GLUTEN AND THE BRAIN
NEW RESEARCH AND TWO CASE HISTORIES
Although there are two chief diets that I've recommend for years for chronically ill people (these can actually be combined into one --- KETOGENIC & PALEO), I always suggest that people start out with an ELIMINATION DIET. Why? Because the tests that most doctors run in their offices provide zero information about food sensitivities. The really cool thing about an Elimination Diet is that it allows you to figure things out for yourself. By eliminating certain foods and then adding them back systematically, you can get a pretty good idea of what foods you might be having various degrees of immune system reactions against. Today I want to talk especially about wheat protein --- GLUTEN. And while I've written mountains about it in the past (HERE), it always amazes me how many people are living under the assumption that MODERN GRAINS are the healthy-equivalent of what your great grandfathers were eating a century ago.
WHAT'S THE DIFFERENCE BETWEEN CELIAC DISEASE AND NON-CELIAC GLUTEN SENSITIVITY (NCGS)?
"It is increasingly evident that many, if not most [wheat intolerant] individuals have 'non-classical' Celiac Disease and, furthermore, that many patients have wheat or gluten-related conditions that do not even fall under the diagnosis of Celiac Disease. The resulting confusion in the scientific literature regarding the definition, diagnosis, and treatment of gluten-related conditions has hampered the clinical management of these conditions. In addition, failure to recognize atypical, non-gastrointestinal symptoms has led to delayed or missed diagnoses of gluten-related disorders with the potential for increased morbidity...." From the American Association for Clinical Chemistry's article, The Spectrum of Wheat Sensitivity: From Non-Celiac Gluten Sensitivity to Celiac Disease
Dr. Aristo Vojdani (the brilliant immunologist who founded CYREX LABS) teamed up with author of Grain Brain, neurologist David Perlmutter, for a study that was published in a 2013 edition of Case Reports in Immunology. Listen carefully. "Celiac disease and nonceliac gluten sensitivity are two distinct conditions triggered by the ingestion of gliadin [a component of gluten]. Although symptoms of nonceliac gluten sensitivity may resemble those of celiac disease, due to the lack of objective diagnostic tests, NCGS is associated with overlapping symptomatologies of autoimmunities and Crohn's disease. Thus, a new paradigm is needed to aid in diagnosing and distinguishing among various gut-related diseases, including CD, NCGS (also known as silent celiac disease), and gut-related autoimmunities." For the record, gluten, whether we are talking about CD or NCGS, is heavily related to autoimmunity (HERE) --- a fact that has been reported since the early 1930's. Are you starting to see how little difference there really is between the two?
In 2015, the World Journal of Gastroenterology (Diagnosis of Gluten Related Disorders: Celiac Disease, Wheat Allergy and Non-Celiac Gluten Sensitivity) said that, "Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes." The study went on to talk about the tests that verify the presence of CD, saying.....
"The ingestion of gluten in genetically predisposed individuals carrying HLA type II DQ2/DQ8 alleles can arouse a T-cell mediated immune reaction against tissue transglutaminase, an enzyme of the extracellular matrix, leading to mucosal damage and eventually to intestinal villous atrophy. To date, the only available therapy for CD is a life-long GFD. The adherence to a restrictive GFD leads to the resolution of symptoms and to the gradual healing of histological abnormalities even if the complete recovery of the intestinal mucosa is rare and low-grade mucosal inflammation seems to persist in many treated celiac patients as shown by follow-up duodenal biopsies."
Let me summarize. As I will show you in a moment, a significant portion of those carrying the genetic makeup for Celiac never get Celiac. Why? It's yet another example of why EPIGENETICS RULE OVER GENETICS (just because you carry a certain gene does not necessarily mean that gene will be expressed). Certain T-Cells become fired up against things they shouldn't be fired up against (in this case, gluten), while others (TREGS) fail in their mission to prevent the immune system from becoming a runaway train, which usually results in immune system reactions against self (autoimmunity). The biggest difference between the celiacs and non-celiacs is that the small intestines are damaged in celiacs (the villi / microvilli) --- it's the tissue the body chooses to attack, making it the hallmark of this disease. Be aware, however, that gluten-induced mucosal damage occurs in non-celiacs as well, in the form of something called LEAKY GUT SYNDROME (various forms of "THE LEAKIES" are a hallmark of all chronic illness). And there it is again --- even though these these folks went on a GFD, the inflammation never seemed to completely resolve (even if their symptoms did). My opinion is that this is at least in part due to so few people understanding cross-reactivity. Again, the unfortunate result of this misunderstanding is that many people who do a GFD, do not get the results they want.
