female reproductive disorders and gluten sensitivity

Posted on April 30, 2010 by Dr. Jonathan

Minverva Ginecologica As the authors of this paper published in the journal Minerva Ginecologica state:

“In the past coeliac disease, or intolerance to gluten, has been considered a rare disease in infancy, whose most important signs were chronic diarrhea with malabsorption and reduced growth. However, besides this classical form, there are a number of other clinical and subclinical forms which may appear even in the adult life and without any overt intestinal sign.”

The authors defined their objective:

“The aim of the present paper is to describe and evaluate the effects of coeliac disease on female reproduction. Such effects include delayed menarche, amenorrhea, infertility and early menopause.”

In addition, they noted that…

“Epidemiological studies show that besides reduced fertility, affected women are at higher risk of reproductive problems such as pregnancy loss, low birthweight of offspring and reduced duration of breastfeeding…the possible prevention or treatment of the reproductive effects is only the lifelong maintenance of a gluten-free diet.”

Another paper published in the Journal of Reproductive Medicine reports on a case that highlights the link between gluten sensitivity and amenorrhea. The authors’ conclusion:

“Celiac disease should be considered in patients presenting with malnutrition and primary amenorrhea.”

This was followed by a much more extensive study published recently in the same journal. The authors summarize an extensive body of literature on the subject:

“In women, this disease (celiac, gluten sensitivity) may have implications on menstrual and reproductive health. The symptom complex includes delayed menarche, early menopause, secondary amenorrhea, infertility, recurrent miscarriages and intrauterine growth restriction. These women benefit from early diagnosis and treatment. Therefore, celiac disease should be considered and screening tests performed on women presenting with menstrual and reproductive problems and treated accordingly.”

They offer an exhortation to doctors in their conclusion:

“Evidence in the literature suggests that celiac disease should be suspected in females with menstrual abnormalities, infertility and adverse pregnancy outcome. All health care providers should be aware of these diverse manifestations of the disease. Treating the disease has a benefit and may lead to prevention of symptoms and improvement in the quality of life…It is challenging to identify women with silent celiac disease and treat them with a gluten-free diet and nutrient supplements, which may lead to prevention of menstrual and other reproductive dysfunction.”

Another paper published in the journal Gynecologic and Obstetric Investigation focuses on the impact of gluten sensitivity on the reproductive cycle, fertility, pregnancy, and menopause. The authors explain that…

“Celiac disease (gluten-sensitive enteropathy) may manifest clinically with an array of nongastrointestinal symptoms among which are: dermatitis herpetiformis; dementia; depression; various neurological symptoms; osteoporosis; osteomalacia; dental enamel defects, and anemia of various types. Important data have accumulated in recent years regarding the association between celiac disease, fertility and pregnancy. Many primary care obstetricians and gynecologists and perinatologists are not aware of these important relationships.”

What does the scientific evidence establish?

“Review of the literature reveals that patients with untreated celiac disease sustain a significantly delayed menarche, earlier menopause, and an increased prevalence of secondary amenorrhea. Patients with untreated celiac disease incur higher miscarriage rates, increased fetal growth restriction, and lower birth weights.”

An interesting paper that dramatically shows the difference between adhering and not adhering to a gluten free diet for female reproductive health was published in the Journal of Clinical Gastroenterology:

“This study shows a broad analysis of gynaecological and obstetrical disturbances in patients with celiac disease in relation to their nutritional status and adherence to a gluten-free diet.”

In their investigation the authors analyzed data on adults and children/adolescents with gluten sensitivity, taking into consideration nutritional status and gluten-free diet adherence, and compared them to adults and adolescents with irritable bowel syndrome (not due to gluten) as a control group. What did the data show?

“…adult celiac patients, irrespective of the nutritional status…presented delayed menarche, secondary amenorrhea, a higher percentage of spontaneous abortions, anemia and hypoalbuminemia…After treatment, patients presented with normal pregnancies and one patient presented spontaneous abortion. The adolescents who were not adherent to gluten-free diet presented delayed menarche and secondary amenorrhea.”

They state what should by now be obvious in their conclusion:

“Therefore, celiac disease should be included in the screening of reproductive disorders.”

Important: gluten sensitivity without celiac manifestations (1) must be treated the same way as celiac disease and (2) cannot be diagnosed by the usual celiac tests for tissue transglutaminase antibodies, etc. Antibody levels, including anti-gliadin (gluten) antibodies, can fluctuate for a number of reasons resulting in false negatives. The gluten gene sensitivity test can be relied on for a dependable result. This post could go on at great length but the message is clear: for female reproductive disorders gluten sensitivity must be considered as a possible contributing cause.

Men: you are not immune. I am finding gluten sensitivity to be a common cause of low testosterone levels (hypogonadia).

If I’m sensitive to gluten, can I eat corn or oats?

Posted on March 11, 2010 by Dr. Jonathan

This becomes an important question when someone realizes how much they benefit from avoiding gluten due to celiac disease or non-celiac gluten sensitivity. The evidence suggests that corn (maize) has to be considered on an individual basis. It is possible, but not certain, that you may react to corn when you are sensitive to wheat gluten.

GUT Consider this study that was published in the journal GUT, An International Journal of Gastroenterology and Hepatology. The authors investigated how nitric oxide is part of the intestinal inflammatory reaction reaction to gluten, and how it relates to the white blood cell response. They noted this in their conclusion:

“Mucosal activation of neutrophils and eosinophils [white blood cells] precedes pronounced enhancement of mucosal NO [nitric oxide] production after rectal wheat gluten challenge in patients with coeliac disease. Some of our coeliac patients displayed signs of an inflammatory reaction, as measured by NO and granulocyte markers, after rectal corn gluten challenge.”

