“The purpose of this study was to investigate whether vitamin B6 supplementation had a beneficial effect on inflammatory and immune responses in patients with rheumatoid arthritis (RA).”

The control group of patients was given 5 mg/day of folic acid only while the study group was given 100 mg/day of vitamin B6 in addition for 12 weeks. Indicators of inflammation (C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lymphocyte subsets were measured on day 1 (week 0) and after 12 weeks (week 12) of the intervention.

At the end of twelves the data painted this picture:

“In the group receiving vitamin B6, plasma IL-6 and TNF-α levels significantly decreased at week 12. Plasma IL-6 level remained significantly inversely related to plasma PLP (pyridoxal 5′-phosphate, B6) after adjusting for confounders.”

The bottom line conclusion is worth bearing in mind when evaluating any autoimmune disorder because underlying causal factors are similar regardless of the specific tissue under attack:

“A large dose of vitamin B6 supplementation (100 mg/day) suppressed pro-inflammatory cytokines (that is, IL-6 and TNF-α) in patients with RA.”

“Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring’s dopamine function.”

The authors measured the adverse behavioral and neurochemical changes from challenging the dopamine circuits with turpentine to trigger an inflammatory immune response, both with and without maternal iron supplementation. They demonstrated that…

“Both the behavioral and neurochemical changes were prevented by maternal iron supplementation.“

We already know that iron is a critical nutrient for dopamine production in the adult. Their conclusion sums up why prenatal iron status is important in preventing neurodevelopmental disorders including schizophrenia in the offspring.

“…mechanisms behind postoperative insulin resistance and impaired glucose utilization…”

They shrewdly analyzed the expression of 21 target genes in abdominal adipose (fat) tissue from samples taken at the beginning and end of patients undergoing abdominal surgery. What did the data show?

“After surgery, both sc [subcutaneous] and omental adipose tissue mRNA levels of genes involved in the IL6 and nicotinamide phosphoribosyltransferase pathways were increased, whereas mRNA levels of insulin receptor substrate 1 and adiponectin were reduced. TNF pathway genes were differently regulated between sc and omental adipose tissue, and glucose transporter 4 mRNA levels were decreased only in omental adipose tissue.”

In other words, surgery elicits a shift in genetic expression that favors insulin resistance and inflammation. The authors conclude:

“The transcriptional output of pivotal inflammatory and insulin signaling pathway genes is altered after surgery…This could be of importance for the metabolic aberrations associated to postsurgical complications…”

This helps to understand why patients who are lucky enough to receive adjunctive support for the insulin and inflammatory signaling pathways and receptors recover faster and with less complications.

“The mechanisms behind postoperative insulin resistance and impaired glucose utilization are not fully understood…In this study, we aimed to specifically evaluate the transcription profile of genes in the insulin and adipokine signaling pathways…after surgical injury.”

Adipokines are cytokines such as IL-6 and TNFα secreted by fat cells. The authors measured changes in the messenger RNA (mRNA) levels that code for insulin signaling and inflammatory cytokines to define how genes alter their expression in response to a surgical trauma. Their data showed a signficant effect:

“After surgery…adipose tissue mRNA levels of genes involved in the IL6 and nicotinamide phosphoribosyltransferase pathways were increased, whereas mRNA levels of insulin receptor substrate 1 and adiponectin were reduced.”

Their conclusion is important for surgeons and their patients:

“The transcriptional output of pivotal inflammatory and insulin signaling pathway genes is altered after surgery…This could be of importance for the metabolic aberrations associated to postsurgical complications, such as insulin resistance and hyperglycemia.”

If you are anticipating an elective procedure and your surgeon is not trained to design a supportive protocol based on an evaluation using the appropriate tests, you may wish to seek out a practitioner experienced in the functional approach.

“Although magnesium may favorably affect metabolic outcomes, few studies have investigated the role of magnesium intake in systemic inflammation and endothelial dysfunction in humans.”

The endothelium is the living lining of blood vessels, alive with functions. The authors correlated magnesium intake with plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α receptor 2 (TNF-α-R2), and other markers of inflammation and endothelial function. Their data amounted to this straightforward conclusion:

“High magnesium intake is associated with lower concentrations of certain markers of systemic inflammation and endothelial dysfunction in postmenopausal women.”