Less than two months ago, the same journal published a study (Non-Celiac Gluten Sensitivity: All Wheat Attack is Not Celiac) which showed that when it comes to diagnosing NCGS, things have not changed that much. "While reliable clinical tests for CD exist, diagnosing individuals affected by NCGS is still complicated by the lack of reliable biomarkers and reliance upon a broad set of intestinal and extra intestinal symptoms possibly provoked by gluten. NCGS has been proposed to exhibit an innate immune response activated by gluten and several other wheat proteins. Features of NCGS and other gluten related disorders call for a review of current distinctive diagnostic criteria that distinguish each, and identification of biomarkers selective or specific for NCGS." Again, I'm not convinced it really matters as the treatment is the same no matter which you have.
The point of this is simply that most people think about this whole thing the wrong way. They see Celiac Disease as being bad --- really bad, but NCGS not being nearly as severe. More of a nuisance than a real problem. Pay attention folks. Although it's certainly not true in every case, NCGS can be every bit as severe CD and in many cases, worse. The biggest difference is that in CD, your body is making antibodies against its own small intestine. With NCGS, it's not. However, NCGS may be inducing the body to create antibodies against any number of other tissues, glands, or organs (for instance, how many of you knew that 90% of the thirty million cases of thyroid disease in America is autoimmune?). I want to shift gears here and discuss a few of the new studies on the potential neurological issues seen with gluten ingestion.
Just a few days ago, the journal Acta Neurologica Begica (Cognitive Impairment in Celiac Disease and Non-Celiac Gluten Sensitivity: Review of Literature...) revealed exactly what I've been telling you --- that both "CD and NCGS can be responsible for neurological complications such as ataxia and peripheral neuropathies but also cognitive impairment. Several mechanisms were proposed to explain the deleterious influence of gluten-related pathologies on cognitive functions: nutritional deficiencies, elevation of circulating cytokine levels due to systemic inflammation, low brain serotonin levels… Several types of dementia such as Alzheimer dementia, vascular dementia, frontotemporal dementia were reported in association with CD. Gluten free diet should be introduced as early as possible because of its potentially protective effect." For those who are interested, I have a COOL ARTICLE on serotonin.
Back in September, the journal Frontiers in Neuroscience (Neurophysiology of the Celiac Brain: Disentangling Gut-Brain Connections) featured a group of European authors talking about diseases associated with gluten. The list included EPILEPSY and other seizure disorders, NEUROPATHY, HEADACHES / MIGRAINE, cerebellar ataxia (we'll discuss it more in a moment), neuropsychiatric disorders, as well as the fact that, "Many adults (over 50%) exhibit significant extra-intestinal involvement even without typical CD manifestations." In other words, there is a better than 50/50 that these individuals will not have the "classic" GI symptoms associated with gluten (bloating, gas, etc). Some of the other neurological symptoms listed included, "cross-reacting antibodies, immune-complex deposition, direct neurotoxicity, other immune-mediated factors, deficiency of vitamin and other nutrients secondary to chronic malabsorption, depression, bipolar disorder, apathy, excessive anxiety, irritability, schizophrenia, eating disorders, attention-deficit / hyperactivity disorder, autism, thyroid disease, and sleep complaints." Listen to them describe what I talked about earlier --- the fact that NCGS only means that you do not have auto-antibodies to your own small intestine. All other tissues, glands, and organs, however, are on the table --- including the brain. No matter what you "officially" label it, it's all about solving gluten-induced inflammation!
"Regarding humoral autoimmunity to neuronal antigens, deposits of anti-tTG2 and anti-tTG6 antibodies have been found not only in the small intestine but also in different CNS sites (cerebellum, pons, medulla, brain blood vessels). Furthermore, a possible blood-brain barrier (BBB) lesion, secondary to diffuse infiltration of T-lymphocytes and inflammatory cells within the perivascular cuffing might expose cerebral tissues to antibodies."
Because a lack of clear thinking, poor decision-making ability, and diminished cognitive function are all increasingly common in today's society, might it be possible that gluten has something to do with it? Could gluten be playing a role, apart from what BLOOD SUGAR IS DOING TO OUR COLLECTIVE BRAINS? A study from February's issue of the Journal of Gastroenterology and Hepatology (Gluten-Induced Cognitive Impairment ('Brain Fog') in Coeliac Disease) helped answer this question in light of BBB (Blood-Brain Barrier) dysfunction (this is a phenomenon known as "Leaky Brain Syndrome" --- see my link on "The Leakies").
