Wednesday, August 24, 2011
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It is alarming. When you read down this long list of brain and nerve problems, it is staggering that so many neurological problems can be caused by gluten. The dismal news is that, currently, most neurologists and medical practitioners remain unaware of that these diseases/symptoms are commonly linked to gluten harm. The standard (old school) thinking is that gluten can only be a factor in the gastrointestinal symptoms of celiac disease. End of story. Obviously this is mistaken.
Marios Hadjivassiliou, in his 2010 paper says: “Most patients who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms. Gluten sensitivity is shown to manifest solely with neurological dysfunction. To improve diagnosis rates, the perception of physicians that gluten sensitivity is solely a disease of the gut must be changed.”
“The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.”
Wow! So many nerve diseases can activated by gluten. The big concern is that once your nerves have been damaged enough to cause you symptoms, it might be too late to get a benefit from a gluten-free diet. Damaged nerves are slow to heal … if ever.
You can read even more about the “grain-brain” connection in my book “Full Of It! The shocking truth about gluten”
The inescapable conclusion is to avoid gluten before you get sick. That means going gluten-free now. That means everyone adopting a gluten-free lifestyle. This is one of the reasons that I eat gluten-free. What about you? What about your family? That means a Gluten-Free Planet.
Next we will explore glutened minds.
Dr Rodney Ford
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Chapter 7. Damaged nerves and brains
Here is Chapter 7 of our eBook Gluten Free Planet.
It makes horrendous reading - how can gluten cause so mauch nerve damage. I would be interested in your thoughts.
You can read even more about the “grain-brain” connection in my book “Full Of It! The shocking truth about gluten”
- follow this link: http://www.drrodneyford.com/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=30&categor
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Chapter 7. Damaged nerves and brains
“The human brain is the most complicated organization of matter that we know.”
Isaac Asimov (from the foreword to The Three-Pound Universe by J. Hooper and D. Teresi, 1986)
You are defined by your brain, your mind, your nerves. So it is a frightening fact that gluten can irreversibly damage and/or interfere with these delicate nerves that crisscross your body. I hear you ask: “how many people are affected by this and what can I do about it?” This might be the most important information that you have ever heard. One of the reasons that I have adopted a gluten-free lifestyle is to protect my brain. If you think that this mumbo-jumbo … then just read on.
The thighbone’s connected to the kneebone
Everything in your body is connected to everything else. You are not a collection of organs, blood and bones. Your body is miracle of inter-connected cells, all talking to each other through your nerves, hormones and blood.
However, because our human bodies are so immensely complicated, the medical system perceives the body as a bunch of separate organs. We have the cardiologist, the chest/respiratory doctors, the ENT (Ear Nose Throat) specialists, the Obstetrics & Gynecology, the Endocrine, the Gastro, the Joint & Bone docs … it goes on. Their thinking is organ based, not body based. But of course this is not how your body works.
So, what would happen if there was a toxic substance that made lots of people very unwell. And what if this toxin affected each organ in a different way. How would it ever be discovered? We would predict that each super-specialty would make a different sort of diagnosis and give it a name.
Well this is the story of gluten. This is why the diagnosis has been missed until now. Find out how gluten can severely affect your nerves and brains.
Gluten Syndrome: a neurological disease
The key publications summarize the nerve affects of gluten are:
Our hypothesis states: “Gluten causes symptoms in both celiac disease and non-celiac gluten-sensitivity by its action on the nervous system”. This hypothesis has been formulated from experiences with gluten-sensitive patients and from the medical literature.
Currently, celiac disease (also known as gluten-sensitive enteropathy) is defined as a gastrointestinal disease. However, the bowel damage (known to be caused through the toxicity of gluten) cannot explain the wide array of symptoms that are observed in these celiac patients.
There must be an alternative mechanism.
The five unanswered gluten questions
As you know, gluten causes celiac disease in about one in every hundred people. Also, gluten is also responsible for significant ill health in one in every ten people. Some of the questions that remain unanswered are:
Occam's razor (the law of succinctness) states that an explanation should make as few assumptions as possible. Defining gluten-sensitivity as a neurological condition achieves this. It explains why there are so many and such varied manifestations of gluten-sensitivity while making a minimal number of assumptions. We propose that gluten injures the nervous networks that control the gut’s functions. In addition, gluten also directly affects the brain, which leads to the primary neurological symptoms that are commonly seen with gluten-sensitivity.
Autonomic nervous system. The smooth faultless running of your body relies upon the autonomic nervous system. This is an elegant system of nerve signals and hormones. It is classified into two parts: the “sympathetic” and “parasympathetic” pathways, which are driven by their respective neuro-transmitters: norepinephrine (noradrenaline) and acetylcholine. The regulation of all your organs depends on this amazing system. The cardiovascular system, the gut, the bladder, the uterus and the glands (pancreas, gall bladder, sweat, saliva) all rely on these vast autonomic nerve networks (also called involuntary nervous system) to work properly. When all goes smoothly you feel well. When it goes wrong, you feel sick.
The evidence
What follows is a detailed account of the medical research into the relationships between gluten-disease and neurological damage. This Table presents the spectrum of neurological symptoms that have been documented to be associated with gluten reactions in celiac disease.
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Table of neurological conditions documented to be associated with gluten
Brain dysfunction
Headaches and Migraine
Cerebella ataxia
Myoclonic ataxia
Chronic neuropathies
Autonomic neuropathy
Epilepsy
Dementia
Myopathy
Mood and Behavior problems
Anger
Learning disorders
Lethargy, low energy
Attention-deficit/hyperactivity disorder (ADHD)
Autism
Depression
Psychiatric disorders
Schizophrenia
Multiple Sclerosis
Gut problems
Reflux
Constipation
Diarrhea
Abdominal pain
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Neurological gut dysfunction
The first report linking neurological disorders with adult celiac disease was published in 1966 (Cooke and Thomas-Smith). The underlying argument of this and many other reports was that gut disease was a prerequisite these neurological problems. But, thirty years later Hadjivassiliou and others, showed that neurological dysfunction could not only precede celiac disease, but could also be its only manifestation (Hadjivassiliou, 1996). A further ten years later, gluten-sensitivity, without histological gut damage, is being shown to cause neurological dysfunction (Hadjivassiliou, 2006).
Marios Hadjivassiliou has reviewed his work in this landmark paper: “Gluten sensitivity: from gut to brain” ( 2010; http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract).
Zelnik (2004) closely investigated the link between celiac disease and brain malfunction. Patients with celiac disease filled in a questionnaire regarding the presence of neurological disorders or symptoms. Those reporting any neurological manifestations were further studied. Their neurological information was compared with a control group: celiac patients were found very much more likely to have neurological disorders (51.4%) in comparison with the control subjects (19.9%). These neurological disorders included: hypotonia, developmental delay, learning disorders and ADHD (attention deficit hyperactivity disorder), headache, and cerebella ataxia. Epileptic disorders were only marginally more common.
Next, they were all put on gluten-free diets. A therapeutic benefit of a gluten-free diet was only demonstrated in patients with transient infantile hypotonia and migraine headache. They concluded that their study had found that the extent of neurological disorders that occurred in celiac disease was much broader than had been previously reported. Over a half were affected.
Gut malfunction
The gut is the place when food and nutrients are processed, absorbed and the waste material is eliminated. Your brain carries out a myriad of regulation and control activities in the everyday function of your gut. These complex tasks happen unconsciously. You know nothing about them until they go wrong!
These tasks include: peristalsis to constantly move food along your gut; esophagus swallowing movements; stomach emptying; small bowel movement; and large bowel actions. Consequently, when these control devices are impaired by gluten, you would expect the following symptoms: gastro-esophageal reflux and heart burn; nausea; bloating; constipation and diarrhea. And this is indeed what you find. When your gut goes wrong, you feel unwell.
Gastro-intestinal motility disorder
Celiac patients often show gastro-intestinal motor abnormalities. About a half of people with celiac disease have dyspeptic symptoms (epigastric discomfort, early satiety) which are suggestive of a gastro-intestinal motility disorder. Data is also available on the presence of a disturbed motility of the esophagus, stomach, small intestine, gallbladder, and colon of untreated celiac patients (Tursi, 2004).