Don’t forget that suboptimal magnesium levels are extremely common, become more likely with stress of various kinds (long-haul air travel for example), and magnesium excretion is increased by alcohol consumption. I have observed over thirty years that it is relatively very rare for lower extremity muscle cramps that occur at rest to not subside when magnesium status is restored. When you make the cramps go away with magnesium you’re accomplishing numerous other benefits.

Note: I have found that when the usually well tolerated bioavailable forms such as magnesium glycinate at appropriate dosages cause diarrhea, there is always a pre-existing intestinal inflammation that must be diagnosed and treated.

“The aim of this randomized, placebo-controlled, double-blind trial was to investigate changes in the content of 10 cytokines in the human peripheral blood after transcutaneous [through the skin] and in vitro [to blood removed from the body] irradiation with polychromatic visible and infrared (IR) polarized light…”

The magnitude of the effect that they observed by just applying the light to the sacral area of the study subjects is surprising:

“A dramatic decrease in the level of pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ was revealed: at 0.5 h after exposure of volunteers (with the initial parameters exceeding the norm), the cytokine contents fell, on average, 34, 12, and 1.5 times. The reduced concentrations of TNF-α and IL-6 were preserved after four daily exposures, whereas levels of IFN-γ and IL-12 decreased five and 15 times. At 0.5 h and at later times, the amount of anti-inflammatory cytokines was found to rise: that of IL-10 rose 2.7–3.5 times (in subjects with normal initial parameters) and of TGF-β1 1.4–1.5 times.”

But if you expose just the area over the sacrum, what happens when that blood mixes with the rest of the circulation?

“Similar regularities of the light effects were recorded after in vitro irradiation of blood, as well as on mixing the irradiated and non-irradiated autologous blood at a volume ratio 1:10 (i.e., at modeling the events in a vascular bed of the exposed person when a small amount of the transcutaneously photomodified blood contacts its main circulating volume).”

In other words, a small limited application causes system-wide effects. Considering how much we need therapies that physiologically modulate the inflammatory response without side effects, the authors’ conclusion is extremely compelling:

“Exposure of a small area of the human body to light leads to a fast decrease in the elevated pro-inflammatory cytokine plasma content and to an increase in the the anti-inflammatory factor concentration, which may be an important mechanism of the anti-inflammatory effect of phototherapy. These changes result from transcutaneous photomodification of a small volume of blood and a fast transfer of the light-induced changes to the entire pool of circulating blood [!].”

Here’s a little more from the large body of research published in the same journal:

• LLLT can modulate inflammatory processes in a dose-dependent manner and can be titrated to significantly reduce acute inflammatory pain in clinical settings.
• Laser therapy was effective in preventing and treating oral effects induced by radiotherapy and chemotherapy, thus improving the patient’s quality of life.
• LLLT reduces inflammatory signs (more effectively than LED) in arthritis.
• Salivary levels of inflammatory cytokines TNF-α and IL-6 are reduced in patients with stomatitis (mouth sores).

By the way, this is interesting in connection with the earlier post on the infrared treatment of depression.

“An experiment…tested the hypothesis that the mere visual perception of disease-connoting cues promotes a more aggressive immune response.”

The experimental subjects were exposed to either photographs depicting symptoms of infectious disease or photographs of guns.

“After incubation with a model bacterial stimulus, participants’ white blood cells produced higher levels of the proinflammatory cytokine interleukin-6 (IL-6) in the infectious-disease condition, compared with the control (guns) condition.”

This may not be the first study to demonstrate this effect, but the authors assert…

“These results provide the first empirical evidence that visual perception of other people’s symptoms may cause the immune system to respond more aggressively to infection.”

It’s well known that though we can cognitively discriminate between a photo depicting infection and the immediate material presence of it, our autonomous physiological response does not. Now consider the significance for autoimmune disease when there is hyperarousal of attention to the possibility of infection. This is one of the reasons why I am convinced that dogmatically insisting on a diagnosis of chronic infection (such as Lyme disease) when the most sensitive and advanced tests provide zero evidence—and at the same time demonstrable autoimmune phenomena are present—is doing patients a disservice.

“Endometriosis is classically described as the presence of both endometrial glandular and stromal cells outside the uterine cavity, mainly in the pelvis. The pathogenesis of this enigmatic disorder still remains controversial despite extensive research. Although multiple theories have been put forth to explain the pathophysiology and pathogenesis of endometriosis, the retrograde menstruation theory of Sampson is the most widely accepted. However, since retrograde menstruation occurs in most of the reproductive age women, it is clear that there must be other factors which may contribute to the implantation of endometrial cells and their subsequent development into endometriotic disease.”