"The most likely explanation for the existence of minor cognition impairments (i.e., brain fog) in patients with untreated CD... is the existence of elevated levels of circulating cytokines associated with the systemic inflammation associated with CD. At elevated levels, circulating pro-inflammatory cytokines bind to blood–brain barrier epithelial cells and facilitate the migration of leukocytes into the brain. Leukocytes promote inflammation in the brain, particularly inflammation of nerve fibers, which, in turn, reduces the speed of neural transmission. The observation of brain fog in patients with multiple sclersois, patients with fibromyalgia, and patients undergoing chemotherapy suggests that the mechanism is not related specifically to gluten ingestion. All of these disorders have one thing in common with CD—they are associated with systemic inflammation. In summary, subjective reports of brain fog from CD patients are both psychologically and neurologically real and can be quantified when sufficiently sensitive cognitive tests are used. The cognitive impairments associated with brain fog improve on a GFD."
One of the things I have shown you repeatedly from the peer-reviewed literature is that children with AUTISM have a high incidence of gluten sensitivity. A study from this month's issue of Metabolic Brain Disorders asked the question of which diet was better for these kids --- a GFD that was also dairy free, or a KETOGENIC DIET (a modified version of the induction phase of the Atkins diet). Although all worked, the authors concluded that the "Ketogenic diet is gaining attention due to its proven effect on neurological conditions like epilepsy in children. Both diet groups showed significant improvement in ATEC and CARS scores in comparison to control group, yet ketogenic scored better results in cognition and sociability compared to GFCF diet group. Depending on the parameters measured in our study, modified Atkins diet and gluten free casein free diet regimens may safely improve autistic manifestations and could be recommended for children with ASD."
Before I show you a few more of the neurological and extra-intestinal manifestations of Gluten Sensitivity, realize that many GFD's fail because they are all too often loaded with GLUTEN-FREE GARBAGE --- the same processed crap widely found in normal food, only without the gluten. It's why I NEVER recommend a GFD unless it's as I've already shown you. By the way, healthy fats are neuro-protective, which is why Keto proved beneficial above.
- EXTRA-INTESTINAL MANIFESTATIONS OF GLUTEN SENSITIVITY: Because the primary mechanism that pathology is induced in gluten sensitive individuals is via SYSTEMIC INFLAMMATION, it would make sense that, as I said earlier, everything is on the table (not just autoimmunity against the small intestine). Two studies from last month, both in the World Journal of Gastroenterology, showed how big a deal these non-GI manifestations of Gluten Sensitivity are. "CD patients exhibited an oxidative imbalance and inflammatory response despite GFD." Did you catch that? OXIDATIVE STRESS and inflammation were both higher even while on the GFD. And although there is a mountain of research on the link between Gluten Sensitivity and MICROBIOME, the second study confirmed this by saying "It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability [Leaky Gut Syndrome], could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis." HOMEOSTASIS of the body without homeostasis in the Gut is a pipe dream. It's why GUT HEALTH is such a big deal. It's also why some of you need to read up on the hottest area of health-related research for the past half decade; FMT.
- OSTEOPOROSIS: 15 researchers from University of Salvador in Buenos Aires, published a study in October's issue of Clinical Gastroenterology and Hepatology that told us all it needed to via its title (Improved Bone Microarchitecture in Patients With Celiac Disease After 3 Years on a Gluten-Free Diet). This should not surprise anyone once we start connecting some dots. We already know that children who react to gluten generally have much higher rates of autism (or vice versa if that's how you want to look at it). However, did you know that autistics have high rates of OSTEOPOROSIS as well --- even as children (interestingly enough, as rates of autism continue to explode, so do childhood fractures --- HERE)? After doing DEXA Scans on groups of healthy 4-8 year old boys and then comparing them to age-matched controls, "Boys with ASD had significantly lower spine bone mass density." Remember that this whole mess is driven by inflammation, and osteoporosis is an inflammatory disease (HERE). Read THIS to learn what calcium supplement is best.
- SPEAKING OF AUTISM: Last month's issue of the Proceedings of the Nutrition Society (Food and the Gut: Relevance to Some of the Autisms) concluded that, "Complex, diverse and rarely appearing without comorbidity, the autism spectrum disorders (ASD) continue to be a source of research interest. The central role of the brain in relation to autism may be at least partially influenced by the functions of other organs. The gastrointestinal (GI) tract represents an important biological system pertinent to at least some autism. The notion of a gut-brain-behaviour axis has garnered support from various findings: an over-representation of functional and pathological bowel states, bowel and behavioural findings showing bidirectional associations, a possible relationship between diet, GI function and autism and recently, greater focus on aspects of the GI tract such as the collected gut microbiota in relation to autism. Science appears to be moving towards defining important GI-related autism phenotypes with the possibility of promising dietary and other related intervention options onward to improving quality of life." I've shown you on more than one occasion that Autism is a literal KICK TO THE GUT!
