Gluten-free diet MAY be unhealthy and MAY increase risk of heart attack (or not)

OK, so I made up the quote above, but it captures a certain zeitgeist that’s in the air right now. The media is all too keen to uncritically give gluten-free and clean diets a kicking at the moment, wagging fingers at all those ‘silly people’ who fell for the anti-gluten message even though they don’t have coeliac disease – what fools!

Except, as we have explained in multiple articles on this site, gluten has a far greater reach than that 1% who have classic coeliac disease. Non coeliac gluten sensitivity (NCGS) is a recognised and studied condition, with an estimated prevalence of up to 6% of the population.

And even a cursory look behind these dismissive headlines shows that the studies they are based on add almost nothing to our understanding of gluten pathology, and indeed contradict themselves. Continue reading

Gluten Update April 2017

The effects of gluten are not confined to just the 1% of the population that suffer with Coeliac Disease and the estimated 6% who suffer with Non-Coeliac Gluten Sensitivity, but can have detrimental effects in everyone. In these updates we share some of the latest research.

  • Effects of gluten on gluten-tolerant mice
  • Relatives of coeliacs often have gluten related disorders
  • NCGS persists even after 8 years on gluten free diet
  • Gluten free diet prevents progression of potential coeliacs
  • Coeliac disease may be triggered by a common virus
  • Coeliac disease and joint and bone problems

Read time: 11 minutes (2000 words)

Effects of gluten in otherwise gluten-tolerant mice

Dietary gluten causes severe disorders like celiac disease in gluten-intolerant humans. However, currently understanding of its impact in tolerant individuals is limited.

A ground breaking study has undertaken the first detailed investigation into the effects of gluten on metabolism and microbiome in gluten tolerant mice. The purpose of the study was to identify the effects of an obesogenic diet with or without gliadin (a key, immunogenic component of gluten).

The team from The National Food Institute, Denmark (Li Zhang et al, 2017) analysed a huge array of parameters, including insulin resistance, histology of liver and adipose tissue, intestinal microbiota in three gut compartments, gut barrier function, gene expression, urinary metabolites and immune profiles in intestinal, lymphoid, liver and adipose tissues.

Using tightly controlled diets the researchers found that a relatively small change (exchanging casein for 4% gliadin) resulted in a considerable impact on the host response in the mouse model. The levels of gliadin used were comparable to that found in bread. The remainder of the diet was, however, higher in fat than a typical human meal (35g fat/100g).

The headline findings include:

  1. Gliadin Intake Affected Glucose and Lipid Metabolic Homeostasis
  2. Gliadin Intake Altered Gut Microbial Composition and Activity
  3. Gliadin Intake Caused Lower Expression of Gut Barrier Function Related Genes in Ileum
  4. Gliadin Intake Changed the Metabolic Signature of Urine
  5. Gliadin Did Not Affect Systemic Inflammatory Markers but Altered Immune Cell Composition in Liver and Inflammatory Phenotype of Visceral Adipose Tissue

The changes were predominately negative, but there is a huge amount of detail to unpack in this research, cetainly more than I want to go into in this post. That said, I will look a little more into the changes to the microbiome as they are particularly fascinating. If you are interested in going into the other areas more deeply then check out the full free text.

Changes to the intestinal microbiome

After nine weeks on the 4% gliadin diet levels of lactobacillus had fallen by more than 90%. (These are generally considered beneficial bacteria). Conversely, bacteria associated with detrimental health changes including Clostridium XI, Dorea and Coriobacteriaceae increased in abundance by more than ten fold.

Strains belonging to Clostridium XI, including also the opportunistic pathogen C. difficile, are associated with compromised health. Dorea spp. are found to be overrepresented in irritable bowel syndrome patients, and patients with non-alcoholic fatty liver disease. Coriobacteriaceae spp. have repeatedly been shown to be involved in host lipid metabolism, and many bacteria within this group are considered as opportunistic pathogens

One apparently positive change observed in the gliadin consuming mice was an increase in Akkermansia in the colon. This species is usually associated with beneficial effects on metabolic health and inflammation. However, it feeds primarily on mucin secreted from the gut wall, and the researchers suggest its proliferation may be due to increased turnover of the small intestine mucosa due to disrupted gut barrier function.

Another recent paper (The gut–kidney axis in IgA nephropathy: role of microbiota and diet on genetic predisposition, Coppo, April 2017) underscores the importance of gluten-microbiome interaction, in this case to the development of IgA nephropathy (Berger’s disease).

The importance of this research is that it is a major piece of work exploring the effects of gluten relevant to the ‘normal’, apparently gluten-tolerant population. It has shown a large range of measurable effects which will need to be investigated further, particularly to establish their relevance in humans. In terms of the gluten iceberg these researchers are undertaking the deep sea diving necessary to establish the extent of the sub surface portion of the gluten phenomena. I am sure we will see more research like this in the coming years.

First degree relatives of Coeliacs often have gluten related disorders despite testing negative for blood markers 

Here at the clinic we see a disproportionate number of patients who at some point in the consultation declare that one of their parents or siblings has coeliac disease, often as if this is some minor point that is hardly worth mentioning. Nothing could be further from the truth: The biggest risk factors for coeliac disease is being a first degree relative of a coeliac, with nearly four times the incidence than the general population.

The first-degree relatives (FDRs) of patients with coeliac disease are the main risk group for disease development.

– Vaquero et al, 2017

Parents, children or siblings of coeliacs should therefore have blood tests regularly, and if positive should immediately adopt a gluten free diet. A study by Nicola Imperatore et al, which I cover later in this post, has demonstrated the importance of early adoption of a gluten-free diet for anyone with positive coeliac blood tests, even when they have no  symptoms, to avoid progression of intestinal damage and immunological problems.

Some patients, however, claim that they have been screened for coeliac disease and have been told ‘they don’t have it’ – i.e. that their blood markers were negative. In many cases, however, I can tell from their symptoms that they are gluten sensitive despite the test results. Many go on to make remarkable progress once they adopt a properly gluten-free diet, but sometimes it can be an uphill struggle convincing them to give it a try. Such is the power of the medical establishment when it makes its decrees.

These clinical observations have recently received confirmation from a study published in the Journal of Gastroenterology and Hepatology (Vaquero et al, 2017), which investigated the value of a gluten free diet in first degree relatives who were negative for coeliac blood markers (anti-endomysial antibodies and raised anti-tissue transglutaminase ). In this study they invited 205 first degree relatives of known Coeliacs who were negative on blood tests to undergo genetic screening (for the HLA-DQ2/8 genes) and duodenal biopsy to check for intestinal damage. Symptoms were established by questionnaire at the start of the study, after which participants followed a three phase diet: (1) baseline diet (gluten containing) (2) gluten free diet (4 weeks) then (3) gluten ‘overload’ diet

Of 139 who completed the study HLA-DQ2/8 was positive in 78.4% of the participants (homozygous, 15.1%; heterozygous, 63.3%). Alterations to the intestinal mucosa were noted in 37.1% of participants who underwent duodenal biopsy (Marsh I, 32.7%; Marsh IIIa, 4.4%). At baseline more than half of the participants had gastrointestinal symptoms (57.6%), mainly associated with bloating (16.5%), constipation (15.1%), diarrhea (14.4%), and abdominal pain (5.8%). During the gluten-free phase this fell to just one quarter and increased agin during the gluten overload phase.

Symptom improvement during the gluten free diet was twice as common among women as men and three times as common among people with an existing autoimmune disorder. Both of these observations fit clinical patterns at Rosemary Cottage Clinic and are similar to risk factors identified in studies of Non Coeliac Gluten Sensitivity.

In conclusion: First degree relatives of coeliacs have a heightened risk of developing coeliac disease. Of those without coeliac blood markers many have intestinal damage. In addition gluten related symptoms are commonly present independent of intestinal damage. Such people would have to be classified as Non Coeliac Gluten Sensitive as they do not fit the definition of Coeliac.

Non Coeliac Gluten Sensistivity persists even after 8 years of a wheat-free diet

In a paper recently published in Gastroenterology (Carroccio et al, 2017) Italian researchers followed up 200 patients that had been diagnosed with NCGS many years earlier. 88% had experienced improved symptoms following their original diagnosis.

8 years later 148 of these individuals were still on a strict wheat-free diet, with virtually all of them (98%) reporting a continuation of symptom reduction. Among those that had not maintained a strict WFD only 58% had symptoms that were improved compared to the time of diagnosis.

The researchers repeated the double-blind placebo-controlled challenge with 22 patients, and found that 20 reacted to wheat.

This study demonstrates that NCGS is persistent, suggesting that it should be treated as a life long condition and a wheat-free diet adhered to.

A gluten-free diet prevents progression in Potential Coeliac Disease even when asymptomatic

Coeliac disease is diagnosed where patients have positive  blood tests (Anti-endomysial antibodies and raised anti-tissue transglutaminase) as well as evidence of villous atrophy on duodenal biopsy. In some cases, however, blood tests are positive, but there is little or no intestinal damage. Such situations are labelled Potential Coeliac Disease (PCD).

Until now it has not been clear whether such patients simply have a mild form of gluten intolerance, or whether they have early stages of Coeliac disease.  Furthermore, for the subset of PCD patients that have no gastrointestinal symptoms.

To answer these questions recent study an Italian team (Nicola Imperatore et al, Mar 2017) followed patients with PCD either on a gluten free diet or a gluten containing diet for a period of six years.

In short, those on the the gluten containing diet had increased intestinal damage and immune related disorders compared to those on the gluten-free diet. In addition, the asymptomatic patients who continued to consume gluten 69% developed coeliac-related symptoms, 46% developed villous atrophy and 61% immune mediated disorders.

This study underlines the importance of starting a gluten free diet as soon as possible following positive blood tests, regardless of symptoms and presence of villous atrophy.

Routine screening for Coeliac blood markers is not currently undertaken as many people that such tests would identify would prove to have no symptoms nor villous atrophy. It has been assumed that there would be no point in starting them on a gluten free diet as it was assumed that they would not go on to develop coeliac disease. This study challenges this position and demonstrates that many of these ‘false positives’ would indeed benefit from starting a gluten-free diet because they are at risk of developing villous atrophy and autoimmune diseases in the long term..

Coeliac Disease may be triggered by a common virus

It has long been known that the risk of coeliac disease is increased after various infections such as campylobacter, rotavirus and gastroenteritis. One hypothesis is that the presence
of both the pathogen and gluten presented simultaneously to the immune system  is enough to trigger coeliac disease.

Now a team from the University of Chicago, has found that exposing mice to a common reovirus called T1L can induce gluten intolerance. This virus was first identified in humans in the 1950s but has not been associated with any disease.

The team found that when they fed gluten to mice, those that were also infected with the virus produced two to three times as many antibodies to gluten as those that were virus free.

One of the Authors of the study Bana Jabri explained “Instead of mounting a tolerant, non-aggressive response, the immune system in the presence of the reovirus views gluten as being dangerous, promoting a destructive inflammatory response,”

The discovery has led the authors to speculate that a vaccine might be possible to prevent people from developing coeliac disease. Personally I think that’s unlikely, for a number of reasons. 1) gluten seems to cause disease by many pathways not just an aggressive immune response, 2) the researchers did not show that the mice went on to develop coeliac disease they just had a heightened immune response to gluten, 3) there is no evidence that all coeliacs had previously been infected with reovirus, and 4) physiological stressors other than pathogens appear to be able to trigger coeliac disease.

Source: New Scientist, Gluten allergy in coeliac disease may be provoked by virus (04/06/2017)

Coeliac Disease and Joint/Bone problems

In a recent letter to the journal Joint Bone Spine, Coline Daron et al report on their analysis finding 20‐30% cumulative incidence of arthralgia and arthritis among coeliac patients. They also identified an increased risk of osteoporosis:

Out of 11 case‐control studies featuring 1,008 patients with celiac disease and 13,706 controls, we noted a 2.73 [1.86‐3.99] higher risk of osteoporosis at any site in the celiac group. This increased risk was significant for femoral osteoporosis (OR=2.03 [95% CI: 1.11‐3.71]), and most of all for spinal osteoporosis (OR=7.2 [95% CI: 3.42‐15.18]. No increased risk of arthritis was noted in celiac patients compared to controls (OR=0.76 [95% CI: 0.16‐3.66]).

The authors call for physicians to undertake coeliac screening in cases of osteoporosis, arthralgia and arthritis where no obvious cause can be identified.


Gluten – what we learned in 2016 (part 2) – the Great Imitator

20+ conditions related to gluten – a review of some 2016 papers

gluten-related-disorders-2016-20🔍 Please feel free to share this infographic or the whole post!