Gastro-intestinal abnormalities from a malfunction of autonomic motility differ in different gastro-intestinal zones:
These alterations in function are the result of the complex interactions in the gastro-intestinal tract. The factors of this interweaving of function include: the reduced absorption of food nutrients (in particular, fat); neurological malfunctions; gut hormonal impairment; and small intestinal bacterial overgrowth (from the predisposing motility disorder).
The whole gut can malfunction
All of these alterations in function can disappear after a gluten-free diet is started. These gut dysmotility disorders can also occur in gluten-sensitivity without the additional need for small bowel histological damage.
Gastro-esophageal reflux disease (GERD). Reflux, or heartburn, occurs when the stomach contents gets pushed back up into the esophagus. The acid in the stomach will then cause an irritation and eventually a burning of the skin in the esophagus. This is very uncomfortable. It hurts. Babies scream and cry. Toddlers whine, moan and get distressed. Older children experience regurgitation of acid in their mouth. They get heartburn. They drink milk. They refuse their food.
In my experience, both children and adults who have troublesome gastro-esophageal reflux symptoms are frequently gluten-sensitive. Indeed, I have found that children who have severe reflux (those who require continuing treatment with acid suppressant medication past 18 months of age) nearly all turn out to be gluten-sensitive. These children have high IgG-gliadin antibody levels. When these children go onto a gluten-free diet, they settle down, they sleep well for the first time, and they begin to eat normally. They also can usually be weaned off their medications within a few months. Their parents are relieved that at last their distressing problems have been solved.
Gastric reflux is extremely common. Anti-reflux medications are prescribed second only to pain killers. It is so common that people think that it is a “normal” symptom. From dealing with these problems every day, I have found that it is frequently precipitated by gluten.
Constipation and soiling. When your colon is not functioning properly, you will experience constipation, soiling (encopresis), bloating, and at times diarrhea. You also will have low immune function – the colon is a very important part of your immune system.
To empty out your colon, the large bowel muscles have to work efficiently to move the fecal contents along. You also have to be able to feel the “call to stool”. That is the urge to download. I have found that the children (and adults) with constipation from gluten-sensitivity have poor sensations about wanting to defecate. They cannot feel it coming. I think that this is due to damaged nerves that control this function. Once going gluten-free, it usually takes about 3–6 months for everything to come right again.
Studies have shown that the explanation for much constipation in children is from a cow’s milk protein intolerance. However, gluten is also a major contributor to this problem.
There is another clue that indicates gluten as a cause of constipation. Gluten can be converted into a morphine-like substance (gluteo-morphine) in the liver. These chemicals cause constipation. Treatment with naloxone, a specific morphine antagonist, has been shown to benefit some children with protracted constipation (Kreek, 1983) and others with chronic irritable bowel.
Diarrhea. Diarrhea refers to having loose bowel motions, also called loose stools. “Runny poos” is a common term used by children and parents. Sometimes there can be a sense of urgency and loss of control can occur. It is a very common symptom and has many possible causes.
Loose bowels motions, as a symptom of celiac disease, are mostly due to the poor absorption of food nutrients from the gut. All of this undigested food in the large bowel causes havoc: it gets fermented by the bacteria in the colon, which creates rectal gas and more fluid. The tummy gets distended and the bowel motions can be explosive.
Curiously, when the small bowel is not damaged, diarrhea can still occur. This can be due to the irritation of the nerve networks of the intestine that will then try to quickly expel the unwanted foods. This is the explanation for tiny amounts of gluten causing large amounts of diarrhea and abdominal pain.
Tummy pain. Abdominal pain can be generated within the gut from spasm of intestinal muscles; or from distention and stretching of the bowel wall; or from inflammation of the surrounding tissues, nerves and glands.
However, stimulation of the autonomic nervous system can also cause a gut ache. Spasms of the muscles and distention by too much gas will give you a colicky pain – these are sharp intermittent pains that often come in waves. When you get these pains it makes you want to double up.
Pains that stem from the inflammation of tissues are more constant and there is a tendency for you to remain still. Pain in the esophagus is sometimes called heart burn. In children, this causes them to squirm, cry or arch their body backwards. Gluten has been implicated as a factor in all of these types of pains.
Abdominal migraine. The term abdominal migraine has been used to describe recurrent abdominal pain with no other apparent cause (idiopathic): a tummy headache. It got this name because the pain could be so severe and associated with nausea. Sometimes a headache could arise as well.
In the headache literature, abdominal migraine is defined as one of the variants of migraine headache. It is also known by other terms including “periodic syndrome.” This variant is reported most typically in children. People who have abdominal migraine usually have a family history of headache migraine. They often go on to develop typical migraine later in their life.
The attacks of abdominal migraine are characterized by periodic bouts of abdominal pain which usually last for a few hours. In addition to the abdominal pain, these sufferers may have other symptoms such as nausea and vomiting, flushing or pallor.
Traditional tests have failed to reveal a cause for this pain. However, occasionally there are EEG findings that are suggestive of epilepsy – but this is rarely related to any convulsions. The usual medical practice is to put such children on long-term medications that are used for treating migraine. These medications do lessen these attacks in most children. Indeed, that is why these abdominal attacks are called abdominal migraine!
They appear to be generated within the tummy brain (the autonomic nervous system. My research has found that most of these children are gluten-sensitive. They have high IgG-gliadin antibodies and immediately get completely better on a gluten-free diet: neurological activity triggered by gluten. See later section for more research on gluten headaches.
Headaches and migraines
Headaches and migraines have repeatedly been reported to be associated with gluten in the diet. Not surprisingly, researchers have found that removing or cutting back on gluten in the diet can greatly reduce these symptoms.
One study (Hadjivassiliou, 2001) reported the findings in ten patients with gluten-sensitivity. Their brain tests (MRI-Magnetic Resonance Imaging) had suggested inflammation of their central nervous system. All of these people had experienced significant chronic headaches. Some had also suffered from unsteadiness and poor muscle coordination.
Headache relief off gluten. The great news for them was that after removing gluten from their diets, all of the nine who went gluten-free had full or partial relief (there was only one patient who would not try the diet).
One of these patients tells his story. He was a 50-year-old man who had complained of headaches and nausea along with confusion and agitation. He initially had experienced intermittent severe headaches for four years but then his attacks got even worse, both in frequency and severity. He was delighted that soon after starting a gluten-free diet he became symptom free. His balance improved rapidly and his headaches cleared completely! After going back on gluten, his headaches returned.
Another of these patients was a 45-year-old man. He had suffered from migraine since he was a child. Over time, his attacks had become more and more severe and resisted every treatment. He had blood tests that showed him to be gluten-sensitive. With the introduction of a gluten-free diet, his headaches completely disappeared. There are hundreds of similar cases in which gluten has been shown to be “the trigger factor”.
Gluten recognized as headache trigger. Migraine people more likely to have celiac disease. A different focus of some studies has been to look at the association between headache and celiac disease. In one study (Gabrielli, 2003), a total of 90 patients affected by migraine (of unknown cause) were enrolled, and compared with 236 blood donors. Four (4.4%) of 90 migraine patients were found to have celiac disease compared with only 0.4% blood donor controls. This was a highly significant difference – that is a ten times difference. These four people were put on a gluten-free diet for the next six months with impressive results. One of the four patients had no more migraine attacks. The remaining three patients experienced an improvement in frequency, duration, and intensity of their migraine. In summary, of those suffering with migraine, celiac disease was found in 4.4% of the migraineurs compared with only 0.4% in blood donors.
Brain blood flow. This study went on to investigate whether there were any regional cerebral blood-flow abnormalities in migraine patients with celiac disease. This is because migraine is associated with changes in brain blood-flow. Brain scans were done (a single photon emission CT brain study) on these migraine patients before and after being on a gluten-free diet. Their first brain scan tests showed a regional reduction in blood-flow in all four patients. But this blood-flow reduction was completely reversed at the follow-up brain scan after six month on a gluten-free diet.
They concluded that a significant proportion of patients with migraine may have celiac disease, and that a gluten-free diet may lead to an improvement in the migraine in these patients. A very high prevalence of headache (migraine and/or tension headaches) was also found in celiac disease patients (46%) when compared with a control group (29%) (Cicarelli, 2003).
Again, looking at celiac disease, headache was the most common neurological condition in those who had been diagnosed in childhood: 27.9% compared with only 8.1% of a control comparison group. Importantly, about half of these neurological symptoms disappeared when on a gluten-free diet (Zelnik, 2004).