The authors argue that immune dysfunction must be playing an important role:

“There is substantial evidence to support that the alterations in both cell-mediated and humoral immunity contribute to the pathogenesis of endometriosis.

They note that immune dysregulation is associated with inadequate removal of ectopic endometrial cells from the peritoneal cavity.

“Moreover, increased levels of several cytokines and growth factors which are secreted by either immune and endometrial cells seem to promote implantation and growth of ectopic endometrium by inducing proliferation and angiogenesis.”

Finally, they make important observation:

“Endometriosis has also been considered to be an autoimmune disease, since it is often associated with the presence of autoantibodies, other autoimmune diseases, and possibly with recurrent immune-mediated abortion.”

This review published recently in the journal Reproduction concentrates on the role of inflammation:

“It is well recognised that many physiological reproductive events such as ovulation, menstruation, implantation and onset of labour display hallmark signs of inflammation. …Moreover, initiation and maintenance of inflammatory pathways are the key components of many pathologies of the reproductive tract and elsewhere in the body. The onset of reproductive disorders or disease may be the result of exacerbated activation and maintenance of inflammatory pathways or their dysregulated resolution.”

Specifically in regard to endometriosis they observe:

“Recent reports suggest that dysregulation of inflammatory factors play a role in endometriosis-associated reproductive failure…The concentration of inflammatory cytokines (IL1B and TNF) and PGs (PGE2 and PGF2{alpha}) produced by peritoneal macrophages and pro-inflammatory chemokines for monocyte/macrophages and for granulocytes is elevated in women with endometriosis…”

What other evidence might we find of inflammatory and autoimmune phenomena in endometriosis? This paper published in the journal Gynecological Endocrinology begins by noting how common a problem this is:

“Endometriosis affects 10–20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.”

The authors studied the correlation of the cytokines interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), glycodelin and other factors in the peritoneal fluid with pain reported by patients undergoing laparoscopy, and pain during menstruation and intercourse. The presence of endometriosis was histologically confirmed (microscopic examination of the cellular structure).

What did their data show?

“TNF-α and glycodelin correlated positively with the level of menstrual pain…Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-α and glycodelin…TNF-α and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.”

If you are treating or you suffer from endometriosis (or severe dysmenorrhea without a diagnosis of endometriosis), is it important to investigate the autoimmune inflammatory components? This and other evidence indicates that it is.

“The response to arterial wall injury is an inflammatory process, which over time becomes integral to the development of atherosclerosis and subsequent plaque instability…In this review, a model of plaque rupture is hypothesized with two stages of inflammatory activity.”

In the first stage buildup of cholesterol crystals inside the “foam” cells that accumulate cholesterol induces their death (“apoptosis”); these dead cells elicit an inflammatory response that gathers more lipids into a vulnerable plaque. In stage two further expansion of crystals leads to intimal (blood vessel wall) injury…

“…which can manifest as a clinical syndrome with a systemic inflammation response…We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion, which can tear the plaque cap. This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome.”

The authors refer to their previous work showing that alcohol, aspirin and statins can dissolve cholesterol crystals. Their conclusion:

“…we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis.”

Of course there are a number of other pathways to  inflammation in cardiovascular disease (please see related posts) but this is one of the reasons why I prefer that patients who have both high cholesterol and evidence of inflammation have the benefit of the natural statin derived from red rice yeast with the necessary supportive and protective cofactors including coenzyme Q10. This paper published recently in the American Journal of Cardiology provides evidence that red rice yeast is as effective and better tolerated than the commonly prescribed drug pravastatin:

“The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia.”

The authors enrolled adults who had to discontinue statins due to muscle pain. Their findings are reassuring for those who prefer a natural alternative to pharma statins:

“The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.”

This is a serious issue. Statin-associated myalgia or the diagnosis rhabdomyolysis does not do justice to the devastating side effects I recently observed in a patient who had a bad reaction to lovastatin.

But how do we know when to intervene since high cholesterol alone is not a reliable risk factor and CRP (c-reactive protein) may not be elevated if the inflammation it is supposed to report is also preventing the liver from making it? One very helpful test for discriminating whether high cholesterol is contributing to vascular disease is the lipoprotein-associated phospholipase A2 (Lp-PLA2, PLAC) test, described here in an earlier post, that is associated specifically with inflammation in plaques. Another relies on the fact that it is cholesterol that has been damaged by oxidation that participates in the vascular lesion. To gauge this we can measure lipid peroxides. As this paper published in the journal Atherosclerosis documents, atherosclerosis is strongly associated with the presence of oxidized LDL:

“We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33–66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness…Regression analysis indicated that the carotid intima-media thickness and…the ox-LDL:LDL ratio…were the only factors associated independently with the severity of coronary atherosclerosis.”