- OCCULT INFECTIONS AND GLUTEN SENSITIVITY: How does one come down with NCGS if there is no genetic predisposition? Although I have covered this at length previously (HERE), a group of Italian researchers writing in last month's issue of Nutrients (A New Proposal for the Pathogenic Mechanism of Non-Coeliac / Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence) said that, "Recently, the involvement of an increased intestinal permeability [Leaky Gut Syndrome] has been recognized in the onset of this clinical condition. According to this new hypothesis, the root cause of NCG/WS is a particular dysbiotic profile." Once again we see that old nemesis, DYSBIOSIS. Research shows that dysbiosis is the twin sibling of LGS --- where you see one you are likely to see the other. Another study; this one from next April's issue of the Journal of Cellular Physiology (The Silent Enemy: Celiac Disease Goes Viral) stated, "A very recent study has begun to shed light on a possible mechanistic basis for this hypothesis, and surprisingly linked intestinal infections caused by common reoviruses to the onset of celiac disease." What are reoviruses? Although they don't usually cause overt symptoms, they can cause URI's, FEVERS, and stomach flu. Just remember that I've shown you how health problems can be caused by OCCULT (HIDDEN) INFECTIONS, including the INFECTION PUMPS we call root canals. Speaking of the mouth.....
- GLUTEN INTOLERANCE OF THE MOUTH: An Italian study published in this month's issue of Nutrients (Tooth Wear Is Frequent in Adult Patients with Celiac Disease) showed that Celiacs who were on a GFD have much more tooth wear than controls. Another study, this one a Portuguese paper from The Open Dentistry Journal (Oral Manifestations in Pediatric Patients with Celiac Disease – A Review Article) said that some of the dental issues seen more commonly in those with gluten sensitivity issues include, "dental enamel defects, recurrent aphthous stomatitis, delayed tooth eruption, multiple caries, angular cheilitis, atrophic glossitis, dry mouth, and burning tongue." BTW, "carries" is another word for CAVITIES.
- THE SIBO / IBS CONNECTION: We know that SIBO (Small Intestinal Bacterial Overgrowth) is intimately associated with IBS --- itself a known autoimmune disease (HERE). What's cool is that there are inexpensive DIY breath tests that can tell you if you have SIBO. A recent issue of Gastroenterology and Hepatology (Outcome of Breath Tests in Adult Patients with Suspected Small Intestinal Bacterial Overgrowth) revealed that of 311 patients that were suspected of having SIBO and then run through several breath tests, "46% had a positive breath test: 18% were positive for methane, 24 % positive for hydrogen and 4% positive for both gases. 50% had a positive lactulose breath result and 37% had a positive glucose breath result." Thirty of the biggest names in European gluten research teamed up for a blockbuster study in last month's issue of Nutrients (The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update). "Non-celiac gluten sensitivity (NCGS), sometimes referred as gluten sensitivity, gluten intolerance, or non-celiac wheat sensitivity, was already described in 1978 but did not receive much recognition from clinicians until the 21st century. It is characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by CD." If you want the latest information as well as a better understanding of FODMAPS, the study is free online. And finally, in a study that could have been written by the venerable ART AYERS (Non-Celiac Gluten Sensitivity: People Without Celiac Disease Avoiding Gluten --- Is it Due to Histamine Intolerance?), last month's copy of Inflammation Research concluded that histamine intolerance is remarkably similar to NCGS (histamine is one of the many markers of inflammation). "A targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets." There has been a lot written about the low histamine diet lately.
- PARKINSON'S OR OTHER CEREBELLAR ATAXIAS: Although I have written about CEREBELLAR ATAXIA in the past; because it looks so similar to other ataxias such as PARKINSON'S and ALS, it's not surprising that there are numerous studies on the subject each and every month. The October issue of Intestinal Research published a study called A Case of Celiac Disease with Neurologic Manifestations Misdiagnosed as Amyotrophic Lateral Sclerosis. Nuff said, but be aware that peer-review abounds with similar case studies concerning a myriad of neurological diseases as related to gluten ingestion. Just three days ago, the journal CNS and Neurological Disorders Drug Targets (Advances in Therapies of Cerebellar Disorders: Immune-mediated Ataxias) said that, "The identification of an increasing number of immune mediated ataxias suggests that the cerebellum is often a target organ for autoimmune insults." Mess up the cerebellum and you are in deep trouble (HERE). If this topic interests you (i.e. you have a family history of ataxias --- lack of voluntary coordination of movements and gait abnormalities), then read Immune-Mediated Cerebellar Ataxias: From Bench to Bedside in the September issue of Cerebellum & Ataxias.
