Inflammation

What Is Inflammation?

Inflammation is our body’s necessary self-defense response and repair mechanism for these assaults:

1) injuries such as cuts, scrapes, sprains, broken bones, burns, insect bites, toxins; 2) invading organisms such as bacteria; and 3) allergens and food sensitivities such as gluten.

Inflammation can be immediate (acute) or persistent (chronic).

Acute inflammation is marked by increased blood flow, migration of white blood cells, and release of defensive proteins and chemicals to the site of injured tissue. Among these chemicals are free radicals in the immune response to injury that are beneficial yet require the activity of anti-oxidants such as vitamin E and vitamin C to control.

Free radicals are chemical particles containing one or more unpaired electrons, which may be part of the molecule. They cause the molecule to become highly reactive.1

The majority of this response takes place in the first 12 to 24 hours after the assault. The inflammatory process continues until all the damaged tissue or invading germs are removed (usually about 5 days).2

Chronic inflammation is marked by persistence weeks to months or longer after tissue damage. Note: high concentrations of free radicals generated in chronic inflammation may be important causes of damage to cell structures. The defensive activity of anti-oxidants such as vitamin E and vitamin C are required to remove free radicals.

Chronic inflammation increases the risk for systemic diseases such as type II diabetes, obesity, heart disease, high blood pressure, arthritis, osteoporosis, chronic fatigue, migraine, autoimmune disease, and vasculitis which may cause stroke, heart attack or deep vein thrombosis (DVT).

Importantly, chronic inflammation is a risk factor for the onset of cancer.3

Q: Are there blood tests available for detecting inflammation?

A: Yes. Your medical health practitioner can order either or both of the following blood tests that measure the amount of inflammation present although not the source of inflammation. Abnormal is an elevation in blood levels.

1. C-reactive protein (CRP). This test measure C-reactive proteins that are released into the bloodstream within a few hours of tissue injury or infection. CRPs are cytokines called ‘acute phase reactants,’ meaning first on the scene. The CRP test is also useful to monitor treatment response and flare-ups of chronic inflammatory disease such as vasculitis, systemic lupus, and inflammatory bowel disease.
2. Erythrocyte sedimentation rate (ESR or sed rate). This test measures the rate of fall of blood cells in a sample tube of blood. An increase in the rate of fall shows inflammation due to an increase of C-reactive proteins in the blood specimen. Alone or with the CRP test, the ESR is especially useful for monitoring inflammation of veins and arteries.

In regards to celiac disease, disappearance of blood antibody levels of tissue transglutaminase IgA (tTG-IgA) indicate that inflammation has also subsided. These antibodies should be checked at 3 months, 6 months if indicated, and one year after diagnosis to monitor healing. On the other hand, raised antibodies indicate that there is definitely ongoing inflammation in the small intestine.

In regards to non-celiac gluten sensitivity, disappearance of blood antibody levels of anti-gliadin IgA and IgG at 3 months, 6 months if indicated, and one year after diagnosis indicate that inflammation has also subsided. On the other hand, raised antibodies indicate that there is definitely ongoing inflammation caused by gluten within the body.

What Is Inflammation In Celiac Disease and/or Gluten Sensitivity?

• Relationship between inflammation and celiac disease. Inflammation is a hallmark of celiac disease and underlies health disorders that may develop. Inflammation results when gluten activates an innate (non-specific local) immune response of the small intestinal lining (producing T-cells) and a humoral (specific) immune response (producing B-cells) that involves production of IgA and IgG type autoantibodies to the enzyme transglutaminase (tTG) within the small intestinal lining where tTG naturally occurs. These antibodies are thus called anti-transglutaminase (anti-tTG). Also, production of IgA and IgG type antibodies to gluten peptides that have entered the body also develops. The available blood test measures antibodies to gliadin in wheat. These antibodies are thus called anti-gliadin.

• Relationship between inflammation and dermatitis herpetiformis. Inflammation is a hallmark of dermatitis herpetiformis, a skin manifestation of celiac disease, that results when gluten activates production of IgA type autoantibodies to the enzyme transglutaminase (tTG) residing within the skin in addition to the immune responses in the small intestinal lining.
• Relationship between inflammation and non-celiac gluten sensitivity. Inflammation is a hallmark of non-celiac gluten sensitivity and underlies health disorders that may develop. Inflammation results when gluten activates an innate (local) immune response of the small intestinal lining and a humoral immune response involving production of IgA and IgG type antibodies to gluten peptides (anti-gliadin), that have entered into the body from the small intestine. Antibodies to transglutaminase are not produced.
• Relationship between inflammation and allergy. Inflammation is a hallmark of allergy and underlies health disorders that may develop. Inflammation results in allergy when proteins, including gluten, in wheat, barley, rye or oats activate an allergic immune response producing IgE type antibodies.