Some of these patients with migraine-like headaches have been shown to have cerebral calcification when studied with head MRI scans. This is probably from long-standing disease.
Surely, the earlier that gluten-sensitivity is diagnosed, the less likely it is going to progress to long-term irreparable damage. Overall, children respond more quickly than adults to a gluten-free diet.
Gluten convulsions
Gluten-sensitivity is linked to epilepsy. Epilepsy is a brain condition. It is the spontaneous discharge of electrical activity in the brain. This causes a sudden change in behavior or motor activity. The symptoms and signs depend upon where in the brain this abnormal activity is occurring. In the general population, about one in every fifty people has some sort of experience of epileptic seizures. Yet again, there is an association between celiac disease and epilepsy, although this does not seem to be very strong. A higher prevalence of epilepsy (3.5–5.5%) has been reported in patients with celiac disease compared with controls (2%). Also, high IgG-gliadin antibody levels are more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%) (Ranua, 2005).
In addition, the specific condition “bilateral occipital cerebral calcification and seizures” has been more strongly associated with celiac disease (Visakorpi, 1970). However, this syndrome seems to be rare. In one study (Fois, 1994), 783 children who presented with seizures were investigated for celiac disease: there were nine children discovered with partial and/or grand mal seizures. Of these, only three (0.3%) had cerebral calcification.
The effect of a gluten-free diet on epilepsy control in celiac disease has been variable. In most patients the beneficial effects of the diet have been reported in terms of better seizure control and a decrease in the amounts of antiepileptic medications – but not the resolution of their seizures. Perhaps, the earlier the diagnosis and treatment with a gluten-free diet, the better the outcome. Again, all children with epilepsy should be investigated for evidence of gluten-sensitivity.
Neuropathy: brain and nerve damage
Neuropathy is the name used to describe the damage to the nerves in your body. The neuropathy can occur in any of your nerves, and each location is given its own special name. Most of the information about nerve damage comes from studies of celiac patients. However, it is the gluten that is causing the damage: so gluten nerve damage is not restricted to those with celiac disease.
Nerve damage: neuropathy
There are nerves running throughout your body. The nerves, which connect your brain up to your skin and muscles, are called the peripheral nerves. This peripheral nerve network is linked to your conscious mind.
You have another set of nerves which fans out to connect your brain up with all of your internal organs – this part of the nervous system is called the “autonomic nervous system” which responds to your unconscious mind and your emotions. I regularly see children who have been diagnosed as having a neurological condition, but turn out to have celiac disease or a gluten-sensitivity. In my opinion, all children (and adults) who have any neurological problems should have a blood test for their gluten and celiac antibody levels.
An underlying nutritional deficiency is a most unlikely explanation for these neuromuscular disorders. There are several arguments to support this:
Peripheral neuropathy
Gluten can cause loss of feeling. Looking through the narrow window of celiac disease, when carefully investigated, up to half (49%) of adults with celiac disease have evidence of a peripheral neuropathy (Cicarelli, 2003). The most common form of neuropathy has been the loss of feelings or a change in sensation felt in the skin. It is usually found in the hands and feet. In a group of 20 patients with neuropathy and confirmed celiac disease, there were nine patients who had complained of their sensory symptoms before the diagnosis of celiac disease had been made (Chin, 2003).
Motor neuropathy
Gluten can cause weakness. In addition to these sensory disturbances, the motor nerves can also be affected. The motor nerves are the nerves that work your muscles, which are attached to your bones. They give you the ability to move.
So when you get a motor neuropathy you will be weak and not be able to move very well. You will tire very easily. This damage is called a motor neuropathy. Serious damage can be detected in the motor nerves by a technique called electro-physiologic studies. Electrodes are placed over the nerve, which is then stimulated by a tiny electric shock. The speed of the nerve conduction can be measured. If the nerve electricity is travelling abnormally slowly, then this is evidence that the nerve has been damaged.
But early on in this condition, the nerve might not be damaged enough to cause a slowing of the current. Of interest, one study (Chin 2003) reported a group of 400 patients who had a neuropathy but had normal electro-physiologic studies. They were all investigated for celiac disease, which was found in 8% of them. This is ten times the number that was expected – as the incidence of celiac disease is about one in one hundred in the population at large.
The reports on the effect of a gluten-free diet on peripheral neuropathy associated with celiac disease are conflicting. Some studies have reported that a gluten-free diet is effective (Kaplan, 1988; Polizzi, 2000). However, others have found that the neuropathy symptoms have persisted despite an adequate gluten-free diet (Luostarinen, 2003). Again, it is likely that the more chronic and established the disease, the less likely it is to respond to a gluten-free diet. I think this is why children respond so well. Most of the studies are in grown-ups!
Autonomic neuropathy
Gluten interferes with our automatic functions. Your autonomic nervous system takes care of your vital day-to-day body functions that you never have to think about. This system keeps going day and night. It keeps you breathing, keeps your heart pumping, and keeps your gut working faultlessly. Although it is not under your conscious control, it is strongly influenced by your emotions. Control of your swallowing, your stomach emptying, the flow of food through your intestines, and your colonic movements are all mediated through this system.
There is ample evidence of upper-gut motor abnormalities in many people with celiac disease. This topic has been carefully researched (Usai, 1977) in an investigation of upper-gut motor activity in 30 celiac patients. They then explored the role played by the autonomic nervous system in these motility disturbances.
Autonomic system malfunctions in most celiacs. They found esophageal motor abnormalities in half of their patients. Abnormal esophageal acid studies (pH-probes) were abnormal in 30%. Delayed gastric emptying was documented in 50%. In total, 75% of celiac patients were shown to have some sort of gastro-intestinal motility alterations. Tests of autonomic dysfunction were positive in 45% of these patients. This indicated that a gluten autonomic neuropathy was playing a role in their reflux.
Gluten can make you wobbly
Ataxia
Ataxia is the word for when you feel wobbly or if you have an unsteady gait or walk. It is a loss of coordination. Ataxia can be due to damage of the cerebellum. The cerebellum looks like a wrinkled clenched fist of tissue at the back of your brain. Your cerebellum coordinates your body movements. Your cerebellum is also involved in the learning of repeated movements. For example, when you catch a ball, or balance on one leg, or use the computer keyboard – when you are carrying out these learned repetitive movements, then you are training your cerebellum.
Movement control. This cerebellum co-ordination of your body movement is achieved by collecting information from all parts of your body. This information of awareness about the position of your body comes hurtling in from all of your nerve sensors (limb position, balance information, speed, and what you can see). Eventually, this stream of information can help you do things like learn how to ride a bike without falling over. And then, magically, your cerebellum remembers this set of instructions, forever.
Some of the symptoms that are associated with damage to the cerebellum or the nervous tracts leading to it are:
Gluten ataxia. Gluten can impair the function of the cerebellum. Evidence shows that gluten is the culprit in causing these symptoms in many people. It was forty years ago that the first cases of ataxia that were linked to celiac disease were reported (Cooke and Smith, 1966). They wrote about a group of 16 patients with celiac disease who also had gait ataxia and peripheral neuropathy. They demonstrated that these patients had cerebella dysfunction.
Many others have subsequently shown that cerebella ataxia, and indeed many other neurological syndromes, may be part of the presenting symptoms of celiac disease. In one such study, a group of patients with cerebella ataxia (of unknown cause) were investigated by small bowel biopsy: 16% (4 of 25) were found to have celiac disease (Pellecchi, 1999).
Gluten the troublemaker. There is ample evidence that gluten can be a troublemaker in the brain both with and without celiac disease. This is now called gluten-sensitivity. Hadjivassiliou (1999) first put it like this: “It remains controversial whether gluten-sensitivity (a state of heightened immunologic responsiveness to ingested gluten) without intestinal involvement should be considered the cause of cerebella degeneration in ataxia of otherwise unknown cause.” However, his research over the last decade had made this an established fact (http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract).
Many others agree, for instance, Hernandez-Lahoz (2011, Rev Neurol. 2011 Sep 1;53(5):287-300. http://www.ncbi.nlm.nih.gov/pubmed/21796607) wrote a paper “Neurological disorders associated with gluten sensitivity”. He concludes: “Gluten sensitivity is a systemic autoimmune disease. Neurological manifestations of gluten sensitivity, with or without enteropathy, are also frequent, their pathogenesis including an immunological attack on the central and peripheral nervous tissue accompanied by neurodegenerative changes. The clinical manifestations are varied, but the most common syndromes are cerebellar ataxia and peripheral neuropathy. The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.”