In part 1 we looked at some of the key developments in understanding gluten sensitivity (coeliac and non-coeliac gluten sensitivity) that emerged in 2016. In part 2 now we take a look at some case studies, and small trials that link gluten to a wider range of conditions.

Read time: 18 minutes (2400 words)

Some of the conditions that were linked to gluten in 2016

When I did my medical training I was examined on clinical diagnostic skills. We students of herbal medicine, like other medical students, were taught that whatever symptoms a patient presented with, our list of possible diagnoses we could always include tuberculosis and syphilis. These two systemic diseases were called the great imitators due to their potential for affecting any tissue or organ. From back pain, to skin rashes and mental illness, these ancient adversaries of Man could be the cause. Misdiagnosis could be serious in that the wrong treatment might be pursued, and the effective treatment missed. What we are seeing with gluten related disorders is another great imitator at play. The conditions that follow will leave you in no doubt that gluten and/or other factor in cereal grains, can play havoc with every corner of the body and should always be considered, properly tested for,m and ruled out by the responsible and updated clinician.

In reading this post there are several points to bear in mind: (1) This is far from an exhaustive list, even of 2016 papers. (2) Gluten related disorders often go unsuspected, undiagnosed and therefore untreated for many many years and 80% of coeliacs remain undiagnosed! (3) Gluten can affect any system or tissue type of the body and should always be considered as part of a differential diagnosis even if there are no intestinal symptoms. A full gluten blood test, not just the standard NHS coeliac tests, should be used, or a minimum of a 6 week exclusion diet. (4) The true extent of the gluten iceberg’s sub-surface volume has yet to be established. These reports give some insight into the extent of the murky mass.

I have seperated these reports into those related to coeliac – where there is adaptive immunity and/or autoimmune factors involved and non coeliac gluten sensitivity (NCGS) – where the innate immune system is principally involved. The latter is particularly important as it indicates the propensity of gluten to affect potentially anyone.

1. Coeliac (autoimmune) related

Coeliac hepatitis: hepatic fibrosis, advanced steatohepatitis and cirrhosis
In a Nov 2016 case study, a 20 year old woman with coeliac disease and severe liver cirrhosis had a near complete reversal once placed on a gluten-free diet.The author called this a “hepatomiracle” [Gaur, Nov 2016]
An Iranian study published in Jul 2016 found that the prevalence of coeliac disease among patients with epilepsy was 6% – about five times higher than in the general population. [Bashiri, Jul 2016]
Chronic Hepatitis C Virus (CHV)
CHV infection can lead to autoimmune diseases and shares one of the same genetic loci as coeliac disease (HLA-DQ2). Liver disease also leads to anti-tissue transglutaminase antibodies (anti-tTG). Some CHV patients develop coeliac disease during interferon therapy. There is a complex relationship with many overlapping features between these two conditions, although it is not yet clear whether the incidence of coeliac disease is higher in CHV or not [Association between celiac disease and chronic hepatitis C, 2016].
Distal Renal Tubular Acidosis Associated with Celiac Disease and Thyroiditis
A case report of a 12 year old girl with a particular form of kidney disease, (distal renal tubular acidosis, RTA) with autoimmune diseases, which is extremely rare in children. [Indian Pediatrics, Nov 2016] “Despite resolution of acidosis on bicarbonate, she continued to have poor growth and delayed puberty. Investigations revealed autoimmune thyroiditis and celiac disease. Levothyroxine and gluten-free diet were initiated. Child gained height and weight and had onset of puberty after gluten withdrawal.”
Psychiatric Case
The BMJ recently published a case study of a girl admitted to a psychiatry ward suffering with suicidal behaviours who then developed an agitated catatonic state. She was unresponsive to antidepressants, anxiolytics, antipsychotics and electroconvulsive therapy, but improved significantly when a gluten-free diet was started [Oliveira-Maia, Dec 2016]. Another recent paper The progression of coeliac disease: its neurological and psychiatric implications, Campagna G, Dec 2016, explores the current understanding of the neurological implications of coeliac disease.
Burning Tongue
An elderly woman presented with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Tests revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Ten weeks on a gluten free diet led to complete symptom resolution [Sherman, Jun 2016].
Macrophage activation syndrome
A case report in Pediatric Rheumatology Online Journal, reports on a six year old girl who was diagnosed with Macrophage activation syndrome – an autoinflammatory or rheumatic disease involving hyper inflammation and an ineffective immune response. Serology indicated coeliac disease and symptoms stabilised with the introduction of a gluten-free diet. Authors state that “Clinicians should have a low threshold for screening children with other autoimmune diseases for coeliac disease.” [Palman, Dec 2016].
Coeliac like disease in dogs
The Veterinary Record [Lowrie, Dec 2016] reports on a case of “gluten-sensitive dyskinesia (previously termed canine epileptoid cramping syndrome) is a condition of Border terriers in which the leading manifestation is neurological… responsive to a gluten-free diet.” As such, the authors suggest that gluten sensitivity in Border terriers “may manifest as a multisystem disease in a similar manner to that seen in human beings.” There is another paper on this topic: Gluten exposure and multisystem disease in dogs [Davies M, Dec 2016], but I have been unable to access it.
Gluten free diet in pregnancy and type 1 diabetes in offspring
As we have previously discussed, gluten has a significant role in the development of type 1 diabetes. A study in the Journal of Diabetes Research [Antvorskov JC, Aug 2016] investigated the a mouse model of type 1 diabetes. Withholding gluten during pregnancy prevented the subsequent development of type 1 diabetes in offspring, even when exposed to gluten after birth. However, the effect disappeared if the mother received a gluten-free diet prior to pregnancy.
Aortic stiffness may explain increased cardiovascular risk
Many studies show an increased risk of cardiovascular disease in coeliac patients which cannot be explained by traditional risk factors. A study from Antalya, Turkey used echocardiograms to compare the aortic function of 81 coeliac patients with that of 63 healthy volunteers. They found an increased level of aortic stiffness and inflammation in coeliac patients. Whilst inflammation decreased with adherence to a gluten free diet, aortic stiffness did not, suggesting that increased cardiovascular risk may persist despite a gluten-free diet. [Bayar, Mar 2016]
Hemophagocytic lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis and is a life-threatening immunodeficiency. It affects people of all ages and ethnic groups. Common symptoms are fevers, enlarged spleen, low blood counts and liver abnormalities. [ref] A recent paper [Fordham NJ Sep 2016] reports a case that did not respond to standard treatment, but following blood tests established undiagnosed coeliac disease. “She initially responded to chemoimmunotherapy specific for hemophagocytic lymphohistiocytosis but relapsed within a few months of cessation of treatment and then achieved complete remission on gluten withdrawal alone.”
Down’s Syndrome
A study in Poland identified high levels of diagnosed coeliac disease among patients with Down’s syndrome (5.4% vs 1% in general population). The authors emphasise that tests for coeliac disease should be carried out in all (Polish) patients with Down’s syndrome, regardless of the clinical picture. [Szaflarska-Popławska, 2016]
Multiple autoimmune syndrome with celiac disease
Reumatologia published a case report of a 32 year old woman who had four co-existing autoimmune diseases: autoimmune hypothyroidism, Sjögren’s syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. The authors point out that patients with single autoimmune disorders are at 25% risk of developing other autoimmune disorders. The case emphasises the need for continued surveillance for the development of new autoimmune disease in predisposed patients. [Harpreet, Dec 2016]

2. Non-coeliac Gluten Sensitivity (NCGS)

NOTE: I am using NCGS as a looser category than is currently accepted to include any studies where withdrawal of gluten or wheat showed clinical benefit.

Intestinal cell damage and systemic immune activation in NCGS
A study published in the BMJ’s journal Gut at the end of 2016, examined serum from 80 individuals meeting the criteria for NCGS (although the authors use the term Non Celiac Wheat Sensitivity). They found increased levels of lipopolysaccharide binding protein – indicating that these patients had raised levels of gut bacteria products passing through a damaged gut wall, known as ‘leaky gut’. Associated with this was raised markers of systemic immune activation. The researchers went on to find raised levels of fatty acid binding protein, indicative of intestinal cell damage. As NCGS patients do not have villous atrophy (which is characteristic of celiac disease) it had been assumed that there is no intestinal damage taking place in NCGS, however, this study shows that damage is indeed taking place. The authors speculate that damage in NCGS may be taking place in the mid section of the small intestine, the jejunum, rather than the first section, the duodenum, from which biopsies are usually taken. Finally, these markers were found to improve with the initiation of a gluten free diet. [Melanie Uhde, 2016]
Psychotic Illness
Schizophrenia has previously been linked to raised kynurenine and reduced tryptophan [Chiappelli, Nature, 2016], both of which are related to the production of Vitamin B3. Researchers hypothesised that this imbalance could be caused by inflammatory immune mediators such as gluten. They found schizophrenic patients had raised levels of anti-gliadin antibodies (IgG) which correlated with kynurenine/tryptophan ratios. They concluded “Our results connect nonceliac gluten sensitivity with the KYN pathway of TRP metabolism in psychotic illness” [Okusaga, 2016]. This links to an long used treatment of schizophrenia which is goodly doses of Vitamin B3 (niacin), the production of which may be getting interfered with by gluten in these patients.
Atopic Dermatitis (Eczema)
A recent study sent 169 atopic dermatitis patients a 61-question survey asking about dietary modifications they had tried and their perceptions and outcomes of such trials. The most common foods eliminated were ‘junk foods’ (68%), dairy (49.7%), and gluten (49%). The best improvement in skin was reported when removing white flour products (37 of 69, 53.6%), gluten (37 of 72, 51.4%) and the nightshade family of vegetables, i.e. potatoes, tomatoes, aubergines, peppers, chilli and paprika (18 of 35, 51.4%). [Nosrati, 2017]
Lymphocytic colitis
(This condition is characterised by chronic watery diarrhoea yet with normal colon cells when sent to the histology lab, but with an accumulation of lymphocytes in the colonic epithelium/lining)
A study in the journal PLoS One found that 91% of lymphocytic colitis patients who were identified as NCGS responded to a double blind gluten challenge indicating a causative role for gluten in these patients. [Rosinach M, Jul 2016]
Nephrotic Syndrome
This is a rare condition in childhood that presents with proteinuria, hypoalbuminemia, and oedema. Kidney function is usually normal however. Most children (>90%) respond to an initial course of oral steroids and are designated as having steroid-sensitive nephrotic syndrome (ssNS). A study in Pediatrics placed 8 children with difficult-to-manage disease (characterized by steroid dependence or frequent relapses) on a gluten-free diet. They all had clinical improvement enabling reduction or discontinuation in steroids. The role of gluten in this condition was confirmed through relapse following re-exposure to gluten. The authors conclude “Elimination of gluten from the diet, may reduce the need for potentially toxic immunosuppressant therapies” [Lemley KV, Jul 2016]
Microscopic colitis
– A new clinical and pathological entity (“lymphocytic enterocolitis”)?
Of patients with Marsh 1 duodenal damage, but no coeliac serology (i.e. negative for anti-endomysium and anti-tissue transglutaminase), half were found to have microscopic colitis. Although this study was not specifically looking at gluten, 14 patients tried a gluten free diet for at least one month and 3 of them (21%) had improvements. [Bonagura, Nov 2016]
Postural orthostatic tachycardia syndrome (POTS)
A study published in the European Journal of Gastroenterology and Hepatology found that 4% of PoTS patients had coeliac antibodies, yet 42% reported gluten sensitivity, suggesting that many POTS patients are NCGS. [Penny HA, Dec 2016]
Eosinophilic oesophagitis
Eosinophilic oesophagitis (also called EoE for those who spell oesophagus without the ‘o’) is a chronic inflammatory oesophageal disease triggered predominantly by food antigens. Although considered a food allergy, EoE is unique in not involving the immunoglobulin IgE antibody response. A recent review identifies milk and gluten elimination as the most promising cure strategies. [Molina-Infante, Dec 2016] How is EoE caused? Until recently it was considered that the oesophagus was relatively impermeable to food antigens and allergic diseases of the oesophagus were unknown. Researchers from the Mayo Clinic wondered if food antigens were present in the oesophageal tissue of sufferers. In a recently published paper they report finding increasing levels of gliadin (gluten) in the oesophageal tissue with increased severity of disease, whilst none was present amongst controls. This suggests a direct causative role of gluten in EoE.


Comparison of total anti-gliadin staining (y-axis) in patients on a gluten free diet (GFD), control patients and patients with inactive and active EoE on gluten (x-axis, 63x). E. V. Marietta, AP&T Nov 2016

Effect of a gluten-free diet in children with autism spectrum disorders
In this randomised clinical trial [Ghalichi F, Nov 2016] 80 children with ASD were randomised to gluten-free diet [40] or regular diet [40].