So it depends on the individual. The more serious your condition the more important it is to check yourself for corn sensitivity with the immunological ‘gold standard’—a properly managed elimination-provocation protocol.

We are also bereft of a perfectly decisive indication for oats because rare individuals can react, though this study published in the Scandinavian Journal of Gastroenterology indicates that most celiac patients can tolerate them. First the authors note that…

“We have…identified three adult coeliac disease patients who developed a flare of active coeliac disease after ingestion of oats, which suggests that oats might not be entirely innocent in coeliac disease.”

They set out to compare the immune response to oats and wheat by comparing production of the main intestinal antibody (IgA) that participates in the reaction. Although other immune activity was observed,…

“No significant differences were found in IgA against oats in oats-eating and non-oats-eating coeliac disease patients.”

Their conclusion:

“Ingestion of oats does not cause increased levels of IgA against oats in adult coeliac disease patients on a gluten-free diet. The findings support the notion that most adult coeliac disease patients can tolerate oats.”

Note the “most”. And even if you are not sensitive to oats, it is important to be sure that they are certified gluten-free. Otherwise they can be contaminated with gluten during storage, transport, processing and packaging.

What about blood tests for food allergies? Too many variables influence antibody tests for them to give a reliable indication. If you have a serious condition with an autoimmune basis, it’s best to consult with a functional medicine practitioner who can help you through an elimination-provocation protocol (eliminating and re-introducing foods), and who knows how to use objective lab tests to profile your immune imbalance.

Gluten sensitivity and brain disease: neuronal transglutaminase

Posted on March 8, 2010 by Dr. Jonathan

The authors of this paper published in Annals of Neurology make an important statement:

“Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity.”

Antibodies directed toward transglutaminase in the gut are a well-known diagnostic feature of celiac disease. These investigators have identified another member of the transglutaminase family:

“…a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.” They found that “Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement.”

(Ataxia is loss of the ability to coordinate muscle movement, especially as it appears with difficulty walking.) Their conclusion:

“Antibodies against transglutaminase 6 can serve as a marker…to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.“

If you are gluten sensitive, you can have neurological disease without celiac involvement.

Gluten can cause brain lesions like ALS

Posted on February 13, 2010 by Dr. Jonathan

Here is another alarming paper published in the American Journal of Neuroradiology reporting a case of apparent Amyotrophic Lateral Sclerosis (ALS, also known as Lou-Gehrig’s Disease) that was caused by a reaction to gluten. ALS is a particularly vicious autoimmune disease that attacks the central nervous system, typically following a terminal course. The authors note regarding celiac disease that “Initial symptom presentation is variable and can includeneurologic manifestations that may comprise ataxia, neuropathy,dizziness, epilepsy, and cortical calcifications rather thangastrointestinal-hindering diagnosis and management.” I’m sure they were relieved to find that “MR imaging findings suggestive of ALS improved after gluten-free diet institution.” (MR = magnetic resonance)

Increase in death risk from gluten-related gut inflammation

Posted on February 2, 2010 by Dr. Jonathan

This paper published in JAMA (The Journal of the American Medical Association) recently examined the risk of death associated with celiac disease. The investigators found a modest but significant increase in risk of death not only with celiac, but also with latent celiac disease and small intestine inflammation. They note that “This risk increase was also seen in children.” The take home message here is that even in the absence of gastrointestinal symptoms (“latent celiac disease”), there is an overall negative impact. The authors’ conclusion: “Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased.”

Atrial fibrillation and subclinical hyperthyroidism (and gluten sensitivity)

Posted on December 8, 2009 by Dr. Jonathan

It’s necessary to bear in mind when dealing with atrial fibrillation that subclinical hyperthyroidism is a common cause. Subclinical means that there are symptoms from excess thyroid hormone activity even though the lab values appear normal. There are a plethora of recent studies that investigate this phenomenon; here are a few. The authors of the first paper state: “Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fibrillation.”

Now the plot thickens. Here is a paper recently published in Nature Reviews Endocrinology discussing the link between celiac disease (gluten sensitivity) and autoimmune thyroiditis. Here is another, fresh off the presses, from the journal Gut. One more for now: this paper published in the journal Thyroid demonstrates that the antibodies involved in celiac disease also bind to thyroid follicles.

Brain lesions like Lou Gehrig’s Disease from reactions to gluten

Posted on December 1, 2009 by Dr. Jonathan

Here is another report just published in the American Journal of Neuroradiology describing a case of white matter (brain tissue) lesions suggesting amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) that turned about to be a neurological manifestation of gluten sensitivity. Of special note: “MR [magnetic resonance] imaging findings suggestive of ALS improved after gluten-free diet institution.”

Schizophrenia and autoimmune diseases

Posted on November 24, 2009 by Dr. Jonathan

This important paper was published in the American Journal of Psychiatry. The authors state, “Thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren’s syndrome had higher prevalence rates among patients with schizophrenia,” and further conclude, “Schizophrenia is associated with a larger range of autoimmune diseases than heretofore suspected. Future research on comorbidity has the potential to advance understanding of pathogenesis of both psychiatric and autoimmune disorders.” In my experience, the autoimmune component must be recognized and treated. A couple related studies:

Vitamin D deficiency and schizophrenia published in Schizophrenia Bulletin in April, 2009
Gluten sensitivity and schizophrenia also in Schizophrenia Bulletin in June, 2009