We have also a fascinating study just published in the German medical journal Seminars in Thrombosis & Hemostasis that shows how oxidized LDL taken up by platelets induces inflammation in the blood vessel:

“Platelets are involved in the initiation of atherosclerosis by adherence to inflamed endothelium…In this study we investigated the functional consequences of oxidized low-density lipoprotein (oxLDL) uptake on platelet function and interaction with the endothelium.”

The authors were actually able to visualize the intracellular vesicles (microscopic sacs) containing the oxidized LDL using immunoflorescence microscopy. They made a fascinating observation: the platelets containing oxLDL provoked more cellular stickiness than regular LDL, oxLDL in the bloodstream or platelets without oxLDL.

“Furthermore, oxLDL-laden platelets induced foam cell development from CD34+ progenitor cells. On endothelial regeneration, oxLDL-laden platelets had the opposite effect: The number of CD34+ progenitor cells (colony-forming units) able to transform into endothelial cells was significantly reduced in the presence of oxLDL-platelets, whereas native LDL had no effect.”

This is a striking insight: it was only the oxidized LDL that prevented the endothelial cells (lining the blood vessel wall) from repairing, not the ‘native’ LDL.

Doctors and patients alike need to bear in mind the summary of their findings:

“Our results demonstrate that activated platelets internalize oxLDL and that oxLDL-laden platelets activate endothelium, inhibit endothelial regeneration, and promote foam cell development. Platelet oxLDL contributes significantly to vascular inflammation and is able to promote atherosclerosis.”

But, you may ask, since diabetes and pre-diabetes (metabolic syndrome) are so strongly associated with cardiovascular disease shouldn’t there be some kind of connection here? This study published in the journal Lipids shows the evidence that there is.

“Oxidized low-density lipoprotein (ox-LDL) plays a key role in the progression of atherosclerosis and diabetes complications. The aim of this study was first, to evaluate the association between ox-LDL and diabetes duration, and second, to examine serum level of ox-LDL in patients with prolonged diabetes and a desirable LDL-cholesterol level.”

It’s important to appreciate that the study group had ‘regular’ LDL in the desirable range, so a typical blood test would appear to be fine. Their very interesting observation is that the longer the person had diabetes (= the longer the risk factor for cardiovascular disease was building up) the more oxLDL they had in proportion to regular LDL:

“The ox-LDL-to-LDL ratio was dramatically higher in patients with diabetes duration >5 years in comparison to newly diagnosed patients and healthy participants. Ox-LDL was significantly associated with diabetes duration.”

Their final comments must be borne in mind by anyone caring for patients with both diabetes and a significant burden of insulin resistance:

“In conclusion, this study showed that the serum ox-LDL level increases with the length of diabetes, even though the patients’ LDL-cholesterol level is maintained at a desirable level. Our findings highlight that possibly more attention should be focused on markers of oxidative stress in the management of lipids in diabetic patients.”

Can we reliably measure oxidized LDL as implied by the lab test mentioned above? This study published in the journal Blood Pressure assure us that we can:

“Cardiovascular diseases are accompanied by the presence of active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using malondialdehyde (MDA)-modified low-density lipoprotein (LDL) analyses as a diagnostic and prognostic biomarker.”

MDA-modified LDL is the same as oxLDL. What conclusion did they draw from their data?

“MDA-modified LDL estimation has a diagnostic accuracy and may be used as an independent biochemical marker for atherosclerosis.”

Truthfully, the functional approach to cardiovascular disease encompasses a number of other important aspects, but I’m wondering if you’ve gotten this far. As a reward for your diligence I’ll conclude this limited post with a few interesting items of satisfying practical significance. First we have a paper just published in The Journal of Steroid Biochemistry & Molecular Biology that reassures us of the benefit of vitamin D in the prevention and treatment of cardiovascular disease.

“Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In type 2 diabetics, the prevalence of vitamin D deficiency is 20% higher than in non-diabetics, and low vitamin D levels nearly double the relative risk of developing CVD compared to diabetic patients with normal vitamin D levels.”