“In the GFD group, the prevalence of gastrointestinal symptoms decreased significantly (P<0.05) after intake of GFD (40.57% vs. 17.10%) but increased insignificantly in the RD group (42.45% vs. 44.05%). GFD intervention resulted in a significant decrease in behavioral disorders (80.03±14.07 vs. 75.82±15.37, P<0.05) but an insignificant increase in the RD group (79.92±15.49 vs. 80.92±16.24).”

Alcohol related cerebellar degeneration
Alcohol-related cerebellar degeneration is one of the commonest acquired forms of cerebellar ataxia, however, the mechanism by which alcohol causes this damage is unknown. The cerebellum is the back part of the brain, responsible for many basic things including walking. ‘Ataxia’ is difficulty in walking. In a recent study from Royal Hallamshire Hospital, Sheffield, England, a group of 38 patients with ataxia were studied. 34% were found to have circulating antigliadin antibodies vs. 12 % in healthy controls, and 39 % were found to have antibodies to transglutaminase 6 (which are neurological antibodies) vs. 4 % of healthy controls. The authors suggest that chronic alcohol abuse increases gut permeability exposing the immune system to increased levels of gluten peptides to which these two antibodies are raised. They conclude “Alcohol induced tissue injury to the central nervous system leading to cerebellar degeneration may also involve immune mediated mechanisms, including sensitisation to gluten.” [Shanmugarajah PD, Oct 2016]


We are in the middle of an epidemic of gluten related disease that have crept up on us over the last few decades. Our European culture has lived with wheat and its associated diseases, for thousands of years, and we have named and described them, yet only now are we becoming aware of the true cost to our health. At the same time, many Central America countries (Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, and Panama), which historically have had very low rates of coeliac disease, are transitioning from a diet based on maize to one increasingly centred around wheat. Maize too has its problems but the prolamine in maize, zein, is less likely to cause immune reactions than is the prolamine in wheat, namely gluten.

A paper published in the journalNutrients  [Amado Salvador Peña* and Jakob Bart Arie Crusius, Sep 2015] provides a salutary reminder of the scope of the problem:

[these] changes permit a prediction of an increase of celiac disease and other autoimmune diseases such as type I diabetes and thyroid disease.

The aim of this review is to… alert authorities responsible for the planning of education and health, to find possibilities to avoid a rise in these disorders before the epidemics start.

– Amado Salvador Peña and Jakob Bart Arie Crusius, Central America in Transition: From Maize to Wheat. Challenges and Opportunities (Nutrients, Sep 2015)

Gluten – what we learned in 2016 (part 1)

toast-head-by-rysunek-kuczynski▲ Image: Pawel Kuczynski

“Give us this day our daily bread (…) but deliver us from evil”

—Matthew 6:11, 13

This is an update on our previous series of articles “Why No One Should Eat Grains” which were published in 2015; we recommend you read them too if you want to get your brain around this topic (before gluten makes toast of it!):


  • Introduction – “deliver us from evil”
  • Gluten related disorders on the rise – but why?
  • Amylase Trypsin Inhibitors – activate myeloid cells
  • Type 1 diabetes – gluten affects the pancreas of even healthy mice
  • Grain globulins – contain coeliac and T1 diabetes reactive proteins
  • Oats – evidence that they should be avoided in coeliac disease
  • IBS and gluten sensitivity – gluten is often the problem
  • New coeliac auto-antibodies identified – linked to autoimmune polyneuropathies
  • Neurological effects of gluten – Simiar in coeliac and NCGS
  • Gluten in Latin America – high levels of self reported gluten avoidance.

Read time: 11 minutes (2200 words)

Continue reading

Why no one should eat grains. Part 3: Ten more reasons to avoid wheat

Wheat's_long_shadowWheat’s long shadow: does anyone escape its effects?

In part 1 we looked at Coeliac Disease (CD) which affects 1% of the population worldwide, but forms only the tip of the gluten iceberg. In part 2 we looked at the latest research on Non Coeliac Gluten Sensitivity (NCGS) which affects 6% of the population. In part 3 we look at ten areas of research that illustrate how gluten’s long shadow affects the lives of the remaining 93%.


This post includes some of the most up-to-date studies on the health effects of gluten and wheat outside of coeliac disease. Many of these were published just this year, yet you are unlikely to have heard about them on any other blog, let alone in the mass media.

Much of what has been learned about gluten’s effects at the cellular level comes from 20 years of intensive research into coeliac disease. To researchers surprise, many of those mechanisms appeared to be active in healthy individuals, leading to speculation that wheat could be involved in other diseases, beyond coeliac. In the last three years, with the recognition of the new clinical entity Non Coeliac Gluten Sensitivity, the wheat cat is well and truly out of the coeliac bag.

Alongside an understanding of gluten’s biochemical effects in non-coeliacs, reports are accumulating of the successful use of gluten-free diets in an extremely diverse range of conditions, showing that gluten’s long shadow extends well beyond gut diseases. This conclusion from a recent review paper summarising our current understanding of how just one gluten protein – gliadin – affects intestinal cells says it all:

In conclusion, gliadin (from gluten) and its undigested peptides have biological effects not only in cells and the intestinal mucosa of patients with celiac disease but also in normal subjects or in different diseases. How these effects can affect the health of non-celiac subjects will be the object of future research. – Maria Barone et al, International journal of molecular sciences (2014)

As this quote indicates, research into gluten’s health effects in non-coeliacs is currently in its infancy; Indeed it is considered to be at least twenty years behind that of coeliac disease. The purpose of this post is to bring together some of the early evidence demonstrating gluten’s involvement in an extraordinary range of disease processes.

Evidence in this post is drawn from

  1. Identified biochemical effects of gluten/wheat/grain components that have been shown to affect non coeliacs
  2. The bidirectional link between coeliac disease and a host of other diseases
  3. Controlled studies showing benefits of a gluten-free diet across a wide range of diseases
  4. Early studies into effects of wheat/gluten/grains on healthy individuals, and finally,
  5. Personal clinical experience – I have had many patients whose health problems have benefited from a grain-free diet when nothing else has worked

An important point to keep in mind as you read what follows is that for most people, the effects of grains do not necessarily manifest as a recognised gluten disorder, but nevertheless may be causing them problems that neither they nor their doctors would associate with the grains in their diet. The only way an individual will discover if they would be better off on a grain-free diet is by trialling it properly for at least six weeks, and preferably three months. The proof of the pudding will be in the (not) eating! If you are thinking ‘but I don’t have any health problems!’ please read post 1, in which I describe a study where relatives of coeliac patients were placed on a gluten-free diet and experienced improvements in symptoms that they had previously been unaware of. The only way to know if grains are adversely affecting your health is to strictly eliminate them from your diet for three months.

So lets get stuck in with a graphical overview of plausible mechanisms by which wheat may exert adverse health effect in non-coeliac conditions…

Aspects of wheat inducing gluten related symptoms

Fig 1. Components in wheat contributing to clinical symptoms among non coeliacs – Aziz et al. The spectrum of noncoeliac gluten sensitivity. Nat. Rev. Gastroenterol. Hepatol. (Jun 2015)

Don’t worry if that’s too much to make sense of right now – the key points to appreciate are: (i) it’s more than just the gluten in wheat that exert negative health effects, and (ii) these mechanisms are at work in healthy individuals, not just coeliacs.

Ten reasons to avoid wheat

1. No one can digest gluten

Gluten is a complex protein that gives dough its elasticity. It is made of many different protein molecules that are still being enumerated. They are classed into groups, known as gliadins, glutenins, albumins and globulins. Each fraction has its story to tell, but the gliadins are notable for their central role in coeliac disease.


Fig 2. Both gliadins and glutenins are now considered as triggers of coeliac disease. Albumins include the amylase trypsin inhibitors which have been shown to drive intestinal inflammation (see 3 below). The albumins and globulins are both linked to allergic reactions. Wheat globulins appear to be involved in the development of Type 1 diabetes.

Few people are aware that gluten is an intrinsically indigestible protein. Whilst most other proteins in the human diet are efficiently broken down into their constituent amino acids by our digestive system – a bit like how a shredding machine reduces paper to confetti, we simply do not have enzymes capable of cleaving the glutamine and prolein-rich sections of gluten. The partially digested residues of gluten are more like screwed up balls of paper – far too large to be properly absorbed. This exposes our small intestines to large undigested fragments known as gluten peptides. Unlike amino-acids, these have the capacity to set up an immune reaction, increase gut permeability and trigger cell proliferation.

Here is one well studied fragment, alpha-gliadin, that is responsible for many, but not all, of gluten’s toxic effects:


Fig 3. There are at least 50 toxic epitopes in gluten peptides exerting cytotoxic, immunomodulatory, and gut-permeating activities. These activities have been partially mapped to specific domains in α-gliadin.” Alessio Fasano, Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. (Physiological Reviews, 2011)

This inability of our digestive system to deal with gluten is a demonstration of evolutionary-medicine: we simply are not adapted to these ‘novel’ foods which have only been in the human diet in significant quantities for 5000 years – a mere blink of the eye in evolutionary terms.

2. Gliadin increases gut permeability in everyone

A key feature of coeliac disease is a ‘leaky gut’. Before autoimmunity can start, dietary antigens need to get through the gut lining and stimulate the immune system. This mechanism appears to be behind many, if not all, autoimmune diseases (such as type 1 diabetes [ref]). Gliadin (the chief immune reactive peptide fraction of gluten) is implicated in coeliac disease as it stimulates the enterocytes (gut lining cells) to release zonulin – a compound that opens the tight junctions between the enterocytes, allowing substances to bypass the gut lining – making it ‘leaky’. This allows the passage of incompletely digested proteins and gut bacteria into the blood, which can set up immune reactions. If there are similarities between these proteins and human tissue ‘cross reactivity’ can occur, leading the immune system to attack its own tissue, causing autoimmunity or even cancer.

The whole process is explained in the following rather technical paper, the title of which tells you most of what you need to know for this post: “Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer” Alessio Fasano, Physiological Reviews (January 2011)


Fig 4. Changes in permeability of intestinal biopsies following exposure to gliadin. The highest level of induced permeability (the lowest curve, orange) was amongst people with active coeliac disease (ACD), followed by gluten sensitive (GS). Gliadin even caused increased permeability in healthy controls (NC). Least affected were recovering coeliacs (RCD) as they were the only ones on a strict gluten-free diet!

In one of their most recently published paper, Fasano’s team show that gliadin increases gut permeability in active coeliacs, recovering coeliacs, NCGS as well as healthy controls – i.e. everyone!

Interestingly, the NCGS and active coeliacs showed the greatest reaction to gluten exposure, suggesting, perhaps, that increased gut permeability is the common factor in both conditions. Confusingly, this is in contraditction to earlier work that found reduced permeability in NCGS.

Even more surprising was the finding that recovering coeliacs had the lowest reaction to gliadin exposure – lower even than healthy controls. Why? Probably because they were the only group that had been on a strict long-term gluten-free diet.

This study provides clear evidence that everyone is affected by gluten, even if they have no symptoms, unless that is, they are on a strict gluten-free diet.

Another aspect of gluten’s effects was reported a 2011 study by Jana Cinova’s team, from the Department of Immunology at the Academy of Sciences of the Czech Republic. They found that gliadin leads to a reduction in the number of mucus producing goblet cells in the intestine wall, however, the effect was modified by the kinds of gut bacteria present.

Researchers exposed the digestive tract of mice to gliadin, with or without various gut bacteria. As you can see in the graph opposite, gliadin reduced the percentage of mucus producing goblet cells in the epithelium, from 55% to 35%.

However, in the presence of pro-biotic ‘good bacteria’ (Bifidobacterium bifidum) these harmful effects of gliadin on goblet cells were significantly reduced. Pathogenic gut bacteria such as Shigella and E. coli on the other hand, magnified the damage induced by gliadin (the two bars at the bottom of Fig 5.)

These data suggest that the health of an individual’s gut microbiome may determine how ‘toxic’ wheat is for them, and go some way to explaining the apparent increase in gluten-related disorders over the last thirty years, coinciding as it has with an increased use of antibiotics, caesarian births, and reduced contact with soil organisms in modern living – all of which contribute to gut dysbiosis (i.e. disordered gut microbes). There is also the possibility that for otherwise healthy individuals, a change in their gut flora due to infection, antibiotics or diet could precipitate gluten sensitivity.