• Relationship between inflammation and digestive ailments. Inflammation caused by gluten increases the risk for a variety of poor health conditions of the digestive tract such as constipation, diarrhea, dysbiosis, leaky gut, lactose intolerance, bloating, infections, erosions, ulcerations, gastritis, duodenitis, jejunitis, ileitis, colitis, malignancies, and of course, malabsorption of nutrients causing nutritional deficiencies.

• Relationship between inflammation and nutritional deficiencies. Nutritional deficiencies in celiac disease add to the inflammatory load while producing digestive system problems like cheilosis, sore tongue, sore mouth, sore gums, rhinitis, sore esophagus, sore stomach, gastric ulcer, sore intestines, and infections like candida albicans (yeast) and H. pylori (bacteria). Among systemic inflammatory problems that may develop from malnutrition are vaginitis, dermatitis, diverticulitis, blepharitis, sinusitis, bronchitis, neuritis, myositis, and, and osteoporosis.
• Relationship between vitamin A and inflammation. Vitamin A promotes healthy mucosal linings and skin, which is our first defense against microbe invasion and infection, and reduces the effect of inflammation; helps regulate the immune system promoting optimal lymphocyte (white blood cell) function in defending against bacterial and viral infections; and plays a role as an antioxidant. ADEQUATE ZINC IS REQUIRED for the body to produce retinol binding protein which transports vitamin A in blood. Therefore, a deficiency in zinc limits the body’s ability to mobilize vitamin A stores from the liver. Both vitamin A and zinc blood levels can be easily determined by a blood draw.
• Relationship between vitamin C and intestinal inflammation caused by gluten. Vitamin C has been shown to down regulate (decrease) the mucosal inflammatory response to gluten in an intestinal biopsy culture model.4
• Relationship between vitamin C deficiency and inflammation in gluten sensitivity (celiac disease, non-celiac disease, allergy to gluten).  Vitamin C, with or without malabsorption, is depleted or used up by its activity in reducing inflammation in gluten sensitivity and any other condition that involves inflammation such as osteoporosis, which is a complication of celiac disease.
• Relationship between vitamin D deficiency and inflammation. Vitamin D is a potent regulator of inflammation by inhibiting acute pro-inflammatory chemical production (cytokines) and helping to turning off chronic inflammatory responses.
• Relationship between vitamin E deficiency and inflammation. Vitamin E limits destructive inflammatory processes in cells while in the reverse, deficiency predisposes to activation of inflammatory diseases such as celiac disease.
• Relationship between DHA deficiency and inflammation. DHA deficiency impairs mucosa integrity5 and worsens the inflammatory response to gluten. Researchers found that intestinal epithelial cells sustain the celiac inflammation, releasing arachidonic acid when stimulated with gliadin and that DHA inhibits the arachidonic acid  release by these cells.6
• Relationship between EPA deficiency and inflammation. EPA deficiency worsens inflammatory and immune responses while on the contrary, EPA is our natural mechanism to limit inflammation.
• Relationship between selenium and inflammation. Low selenium levels negatively alter genes that regulate the inflammatory response to injury. Selenium deficiency promotes inflammation of blood vessels and the thyroid gland.
• Relationship between selenium deficiency and damaged cells. In celiac disease there is an over production of inflammatory interleukin-15 (IL-15) which inhibits the correct removal of damaged intraepithelial lymphocytes (white blood cells) caused by the reaction to gluten. On the reverse, selenium proteins promote the removal of damaged cells. Therefore, selenium deficiency is a key factor directly leading to intestinal damage because of the failure to remove cells affected by oxidative damage. Serum levels of IL-15 are directly correlated with the seriousness of tissue damage.7

• Relationship between inflammation and dysbiosis. It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis (imbalances in the intestinal microbiota) in celiac disease patients, untreated and treated with a gluten-free diet, compared to healthy controls.8

  Furthermore, because patients with celiac disease have imbalances in the intestinal microbiota, which are not fully normalized despite their adherence to a gluten-free diet, it is hypothesized that the disease can promote dysbiosis that aggravates celiac disease pathogenesis, and dysbiosis, in turn, can initiate and sustain inflammation through the expansion of proinflammatory pathobionts (bad bacteria) and decline of anti-inflammatory mutualistic bacteria (good bacteria).9

• Relationsip between inflammation and plant lectins. Dietary lectins are tiny proteins in plants that are involved in the development of several inflammatory diseases, including celiac disease. Research by Gong et al. indicates that plant lectins can act as a “danger signal” able to activate the NLRP3 inflammasome and suggest that dietary lectins might promote inflammatory diseases via the NLRP3 inflammasome.10Inflammasomes are large multiunit complexes that are activated by a variety of danger signals that are threats to cells such as bad bacteria. Inflammasomes regulate the secretion or release of inflammation causing cytokines (chemicals) from white blood cells. Chronic disease such as celiac disease emerges from dysregulated inflammation.