Various studies have found that the prevalence of positive IgG-gliadin antibodies in ataxia (of unknown cause) has varied between 0–41%. However, raised IgG-gliadin antibodies are found more frequently in ataxia (30%) than in the general population (8–12%). This is excellent evidence for a causal association between cerebella degeneration and gluten-sensitivity.
Evidence of gluten nerve damage
Gluten antibodies cross-react with brain cells. There are some very sensitive cells in the cerebellum (the part of the brain responsible for coordination). They are called “Purkinje cells” and function as the output neurons of the cerebellum. These are the cells that appear to be most susceptible to damage in patients with this gluten-ataxia. Recent study results have shown that patients with gluten-ataxia have antibodies against these Purkinje cells.
Additionally, they found that antibodies directed against gluten (the IgG-gliadin antibodies) actually cross-react with Purkinje cells (Hadjivassiliou). To explain, this means that although the initial immune reaction was mounted against the gluten protein, by chance, this antibody also reacted to the Purkinje nerve cells. This is a fatal attraction and causes subsequent nerve damage in the cerebellum.
“Neurological dysfunction of unknown cause”
High IgG-gliadin antibodies are found in brain dysfunction. In medicine, the causes of many illnesses are unknown. In the brain areas, the phrase used to describe such unknown diseases is “neurological dysfunction of obscure etiology.” When such a group of patients was investigated for gluten reactions, a high prevalence of anti-gliadin antibodies (57%) was found in their blood compared with two control groups (5–27%). But only a third of these patients had histological evidence of celiac disease.
The conclusion drawn was that the remaining two thirds (65%) had gluten-sensitivity. The target organ in this case was the cerebellum or the peripheral nerves.
Finally, both the ataxia (from cerebella damage) and the neuropathy are often reversible on a strict gluten-free diet. The authors (Hadjivassiliou 1998) went on to say, “These results strengthen our contention that eliminating these antibodies through strict adherence to a gluten-free diet may have important therapeutic implications for patients with gluten ataxia.” Here the focus is on antibody reduction rather than just the elimination of gluten. Surely there is a strong case for investigating for gluten-sensitivity in all patients with any neurological dysfunction.
How gluten causes nerve damage
Gluten can damage the neural tree is many different ways. It is of concern that there are so many ways to upset your nerve cells. Once nerve cells are damages, they are hard to repair.
Gluten-driven brain inflammation. Gluten reactions can be inflammatory. The mechanisms of how this damage is caused is still uncertain. It also is controversial whether the IgG-gliadin antibodies might directly interact with the nervous system. However, there are some case histories, which provide evidence that the gluten damage is from inflammatory disease.
For example, a patient described in this following case report demonstrates the gluten-driven inflammation (Ghezzi, 1997). A patient with both celiac disease and progressive brain symptoms (suggesting brainstem and cerebella involvement) had a series of MRI brain scans. The first examination showed multiple brain lesions. Soon after, a large cerebella lesion appeared, and then this was followed by severe cerebella atrophy. The presence of structural neuronal damage was confirmed by another type of brain scan (proton MR spectroscopy and magnetization transfer imaging). The MRI results and spinal fluid tests suggested that these neurological complications were more likely due to an inflammatory process.
Neural antibodies. Nerve damage can come about through autoimmune damage. A number of nerve and brain antibodies have been detected. For example, one study demonstrated “anti-ganglioside” antibodies in 64% of patients with celiac disease who had also been troubled with some sort of neuropathy (Volta, 2006). These auto-antibodies have been shown to bind to a number of critical nerve sites that will go on to damage the nerve. They have also been shown to attack the “Schwann cell” surface, part of the protective coat of the nerve, and also axons in peripheral nerves. De-myelination is the process that is seen in multiple sclerosis (MS).
Immune complex disease . An inflammatory reaction to gluten in and around the nerve tissues is the mostly likely explanation for the ongoing neuronal malfunction. There is evidence for this. When gluten gets into the body, it stimulates the production of the gluten antibodies by the immune system. The next phase is the formation of “gluten/gluten-antibody” immune complex reactions. Although this may start off as a non-specific inflammatory reaction, but nerve tissue is very sensitive to surrounding inflammatory activity.
Excitotoxins. The activity of excitotoxins is another factor that could invoke neurological damage. Excitotoxins are biochemical substances (usually amino acids) that can react with special neuronal receptors called “glutamate receptors”. This can happen both in the brain and in the spinal cord. This type of reaction is harmful (note that these substances are toxins). It can cause injury or even death to neurons.
These chemicals are called excitotoxins because they are neurotransmitters (such as glutamate or aspartate), which in too higher levels can excite the nerves to death. It is therefore crucial that the levels of these neurotransmitters are regulated properly.
In a normally functioning nerve, if a high level of these neurotransmitters is generated, then they are re-converted to the more calming neurotransmitter, called GABA. But in the inflamed state, this might not happen.
The way that the nerve death occurs is that the excess of these excitotoxins causes an imbalance in the flow of calcium into the nerve cell. This leads to the activation of an inflammatory cascade, and the subsequent release of even more inflammatory substances. This leads to neural malfunction and eventual nerve cell death.
It is possible that gluten or the “gluten/antibody immune complex” might disturb this delicate balance. Yes, nerve cells can be excited to death.
Interfere with neurotransmitters. Secretin is a gut hormone that has a central role in messaging between the nerve cells in the gut. However, secretin is perhaps best known in its role to stimulate the pancreas to release bicarbonate to neutralize the acid, which the stomach has produced.
Secretin has been shown to cross the blood/brain barrier, which may regulate cells nearby to produce GABA, the calming neurotransmitter. In addition, secretin appears to activate neurons in the amygdala, an area of the brain that integrates social and emotional stimuli. It is possible that gluten may interfere with the secretin receptor or messaging activity.
To date, the effects of gluten on nerve tissue functions have not really been investigated. So at this stage, any “neurotoxic” effect of gluten in speculative. However, there is plenty of objective evidence that brain and nerve damage does occur in association with gluten ingestion.
Also there is actual brain cell evidence. Some evidence of brain damage has been obtained from an examination of the brain tissue under the microscope. This is called histology or pathology. If there is damage in parts of the brain that control the gut, then it can be inferred that the gut symptoms are directly due to the brain damage rather than gluten acting on the gut.
Verdict
It is alarming. When you read down this long list of brain and nerve problems, it is staggering that so many neurological problems can be caused by gluten. The dismal news is that, currently, most neurologists and medical practitioners remain unaware of that these diseases/symptoms are commonly linked to gluten harm. The standard (old school) thinking is that gluten can only be a factor in the gastrointestinal symptoms of celiac disease. End of story. Obviously this is mistaken.
Marios Hadjivassiliou, in his 2010 paper says: “Most patients who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms. Gluten sensitivity is shown to manifest solely with neurological dysfunction. To improve diagnosis rates, the perception of physicians that gluten sensitivity is solely a disease of the gut must be changed.”
“The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.”
Wow! So many nerve diseases can activated by gluten. The big concern is that once your nerves have been damaged enough to cause you symptoms, it might be too late to get a benefit from a gluten-free diet. Damaged nerves are slow to heal … if ever.
You can read even more about the “grain-brain” connection in my book “Full Of It! The shocking truth about gluten” - follow this link: http://www.drrodneyford.com/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=30&categor
The inescapable conclusion is to avoid gluten before you get sick. That means going gluten-free now. That means everyone adopting a gluten-free lifestyle. This is one of the reasons that I eat gluten-free. What about you? What about your family? That means a Gluten-Free Planet.
Next we will explore glutened minds.
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Comments please
Help write our eBook.
So much evidence to adopt a gf diet for everyone right now!
Dr Rodney Ford
www.drrodneyford.com
It makes horrendous reading - how can gluten cause so mauch nerve damage. I would be interested in your thoughts.
You can read even more about the “grain-brain” connection in my book “Full Of It! The shocking truth about gluten”
- follow this link: http://www.drrodneyford.com/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=30&categor
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Chapter 7. Damaged nerves and brains
“The human brain is the most complicated organization of matter that we know.”
