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    For Persistent Fatigue on a Gluten-Free Diet, Consider Adrenal Dysfunction


    Wendy Cohan

    Celiac.com 03/02/2009 - Many people suffer symptoms of fatigue prior to being diagnosed with celiac disease or gluten intolerance.  For some, fatigue is a major reason for initially seeking medical attention.  In both Celiac disease and gluten intolerance, malabsorption of nutrients can result in weakness, lack of energy, and even iron-deficiency anemia.  Iron-deficiency anemia can be compounded by gynecological conditions, especially in peri-menopause.


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    A thorough physician will test for and sometimes treat underlying vitamin and mineral deficiencies common in malabsorption disorders such as celiac disease and gluten intolerance, and after three-to-six months, many symptoms related to such deficiencies will resolve.  Some alternative practitioners even offer injectables such as B-Vitamins and Magnesium.  Oral supplements range from plant-based liquid concentrates, to sublingual drops, to tablets and capsules, allowing a range of options for sensitive individuals.

    Recently I spoke to a gluten intolerance group where a woman raised an important question.  She described her symptoms, which included profound fatigue and asked, “What can you do if extreme fatigue persists on a strict gluten free diet and supplements, even after a year or two?”  At the time, I wasn’t sure how to answer her, other than to suggest, off the top of my head, that she ask her Naturopath to do a saliva-based adrenal function panel.  I guess my reasons for doing so were based on fifteen years of nursing experience and the fact that she was probably about my age, and possibly in peri-menopause, which I knew places an additional strain on the adrenals.

    In women the sex hormones are produced in varying amounts in both the ovaries and adrenal glands.  A smooth transition through menopause would involve a gradual transition that decreased production of sex hormones by the ovaries, and increased production of sex hormones by the adrenal glands.  But, what happens if there are other factors in a woman’s life that prevent the adrenals from assuming this additional burden?  Coupled with the added strain that menopause places on the body and indirectly on the adrenals, a triggering event like a significant accidental gluten exposure, an increase in food allergies, or infection with a virus or bacterial illness, could simply tax the adrenals beyond their ability to meet this increased demand.

    The Gluten Connection

    Although relatively tiny, the adrenals have a very big job.  Adequate levels of the adrenal hormone cortisol are required by the body to help prevent inflammation and tissue destruction, keep blood sugars level, moderate nervous system responses, and attempt to maintain homeostasis, or the steady-state of balance in the body.    Periodically experiencing incredibly painful episodes of inflammation and tissue destruction from an accidental exposure to gluten, the protein found in wheat, barley, and rye, places a huge strain on the adrenals, including a sudden demand for high cortisol levels to help moderate the inflammatory response.  Each time, the body is able to cope, but with each experience it may take longer for the adrenals to recover.  When stress is prolonged, these high levels of cortisol must be maintained.  And if there is no significant recovery period during which the adrenals can rest and replenish themselves, adrenal fatigue results.

    After doing some research for a new book I’m working on, I found another possible connection, especially for those with celiac disease.  Many of us are aware of the strong, well-documented association between celiac disease and autoimmune thyroid disorders like Hashimoto’s thyroiditis.  We also know there is a relationship between celiac disease and another endocrine gland, the pancreas.  (Diabetes has a strong correlation with celiac disease.)  Autoimmune hepatitis affects the liver – the body’s largest internal organ. Nephropathy, which affects the kidneys, is a very serious, less familiar disorder linked to celiac disease.  But, we rarely hear about the adrenals, especially in relation to celiac disease. Could there be a connection?  In fact, there are several important connections that are often over-looked.

    In researching autoimmune disorders, I learned about a disorder called “Autoimmune Adrenal Hypofunction” or “Autoimmune Hypo-Adrenalism”, which sometimes occurs together with other autoimmune disorders.  As in other autoimmune disorders, the body produces antibodies targeted against its own tissues, in this case, the two walnut-sized adrenal glands that sit atop the kidneys.  While thought to be relatively uncommon, Autoimmune Hypo-Adrenalism is most closely associated with celiac disease.  In fact, I was quite surprised by the wealth of information on this association, based on many studies done in Italy and Ireland, both countries where celiac disease is common.  While the connection between other autoimmune disorders and celiac disease is generally accepted in the U.S., the case for adrenal insufficiency in relation to celiac disease has not appeared to have received as much attention.  So, it can’t hurt to mention this link here, since it has the potential to affect those with persistent fatigue and/or chronic inflammatory disorders such as interstitial cystitis, in which low cortisol levels may play an important role.


    Stress, Food Allergies, and Nutrition

    As anyone who has studied stress and the allergenic response knows, diet does matter.  One of the least recognized forms of stress is untreated or unidentified food allergies and sensitivities. 

    In Dr. Wilson’s book, “Adrenal Fatigue – the 21st Century Stress Syndrome”, he writes, “It has long been observed that people suffering from adrenal fatigue have a definite increase in allergic responses or become allergic to things that did not previously bother them.” This is because levels of the adrenal hormone cortisol, the most powerful anti-inflammatory substance in the body drop, making it “more likely that the body will have severe allergic (inflammatory) reactions and that these reactions will be more severe.”

    Another factor in adrenal function through is nutritional status.  As we know, many people with Celiac disease or gluten intolerance do have some underlying nutritional deficiencies, and these become more difficult to address as we age.  Certain vitamins and minerals are essential to replenishing and nourishing the adrenal glands.  Ideally, we’d obtain these essential nutritional components through our diet.  In cases of adrenal fatigue, it is important to discuss with your physician what you can do to help your adrenals recover, both by eating an ideal diet, and taking recommended supplements, including B-Vitamins, Vitamin C, Magnesium, and specific herbs and amino acids.