• Relationship between inflammation and stress. Stress worsens both inflammation and dysbiosis. Psychological stress activates multiple physiological processes aimed at maintaining balance within the body. These physiological processes also have the capacity to influence the composition of microbial communities in the digestive tract, and research now indicates that exposure to stressful stimuli leads to gut microbiota dysbiosis and inflammation.11

  While the relative abundance of many different bacterial types can be altered during stressor exposure, findings in nonhuman primates and laboratory rodents, as well as humans, indicate that bacteria in the genus Lactobacillus are consistently reduced in the gut during stress.11

• Relationship between inflammation and chronic fatigue syndrome. Chronic fatigue syndrome is an associated inflammatory disorder of celiac disease. Celiac disease may be involved in chronic fatigue syndrome symptom presentation and oxidation by triggering cytokine production.12 Cytokines are chemical messengers that enable cells of the immune system to interact with each other. In this respect, the omega fatty acids in fish oil and primrose oil are shown to reduce cytokines that produce inflammation.
• Relationship between inflammation and non-response to gluten free diet. Celiac disease patients with persistent gastrointestinal symptoms despite a gluten free diet should trigger evaluation for underlying inflammatory bowel disease.13

How Prevalent Is Inflammation In Celiac Disease and/or Gluten Sensitivity?

100% of people with any form of gluten sensitivity (celiac disease, non-celiac gluten sensitivity, gluten allergy) have inflammation.

What Are The Symptoms Of Inflammation In Celiac Disease and/or Gluten Sensitivity?

DIGESTIVE SYMPTOMS  

• Associated Autoimmune Diseases causing inflammation of digestive tract such as Sjögren’s Syndrome and Lupus.
• Bloating.
• Canker Sores (ulcers of mouth).
• Carbohydrate intolerance (FODMAPS).
• Colitis (Lymphocytic, Collagenous).
• Constipation.
• Diarrhea.
• Duodenitis (first part of small intestine).
• Dysbiosis (imbalance of gut microbes).
• Esophagitis.
• Erosions.
• Gas, painful/ stinky.
• Gastric Esophageal Reflux Disease (GERD).
• Gastritis (Lymphocytic, Collagenous).
• Heartburn.
• Hoarseness.
• Ileitis (third part of small intestine).
• Inflammatory diseases like Crohn’s and Ulcerative Colitis, worsening of.
• Infections such as H. Pylori, Candida Yeast, Small Intestinal Bacterial Overgrowth, Giardia.
• Jejunitis (second part of small intestine).
• Leaky gut.
• Lactose intolerance (inability to digest milk sugar).
• Malabsorption of nutrients causing nutritional deficiencies.
• Malignancies.
• Swallowing Problems.
• Ulcerations.

GENERAL SYSTEMIC SYMPTOMS  involving parts of the body other than the digestive tract:

Metabolic: 

• Fatigue or malaise (low energy).
• Fever possible depending on involvement.

Muscular:

• Muscle pains (stiff and sore).

Neurologic:

• Brain fog (apathy, poor concentration, faulty thinking and judgment).
• Memory impairment (both formation of memories and recall).

Organ dysfunction: varies such as adrenal, thyroid or pancreatic  insufficiency.

Skeletal:

• Bone pains.
• Joint pains.

NUTRITIONAL DEFICIENCY SYMPTOMS  

• B Vitamin deficiencies – B2 (riboflavin), B3 (niacin), B6 (pyridoxine), B9 (folic acid), and B12 – are marked by these symptoms that involve inflammation:

• Atherosclerosis due to increased homocysteine levels (B6), (B9), (B12).
• Burning and itching of eyes, redness (B2).
• Burning of lips (B2), (B6).
• Burning of mouth, throat, esophagus, and stomach (B3).
• Cracking at corners of mouth called cheilosis (B2), (B6).

Cracked, itchy, red rash advancing to crusting in sunshine (B3).

Esophagitis (B3).

Gastritis (B3).

• Impaired cellular immunity (B6).
• Infection susceptibility increased (B6).
• Inflammation urethra (B3).
• Migraine (folic acid).
• Neuritis (B3), (B6), (B12).
• Peptic ulcer (B9).
• Red, sore, swollen tongue (B2), (B12).
• Seborrhea dermatitis (B2), (B6).