Isaac Asimov (from the foreword to The Three-Pound Universe by J. Hooper and D. Teresi, 1986)
- The thighbone’s connected to the kneebone
- Gluten Syndrome: a neurological disease
- Neurological gut dysfunction
- Headaches and migraines
- Neuropathy: brain and nerve damage
- Gluten can make you wobbly
- Evidence of gluten nerve damage
- Verdict
You are defined by your brain, your mind, your nerves. So it is a frightening fact that gluten can irreversibly damage and/or interfere with these delicate nerves that crisscross your body. I hear you ask: “how many people are affected by this and what can I do about it?” This might be the most important information that you have ever heard. One of the reasons that I have adopted a gluten-free lifestyle is to protect my brain. If you think that this mumbo-jumbo … then just read on.
The thighbone’s connected to the kneebone
Everything in your body is connected to everything else. You are not a collection of organs, blood and bones. Your body is miracle of inter-connected cells, all talking to each other through your nerves, hormones and blood.
However, because our human bodies are so immensely complicated, the medical system perceives the body as a bunch of separate organs. We have the cardiologist, the chest/respiratory doctors, the ENT (Ear Nose Throat) specialists, the Obstetrics & Gynecology, the Endocrine, the Gastro, the Joint & Bone docs … it goes on. Their thinking is organ based, not body based. But of course this is not how your body works.
So, what would happen if there was a toxic substance that made lots of people very unwell. And what if this toxin affected each organ in a different way. How would it ever be discovered? We would predict that each super-specialty would make a different sort of diagnosis and give it a name.
Well this is the story of gluten. This is why the diagnosis has been missed until now. Find out how gluten can severely affect your nerves and brains.
Gluten Syndrome: a neurological disease
The key publications summarize the nerve affects of gluten are:
- “Gluten sensitivity: from gut to brain” by Marios Hadjivassiliou (2010; The Lancet Neurology, Volume 9, Issue 3, Pages 318 - 330, March 2010. http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract).
- “The gluten syndrome: A neurological disease” by Rodney Ford (2009, Medical Hypotheses 73 (2009) 438–440; http://www.medical-hypotheses.com/article/S0306-9877(09)00223-0/abstract) Full text available: http://www.slideshare.net/dennis43/the-gluten-syndrome-a-neurological-disease.
Our hypothesis states: “Gluten causes symptoms in both celiac disease and non-celiac gluten-sensitivity by its action on the nervous system”. This hypothesis has been formulated from experiences with gluten-sensitive patients and from the medical literature.
Currently, celiac disease (also known as gluten-sensitive enteropathy) is defined as a gastrointestinal disease. However, the bowel damage (known to be caused through the toxicity of gluten) cannot explain the wide array of symptoms that are observed in these celiac patients.
There must be an alternative mechanism.
The five unanswered gluten questions
As you know, gluten causes celiac disease in about one in every hundred people. Also, gluten is also responsible for significant ill health in one in every ten people. Some of the questions that remain unanswered are:
- Why are symptoms from gluten so common?
- How can gluten cause such a diverse range of symptoms?
- What mechanism is responsible for these symptoms?
- Why people recover so quickly when gluten is removed?
- Why do they deteriorate so rapidly when only tiny amounts of gluten are eaten?
Occam's razor (the law of succinctness) states that an explanation should make as few assumptions as possible. Defining gluten-sensitivity as a neurological condition achieves this. It explains why there are so many and such varied manifestations of gluten-sensitivity while making a minimal number of assumptions. We propose that gluten injures the nervous networks that control the gut’s functions. In addition, gluten also directly affects the brain, which leads to the primary neurological symptoms that are commonly seen with gluten-sensitivity.
Autonomic nervous system. The smooth faultless running of your body relies upon the autonomic nervous system. This is an elegant system of nerve signals and hormones. It is classified into two parts: the “sympathetic” and “parasympathetic” pathways, which are driven by their respective neuro-transmitters: norepinephrine (noradrenaline) and acetylcholine. The regulation of all your organs depends on this amazing system. The cardiovascular system, the gut, the bladder, the uterus and the glands (pancreas, gall bladder, sweat, saliva) all rely on these vast autonomic nerve networks (also called involuntary nervous system) to work properly. When all goes smoothly you feel well. When it goes wrong, you feel sick.
The evidence
What follows is a detailed account of the medical research into the relationships between gluten-disease and neurological damage. This Table presents the spectrum of neurological symptoms that have been documented to be associated with gluten reactions in celiac disease.
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Table of neurological conditions documented to be associated with gluten
Brain dysfunction
Headaches and Migraine
Cerebella ataxia
Myoclonic ataxia
Chronic neuropathies
Autonomic neuropathy
Epilepsy
Dementia
Myopathy
Mood and Behavior problems
Anger
Learning disorders
Lethargy, low energy
Attention-deficit/hyperactivity disorder (ADHD)
Autism
Depression
Psychiatric disorders
Schizophrenia
Multiple Sclerosis
Gut problems
Reflux
Constipation
Diarrhea
Abdominal pain
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Neurological gut dysfunction
The first report linking neurological disorders with adult celiac disease was published in 1966 (Cooke and Thomas-Smith). The underlying argument of this and many other reports was that gut disease was a prerequisite these neurological problems. But, thirty years later Hadjivassiliou and others, showed that neurological dysfunction could not only precede celiac disease, but could also be its only manifestation (Hadjivassiliou, 1996). A further ten years later, gluten-sensitivity, without histological gut damage, is being shown to cause neurological dysfunction (Hadjivassiliou, 2006).
Marios Hadjivassiliou has reviewed his work in this landmark paper: “Gluten sensitivity: from gut to brain” ( 2010; http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract).
Zelnik (2004) closely investigated the link between celiac disease and brain malfunction. Patients with celiac disease filled in a questionnaire regarding the presence of neurological disorders or symptoms. Those reporting any neurological manifestations were further studied. Their neurological information was compared with a control group: celiac patients were found very much more likely to have neurological disorders (51.4%) in comparison with the control subjects (19.9%). These neurological disorders included: hypotonia, developmental delay, learning disorders and ADHD (attention deficit hyperactivity disorder), headache, and cerebella ataxia. Epileptic disorders were only marginally more common.
Next, they were all put on gluten-free diets. A therapeutic benefit of a gluten-free diet was only demonstrated in patients with transient infantile hypotonia and migraine headache. They concluded that their study had found that the extent of neurological disorders that occurred in celiac disease was much broader than had been previously reported. Over a half were affected.
Gut malfunction
The gut is the place when food and nutrients are processed, absorbed and the waste material is eliminated. Your brain carries out a myriad of regulation and control activities in the everyday function of your gut. These complex tasks happen unconsciously. You know nothing about them until they go wrong!
These tasks include: peristalsis to constantly move food along your gut; esophagus swallowing movements; stomach emptying; small bowel movement; and large bowel actions. Consequently, when these control devices are impaired by gluten, you would expect the following symptoms: gastro-esophageal reflux and heart burn; nausea; bloating; constipation and diarrhea. And this is indeed what you find. When your gut goes wrong, you feel unwell.
Gastro-intestinal motility disorder
Celiac patients often show gastro-intestinal motor abnormalities. About a half of people with celiac disease have dyspeptic symptoms (epigastric discomfort, early satiety) which are suggestive of a gastro-intestinal motility disorder. Data is also available on the presence of a disturbed motility of the esophagus, stomach, small intestine, gallbladder, and colon of untreated celiac patients (Tursi, 2004).
Gastro-intestinal abnormalities from a malfunction of autonomic motility differ in different gastro-intestinal zones:
- Slower esophageal transit (slow swallowing)
- Delayed gastric emptying (full tummy for longer)
- Impaired gallbladder emptying (fat digestion problems)
- Slower mouth-to-caecum transit time (bloating)
- Faster colonic transit (diarrhea).
These alterations in function are the result of the complex interactions in the gastro-intestinal tract. The factors of this interweaving of function include: the reduced absorption of food nutrients (in particular, fat); neurological malfunctions; gut hormonal impairment; and small intestinal bacterial overgrowth (from the predisposing motility disorder).
The whole gut can malfunction
All of these alterations in function can disappear after a gluten-free diet is started. These gut dysmotility disorders can also occur in gluten-sensitivity without the additional need for small bowel histological damage.