    Symptoms of Adrenal Fatigue

    Ten relatively common symptoms of adrenal fatigue are listed below:

    • Fatigue
    • Depression and memory difficulties
    • Sleep Disturbances
    • Migraine Headache
    • An increase in allergies or the development of new allergies
    • Alcohol Intolerance
    • Low Blood Pressure and Low Body Temperature
    • Blood Sugar Regulation Problems (Hypoglycemia)
    • Low Libido & Hormonal Imbalances
    • Inflammation

    Adrenal Testing

    Testing for adrenal insufficiency isn’t rocket-science, but an established and useful diagnostic tool that might have important implications for poor regulation of inflammation as well as for general health.

    The first step is to check for a low cortisol level, in combination with other hormones, including DHEA, Progesterone, Estrogen, and Testosterone.  This is easily done with a safe, reliable, and cost-effective serial saliva test, with four samples taken at specified time periods throughout the day.  Your physician often stocks these kits in the office, and can provide one for you to use and then mail to the laboratory.  The laboratory will perform the tests, and send the results to your physician, who will discuss them with you.  The whole process takes a week or two, and can be repeated every few months to track your recovery.  It is not expensive, and may even be covered by your insurance.

    In fact, you do not need a doctor to order the test, but the results will be of little value without a physician to interpret them, make a plan to address any abnormal findings, and support and monitor you in your treatment.

    Blood tests, including and ACTH challenge, may be indicated, but a serial saliva test is a good first step.

    Adrenal Recovery

    Any program of adrenal recovery must incorporate lifestyle changes that include avoiding stress or dealing with stress in healthy ways, such as exercise, relaxation, and meditation.  Eating an anti-inflammatory diet, free of sugars and alcohol, is essential, as continuing to follow a strict gluten-free diet.


    This article is partially excerpted from “The Better Bladder Book – a Holistic Approach to Healing Interstitial Cystitis & Chronic Pelvic Pain through Diet, Lifestyle, & Self-Treatment”, available soon through my website.  The book provides documentation for all research and factual content, including the information in this article.


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    Guest Debbie

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    I very glad to see this article to raise awareness of these issues.

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    Guest Maryl

    Posted

    Wow thanks for linking these two concerns of mine. I've been on a gluten free diet for 4 years but am still having trouble that all points to adrenal problems. This is a big help.

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    Guest Dr. George

    Posted

    Excellent article. I think that the celiac - adrenal (and also, diabetes) connection is poorly understood, and hence, seldom investigated by traditional medicine.

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    Guest Glenda

    Posted

    I have celiac and my husband has Crohn's. HE is the one who has 7 of the 10 symptoms of adrenal fatigue! He has mentioned fatigue to his G.I. specialist and was told it was 'part of having Crohn's'. Now I am going to print this article and show it to him at his next appointment. Thanks for the detailed article!

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    Guest Heather

    Posted

    Very informative, a real eye opener for me! I had undiagnosed celiac disease for 25 years. Recently my husband stumbled across an article which lead to my diagnosis. Since going gluten free I have still noticed the symptoms you mentioned. I have a sibling and cousin who have serious adrenal gland problems and never though I may also. Thank you so very much, I am going to have the test done as soon as possible.

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    Guest nun ya bidnes

    Posted

    I suffer daily due to Addison's Disease - the actual medical diagnosis of true adrenal insufficiency that, left untreated, will kill you. I call BS on adrenal FATIGUE - for those with celiac disease, imagine someone with mild gas saying they have "gluten sensitivity," or someone with sunburn claiming "PRE-skin cancer."

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    Guest plop

    Posted

    Post withdrawal syndrome for opiates can last a couple months or more. Gluten binding to opiate receptors and with the similarity of symptoms I would guess that one would experience more severe symptoms of fatigue, fluish, emotional unrest the first couple of weeks and then a gradual lessening of these symptoms over the next month.

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    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

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    Jefferson Adams
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    The research team included Y.‐H. Dong; Y. Jin; TN Tsacogianis; M He; PH Hsieh; and JJ Gagne. They are variously affiliated with the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston, MA, USA; the Faculty of Pharmacy, School of Pharmaceutical Science at National Yang‐Ming University in Taipei, Taiwan; and the Department of Hepato‐Gastroenterology, Chi Mei Medical Center in Tainan, Taiwan.
    To get solid data on the issue, the team conducted a cohort study among ARB initiators in 5 US claims databases covering numerous health insurers. They used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy‐related outcomes, including celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy. In all, they found nearly two million eligible patients. 
    They then assessed those patients and compared the results for olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. They found unadjusted incidence rates of 0.82, 1.41, 1.66 and 29.20 per 1,000 person‐years for celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy respectively. 
    After PS matching comparing olmesartan to other ARBs, hazard ratios were 1.21 (95% CI, 1.05‐1.40), 1.00 (95% CI, 0.88‐1.13), 1.22 (95% CI, 1.10‐1.36) and 1.04 (95% CI, 1.01‐1.07) for each outcome. Patients aged 65 years and older showed greater hazard ratios for celiac disease, as did patients receiving treatment for more than 1 year, and patients receiving higher cumulative olmesartan doses.
    This is the first comprehensive multi‐database study to document a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, though absolute rates were low for both groups.
    Source:
    Alimentary Pharmacology & Therapeutics

    Jefferson Adams
    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.
    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.
    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 
    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.
    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.
    Source:
    Gut. 2017 Feb;66(2):250-257. &nbsp;doi: 10.1136/gutjnl-2015-310148.