Sore mouth and tongue (B2), (B6), (B9).

Ulceration of esophagus (B3).

Vaginitis that is non-infectious (B3).

Please see post for individual B vitamin deficiency for other symptoms.

• Vitamin C deficiency is marked by these symptoms that involve inflammation:

• Bone weakening and thinning (osteopenia) that can advance to osteoporosis.
• Edema of the lower extremities (appears late).
• Fatigue.
• Gingivitis – swollen gums appear red in children and purplish in adults.

Immunity, lowered.

Inflammatory conditions worsen.

Joint tenderness (arthritis resembling rheumatoid arthritis).

Muscle weakness.

Periodontal disease with eventual tooth loss from infection.

Poor wound healing.

Refusal to walk in young children due to pain.

Rheumatic pains in legs.

Please see post for vitamin C deficiency for other symptoms.

• Vitamin A deficiency is marked by these symptoms that involve inflammation:

• Infections of the skin, hair, and nails.
• Worsened skin conditions such as psoriasis, eczema, and acne. A nationwide population study found a small

excess risk of celiac disease in patients with acne.¹⁰

Chronic dry eyes (both).

Impaired immune function with repeat infections and poor recovery.

Low mucous production in the digestive tract predisposing to inflammation and infection.

Low mucous production in the respiratory, urinary and reproductive tracts all of which predispose to inflammation and infection.

Xerosis (dryness) of the bulbar conjunctiva (white of eye) predisposing to inflammation and infection.

Please see post for vitamin A deficiency for other symptoms.

• Vitamin E deficiency is marked by these symptoms that involve inflammation:

• Anti-oxidant capability to remove damaged cells is impaired. Note: inflammation generates harmful free radicals which require anti-oxidants such as vitamin E to remove.
• Eczema.
• Hardening of the arteries.
• Increased risk of cancer.
• Peripheral neuropathy.

Please see post for vitamin E deficiency for other symptoms.

• Vitamin D deficiency  is marked by these symptoms that involve inflammation:

• Bone weakening and thinning (osteopenia) that can advance to osteoporosis.
• Chronic vitamin D deficiency results in decreased calcium absorption causing osteoporosis (inflammation of bones) and secondary hyperparathyroiditis (inflammation of the parathyroid glands).
• Muscle pain.
• Poor immune function.

Please see post for vitamin D deficiency for other symptoms.

• EPA Omega-3 fatty acid deficiency is marked by these symptoms that involve inflammation:

• Long inflammatory response to infection and injury.
• Skin disorders including dry rough skin, eczema, acne, worsening of psoriasis.
• Vascular disorders including hypertension and atherosclerosis (hardening of the arteries).

Please see post for EPA deficiency for other symptoms.

•  DHA deficiency is marked by these symptoms that involve inflammation:

• Long inflammatory response to infection and injury.
• Vascular disorders including hypertension and atherosclerosis.

Please see post for DHA deficiency for other symptoms.

• Selenium deficiency is marked by these symptoms that involve inflammation:

• Cardiomyopathy (damage to heart muscle causing enlargement).
• Osteoporosis, contributes to.
• Inflammatory conditions.
• Lowered resistance to infection.

Please see post for Selenium deficiency for other symptoms.

How Does Inflammation In Celiac Disease and/or Gluten Sensitivity Develop?

• Inflammation of digestive tract mucosa results from an immune response to gluten.

• Vitamin A  deficiency exacerbates inflammation because of loss of tissue integrity (health): low mucous production to protect tissues,  negative impact on cell differentiation, and poor regeneration of mucous membranes. Note: ADEQUATE ZINC IS REQUIRED for the body to produce retinol binding protein which transports vitamin A in blood. Therefore, a deficiency in zinc limits the body’s ability to mobilize vitamin A stores from the liver.
• Omega-3 fatty acid deficiency (DHA and EPA) exacerbates inflammation because of inability to produce “good” eicosanoids that counteract the “bad” eicosanoids that cause inflammation.
• Vitamin C deficiency  exacerbates inflammation because of loss of its major anti-inflammatory action and as a nutrient essential for the production of “new” mucosa cells to replace damaged cells.
• Stress exacerbates inflammation and causes dysbiosis, which in turn exacerbates inflammation.
• Dysbiosis found in gluten sensitivity, with or without treatment, exacerbates inflammation in the digestive tract.

Does Inflammation In Celiac Disease and/or Gluten Sensitivity Respond To Gluten-Free Diet?