The authors endeavored to uncover the mechanism behind vitamin D’s benefit:

“We found that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein (AcLDL) and oxidized low density lipoprotein (oxLDL) cholesterol uptake in diabetics only. …In addition, 1,25(OH)2D3…improved insulin signaling, downregulated SR-A1 expression, and prevented oxLDL- and AcLDL-derived cholesterol uptake.”

You can remember their conclusion when getting your vitamin D level checked:

“The results of this research reveal novel insights into the mechanisms linking vitamin D signaling to foam cell formation in diabetics and suggest a potential new therapeutic target to reduce cardiovascular risk in this population.”

Throw some nuts in there too. A nice original study was published not long ago in The Anatolian Journal of Cardiology evaluated the benefit of hazelnuts (filberts) on atherosclerosis. The authors observed a number of interesting effects:

“Lag time for oxidation and α-tocopherol content of LDL were found to be increased while ox-LDL levels decreased during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo) B and apo B/apo AI ratio were found to be significantly lower while apo AI was higher. In respect to LDL subfraction, ratio of large/small LDL was significantly increased at the end of the study.”

They summed up their ‘take home’ message  on hazelnuts (which earlier posts suggest applies to most if not all nuts) accordingly:

“Hazelnut-enriched diet may play important role in decrease in atherogenic tendency of LDL by lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and increasing the ratio of large/small LDL beyond its beneficial effect on lipid and lipoprotein levels.”

Helicobacter pylori infection is, as you likely know, extremely common—according to WHO the most common infection in the world. It is a causative agent in almost all gastric ulcers. We see it here all the time. Finding out if you have it and getting it treated is another important therapeutic point for cardiovascular disease as this paper just published in the journal Digestive Diseases and Sciences reminds us. The authors investigated the impact of H. pylori infection on coronary atherosclerosis by examining the effects of infection on levels of serum lipid, high-sensitivity C-reactive protein (hsCRP) and oxidized low-density protein (oxLDL). What did their data show?

“The levels of total cholesterol, LDL, apolipoprotein B, serum hsCRP, oxLDL were significantly elevated and the severity of coronary atherosclerosis was significantly increased in H. pylori…group.”

Their conclusion echoes the findings of other investigators:

“More serious coronary atherosclerosis was observed in CHD patients with H. pylori…infection. H. pylori…infection might be involved in coronary atherosclerosis by modifying serum lipids, enhancing LDL oxidation, and activating the inflammatory responses.”

Remember, the most reliable ways to diagnose H. pylori infection are by stool antigens, a provoked breath test, or PCR (DNA amplification). H. pylori antibodies are not dependable.

Although it’s a major topic that deserves more space, mention at least much be made of the autoimmune aspect of cardiovascular disease as described in this recent paper published in the journal Angiology:

“Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis.”

The authors then describe their investigation of immune complexes, antibodies and receptor signaling in this process. Certain cases demand a thorough evaluation of the autoimmune component of their CVD.

It would also not be appropriate to close without at least alluding to the influence of hormones on cardiovascular disease, a topic that has many aspects treated in other posts. This paper recently published in the journal Endocrinology makes a very important but little known point for men (for whom most everyone knows that too little testosterone or excess conversion to estrogen is a big risk factor for CVD). Testosterone is normally converted into its dihydrotestosterone form (DHT) which does a lot of the heavy lifting because it’s ten times stronger than the original. Men with prostate disease are commonly prescribed medications (including saw palmetto) that block the conversion of testosterone to DHT, but without first measuring the levels of the bioactive forms of these hormones. These medications don’t always help because not everyone with a prostate condition has too much DHT. Moreover, DHT is important for protection against cardiovascular disease. The authors…

“…investigated the effect of…dihydrotestosterone (DHT) on the rabbit atherogenesis in relation to…oxidized-low-density lipoprotein receptor-1 (LOX-1) and its downstream molecules.”

What did they find?

“…DHT significantly reduced HCD-induced [high cholesterol diet-induced] foam cell formation…DHT inhibited the formation of foam cells induced by oxidized low-density lipoprotein. Moreover, the expression of LOX-1 and inflammatory cytokines in the cultured macrophages was significantly suppressed by DHT.”

Inappropriately blocking the conversion of testosterone to DHT can thus open a door to cardiovascular disease. So remember, both gentlemen and ladies: no hormone interventions without measuring the free-fraction bioactive levels before and after!

“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.