Other ways in which gliadin affects intestinal cells of coeliacs and non-coeliacs alike, include:

  • Changes to the shape and structure of enterocytes and fibroblasts
  • Changes in permeability
  • Changes in the movement and structure of dendritic cells
  • Deregulation of NF-κB-related gene expression
  • Increasing inflammatory markers such as IL-15

“In the general issue of food and tissue inflammation, gliadin and its undigested peptides plays a leading role.” – Maria Barone et al, International journal of molecular sciences (2014)

3. Wheat amylase trypsin inhibitors drive intestinal inflammation

Apart from gliadin, wheat proteins contain albumins, one subset of which includes the amylase trypsin inhibitors. These proteins – part of wheat’s natural pesticide armoury – had previously only been linked to wheat allergies like baker’s asthma and exercise induced wheat anaphylaxis, affecting approximately 0.2% of the population (a mere 14 million people worldwide!) However, in 2012 Detlef Schuppan’s group published evidence that amylase trypsin inhibitors in wheat can drive intestinal inflammation via the innate immune system, activating monocytes, macrophages and dendritic cells. This contrasts with coeliac disease where it is primarily the adaptive immune system that causes the inflammatory damage.

Consequently, wheat amylase trypsin inhibitors are now suspected of fueling inflammation and immune reactions in several intestinal and non-intestinal immune disorders, in coeliacs and non-coeliacs:

“ATIs represent up to 4% of total wheat protein and are highly resistant to intestinal [digestion]. In line with their dose-dependent function as co-stimulatory molecules in adaptive immunity of celiac disease, they appear to play a role in promoting other immune-mediated diseases within and outside the GI tract. Thus, ATIs may be prime candidates of severe forms of non-celiac gluten (wheat) sensitivity.” Schuppan & Zevallos, Digestive diseases (2015) 

4. Fructans in wheat can cause bloating, intestinal discomfort and diarrhoea

Fructans are oligosaccharides – chains of sugar molecules resistant to digestion, found in high levels in wheat, barley and rye. When these simple carbohydrates reach the colon they can be rapidly fermented by bacteria. As well as pain from the gas that is produced these molecules have an osmotic effect pulling water into the bowel causing diarrhoea. A study in Gastroenterology in 2013 found that 37 IBS patients placed on a diet low in these poorly digested carbohydrates (FODMAPs) improved markedly and did not relapse when purified gluten was added to their diets.

An initial interpretation of these results was that NCGS might not be caused by gluten but by FODMAPS. Studies since, however, have shown that gluten is a factor in many cases of NCGS [ref]. Furthermore, many of the participants in the 2013 study reverted to a gluten-free diet even when the results were explained to them, suggesting that avoiding gluten-containing foods had an even better effect on their symptoms than simply avoiding fructans. A further point to consider before dismissing a specific problem with grains is that fructans are high in onions and other vegetables, yet most NCGS sufferers find their symptoms improve on a gluten-free diet without avoiding these other sources of FODMAPs.

Either way, the fructans in wheat are yet another reason to give it second thoughts, especially if you suffer gastro-intestinal symptoms like bloating, IBS, constipation or diarrhoea.

5. Modern wheat is more allergenic

Cardiologist William Davis in his book Wheat Belly posited, somewhat controversially, that modern wheat has become more toxic due to intensive breeding. Initially scoffed at, this concept is now taken seriously by some researchers who have put the hypothesis to the test. The first randomised controlled trial comparing ancient vs modern wheat in patients with irritable bowel syndrome (IBS) found that symptoms were significantly worse when on modern wheat (read our report here).

More recently a detailed and comprehensive study has been undertaken of the effects of ancient and modern wheat strains on immune cell (cytokine) reactivity in NCGS compared to healthy controls. Key results are summarised in Fig 6.


Fig 6. CXCL10 secretion by cultured PBMC stimulated with different wheat protein extracts. PBMC obtained from healthy donors (A) or from NCGS patients (B) were stimulated for 24 h with total wheat protein extracts from different wheat cultivars. After Valerii , June 2015

As you can see, compared to rice, all wheat strains caused raised cytokine responses in both healthy and NCGS, but the response was far greater in the NCGS group, and stronger for modern, compared to ancient strains. Whilst this may go someway to explaining the increased incidence of NCGS and coeliac in recent years, it would be a mistake to think that gluten problems will be resolved by switching to ancient wheat varieties as the response may be reduced, but not eliminated. In the case of coeliac disease, ancient and modern varieties have been shown to be just as damaging. [ref]

“Our findings provide further evidence for the need for a strict gluten-free diet in coeliac patients, including avoidance of ancient strains of wheat.”

– Šuligoj T et al, Clinical nutrition (2013)

Rice, which was used as a control in the above study, is one of the least reactive and least problematic grains. For people struggling to adapt to a grain-free diet, rice in moderation can often be safely consumed. That said, I have had patients – especially those with severe gastrointestinal symptoms such as ulcerative colitis and Crohn’s that cannot even tolerate rice. Another problem with eating large quantities of rice is that it is often high in arsenic, and has actually led to poisoning in at least one case of coeliac disease. [ref] Issues around the grains that are typically used in gluten-free foods will be the subject of another post, but suffice it to say, I recommend a fully grain-free paleo type diet for maximum health benefits.

6 Modern wheat is less nutritious

Whilst becoming more antigenic in the last half century, wheat has simultaneously become depleted of minerals. Graphs showing the decrease in mineral content of wheat since the Green RevolutionThe graphs above show wheat yields and mineral content between 1880 and 2000. With the development of dwarf wheat varieties and artificial fertilisers in the 1950’s, yields doubled (top two graphs), however, starting from the same time, we see levels of zinc and copper in wheat decline by half whilst iron and magnesium fall by 25%. (graphs c to f)

7. Phytates in grains reduce absorption of essential minerals


Fig 7. Increase in iron absorption when phytic acid is removed from the grain

Soy, maize and many other seeds, nuts and grains, but especially wheat contain phytate – also known as phytic acid – a recognised anti-nutrient. Phytic acid is a phosphorous storage compound found in seeds, primarily in the bran; hence levels are higher in whole wheat rather than than white flour products.

Phytate binds to iron, zinc, calcium and magnesium in the digestive tract making these minerals far less available for absorption. Indeed phytate can bind minerals from other foods eaten concurrently, potentially leading to mineral deficiencies. Figure 7 shows the increase in iron absorption when phytic acid is removed from various grains. As usual wheat is the worst offender.

In countries with a high dependence on grains, especially where grain based porridges are used through the critical period of child weaning, dietary phytates cause widespread mineral deficiencies – a direct indication of their suboptimal nutritional quality.

“Even though iron and zinc are present in significant amounts in the plant-based diets typically consumed in developing countries, their bioavailability is low due to high levels of absorption inhibitors such as phytate. “- Troesch B et al. Food Nutr Bull. (Jun 2013)

However, even in Europe, mineral deficiencies are prevalent amongst weaning children with one study finding that across 11 European countries the prevalence of iron deficiency at 12 months was 7.2% [ref]. A Danish study [ref] found that iron status from 6 to 9 months was:

  • Positively associated with meat and fish intake
  • Negatively associated with cows milk and bread intake

Finally, reductions in calcium absorption may be an important contributing factor in the development of osteoporosis in postmenopausal women. In Japan, the chief source of phytate in this age group is soy. A study published in January 2015 in the International Journal of Molecular Sciences investigated the role of phytate in age related osteoporosis, using phytate-removed soy which prevented osteoporosis in a rat model. [ref]

Whilst phytate can have positive effects on gut microbiota similar benefits can be maintained by increasing vegetable consumption – a far better fibre source with fewer down sides than grains can provide.

8. Lectins in wheat germ inhibits gut cell repair

Lectins are a class of protein present in many foods, some of which are toxic to humans. They are found in particularly high levels in black beans, soybeans, kidney beans, and whole grains [ref]. Wheat contains a lectin called wheat-germ agglutinin (WGA), which is present in whole wheat or whole meal products. Whilst most people know that if you do not cook kidney beans thoroughly you can expect to get severe gastrointestinal pain, most people are unaware of any such requirement for wheat germ. One reason for this is that WGA’s effects are far more subtle, so sprinkling wheat germ on one’s muesli is unlikely to produce the extreme reaction associated with raw kidney beans.

The second reason is that most wheat products commonly consumed have been cooked, deactivating most of the WGA. Because of this some authors claim that WGA represents a negligible risks, but there are reasons to question this assumption, not least of which is that many people have antibodies to WGA. This would not be possible if dietary WGA was 100% destroyed by cooking. Furthermore, the world experts on non coeliac gluten sensitivity do not rule it out as shown in figure 1.

So what does this wheat lectin do? WGA binds to the surface of a range of cells in the digestive tract. In fact it is one of the most potent lectins in this respect: “Compared to other plant lectins, WGA binds to intestinal cell lines of human origin, human colonocytes, and prostate cancer cells at the highest rate” [ref]. Studies in the last 30 years have shown that its ingestion causes increased permeability and changes to the structure of villi in the gut lining [ref]. Prior to the identification of gliadin as the causative factor in coeliac disease WGA was considered a potential candidate.

Whilst WGA might not be the primary cause of coelaic disease it is most certainly not out of the frame of gluten-related damage. In 2007, an elegant study showed that WGA has a direct effect on the cellular repair mechanism of gut lining cells, reducing protective mucous production, and increasing cell death. [ref] This finding has implications for all of us, whether we are coeliac, NCGS or not. Furthermore, although only ~0.1% of WGA gets through the intestinal barrier, it has been shown that even at nano-molar concentrations it is inflammatory:

“At nanomolar concentrations WGA stimulates the synthesis of pro-inflammatory cytokines and thus the biological activity of WGA should be reconsidered by taking into account the effects of WGA on the immune system at the gastrointestinal interface. These results shed new light onto the molecular mechanisms underlying the onset of gastrointestinal disorders observed in vivo upon dietary intake of wheat-based foods.” – Chiara Dalla Pellegrina et al. Toxicology and applied pharmacology (2009)

9. IgE reactions to cereal grains

IgE reactions are associated with allergic asthma, sinusitis, allergic rhinitis, food allergies, some chronic urticaria and atopic dermatitis (eczema).

Allergic reactions to wheat have been known about for many years, and in adults include Baker’s asthma, exercise induced wheat allergy and wheat anaphylaxis (as serious as peanut allergy). These affect a relatively small, though not insignificant, number of people (0.2%). However, among infants and children the prevalence is between 0.4% and 1%. Symptoms can range from immediate type anaphylaxis, urticaria, vomiting or wheezing or worsening of eczema after ingestion of wheat-containing products. Most children outgrow the disease by school age, or in their teens.

Just this month a study comparing IgE responses in allergic and non-allergic children found that both groups formed IgE antibodies to multiple components of ingested wheat [ref].

“in children, suffering from eczema, the major allergens belong to the water and salt soluble proteins [of wheat], whereas the storage protein ω5-gliadin affects adults struggling with urticaria and anaphylaxis.” – S Sievers et al. Pediatric allergy and immunology (Oct 2015)

Varjonen E et al published a paper in Clinical and Experimental Allergy in 1995, in which they report administering skin prick allergy tests to 34 children with severe atopic dermatitis. 33 were positive for wheat, 18 reacted to oats and 16 to rice, maize, millet and buckwheat. Further, they found that gliadin only produced skin prick reactions in those children that also had a reaction to oral gluten challenge. This shows that there are IgE cereal allergens beyond gluten and the gluten containing grains. (We will look at the problems with grains other than wheat in a future post)

Many people are allergic to grass pollen – evident as hayfever in the summer. Should we be surprised that they are also allergic to the grasses (cereal grains) that they eat?

10. Gluten in diverse diseases


Fig 8. Increased incidence of various diseases and coeliac disease. (compiled from Luddvigson, 2006,2007, 2011 and Olen 2008)

Coeliac’s are at an increased risk of many other diseases subsequently, and conversely, many of those diseases, when diagnosed first, indicate a higher risk of developing coeliac disease after.

A good example of this is tuberculosis (TB), where coeliacs have a threefold higher risk of contracting TB and six times the risk of death from TB. Conversely, those who have previously had TB are at a 2.5 times risk of subsequently being diagnosed with coeliac disease. [ref]

This bi-directional relationship suggests that gluten containing grains may contribute to the initiation of a wide range of diseases possibly even in those who do not go on to develop coeliac.