Gastro-esophageal reflux disease (GERD). Reflux, or heartburn, occurs when the stomach contents gets pushed back up into the esophagus. The acid in the stomach will then cause an irritation and eventually a burning of the skin in the esophagus. This is very uncomfortable. It hurts. Babies scream and cry. Toddlers whine, moan and get distressed. Older children experience regurgitation of acid in their mouth. They get heartburn. They drink milk. They refuse their food.
In my experience, both children and adults who have troublesome gastro-esophageal reflux symptoms are frequently gluten-sensitive. Indeed, I have found that children who have severe reflux (those who require continuing treatment with acid suppressant medication past 18 months of age) nearly all turn out to be gluten-sensitive. These children have high IgG-gliadin antibody levels. When these children go onto a gluten-free diet, they settle down, they sleep well for the first time, and they begin to eat normally. They also can usually be weaned off their medications within a few months. Their parents are relieved that at last their distressing problems have been solved.
Gastric reflux is extremely common. Anti-reflux medications are prescribed second only to pain killers. It is so common that people think that it is a “normal” symptom. From dealing with these problems every day, I have found that it is frequently precipitated by gluten.
Constipation and soiling. When your colon is not functioning properly, you will experience constipation, soiling (encopresis), bloating, and at times diarrhea. You also will have low immune function – the colon is a very important part of your immune system.
To empty out your colon, the large bowel muscles have to work efficiently to move the fecal contents along. You also have to be able to feel the “call to stool”. That is the urge to download. I have found that the children (and adults) with constipation from gluten-sensitivity have poor sensations about wanting to defecate. They cannot feel it coming. I think that this is due to damaged nerves that control this function. Once going gluten-free, it usually takes about 3–6 months for everything to come right again.
Studies have shown that the explanation for much constipation in children is from a cow’s milk protein intolerance. However, gluten is also a major contributor to this problem.
There is another clue that indicates gluten as a cause of constipation. Gluten can be converted into a morphine-like substance (gluteo-morphine) in the liver. These chemicals cause constipation. Treatment with naloxone, a specific morphine antagonist, has been shown to benefit some children with protracted constipation (Kreek, 1983) and others with chronic irritable bowel.
Diarrhea. Diarrhea refers to having loose bowel motions, also called loose stools. “Runny poos” is a common term used by children and parents. Sometimes there can be a sense of urgency and loss of control can occur. It is a very common symptom and has many possible causes.
Loose bowels motions, as a symptom of celiac disease, are mostly due to the poor absorption of food nutrients from the gut. All of this undigested food in the large bowel causes havoc: it gets fermented by the bacteria in the colon, which creates rectal gas and more fluid. The tummy gets distended and the bowel motions can be explosive.
Curiously, when the small bowel is not damaged, diarrhea can still occur. This can be due to the irritation of the nerve networks of the intestine that will then try to quickly expel the unwanted foods. This is the explanation for tiny amounts of gluten causing large amounts of diarrhea and abdominal pain.
Tummy pain. Abdominal pain can be generated within the gut from spasm of intestinal muscles; or from distention and stretching of the bowel wall; or from inflammation of the surrounding tissues, nerves and glands.
However, stimulation of the autonomic nervous system can also cause a gut ache. Spasms of the muscles and distention by too much gas will give you a colicky pain – these are sharp intermittent pains that often come in waves. When you get these pains it makes you want to double up.
Pains that stem from the inflammation of tissues are more constant and there is a tendency for you to remain still. Pain in the esophagus is sometimes called heart burn. In children, this causes them to squirm, cry or arch their body backwards. Gluten has been implicated as a factor in all of these types of pains.
Abdominal migraine. The term abdominal migraine has been used to describe recurrent abdominal pain with no other apparent cause (idiopathic): a tummy headache. It got this name because the pain could be so severe and associated with nausea. Sometimes a headache could arise as well.
In the headache literature, abdominal migraine is defined as one of the variants of migraine headache. It is also known by other terms including “periodic syndrome.” This variant is reported most typically in children. People who have abdominal migraine usually have a family history of headache migraine. They often go on to develop typical migraine later in their life.
The attacks of abdominal migraine are characterized by periodic bouts of abdominal pain which usually last for a few hours. In addition to the abdominal pain, these sufferers may have other symptoms such as nausea and vomiting, flushing or pallor.
Traditional tests have failed to reveal a cause for this pain. However, occasionally there are EEG findings that are suggestive of epilepsy – but this is rarely related to any convulsions. The usual medical practice is to put such children on long-term medications that are used for treating migraine. These medications do lessen these attacks in most children. Indeed, that is why these abdominal attacks are called abdominal migraine!
They appear to be generated within the tummy brain (the autonomic nervous system. My research has found that most of these children are gluten-sensitive. They have high IgG-gliadin antibodies and immediately get completely better on a gluten-free diet: neurological activity triggered by gluten. See later section for more research on gluten headaches.
Headaches and migraines
Headaches and migraines have repeatedly been reported to be associated with gluten in the diet. Not surprisingly, researchers have found that removing or cutting back on gluten in the diet can greatly reduce these symptoms.
One study (Hadjivassiliou, 2001) reported the findings in ten patients with gluten-sensitivity. Their brain tests (MRI-Magnetic Resonance Imaging) had suggested inflammation of their central nervous system. All of these people had experienced significant chronic headaches. Some had also suffered from unsteadiness and poor muscle coordination.
Headache relief off gluten. The great news for them was that after removing gluten from their diets, all of the nine who went gluten-free had full or partial relief (there was only one patient who would not try the diet).
One of these patients tells his story. He was a 50-year-old man who had complained of headaches and nausea along with confusion and agitation. He initially had experienced intermittent severe headaches for four years but then his attacks got even worse, both in frequency and severity. He was delighted that soon after starting a gluten-free diet he became symptom free. His balance improved rapidly and his headaches cleared completely! After going back on gluten, his headaches returned.
Another of these patients was a 45-year-old man. He had suffered from migraine since he was a child. Over time, his attacks had become more and more severe and resisted every treatment. He had blood tests that showed him to be gluten-sensitive. With the introduction of a gluten-free diet, his headaches completely disappeared. There are hundreds of similar cases in which gluten has been shown to be “the trigger factor”.
Gluten recognized as headache trigger. Migraine people more likely to have celiac disease. A different focus of some studies has been to look at the association between headache and celiac disease. In one study (Gabrielli, 2003), a total of 90 patients affected by migraine (of unknown cause) were enrolled, and compared with 236 blood donors. Four (4.4%) of 90 migraine patients were found to have celiac disease compared with only 0.4% blood donor controls. This was a highly significant difference – that is a ten times difference. These four people were put on a gluten-free diet for the next six months with impressive results. One of the four patients had no more migraine attacks. The remaining three patients experienced an improvement in frequency, duration, and intensity of their migraine. In summary, of those suffering with migraine, celiac disease was found in 4.4% of the migraineurs compared with only 0.4% in blood donors.
Brain blood flow. This study went on to investigate whether there were any regional cerebral blood-flow abnormalities in migraine patients with celiac disease. This is because migraine is associated with changes in brain blood-flow. Brain scans were done (a single photon emission CT brain study) on these migraine patients before and after being on a gluten-free diet. Their first brain scan tests showed a regional reduction in blood-flow in all four patients. But this blood-flow reduction was completely reversed at the follow-up brain scan after six month on a gluten-free diet.
They concluded that a significant proportion of patients with migraine may have celiac disease, and that a gluten-free diet may lead to an improvement in the migraine in these patients. A very high prevalence of headache (migraine and/or tension headaches) was also found in celiac disease patients (46%) when compared with a control group (29%) (Cicarelli, 2003).
Again, looking at celiac disease, headache was the most common neurological condition in those who had been diagnosed in childhood: 27.9% compared with only 8.1% of a control comparison group. Importantly, about half of these neurological symptoms disappeared when on a gluten-free diet (Zelnik, 2004).
Some of these patients with migraine-like headaches have been shown to have cerebral calcification when studied with head MRI scans. This is probably from long-standing disease.
Surely, the earlier that gluten-sensitivity is diagnosed, the less likely it is going to progress to long-term irreparable damage. Overall, children respond more quickly than adults to a gluten-free diet.