GLUTEN-RELATED CASE HISTORIES
Good morning from across the pond.
I just read your article regarding Gluten-Related Neurological Problems [HERE] and found it jaw dropping. I also saw a lot of myself in the article. I am 29 female and in 2011 began twitching. By 2014 it had spread all over, accompanied by numbness burning and tingling in my hands and feet. All tests performed have come back clear apart from my MRI, which shows a white matter lesion about the size of a ping pong ball behind my left eye.
My question is could an autoimmune gluten response cause brain lesions? My neurologist isn't interested in my case anymore and refuses to perform a lumber (my mum has MS) and is taking a wait-and-see approach, so I'm outta luck and on my own to find answers and get better. Thanks you for taking the time out of your day to read this.
Ally D, UK
When I hear the word "autoimmune," I automatically assume some sort of gluten sensitivity is at play. Not that the relationship is necessarily causal, but that any hidden sources of inflammation can be murderous to someone with genetic predispositions toward certain diseases. And with a family history of MULTIPLE SCLEROSIS (yes, it's an autoimmune disease) I would definitely do an Elimination Diet. A friend of mine who is also a patient has essentially put her's into remission by strictly following the WAHL'S PROTOCOL (a version of a Paleo Diet). Honestly, whether you are officially diagnosed with MS or not, you are at risk. DO NOT wait for them to actually diagnose you to take matters into your own hands! More information below. Good luck and God Bless!
Hello Dr. Schierling,
I had to contact you because you really seem passionate about your work and know a lot of things that are being ignored within the medical community.
Two years ago, I started training soccer very seriously, hours on end daily. Being the naive teenager I was, I thought I could just train everyday without any problems occurring. Yeah, that proved to be false. Within two weeks I had developed acute pain in my right hip flexor, my lower back and right hamstring. I also felt my knees had moved up a bit? I went to a clinic and was told to take NSAIDs (duh) and just rest and the problems would go away.
I did the what the doctors suggested, but instead of resting, I played computer games daily for about 2 weeks, First-Person-Shooters, so I had to move my right arm a lot. What bad can a little gaming do, right? Turns out, a lot... I developed similar pain in my right arm also and had to rest completely. After a month of "resting" (I was working in a grocery store at the same time, having to carry products to the shelves all the time and so on) the pain seemed to go away.
The thing is, even though the pain went away, it would come back fast if I tried to do any sports. I now have these "lumps" that can be moved under my skin. Running from behind my knees up to my hamstrings and in both of my triceps. After reading your page a lot, I'm thinking I probably have tendinosis. It doesn't hurt a lot (yet), I can do daily activities normally. Sometimes I do have these dull aches. I can workout fine, no pain during push-ups, pull-ups etc. I have chosen not to do those because they can aggravate the injury.
A thing that should be noted also is that I have "ADHD". I was medicated with Methylphenidate 32mg, from the ages seven to eleven, and my grandfather from my dads side has gluten intolerance. I am 19 years old, and a male. Any insight from you would be GREATLY appreciated.
Despite the fact that tendinosis is largely a degenerative condition (HERE), we now know that it is driven by inflammation on some level (HERE). It's possible (although far from certain) that gluten could be that driver --- especially if you are fair-skinned, fair-haired, and blue-eyed (more likely to fit the genetic profile ---- HERE is a recent example from my clinic). Not sure what the knots are (could be TRIGGER POINTS but I doubt it), but I am not sure that these are tendinosis (here is material on HIP FLEXOR issues and HAMSTRING TENDINOSIS). Also, if you have problems all over the place --- multiple joints affected both above and below the waist, and on both the right and left side --- it is likely you have SYSTEMIC TENDINOSIS or SYSTEMIC FASCIAL ADHESIONS.
There is also tons of info linking various forms of Gluten Sensitivity to ADD / ADHD, which is usually treated by giving people METHAMPHETAMINES (see name of drug above --- Ritalin). At some point read my stuff on PLAYING VIDEO GAMES. Also read THIS POST on what it may take to address the inflammation that is wreaking havoc on your life. Oh; and whatever you do, never (NEVER) under any circumstances take a FLUOROQUINOLONE ANTIBIOTIC as you are more likely to be sensitive than the average person. It seems you already figured out what NSAIDS and CORTICOSTEROIDS do to INFLAMED CONNECTIVE TISSUES --- they slowly (or in some cases, not so slowly) destroy it.