One example is iron deficiency anemia which was found to be present in approximately half of undiagnosed coeliacs identified by screening. Conversely studies screening patients suffereing with iron deficiency anemia consistently find 5-6% have celiac disease. [ref] Some of these bidirectional risks are summarised in the Fig 8. (click to enlarge)

Research in this potentially vast field is currently in its infancy, but already some findings are coming to light:

  • IgA nephropathy (IgAN) – in a paper published in March this year, gluten was found to accelerate IgA nephropathy in a rodent model, and a gluten free diet prevented disease progression. The authors state: “Our results indicate that an early treatment with gluten-free diet in patients with sera positive for IgA AGA [Anti gliadin antibodies] and without renal function decline may represent a safe and simple approach for the prevention of IgAN progression.”[ref]
  • Schizophrenia, bipolar and ASD – there is a marked increase in gluten and casein antibodies in sufferers of these conditions. Whether these have a causative or subsequent relationship is not known, but in some studies a gluten-free diet has had dramatic effects with partial or complete reversal of neurological symptoms (see below). Also: see our post Gluten and Schizophrenia – does it all start in the womb?
  • Type 1 diabetes – there is a clear link between type 1 diabetes (T1D) and coeliac disease. Where both occur it is usual for T1D to be diagnosed first – “probably due to the diabetes-protective effect of a gluten-free diet”. However, gluten-induced inflammation has been identified in T1D individuals without the genetic risk for coeliac disease, suggesting “a direct, diabetes-specific effect of gluten.”
    Current studies suggest “that gluten, and perhaps other wheat proteins, influence the development of type 1 diabetes.”[ref] Indeed, the two animal models for studying type 1 diabetes, (the non-obese-diabetic (NOD) mouse and the diabetes-prone BioBreeding (BBdp) rat) spontaneously develop the disease on a normal wheat based diet, but have a lower incidence and the disease takes longer to manifest, when fed a gluten-free diet. One research team stated: “In studies of [these] rats… wheat gluten was the most potent diabetes-inducing protein source.” [ref] Indeed, they went on to identify a wheat globulin with an amino acid sequence identical to a protein in pancreatic islet cells, and identified pancreatic auto-antibodies for that wheat protein in type 1 diabetics, but not in healthy controls.
  • IgA deficiency – is the commonest human immunodeficiency, is 10–15 times more common in patients with coeliac disease with a prevalence that may reach 3% [ref]

Interestingly, gluten’s role in IgA nephropathy and schizophrenia both involved alterations in immune complex formation (part of the antigen-antibody system). In the case of schizopheria, this occurs in-utero whilst the baby is developing, in the case of IgA nephropathy it appears to happen early in the development of the disease. In both cases the implication is that initiation of a gluten-free diet would be better earlier. At present there is no way of identifying who would benefit from early gluten withdrawal, and in most cases once symptoms appear significant damage has already been done.

Fortunately, as gluten-free foods, recipes and internet support-sites have increased many more people are trying gluten free diets for themselves. And despite skepticism from some authors who see the popular faddy side of the diet’s rise, many researchers now acknowledge the very real benefits for some patients:

“A lot of people spontaneously adopt a gluten free diet, solving their intestinal and extra-intestinal symptoms such as diarrhea, abdominal discomfort or pain, bloating, flatulence and headache, lethargy, attention-deficit/hyperactivity disorder, ataxia or recurrent oral ulceration.” – Veronica Bonciolini, University of Florence, (2015)

Now research beyond the coeliac population is under way, gluten-free diets are being found to benefit patients with many conditions. Examples of improvement or remission in humans (as opposed to animal models) include:

Inflammatory bowel disease (IBD) – not to be confused with IBS – includes ulcerative colitis and Crohn’s disease – both severe chronic autoimmune diseases of the small and large bowel. The prevalence of IBD in Europe is approximately 0.8% (6 million people) and increasing over time [ref]. In a paper published last year, a survey of 1647 IBD patients found that nearly a fifth had tried a gluten-free diet, two thirds of whom experienced improvement in symptoms. The improvements in symptoms they reported are shown in Fig 9. [ref]


Fig 9. Reported improvement in symptoms among IBD sufferers during self imposed gluten-free diet.

Gluten and the skin


Fig 10. Dermatitis herpetiformis is a gluten-induced autoimmune skin disease, often referred to as coeliac of the skin.

Dermatitis herpetiformis

Almost everyone has heard of coeliac disease, and an increasing number have heard of non coeliac gluten sensitivity, but much less well known, is dermatitis herpetiformis, an autoimmune skin condition induced by gluten for which the only treatment is life-long adherence to a gluten-free diet. It is often referred to as ‘coeliac of the skin’. [Fig 10]

Interestingly, patients with dermatitis herpetiformis who have been on long term gluten-free diets to resolve their symptoms are found to have decreased incidents of heart disease [ref] and overall mortality [ref, ref] compared to healthy (gluten consuming) controls. This is despite the increased incidence of cancers and type 1 diabetes similar to that observed in coeliac disease.

I can see a couple of possible explanations for this. (i) that the genes that predispose an individual to dermatitis herpetiformis also confer some positive health benefit (ii) that gluten-free diets are healthier overall, reducing heart disease and all cause mortality in everyone.

I think hypothesis (i) is unlikely as the genetic risk factors for coeliac and dermatitis herpetiformis have been well studied, and no such benefit has been reported to my knowledge. Hypothesis (ii) is more likely to my mind, but would be undocumented for different reasons. To identify the benefits of gluten-free diets you would need a large enough population of otherwise healthy people on a long-term gluten-free diet. No such population exists. We are left then with the question of why this reduced mortality is not seen in coeliac patients – and I would suggest this is because coeliac disease, being of the gut rather than the skin, has life-long effects on digestion. i.e. in coeliac the long term harm masks the added benefits of a gluten-free diet.

Cutaneous Gluten Sensitivity – a new clinical entity

A paper from The University of Florence, published last month in the prestigious journal Nutrients, has begun to outline a new clinical entity they are calling cutaneous gluten sensitivity (CGS). They examined the skin lesions of 17 diagnosed non-coeliac gluten sensitive patients before and after the adoption of a gluten free diet. Initially their rashes were severely itchy, similar to psoriasis, eczema or dermatitis herpetiformis. Most of them had suffered with these symptoms for many years. Once they adopted a gluten-free diet the skin lesions resolved or significantly improved in a month or so.

In their conclusion the authors suggest that anyone presenting with gastrointestinal disorders and a severe skin itch should “adopt a gluten-free diet for at least three months assessing any positive effects.”

As a herbalist, this is no surprise to me, as part of the herbalist perspective has always been that the gut and skin are a clinical continuum, and when treating skin conditions I always look to treat any underlying gut pathology.

Neurological and psychotic disorders

Gluten Ataxia


Fig 11. An example of gluten ataxia, a condition in which coordination and movement become increasingly disrupted. It is shocking that such a condition can be caused and maintained by such a common food as wheat.

Whilst neurological symptoms have always been part of the picture of coeliac disease, it was only in 1996 that researchers identified gluten as a causative factor in a majority of sporadic ataxias – a condition in which coordination and movement become increasingly impaired. [Fig 11]

Marios Hadjivassiliou, a consultant gastro-enterologist at The Royal Hallamshire Hospital, Sheffield, UK, discovered and named gluten ataxia. His team found gluten to be the single biggest cause of sporadic idiopathic ataxia.

In his 2003 paper in the BMJ, he describes how these patients were significantly more likely to test positive for antigliadin antibodies (AGA) than patients whose ataxia could be explained by other causes such as brain injury or stroke. Unlike coeliac disease, gluten ataxia patients rarely exhibit gastrointestinal symptoms. The main treatment is a life long gluten-free diet. Recovery depends on how far the disease has progressed. It appears that the anti-gliadin antibodies cross-react with Purkinje cells in the brain – if the damage has gone too far it cannot be fully reversed.

Other neurological conditions

In the following video Professor Alessio Fassano discusses the possible link between gluten and schizophrenia and autism – just two aspects of gluten-related neurological conditions

Whilst Coeliac disease and Non Coeliac Gluten Sensitivity are widely recognised as including a range of neurological symptoms from depression to gluten ataxia and encephalopathies [ref], there is increasing evidence that gluten’s effects on the brain extend beyond these two groups. Whilst the link between gluten and psychosis remains controversial there is increasing evidence that a sub-set of patients are indeed gluten sensitive and benefit from a gluten-free diet. Some recent papers investigating gluten-related psychoses are illuminating:

The papers above are mostly looking at a gluten-free diet after psychotic symptoms have already manifested. However, if gluten is responsible for the development of these diseases then a gluten-free diet before symptom manifestation would be infinitely preferable!

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. – Hernandez-Lahoz C et al. Rev Neurol. (Sep 2011)

In some cases this early intervention may extend back to the diet of the mother. (See our article Gluten and Schizophrenia – does it all start in the womb?)


So there you have it: You don’t have to be coeliac or even diagnosed with non coeliac gluten sensitivity for wheat to have a negative impact on your health. Although our understanding of how gluten affects health outside coeliac disease is still in its infancy, an increasing number of conditions are being linked to its consumption. Furthermore, the list of conditions that respond to a gluten-free diet is growing.

If you want to find out if a gluten-free diet can improve your health the only way is to do it properly. That means at least six weeks, and prefereably three months, being 100% scrupulous. During that time instead of switching to ‘gluten-free’ substitute foods (bread, biscuits, cakes etc), try a paleo diet based around real foods that are naturally gluten free – fish, meat, vegetables, nuts and fruit. You can include dairy if you tolerate it well. There are plenty of recipes on this blog to help you make the change. If you need further support get in touch or come to one of my public talks. If you wish to see me as a patient I will provide on-going support and a personalised diet, supplements and herbal medication as indicated in your particular case,

Then let me know how you are getting on!


More Evidence William Davis Was Right: Wheat Does Increase Obesity According to New Study

SCOOP: new trial demonstrates that gluten increases weight gain independent of calories via suppression of thermogenesis

Mouse in the wheat -

A new study found that when gluten was added to the diets of mice they had increased weight gain, even though they consumed the same calories as the mice without gluten in the diet.

Cardiologist William Davis has been accused of stirring up unnecessary fears over gluten when, in his New York Times bestseller Wheat Belly, he claimed that wheat causes obesity, heart disease and a host of other metabolic and digestive problems. Continue reading

Why no one should eat grains. Part 2 – The definitive guide to Non Coeliac Gluten Sensitivity


In the past few years it has become apparent that “classic” coeliac disease represents the tip of the iceberg of an overall disease burden

– Anna Sapone, BMC medicine, 2011

In part 1 we looked at coeliac disease which affects 1% of the population worldwide, but forms only the tip of the gluten iceberg. In this post I will examine the research around the emerging clinical entity known as Non Coeliac Gluten Sensitivity which affects at least six times as many people.

In brief

  • Non Coeliac Gluten Sensitivity (NCGS) shares certain features with coeliac disease (CD): symptoms are primarily gastrointestinal (GI), but commonly also systemic (mainly neurological), and symptoms improve or fully resolve on a gluten-free diet (GFD).
  • However, unlike coeliac disease NCGS has no identified genetic risk factors (e.g.  HLA-DQ2/8 which is associated with coeliac), and has no specific serum markers, making it a diagnosis of exclusion. Furthermore, NCGS is not an autoimmune disease and does not show small intestine atrophy.
  • Defining and diagnosing NCGS is problematic, but the prevalence of NCGS appears to be six times higher than coeliac disease.

Early evidence for gluten sensitivity outside of coeliac disease

The first confirmation of gluten reactions in non-coeliacs goes back to a paper in Gastroenterology in 1980:

Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge.

– Cooper BT et al, Gluten-sensitive diarrhea without evidence of celiac disease. Gastroenterology (1980)

These patients are typical of what is now called Non Coelaic Gluten Sensitivity (NCGS) – predominately female, IBS-like symptoms, improving on a gluten free diet (GFD).

By 2011 it was clear that gluten pathology outside coeliac disease was real. A consensus meeting summarised it thus:

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns.

– Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine (2012)

Non Coeliac Gluten Sensitivity (NCGS)

The term Non Coeliac Gluten Sensitivity first appeared in the Lancet in 1978 in a paper by Ellis and Linaker entitled “Non coeliac gluten sensitivity?” [ref]. However, its use as a name for real medical condition has only been in accepted use since 2011 when gastroenterologists gathered in Oslo to reach a consensus on what this new gluten sensitivity phenomena should be called.

Prior to this meeting a plethora of terms had arisen to describe coeliac and gluten-related disorders, including: asymptomatic celiac, atypical, classical, latent, non-classical, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. It was a giant mess, with different researchers using different terminology. The Oslo meeting attempted to sort it out once and for all. I have summarised the key terminology they agreed on at at the end of this post, but for now, let’s focus on their definition of Non Coeliac Gluten Sensitivity:

The term NCGS relates to one or more of a variety of immunological,  morphological or symptomatic manifestations that are precipitated by the ingestion of gluten in people in whom coeliac disease has been excluded.