Gluten convulsions
Gluten-sensitivity is linked to epilepsy. Epilepsy is a brain condition. It is the spontaneous discharge of electrical activity in the brain. This causes a sudden change in behavior or motor activity. The symptoms and signs depend upon where in the brain this abnormal activity is occurring. In the general population, about one in every fifty people has some sort of experience of epileptic seizures. Yet again, there is an association between celiac disease and epilepsy, although this does not seem to be very strong. A higher prevalence of epilepsy (3.5–5.5%) has been reported in patients with celiac disease compared with controls (2%). Also, high IgG-gliadin antibody levels are more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%) (Ranua, 2005).
In addition, the specific condition “bilateral occipital cerebral calcification and seizures” has been more strongly associated with celiac disease (Visakorpi, 1970). However, this syndrome seems to be rare. In one study (Fois, 1994), 783 children who presented with seizures were investigated for celiac disease: there were nine children discovered with partial and/or grand mal seizures. Of these, only three (0.3%) had cerebral calcification.
The effect of a gluten-free diet on epilepsy control in celiac disease has been variable. In most patients the beneficial effects of the diet have been reported in terms of better seizure control and a decrease in the amounts of antiepileptic medications – but not the resolution of their seizures. Perhaps, the earlier the diagnosis and treatment with a gluten-free diet, the better the outcome. Again, all children with epilepsy should be investigated for evidence of gluten-sensitivity.
Neuropathy: brain and nerve damage
Neuropathy is the name used to describe the damage to the nerves in your body. The neuropathy can occur in any of your nerves, and each location is given its own special name. Most of the information about nerve damage comes from studies of celiac patients. However, it is the gluten that is causing the damage: so gluten nerve damage is not restricted to those with celiac disease.
Nerve damage: neuropathy
There are nerves running throughout your body. The nerves, which connect your brain up to your skin and muscles, are called the peripheral nerves. This peripheral nerve network is linked to your conscious mind.
You have another set of nerves which fans out to connect your brain up with all of your internal organs – this part of the nervous system is called the “autonomic nervous system” which responds to your unconscious mind and your emotions. I regularly see children who have been diagnosed as having a neurological condition, but turn out to have celiac disease or a gluten-sensitivity. In my opinion, all children (and adults) who have any neurological problems should have a blood test for their gluten and celiac antibody levels.
An underlying nutritional deficiency is a most unlikely explanation for these neuromuscular disorders. There are several arguments to support this:
- Many of the neuromuscular disorders which are described in association with celiac disease and gluten-sensitivity have an inflammatory or autoimmune basis which cannot be simply generated by food deficiencies.
- Many neurological disorders are seen in the absence of any gastro-intestinal disorder.
- Many people with gluten related neuropathy have no physical or biochemical evidence of malabsorption or nutritional deficiency.
Peripheral neuropathy
Gluten can cause loss of feeling. Looking through the narrow window of celiac disease, when carefully investigated, up to half (49%) of adults with celiac disease have evidence of a peripheral neuropathy (Cicarelli, 2003). The most common form of neuropathy has been the loss of feelings or a change in sensation felt in the skin. It is usually found in the hands and feet. In a group of 20 patients with neuropathy and confirmed celiac disease, there were nine patients who had complained of their sensory symptoms before the diagnosis of celiac disease had been made (Chin, 2003).
Motor neuropathy
Gluten can cause weakness. In addition to these sensory disturbances, the motor nerves can also be affected. The motor nerves are the nerves that work your muscles, which are attached to your bones. They give you the ability to move.
So when you get a motor neuropathy you will be weak and not be able to move very well. You will tire very easily. This damage is called a motor neuropathy. Serious damage can be detected in the motor nerves by a technique called electro-physiologic studies. Electrodes are placed over the nerve, which is then stimulated by a tiny electric shock. The speed of the nerve conduction can be measured. If the nerve electricity is travelling abnormally slowly, then this is evidence that the nerve has been damaged.
But early on in this condition, the nerve might not be damaged enough to cause a slowing of the current. Of interest, one study (Chin 2003) reported a group of 400 patients who had a neuropathy but had normal electro-physiologic studies. They were all investigated for celiac disease, which was found in 8% of them. This is ten times the number that was expected – as the incidence of celiac disease is about one in one hundred in the population at large.
The reports on the effect of a gluten-free diet on peripheral neuropathy associated with celiac disease are conflicting. Some studies have reported that a gluten-free diet is effective (Kaplan, 1988; Polizzi, 2000). However, others have found that the neuropathy symptoms have persisted despite an adequate gluten-free diet (Luostarinen, 2003). Again, it is likely that the more chronic and established the disease, the less likely it is to respond to a gluten-free diet. I think this is why children respond so well. Most of the studies are in grown-ups!
Autonomic neuropathy
Gluten interferes with our automatic functions. Your autonomic nervous system takes care of your vital day-to-day body functions that you never have to think about. This system keeps going day and night. It keeps you breathing, keeps your heart pumping, and keeps your gut working faultlessly. Although it is not under your conscious control, it is strongly influenced by your emotions. Control of your swallowing, your stomach emptying, the flow of food through your intestines, and your colonic movements are all mediated through this system.
There is ample evidence of upper-gut motor abnormalities in many people with celiac disease. This topic has been carefully researched (Usai, 1977) in an investigation of upper-gut motor activity in 30 celiac patients. They then explored the role played by the autonomic nervous system in these motility disturbances.
Autonomic system malfunctions in most celiacs. They found esophageal motor abnormalities in half of their patients. Abnormal esophageal acid studies (pH-probes) were abnormal in 30%. Delayed gastric emptying was documented in 50%. In total, 75% of celiac patients were shown to have some sort of gastro-intestinal motility alterations. Tests of autonomic dysfunction were positive in 45% of these patients. This indicated that a gluten autonomic neuropathy was playing a role in their reflux.
Gluten can make you wobbly
Ataxia
Ataxia is the word for when you feel wobbly or if you have an unsteady gait or walk. It is a loss of coordination. Ataxia can be due to damage of the cerebellum. The cerebellum looks like a wrinkled clenched fist of tissue at the back of your brain. Your cerebellum coordinates your body movements. Your cerebellum is also involved in the learning of repeated movements. For example, when you catch a ball, or balance on one leg, or use the computer keyboard – when you are carrying out these learned repetitive movements, then you are training your cerebellum.
Movement control. This cerebellum co-ordination of your body movement is achieved by collecting information from all parts of your body. This information of awareness about the position of your body comes hurtling in from all of your nerve sensors (limb position, balance information, speed, and what you can see). Eventually, this stream of information can help you do things like learn how to ride a bike without falling over. And then, magically, your cerebellum remembers this set of instructions, forever.
Some of the symptoms that are associated with damage to the cerebellum or the nervous tracts leading to it are:
- Ataxia (difficulty in coordinating movements)
- Tremors
- Loss of balance, vertigo, and dizziness
- Muscle weakness
- Difficulty in performing rapid alternating movements
- Loss of postural tone.
Gluten ataxia. Gluten can impair the function of the cerebellum. Evidence shows that gluten is the culprit in causing these symptoms in many people. It was forty years ago that the first cases of ataxia that were linked to celiac disease were reported (Cooke and Smith, 1966). They wrote about a group of 16 patients with celiac disease who also had gait ataxia and peripheral neuropathy. They demonstrated that these patients had cerebella dysfunction.
Many others have subsequently shown that cerebella ataxia, and indeed many other neurological syndromes, may be part of the presenting symptoms of celiac disease. In one such study, a group of patients with cerebella ataxia (of unknown cause) were investigated by small bowel biopsy: 16% (4 of 25) were found to have celiac disease (Pellecchi, 1999).
Gluten the troublemaker. There is ample evidence that gluten can be a troublemaker in the brain both with and without celiac disease. This is now called gluten-sensitivity. Hadjivassiliou (1999) first put it like this: “It remains controversial whether gluten-sensitivity (a state of heightened immunologic responsiveness to ingested gluten) without intestinal involvement should be considered the cause of cerebella degeneration in ataxia of otherwise unknown cause.” However, his research over the last decade had made this an established fact (http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract).
