“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.

“Iron is essential for a number of enzymes involved in neurotransmitter synthesis. Analysis of cerebrospinal fluid in fibromyalgia syndrome (FMS) has shown a reduction in the concentration of biogenic amine metabolites, including dopamine, norepinephrine and serotonin. This study aimed to investigate the association of ferritin with FMS.”

To investigate this association serum ferritin, vitamin B12 and folic acid were measured in 46 patients with primary FMS and 46 healthy controls. Their data paints a very interesting picture:

“Binary multiple logistic regression analysis…showed that having a serum ferritin level <50 ng/ml caused a 6.5-fold increased risk for FMS.”

Here’s what the authors concluded from their findings:

“Our study implicates a possible association between FM and decreased ferritin level, even for ferritin in normal [see note below] ranges. We suggest that iron as a cofactor in serotonin and dopamine production may have a role in the etiology of FMS.”

Important: there is earlier research that validates 50 ng/ml as the correct low point for serum ferritin, but many labs have not caught up and still have a report with a reference range for ferritin that is too low. This is a key point in clinical practice.

“Iron is essential for a number of enzymes involved in neurotransmitter synthesis. Analysis of cerebrospinal fluid in fibromyalgia syndrome (FMS) has shown a reduction in the concentration of biogenic amine metabolites, including dopamine, norepinephrine and serotonin. This study aimed to investigate the association of ferritin with FMS.”

Ferritin, a protein that stores iron, is the most accurate single quantifier for iron stores in the body. Adequate iron is mandatory for the production of neurotransmitters including dopamine and serotonin (one of the reasons why depression occur around the time of menses). What did their data show?

“…having a serum ferritin level <50 ng/ml caused a 6.5-fold increased risk for FMS.”

Doctors (and everyone), notice the serum ferritin level. Many practitioners are not aware of other research showing that the common laboratory reference ranges for ferritin are too low and that 50 ng/ml should be the cut-off point. Additionally, there are a number of mechanisms by which suboptimal dopamine and/or serotonin production can affect the experience of pain and fatigue with FMS.

The authors’ conclusion is consonant with the existing evidence:

“Our study implicates a possible association between FM and decreased ferritin level, even for ferritin in “normal” ranges [quotation marks added]. We suggest that iron as a cofactor in serotonin and dopamine production may have a role in the etiology of FMS.”

If there is a question about iron, have your serum ferritin checked (at least) and make sure that it is not lower than 50 ng/ml.

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