 Jonas F Ludvigsson et al, The Oslo definitions for coeliac disease and related terms, BMJ Gut (Jan 2012)

Initially this appears to be very reasonable, but the phrase “immunological, morphological or symptomatic manifestations upon gluten exposure” has proven problematic. For example, studies since that meeting in Oslo have shown that exposure of the small intestine cells to gluten elicits morphological changes in everyone [ref]. Taken at face value the Oslo definition would classify the entire population as NCGS! Similarly, innate immune activation and raised wheat protein antibodies are being identified in a large percentage of the apparently healthy population. Consequently, in just three short years the working definition of NCGS has been narrowed to include only the symptomatic manifestations, that is, NCGS now only includes people who have gastrointestinal symptoms which improve on a gluten free diet (GFD).

Problems defining NCGS

NCGS is a very recently identified condition. Consequently, the medical understanding of it is still very much in its infancy, similar, perhaps, to where we were with coeliac disease twenty years ago.

There are three areas of uncertainty that make the definition of NCGS and its diagnosis difficult:

  1. The causative factor is still unclear. Multiple components of wheat and other grains are implicated (e.g. gluten, ATIs*, FODMAPS*). There may be different subsets of patients that react to different components.
  2. There is no definitive blood or histological test. Although NCGS patients typically have blood serum abnormalities e.g. 66% have raised IgG anti-gliadin antibodies (AGA) compared to 10% of the healthy population (see second video below). Diagnosis therefore, is based on symptom improvement on a gluten free diet (GFD)
  3. Diagnostic criteria are problematic. The current ‘gold standard’ diagnostic test requires worsening of symptom following a double blinded gluten challenge after symptomatic improvement on a gluten free diet. However, standardising this test is proving difficult (see first video below).

These problems make studying the condition difficult. Even the name NCGS is problematic: Non Coeliac Gluten Sensitivity should only strictly apply to patients who react to pure gluten, and would exclude those who react to ATIs*, FODMAPs* or other grain components. Consequently, some researchers use the term Non Coeliac Wheat Sensitivity, but this implies that other gluten containing grains, such as barley and rye are safe. The term I prefer, “Non Coeliac Gluten Containing Grain Sensitivity” is just too much of a mouthful. (Pun intended!)


Amylase trypsin inhibitors (ATIs)
These are part of the non-gluten proteins in wheat and related grains. A 2014 study demonstrated that they can cause intestinal inflammation via the innate immune system, providing an alternative mechanism in ‘gluten’ related pathology [ref]

Fermentable Oligo-Di-Monosaccharides and Polyols (FODMAPs)
These are short chain carbohydrates resistant to digestion that find their way into the colon where they can be fermented by microbes. The resulting gas can cause painful bloating and osmotic diarrhea. Wheat contains high levels of FODMAPs called fructans, which may contribute to some of the symptoms seen in NCGS. [ref] FODMAPs are also present in other foods such as onions.

There are many other grain components implicated in disease processes, which are considered potential candidates in NCGS, including wheat globulins, gluten ‘exorphins’ and wheat germ agglutinin.

Homing in on NCGS as a defined clinical entity

So as we have seen, to be classified as NCGS a patient has to have a reduction of symptoms when on a GFD where coeliac disease (CD) and wheat allergy(WA) have been ruled out. This on its own however is insufficient as patients know they are on a GFD and may be subject to the placebo effect. Many researchers are calling for a ‘gold standard’ test where suspected patients are subjected to a double blinded gluten challenge.

Enter the Salerno Experts group, who recently convened to develop a protocol for identifying NCGS (Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria Nutrients, June 2015).

In the video below, from the 16th International Coeliac Disease Symposium 2015, one of the Salerno Experts, Dr Luca Elli, unpacks the complexities of studying NCGS.

  • (0:00) Gluten and gastrointestinal functional disorders
  • (1:15) No biomarkers for GI functional disorders; symptoms and treatment
  • (2:25) Up to 50% placebo effect of food exclusion diets
  • (3:15) NCGS definition
  • (4:17) The need for a blinded gluten challenge
  • (5:18) Problems in devising the protocol
  • (6:45) Review of NCGS trials, protocols and findings
  • (11:00) The GLUTOX trial results
  • (13:04) Prevalence of NCGS in GLUTOX trial = 20% of GI Functional patients
  • (13:30) Best practice for blinded gluten challenge
  • (15:00) Conclusions

You will see from this video that NCGS patients are being identified from among patients with ‘Gastrointestinal functional disorders’ (e.g. IBS). Hence, current studies and prevalence estimates for NCGS do not include people who have gluten induced non-gastrointestinal symptoms, such as neurological or skin manifestations, yet in my clinic I regularly deal with patients that have these symptoms with only minor GI involvement, and who improve on a GFD. They are not coeliac. They are not NCGS. Oslo fails to give me a name for them! This is why the gluten iceberg goes deeper still – and that will be covered in part 3.

Dr Elli’s own study (the GLUTOX trial) found that just over 80% of the enrolled patients who had gastrointestinal functional disorders reported improvements when on a strict GFD. Of those that improved, only 1/3 of them relapsed when subjected to a randomised gluten challenge. The other 2/3, therefore may have been reacting to other components of the wheat, or were under the influence of a placebo effect. [Details: The GLUTOX Trial: Getting closer to identifying nonceliac gluten sensitivity]. EDIT (28/08/13): a similar proportion of patients responding to a blinded gluten challenge (1/3) has just been found in this study.

Regardless of these difficulties, the term NCGS has become a household name, at least among nutrition journalists and a subset of the public. UK doctors have yet to catch up. However, it is important to realise that even the current usage of the term ‘NCGS’ in the literature and media, by no means covers all research related to the pathology of gluten and grains. Hence, even with NCGS we have not reached the bottom of the gluten iceberg. In post 3 of this series I will look at the effects of gluten beyond coeliac and NCGS.

Case 1 – NCGS Skin Rash

A man in his 50’s had been attending my public talks for several years, and had discussed his skin problems with me informally a number of times. His legs were involved and it looked like eczema.
His wife recently wrote to me to say that they had eventually taken the plunge and given the grain-free diet a proper go, and were amazed that his skin condition completely resolved.
This case is interesting, as the absence of gut symptoms would not lead researchers to even consider a gluten related cause. However, the complete resolution of skin symptoms on a GFD means he is actually NCGS or whatever the correct term should actually be. We do not know if the rash would have resolved if he had just removed wheat, or just removed oats, etc, as he ditched the lot and is so pleased with the results that he has no intention of eating anything remotely grain like ever again. He does not care what it might be called if only we knew the exact cause, all he cares about is that it has resolved.

Italy leads the field in the study of pizza pasta gluten related disorders

As the understanding of coeliac disease increased throughout the 2000’s specialist centres emerged all over the world. It is ironic, perhaps, that researchers from the great pasta and pizza eating nation of Italy have risen to prominence in the field of gluten related disorders. Both the videos and many of the references in this article are by Italian authors.

And here is another: a one year survey of suspected NCGS patients identified at 38 Italian centres [ref] found the following which is a typical picture of what other researchers find…

  • 486 patients with suspected NCGS were identified in this 1-year period.
  • The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81)
  • The clinical picture included gastrointestinal and systemic manifestations (see graphs below)
  • Reaction to gluten was quick: appearance of symptoms varied from a few hours to 1 day.
  • Associated disorders included irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%) (i.e. classical allergy type manifestation).
  • An associated autoimmune disease was detected in 14% of cases.
  • 18% of patients had a relative with celiac disease, but no correlation was found between NCGS and HLA-DQ2/-DQ8 genes.
  • IgG anti-gliadin antibodies were detected in 25% of the patients tested.
  • Of patients who underwent duodenal biopsy; 69% showed normal intestinal mucosa, 31% showed mild increase in intraepithelial lymphocytes.

NCGS symptoms

The two graphs below show the prevalence of symptoms identified in the Italian study. As you can see the range of symptoms associated with NCGS is vast, and like coeliac disease can involve many organ systems.


Gastrointestinal symptoms in suspected non-celiac gluten sensitivity (NCGS). Prevalence (expressed as percentage) of gastrointestinal manifestations in the 486 patients with suspected NCGS identified in 38 Italian centers skilled in the diagnosis of gluten-related disorders.

These gastrointestinal symptoms are similar to those seen in IBS, which has led some to say that NCGS is really just IBS. However, what distinguishes NCGS from IBS is the common occurrence of extra-intestinal (especially neurological) symptoms such as those below. (We will look at NCGS v IBS in more detail later)

If you or anyone you know have any of the above, it is certainly worth trying a strict gluten-free diet for a month to see if things improve. In fact, I would say go as far as to remove all grains, not just the standard gluten containing ones (wheat, rye and barley) as in my clinical experience, some people do not improve unless all grains are excluded.

Case 2 – NCGS symptoms are easy to miss before trying a GFD

A few years ago a 50 year old professor of medicine from London – let’s call him James – discovered he was sensitive to gluten quite by chance. The story of how he discovered this is a cautionary tale for all of us.
James and his family regularly had foreign students staying with them. They were expecting a Chinese student and were told in advance that this student suffered with coeliac disease. They decided that the easiest way to accommodate this student’s needs would be for the entire household to go gluten free for the weeks the student would be with them. To his amazement during this time James experienced relief from a range of symptoms he had been suffering with but had never connected.
James and I were put in touch with each other through a mutual contact, and he and his wife (who is a medical consultant in a London hospital) met with me to go through my public presentation on grains. When I got to the slides showing the two symptom graphs from the Italian study above he and his wife leaned forwards and she said to him “You had all of those!”
Following my presentation, which looked at problems with all grains – not just gluten containing ones, James embraced a full paleo diet, ditching the ‘gluten-free’ substitutes he had previously been using.

The Prevalence of Non Coeliac Gluten Sensitivity

Based on the blinded-gluten challenge outlined above, the prevalence of NCGS appears to be about 6% in the general population, but the Salerno Experts group admit that they do not really know the true prevalence as they are still grappling with defining the condition.

On the other hand, in a recent UK survey the percentage of people self-reporting as gluten sensitive reached 13% [ref]. A similar study in Mexico found a similar number (12%) [ref] whilst a survey in Australia found 10% [ref].TIME_gluten_free_fad

The discrepancy between the diagnosed (confirmed) and self reported figures is often dismissed by the media as simply due to the “gluten-free fad”, as typified by this article in TIME magazine (click on image to read). I love that TIME has decided – ahead of the experts in this field – that anyone outside of the identified 6% NCGS who claims that on a GFD “they feel better, fitter, more energetic, that their withdrawn child has suddenly blossomed and that their man is healthier and happier” is probably just subject to the placebo effect!

“Is gluten sensitivity fad or fact?”

As discussed above, it is not clear yet whether it is the gluten, the carbohydrate content of grains, or other proteins in wheat and other grains which are causing symptoms. The likelihood is that different sub-groups are being triggered by different factors. Understanding exactly which aspect of wheat or grains causes which problems is still in its infancy, and researchers are saying:

Inaccurate attribution will be associated with suboptimal therapeutic advice and at least partly underlies the current gluten-free epidemic gripping the Western world

Gibson et al, Digestive diseases (2015)


Prof. Alessio Fasano explaining that not all of the increased popularity in the gluten-free diet is ‘fad’. From his excellent presentation “Spectrum of Gluten-Related Disorders: People Shall Not Live by Bread Alone”

Although the prevalence rate for NCGS quoted by the experts is likely to change as research continues in the coming years, we should bear in mind that the diagnostic criteria of NCGS inevitably excludes certain people who would benefit from a gluten-free diet. Furthermore, there are different kinds of gluten-free diets: At one extreme all normal wheat based foods (breakfast cereals, cakes, bread etc) are replaced with their gluten-free simulacra (gluten free cereals, cakes, biscuits and bread), whilst at the other end additional meat, eggs, fruit and veg make up for the lost calories. It is the latter diet – a paleo or primal diet which excludes all grains, that I consider a true gluten-free diet. I would argue that the prevalence of NCGS would be much higher if this kind of gluten free diet were used in the diagnosis.

Biomarkers for NCGS

As already mentioned, there are currently no biomarkers for NCGS, however, that does not mean there are no serological abnormalities. In the following video Professor Umberto Volta, one of the Salerno Expert group and author of many published papers on matters around gluten, summarises the serum and tissue anomalies in NCGS.