Many others agree, for instance, Hernandez-Lahoz (2011, Rev Neurol. 2011 Sep 1;53(5):287-300. http://www.ncbi.nlm.nih.gov/pubmed/21796607) wrote a paper “Neurological disorders associated with gluten sensitivity”. He concludes: “Gluten sensitivity is a systemic autoimmune disease. Neurological manifestations of gluten sensitivity, with or without enteropathy, are also frequent, their pathogenesis including an immunological attack on the central and peripheral nervous tissue accompanied by neurodegenerative changes. The clinical manifestations are varied, but the most common syndromes are cerebellar ataxia and peripheral neuropathy. The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.”
Various studies have found that the prevalence of positive IgG-gliadin antibodies in ataxia (of unknown cause) has varied between 0–41%. However, raised IgG-gliadin antibodies are found more frequently in ataxia (30%) than in the general population (8–12%). This is excellent evidence for a causal association between cerebella degeneration and gluten-sensitivity.
Evidence of gluten nerve damage
Gluten antibodies cross-react with brain cells. There are some very sensitive cells in the cerebellum (the part of the brain responsible for coordination). They are called “Purkinje cells” and function as the output neurons of the cerebellum. These are the cells that appear to be most susceptible to damage in patients with this gluten-ataxia. Recent study results have shown that patients with gluten-ataxia have antibodies against these Purkinje cells.
Additionally, they found that antibodies directed against gluten (the IgG-gliadin antibodies) actually cross-react with Purkinje cells (Hadjivassiliou). To explain, this means that although the initial immune reaction was mounted against the gluten protein, by chance, this antibody also reacted to the Purkinje nerve cells. This is a fatal attraction and causes subsequent nerve damage in the cerebellum.
“Neurological dysfunction of unknown cause”
High IgG-gliadin antibodies are found in brain dysfunction. In medicine, the causes of many illnesses are unknown. In the brain areas, the phrase used to describe such unknown diseases is “neurological dysfunction of obscure etiology.” When such a group of patients was investigated for gluten reactions, a high prevalence of anti-gliadin antibodies (57%) was found in their blood compared with two control groups (5–27%). But only a third of these patients had histological evidence of celiac disease.
The conclusion drawn was that the remaining two thirds (65%) had gluten-sensitivity. The target organ in this case was the cerebellum or the peripheral nerves.
Finally, both the ataxia (from cerebella damage) and the neuropathy are often reversible on a strict gluten-free diet. The authors (Hadjivassiliou 1998) went on to say, “These results strengthen our contention that eliminating these antibodies through strict adherence to a gluten-free diet may have important therapeutic implications for patients with gluten ataxia.” Here the focus is on antibody reduction rather than just the elimination of gluten. Surely there is a strong case for investigating for gluten-sensitivity in all patients with any neurological dysfunction.
How gluten causes nerve damage
Gluten can damage the neural tree is many different ways. It is of concern that there are so many ways to upset your nerve cells. Once nerve cells are damages, they are hard to repair.
Gluten-driven brain inflammation. Gluten reactions can be inflammatory. The mechanisms of how this damage is caused is still uncertain. It also is controversial whether the IgG-gliadin antibodies might directly interact with the nervous system. However, there are some case histories, which provide evidence that the gluten damage is from inflammatory disease.
For example, a patient described in this following case report demonstrates the gluten-driven inflammation (Ghezzi, 1997). A patient with both celiac disease and progressive brain symptoms (suggesting brainstem and cerebella involvement) had a series of MRI brain scans. The first examination showed multiple brain lesions. Soon after, a large cerebella lesion appeared, and then this was followed by severe cerebella atrophy. The presence of structural neuronal damage was confirmed by another type of brain scan (proton MR spectroscopy and magnetization transfer imaging). The MRI results and spinal fluid tests suggested that these neurological complications were more likely due to an inflammatory process.
Neural antibodies. Nerve damage can come about through autoimmune damage. A number of nerve and brain antibodies have been detected. For example, one study demonstrated “anti-ganglioside” antibodies in 64% of patients with celiac disease who had also been troubled with some sort of neuropathy (Volta, 2006). These auto-antibodies have been shown to bind to a number of critical nerve sites that will go on to damage the nerve. They have also been shown to attack the “Schwann cell” surface, part of the protective coat of the nerve, and also axons in peripheral nerves. De-myelination is the process that is seen in multiple sclerosis (MS).
Immune complex disease . An inflammatory reaction to gluten in and around the nerve tissues is the mostly likely explanation for the ongoing neuronal malfunction. There is evidence for this. When gluten gets into the body, it stimulates the production of the gluten antibodies by the immune system. The next phase is the formation of “gluten/gluten-antibody” immune complex reactions. Although this may start off as a non-specific inflammatory reaction, but nerve tissue is very sensitive to surrounding inflammatory activity.
Excitotoxins. The activity of excitotoxins is another factor that could invoke neurological damage. Excitotoxins are biochemical substances (usually amino acids) that can react with special neuronal receptors called “glutamate receptors”. This can happen both in the brain and in the spinal cord. This type of reaction is harmful (note that these substances are toxins). It can cause injury or even death to neurons.
These chemicals are called excitotoxins because they are neurotransmitters (such as glutamate or aspartate), which in too higher levels can excite the nerves to death. It is therefore crucial that the levels of these neurotransmitters are regulated properly.
In a normally functioning nerve, if a high level of these neurotransmitters is generated, then they are re-converted to the more calming neurotransmitter, called GABA. But in the inflamed state, this might not happen.
The way that the nerve death occurs is that the excess of these excitotoxins causes an imbalance in the flow of calcium into the nerve cell. This leads to the activation of an inflammatory cascade, and the subsequent release of even more inflammatory substances. This leads to neural malfunction and eventual nerve cell death.
It is possible that gluten or the “gluten/antibody immune complex” might disturb this delicate balance. Yes, nerve cells can be excited to death.
Interfere with neurotransmitters. Secretin is a gut hormone that has a central role in messaging between the nerve cells in the gut. However, secretin is perhaps best known in its role to stimulate the pancreas to release bicarbonate to neutralize the acid, which the stomach has produced.
Secretin has been shown to cross the blood/brain barrier, which may regulate cells nearby to produce GABA, the calming neurotransmitter. In addition, secretin appears to activate neurons in the amygdala, an area of the brain that integrates social and emotional stimuli. It is possible that gluten may interfere with the secretin receptor or messaging activity.
To date, the effects of gluten on nerve tissue functions have not really been investigated. So at this stage, any “neurotoxic” effect of gluten in speculative. However, there is plenty of objective evidence that brain and nerve damage does occur in association with gluten ingestion.
Also there is actual brain cell evidence. Some evidence of brain damage has been obtained from an examination of the brain tissue under the microscope. This is called histology or pathology. If there is damage in parts of the brain that control the gut, then it can be inferred that the gut symptoms are directly due to the brain damage rather than gluten acting on the gut.
Verdict
It is alarming. When you read down this long list of brain and nerve problems, it is staggering that so many neurological problems can be caused by gluten. The dismal news is that, currently, most neurologists and medical practitioners remain unaware of that these diseases/symptoms are commonly linked to gluten harm. The standard (old school) thinking is that gluten can only be a factor in the gastrointestinal symptoms of celiac disease. End of story. Obviously this is mistaken.
Marios Hadjivassiliou, in his 2010 paper says: “Most patients who present with neurological manifestations of gluten sensitivity have no gastrointestinal symptoms. Gluten sensitivity is shown to manifest solely with neurological dysfunction. To improve diagnosis rates, the perception of physicians that gluten sensitivity is solely a disease of the gut must be changed.”
“The early detection of cases of gluten sensitivity with neurological manifestations and subsequent treatment with the gluten-free diet could provide remarkable benefits to the patients.”
Wow! So many nerve diseases can activated by gluten. The big concern is that once your nerves have been damaged enough to cause you symptoms, it might be too late to get a benefit from a gluten-free diet. Damaged nerves are slow to heal … if ever.
You can read even more about the “grain-brain” connection in my book “Full Of It! The shocking truth about gluten” - follow this link: http://www.drrodneyford.com/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=30&categor
The inescapable conclusion is to avoid gluten before you get sick. That means going gluten-free now. That means everyone adopting a gluten-free lifestyle. This is one of the reasons that I eat gluten-free. What about you? What about your family? That means a Gluten-Free Planet.
Next we will explore glutened minds.
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So much evidence to adopt a gf diet for everyone right now!
Dr Rodney Ford
www.drrodneyford.com