Yes. A gluten free diet prevents inflammation by eliminating gluten as the cause. However, the gluten free diet must also address other digestive problems that contribute to inflammation such as:

• Dysbiosis, which requires a diet that has adequate probiotics, prebiotics and soluble fiber. This fiber promotes movement of contents through the digestive tract and feeds the billions of normal, essential microbes that inhabit the gut, which are necessary for colon health and fight inflammation. (Please view Dysbiosis post.)
• Nutrient deficiencies that impact the mucosa, especially vitamin A, vitamin C, and omega-3 fatty acids, require a diet with adequate nutrition.
• Infections that require a specific diet such as candida (yeast) which restricts carbohydrates, especially sugars that is gluten free.
• Inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, which  require a specific diet that is gluten free to promote healing.

Note: Caraway is particularly helpful to reduce digestive inflammation. Please see below under Carminatives, Step #6

Chronic inflammation is a risk factor for the onset of cancer and the regular use of low dose aspirin reduces the risk of cancer development by counteracting the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6.14

6 Steps To Improve Inflammation In Celiac Disease and/or Gluten Sensitivity:

1

Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

2

 Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

• 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• 4 Manage Your Medications Safely:

• 5Nutritional Supplements To Help Correct Deficiencies:

• 6Manage Natural Remedies: 

What Do Medical Research Studies Tell About Inflammation?

RESEARCH STUDY SUMMARIES

“Altered transcription of inflammation-related genes in dental pulp of celiac children.” The dental pulp plays a pivotal role in the immune defense against possible entry of pathogens(germs) from teeth.

This study investigated quantitative transcription levels of selected genes (IL-9, IL-11, IL-15, IL-18, IL-21, IL-27, MICA, IFN-γ) coding for pro-inflammatory immune innate activities in the pulp of primary teeth from healthy children and children with celiac disease. Researchers found for the first time in dental pulp of children possible relationships between celiac disease and modulation in transcription of cytokine-dependent inflammatory activities.

The pulp from primary teeth of 10 healthy children and 10 children with celiac disease was used to extract RNA and prepare cDNA for quantitative PCR transcription analysis employing commercial nucleotide probes for selected genes.

In children with celiac disease, the genes coding for pro-inflammatory cytokines IFN-γ, IL-11, IL-18, and IL-21 were significantly overexpressed, suggesting the possible importance of these cytokines in the relationships between celiac disease and dental disorders.18

“Ascorbate-dependent decrease of the mucosal immune inflammatory response to gliadin in celiac disease patients.“ This study investigating if  ascorbate (vitamin C) supplementation to gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in celiac disease found that ascorbate does decrease the mucosal inflammatory response to gluten in an intestinal biopsy culture model.

Duodenal biopsy explants from treated celiac disease patients were gliadin challenged in vitro (100 μg/ml) with and without 20mM vitamin C. An extra tissue explant in basal culture was used as internal control.

The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of the pro-inflammatory cytokines nitrites, IFNγ, TNFα, IFNα, and IL-6 compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures.

Gliadin-challenge induced IL-15 (interleuken-15) production in biopsies from treated celiac disease patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated celiac disease-patient who had basal IL-15 production.19

“Is it necessary to assess for fat-soluble vitamin deficiencies in pediatric patients with newly diagnosed celiac disease?” This retrospective medical record review of 83 pediatric patients with a confirmed diagnosis of celiac disease and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic showed that 2 patients had vitamin E deficiency. Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy.

Patients’ demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected from the charts of 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys.

The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of celiac disease was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 μg/dL, respectively. None of the patients were receiving vitamin supplements at the time of diagnosis.20

“Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients.” This study aiming to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult celiac disease (CD)-patients in the Netherlands found that vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Vitamin (25-hydroxy) D deficiency was found in 4.5% of these study patients.

Eighty newly diagnosed adult CD-patients were included and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, vitamin B6, vitamin B12, and (25-hydroxy) vitamin D, zinc, hemoglobin (Hb) and ferritin were determined before prescribing gluten free diet. Almost all CD-patients (87%) had at least one value below the lower limit of reference.

Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.21

“Vitamin E levels in patients with celiac disease.” This study investigating vitamin E status in patients with active celiac disease and patients on a GFD demonstrated that plasma concentrations of vitamin E were significantly lower in untreated celiac disease patients. Vitamin E correction may offer benefit to newly diagnosed and those who fail to adhere to strict GF diet.22

“Serum carnitine and selenium levels in children with celiac disease.” This study investigating serum levels of selenium in children with celiac disease having type 3 duodenal lesions demonstrated that selenuim and carnitine levels are decreased in children with celiac disease, with and without diarrhea.23

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