  • (3:10) IgG Antigliadin antibodies (AGA) are raised in 66% of NCGS patients. They fall within several months of a GFD, along with symptom resolution, whereas in coeliac disease they remain raised.
  • (5:14) NCGS patients tend to have raised antibodoes to gliadin, glutenin, albumins and globulins, at similar levels to coeliac patients, but only coeliac patients have raised auto-antibodies (anti-deamidated gliadin and anti-tissue transglutaminase).
  • (6:10) in NCGS and IBS patients on a GFD, peripheral blood mononucleated cells (PBMCs) responded to gluten exposure with increased levels of IL-10 and TNFα
  • (6:40) in NCGS PBMCs responded to wheat extract with increased excretion of CXCL10 (interestingly, more so with modern wheat cultivars than ancient wheat varieties)
  • (7:15) Compared to controls and IBS sufferers, NCGS patients had raised zonulin levels (an indicator of gut permeability) similar to coeliac disease patients.
  • (8:00) NCGS patients had raised sub-mucosal mast cell density, again, similar to coeliacs, compared to healthy controls.
  • (8:58) Intestinal deposits of anti-tissue transglutaminase found in some NCGS patients suggesting they may be at higher risk of developing coeliac disease.
  • (10:03) No difference between NCGS and general population in HLA-DQ2/8. (i.e. no link to coeliac genetic markers)
  • (10:48) Possibly NCGS show unique pattern of raised T-lymphocyte infiltration around villi
  • (11:54) Summary: Although none of the above biomarkers is sufficently specific or sensitive for NCGS, they may contribute as part of a diagnosis.

Links between NCGS and irritable bowel syndrome (IBS)

As already mentioned NCGS and IBS share many symptoms. The key features of IBS are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms. According to a review in BMJ Clinical Evidence (July 2015), the prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20% of the US population. [ref]. Incredibly, as many as 42% of IBS sufferers claim to improve on a gluten free diet [ref].

Some authors go so far as to claim that all NCGS is really IBS, and that the problem is really with other wheat components such as FODMAPS (which are present in other foods not just grains) not gluten per se. [ref]. However, the Salerno Experts group, point out that “NCGS patients often report symptoms outside of the intestinal tract, e.g., headache and/or foggy mind, which cannot be accounted for by lactose, and/or FODMAPs intolerance.” [ref]

Four lines of evidence showing differences between IBS and NCGS

The following four lines of evidence not only show how NCGS is distinct from IBS in many ways, but it also gives insight into the range of damaging effects that gluten/wheat/grains can cause.

1. Bone loss and NCWS

Here is further evidence that IBS and NCWS* are distinct.

[*note: In two of the following studies authors use Non-Coeliac Wheat Sensitivity (NCWS or WS) as they employed a blinded wheat challenge to identify subjects]


Percentage of the patients of the three groups who had normal BMD, osteopenia or osteoporosis, evaluated both at the lumbar spine and femoral neck. Note: WS = Non Coeliac Wheat Sensitive patients. – Antonio Carroccio et al, BMC Medicine, 2014

This 2014 study looked at bone mineral density (BMD) in three groups of patients: 60 coeliacs, 75 NCWS and 65 IBS controls. They examined the BMD in the femoral neck and lumber spine of each patient.

As you can see from the graphs above the incidence of bone loss – either osteopenia or osteoporosis – is significantly higher in NGWS compared to IBS sufferers (as expected, coeliac patients had the highest incidence of the three groups). What the graphs don’t show, is that nearly half (46.6%) of the NCWS patients had low bone mineral density in at least one of the two sites checked, whereas half of coeliac patients had bone loss from both.

Compared to the IBS controls, the NCWS group also had higher frequencies of weight loss, anemia (90% had iron deficiency anemia), coexistent atopic diseases (which include asthma, eczema and hayfever) and a family history of coeliac disease than IBS controls.

2. Multiple food allergies in NCWS patients

As part of the initial screening for the above study, a double blind wheat challenge was used to seperate NCGS patients from IBS. However, the researchers went further, and conducted double blind challenges for a range of other foods.

30 of the 75 NCWS patients were found not only to react to wheat, but to cows milk proteins (casein). Moreover, eight of these thirty patients experienced IBS-like symptoms after open challenges with egg (four cases), tomato (three cases) or chocolate (two cases).

3. High levels of autoimmune disease found among NCWS

Hot off the press, a new study matched patients with diagnosed non coeliac wheat sensitivity(NCWS) with a similar number of IBS cases (who were not NCWS) and a similar number of coeliac cases. What they found is that among those with NCWS approximately 25% had autoimmune disease (mainly Hashimoto’s thyroiditis). This was similar to the number of autoimmune cases found in the coeliac group, whereas among the IBS group the rate was only 4% [ref], which is similar to the rate in the general population (i.e. 3%) [ref]

Another study found autoimmune diseases were present in 14% of NCGS patients, two thirds of whom had autoimmune thyroiditis. Psoriasis and Graves’ disease were frequently seen, whereas myasthenia gravis, atrophic autoimmune gastritis, scleroderma, type 1 diabetes mellitus, Crohn’s disease and IgA deficiency were infrequent. [ref]

4. Neurological symptoms in NCGS – e.g. depression

As already mentioned, one of the distinguishing features of NCGS is the common occurrence of neurological symptoms. These include headaches, anxiety, foggy mind, tiredness or simple lack of wellbeing.

Interestingly, a subset of patients excluded from a NCGS study category – for example if their IBS-like symptoms did not improve on a gluten-free diet – choose to stay on a GFD after the study, explaining that they simply “felt better”.

This prompted a study, published in 2014 [ref], looking at the effects of gluten on feelings of depression. They concluded “Short-term exposure to gluten specifically induced current feelings of depression with no effect on other indices or on emotional disposition. Such findings might explain why patients with non-coeliac gluten sensitivity feel better on a gluten-free diet despite the continuation of gastrointestinal symptoms.”

The current gastrointestinal focus of NCGS research may be missing more widespread effects of gluten and grains, making it likely that the quoted NCGS prevalence of 6% is likely to be an underestimate.

When Carroccio et al, compared 276 NCWS to IBS controls they found the following significant differences [ref]:

  • a personal history of food allergy in the pediatric age
  • coexistent atopic diseases
  • positive serum anti-gliadin and anti-betalactoglobulin antibodies
  • positive cytofluorimetric assay revealing in vitro basophil activation by food antigens
  • a presence of eosinophils in the intestinal mucosa biopsies

These differences led them to suggest that NCWS patients “might be suffering from non-IgE-mediated food allergy”.

When considering research about conditions associated with NCGS, it is important to realise that the reverse is also true. In other words, people suffering with IBS, osteopoenia, food intolerance, depression or an autoimmune disease are at higher risk of having NCGS (and coeliac disease).

The Gluten-free diet

Anyone diagnosed with conditions linked to NCGS if not NCGS itself, should try a proper gluten-free diet to see if it will benefit them, but they should do the proper paleo grain-free version, not the half-baked gluten-free copy-cat version which continues to beguile the coeliac charities.

Support literature from Coeliac UK, for example, is jam packed with adverts for ‘gluten free’ products, products which have no place in a diet intended to actually nourish us. Indeed these so-called gluten-free products are nutritionally sub-standard and can contribute to deficiencies. A 2013 study into nutritional status of coeliac patients on a typical gluten-free diet found pre-diagnosis deficiencies in thiamin, folate, vitamin A, magnesium, calcium, iron and zinc were not resolved after 2 years on a standard gluten-free diet, in fact thiamin and vitamin A intakes declined. They concluded: “dietary inadequacies are common and may relate to habitual poor food choices in addition to inherent deficiencies in the gluten free diet” (my emphasis)

A gluten-free diet should be seen as an opportunity to move one’s diet away from highly processed foods, towards real, natural produce, as illustrated below. If the NHS and Coeliac UK embraced this ethos they would be doing a world of good, instead of attracting headlines like “NHS handed out £116m of gluten-free junk food on prescription in the past year“.

Gluten-free products like those shown on the left are promoted by coeliac charities and the NHS, but contribute to sub-standard nutrition [ref]. Real foods that are naturally free of gluten are a better choice and can lead to an overall improvement in dietary quality.

Not all gluten-free foods are created equal! Gluten-free products like those shown on the left are promoted by coeliac charities and the NHS, but have been linked to sub-standard nutrition as they are often high in refined starches, additives and sugar. Real, unprocessed foods, like those on the right, which are naturally free of gluten can lead to an overall improvement in dietary quality.

What this means for you – and why I say no one should eat grains

Using Professor Alessio Fasano’s figures (1% of the population is coeliac, 6% are NCGS) for each of us the chance of currently suffering from a gluten/wheat induced health problems of about 7%.

For an entirely avoidable health risk this is a huge percentage and represents a significant degree of misery, burden on the health service and risk of serious diseases in the future.

Although some people will consider a 7% personal risk to be small it starts to look different if you extend your consideration to the circle of people closest to you.

If you consider the ten most important people in your life – you and your nine nearest and dearest (spouse, parents, children and best friends), then the chance of at least one of you having a wheat/gluten induced health problem right now is greater than 50%. The chance of one of you having full blown autoimmune coeliac disease is 10%.

[For the maths geeks: 0.93^10=0.484, and 0.99^10=0.904]

Remember, you cannot tell in advance who will develop these conditions or when. There are no screening tests, and these conditions often go undiagnosed for many years, meaning that you or a loved one is likely to be suffering, and probably receiving inappropriate treatment, for a long time before the true cause is identified.

Whilst the whole extended family is complacently eating a normal wheat-based diet it will be almost impossible for anyone suffering with undiagnosed CD or NCGS to stumble upon the solution accidentally. Even if they start to suspect that they might be better off on a GFD social habits and pressure are likely to make it difficult for them to remain gluten free for long. Being the only one on a GFD is isolating and is one of the main reasons for poor adherence and relapses.

The only preventative measure you can take is for you and your loved ones to adopt a proper grain-free/gluten-free diet now. Done correctly it will actually improve your nutrition and health. Done together it will dispel the social isolation and stigma. What’s to lose?

The final point I will leave you with reflects researchers thoughts about why so many people are affected by such a common food as wheat and related grains:

Possibly, the introduction of gluten-containing grains, which occurred about 10,000 years ago with the advent of agriculture, represented a “mistake of evolution” that created the conditions for human diseases related to gluten exposure – Sapone, BMC medicine, 2013

Which is why a pre-agricultural, or paleolithic diet probably offers the best template for a healthy diet, which I would argue is a diet free of all grains – not just wheat, rye, barley and oats!

Finally, a case illustrating how quickly symptoms can improve with proper dietary advice:

Case 3 – A triathlete improves rapidly on a proper GFD

A 53 year old woman – a very fit triathlete – came to me, as for a year she had suffered increasingly distressing symptoms including intense fatigue, large, pustular spots under her chin and sensations of impending ‘flu. She could not eat properly as a single bite of food gave her a full feeling in her stomach.The symptoms that worried her most, however, were a new sense of anxiety and depression that had developed over the year. She had been seen by a consultant gastroenterologist, but had been told her she was fine!
I gave her advice on how to implement a low-carb, grain-free paleo type diet and I provided here with probiotics.
Within three days she felt much better. She slept properly again. After four weeks the ‘flu sensations had almost gone, the stomach issue resolved and the spots cleared. Depression and anxiety had gone.

Supplementary Information

Table 1: The OSLO accepted definitions for gluten related disorders

Non-classical CD Presents without signs and symptoms of malabsorption.
Subclinical CD Below the threshold of detection without signs or symptoms sufficient to trigger CD testing in routine practice.
Symptomatic CD Clinically evident gastrointestinal and/or extraintestinal symptoms attributable to gluten intake.
Refractory CD Persistent or recurrent malabsorptive symptoms and signs with villous atrophy (VA) despite a strict GFD for more than 12 months
Potential CD Normal small intestinal mucosa who are at increased risk of developing CD as indicated by positive CD serology.
CD autoimmunity Increased TTG or EMA on at least two occasions when status of the biopsy is not yet known.
Genetically at risk of CD Family members of patients with CD that test positive for HLA DQ2 and/or DQ8
Gluten-related disorders Used to describe all conditions related to gluten. May include gluten ataxia, DH, non-coeliac gluten sensitivity (NCGS) & CD
Non-coeliac gluten sensitivity Is a condition in which gluten ingestion leads to morphological or symptomatic manifestations despite the absence of CD
Gluten ataxia Idiopathic sporadic ataxia and positive serum antigliadin antibodies even in the absence of duodenal enteropathy
Dermatitis herpetiformis Cutaneous manifestation of small intestinal immunemediated enteropathy precipitated by exposure to dietary gluten

Why no one should eat grains. Part 1 – The tip of the Iceberg

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Whilst ‘only’ 1% of the population is strictly coeliac, there is mounting evidence that a much larger proportion are harmed by gluten. In this series of posts I’ll draw on the most up to date research which is revealing the incredible web of health implications linked to cereal grain consumption.

The gluten iceberg is a pertinent metaphor for this hidden, and much larger, mass of problems that lurk below the surface. As researchers begin to unravel the complexities of the sub-surface gluten iceberg it is sobering to realise that its dimensions remain largely unknown, yet evidence is now indicating that all of us are affected to some degree.

As a clinician I get to see first hand how a grain-free diet can be key to making significant medical progress in patients with complex and apparently unrelated medical problems. This enables me to provide additional and, I hope, interesting perspectives on this story.

PART 1 Coeliac disease – the tip of the iceberg

Coeliac disease affects at least 1% of the population of which 76% remain undiagnosed

Classic coeliac disease is a serious autoimmune enteropathy (gut disorder), with no cure. The only treatment is lifelong adherence to a gluten-free diet.

The true prevalence of coeliac disease in the population is hard to establish as many cases go undiagnosed, but a figure of 1% is frequently quoted for Western countries [ref]. However, this figure is creeping up, and in 2014 an article in the journal Gastroenterology stated “Screening studies have shown the prevalence in the European and North American population to be 1%–2%, and to be increasing over time.” [ref] A 2014 study in the Netherlands found that between 1995 and 2010 – a mere 15 years – biopsy-proven coeliac disease increased nearly threefold [ref].

Among some populations the prevalence is even higher: “It is now considered one of the most common genetic disorders in Europe and Asian Pacific region with a prevalence of up to 2.67% of the population. The true prevalence of celiac disease may still be underestimated.” [ref].

Even taking the more conservative figure of 1% that is a huge number: 650,000 people in the UK, 7.4 million across Europe, 3.2 million in the USA. At present you have no way of telling if you or one of your loved ones will one day be diagnosed.

Coeliac diagnosis – the complex criteria

The diagnosis of coeliac disease requires four of the following five criteria [ref]:

  1. Typical symptoms of coeliac disease
  2. Serum coeliac autoantibodies at high levels (anti-tissue transglutaminase; anti-endomysial antibodies)
  3. Human leukocyte antigen HLA-DQ2 or -DQ8 genotypes
  4. Coeliac enteropathy shown by small bowel biopsy
  5. Improvement on a gluten-free diet.

Why only four out of the five? Because of the many cases of non-typical coeliac disease where any of the above can be absent. Lets take each criteria in turn and consider the exceptions.

Non-typical coeliac can present as an exception to each rule:

1. Non-typical symptoms: It is estimated that 76% of coeliacs remain undiagnosed (see below). A proportion of these have few classic symptoms, yet have clear serum antibodies and genetic risk (HLA DQ2/8). A very recent screening study in the UK found that the prevalence of undiagnosed coeliac disease was 1.3%. [Article in press]

2. No serum coeliac antibodies: 6-9% of diagnosed coeliacs do not have serum antibodies [ref].

3. Absence of coeliac human leukocyte antigens: Likewise, although 94% of coeliacs have either HLA-DQ2 or DQ8 gentic type, 4% have variant DQ2.2 and 2% do not have any of the identified HLA genetic risk factors [ref]

4. No coeliac enteropathy evident upon biopsy: In 2001 a study looked at 10 suspected coeliac patients who had only mild intestinal inflammation without villous atrophy (damage to the gut lining). Yet they all had typical coeliac symptoms and HLA-DQ2 genotype. Eight of the 10 were positive for anti-endomysial antibodies (EMA), seven for anti gliadin antibodies (AGA), and nine for anti tissue transglutaminase antibodies (tTg); all of which normalized on a gluten free diet. Eight of them also had osteopenia – early stage osteoporosis – which is very common in coeliacs. [ref] A 2011 paper describes such patients as “potential coeliac”, and says that the condition is “well known”. It goes on to say that 30% of children with this presentation develop intestinal atrophy in 4 years [ref]

5. No improvement on a gluten free diet:  Up to 2% of diagnosed coeliacs are classed as ‘refractory’ or ‘complicated’ because they do not improve on a gluten-free diet. Their prognosis is particularly bad, with a very high mortality rate: approximately 25% will actually die within 5 years of diagnosis. [ref]

This of course begs the question: what about individuals that meet only two or three of the coeliac criteria? They will not be considered coeliac, yet may suffer unless they too go on a gluten-free diet. Until recently they would have been dismissed as ‘not being coeliac’ and would have been dissuaded from trying a gluten-free diet. Hopefully this situation will change, as there is now a recognition that gluten can cause symptoms without coeliac disease. This newly recognised medical entity has been called non-coeliac gluten sensitivity (NCGS), and I will go into this in part 2, next week.

Risk factors for Coeliac

So, who’s at risk? Coeliac is a pretty horrible and common disease, so it would be nice to know if one was at risk of developing it or not. Unfortunately, this is not possible.

One of the main risk factors for coeliac disease is genetic, however, there is little point in having a coeliac gene test. Firstly, because as we have seen, 2% of coeliac cases occur in people without the coeliac genes, and secondly, nearly 40% of the general population carry the high-risk HLA-DQ2 or DQ8 genes, yet only 1 in 20 of them go on to develop the disease. What pushes one person over the edge into autoimmunity and not another is currently unknown. Some theories implicate infections, toxins, leaky gut – but for now at least, the jury is out.

So what about antibody blood tests? Tests for serum EMA and tTG antibodies are available on the NHS, but unless you have clear coeliac symptoms your GP is unlikely to oblige. Alternatively, a more comprehensive range of tests are available privately on request at clinics like mine. Whilst these tests are very reliable at identifying coeliac disease or cereal reactivity they only tell you that damage has already begun. If they come back negative they tell you nothing about your future risk.

The only absolute protection, therefore, is to avoid gluten in the first place – you simply can’t develop coeliac disease if you don’t eat wheat, rye and barley.

For the majority of people on a standard western diet, the first indication that they are developing coeliac is when they start getting symptoms. Trouble is neither they nor their doctors are likely to link these symptoms to gluten – not until significant damage has been done.

Coeliac symptoms

People with coeliac disease can exhibit a huge range of intestinal and extra-intestinal symptoms – see chart A and B below. These can easily produce a symptom picture that overlaps with other conditions, making diagnosis complicated and misdiagnoses all too common.


Percentages of patients with gastrointestinal and extraintestinal symptoms in a sample of 770 coeliac patients.  Volta U 2014

These, however, are only the most common symptoms. Before reading on take a moment to skim through the staggering list of symptoms and conditions that appear on the NICE recommendations for coeliac testing. (BTW – don’t expect your GP to have read these!)

If you took a look at the NICE guidelines, you won’t be surprised that in the UK an estimated 76% of coeliac cases go undiagnosed [ref].

The delay in diagnosis is reported to range from 4.5 years to 9.0 years. Patients may present on numerous occasions to both primary and secondary care without coeliac disease being considered. – Adult coeliac disease, BMJ 2007

Also, many are misdiagnosed, for example as suffering from irritable bowel syndrome (IBS). This is bad news as untreated coeliacs are at markedly increased risk of developing other diseases including multiple autoimmune diseases, cardiac problems and cancers.

[EDIT 28 June 2015]

The consequences of undiagnosed CD include not only underachievement and a 5-fold higher risk of non-Hodgkin’s lymphoma but also a 4-fold increase in all-cause mortality. – Aristo Vojdani, ISRN Allergy, 2011

[end EDIT]

Patient Case 1 – Late diagnosed coeliac with multiple early symptoms

This lady was not a formal patient, but a somewhat distant relative who I helped with her gluten-free diet following a coeliac diagnosis in her 70s. It is not clear how long she had been coeliac prior to diagnosis, but her medical history suggests it may have been a decade or more: In her 60s she was diagnosed with osteoporosis and hyperparathyroidism which led to a parathyroid gland being removed. Then came knee arthritis and surgery, then hives and finally the diagnosis of coeliac disease. Later, unfortunately, she went on to suffer a stroke.
No one can say for sure which, if any, of her health problems were directly related to coeliac, but several of her early symptoms are indicative: First, osteoporosis is common among coeliacs [ref] due to calcium and vitamin D malabsorption. Untreated this can lead to parathyroid dysfunction [ref]. Risk of joint pain and arthritis are more than doubled among coeliacs [ref]. Finally, hives are an early sign of coeliac – and was the only one that any of her various doctors picked up on leading to the eventual diagnosis of coeliac disease.
Without mass screening, there is no way to tell if patients suffering osteoporosis, parathyroid dysfunction or arthritis have early stage coeliac. Yet I am confident that if she had undertaken a grain-free diet in her 50’s she probably would have been spared many of the ensuing health problems.


How far does the damage go?

Many people assume, incorrectly, that coeliac disease is a mild condition – akin to food intolerance – but even when well controlled with a gluten-free diet it markedly increases risks of many other diseases. When untreated, the risks are even higher. Medical research into coeliac disease has burgeoned in the last twenty years and currently nearly one hundred new papers are published each month! Here are just a few such papers that indicate the range of problems linked to coeliac:

Furthermore, other autoimmune diseases are common among coeliacs – in one study [ref] of 381 adult patients the prevalence of concomitant autoimmune disease was 21%, including:

  • hypothyroidism 
  • dermatitis herpetiformis
  • hyperthyroidism
  • type 1 diabetes mellitus
  • Crohn’s disease
  • autoimmune hepatitis
  • ulcerative colitis

It’s a simple fact: no other ubiquitous food is responsible for so many health problems for so many people – and we are still only considering the 1% tip of the iceberg.

Patient Case 2 – A grain-free diet helped resolve multiple symptoms

A young man in his thirties came to me complaining of a ten-year history of severe headaches, lasting 4-5 days every couple of weeks leading to debility and exhaustion. He also had joint pains which, when investigated by his GP, were found not to be due to rheumatoid arthritis, though that is how it appeared clinically. He had also gained considerable weight over this period and he had a painful anal fissure – another symptom which seems to be common among coeliacs.
Further, I identified a vulnerability to type 2 diabetes, which his father and sister had, and not only made dietary adjustments involving a marked reduction in all carbohydrates and avoidance of all cereal grains but also prescribed medicinal herbs to quickly deal with the headaches, which were so debilitating, in order to restore this hard-working family man to health.
The headaches all but vanished, showing up only under major work pressure, and he lost weight, happily regaining his overall health. On one occasion he had a slip up with the diet, not realising that beers and largers contains gluten, he ended up vomiting after downing a pint of shandy. This illustrates his high sensitivity to gluten.
Whether he is actually ‘coeliac’ we may never know, but he has learned through his own experience that he needs to avoid grains to stay healthy. So why doesn’t he get tested for coeliac now? Read on!


Why people with self identified gluten sensitivity may not be able to get a coeliac diagnosis

With the rise in popularity of the gluten-free diet, many people have experienced significant, sometimes unexpected, improvements in their health following gluten exclusion. However, they then find themselves in the difficult position of being required to go back on gluten for six weeks (knowing they will feel dreadfully ill again) so that they can receive the coeliac antibody tests and/or have a duodenal biopsy. If they remain gluten-free the tests are likely to produce a false negative, yet without these tests they are extremely unlikely to be diagnosed as coeliac. You can read a real-life story of TV actress Caroline Quentin who found herself in just this double-bind by clicking on the image below.

Actress Caroline Quentin confesses to ‘poisoning’ herself with toast in video diary to finally prove she has coeliac disease – Daily Mail Online 6-May-2015

When gluten-free is not enough

Many coeliacs who go on a strict gluten-free diet do not recover fully. As mentioned above, those whose symptoms do not improve are considered refractory – and can have a very poor prognosis. However, there is another group where a standard ‘gluten-free diet’ is insufficient – those whose symptoms do improve, but who on biopsy show evidence of continuing intestinal damage. Whilst their symptoms may have improved, they are at risk of going on to develop overt refractory coeliac disease or other complications over time.

It is recognised that at least 5% of childhood cases have incomplete intestinal recovery after 2 years on a gluten-free diet, which can lead to significant malnutrition affecting growth and development. In the case of adult coeliacs, a 2010 study [ref] found very high numbers without intestinal recovery on follow-up. Among 241 cases who were checked, more than half had incomplete recovery, regardless of whether they had only partial or complete villous atrophy at their initial diagnosis.

The most obvious explanation would be lack of adherence to the diet – although in this study population adherence was considered very good. Even so, it underscores the importance of coeliacs being scrupulous in gluten avoidance. Hardly easy when, as one recent study found, approximately 20% of products labelled ‘gluten-free’ actually contained gluten above the limit of 20 mg/kg!

These results may be of concern, as gluten sensitivity is known to vary among celiac disease patients.
Lee et al, Journal of food protection (Oct 2014)

To underscore the importance of trace gluten in ‘gluten-free’ products, in a 2013 study long term coeliac patients that had not recovered on a gluten-free diet after an average of 3 years were placed on a ‘Gluten Contamination Elimination Diet’. This diet avoided all commercial gluten-free products and common gluten contaminated foods, allowing only:

…brown and white rice; all fresh (no frozen, canned or dried) fruits, vegetables and herbs; fresh meats, poultry, fish and other non-processed protein sources. Unflavored, unseasoned dairy products are introduced on week 4.

All cereal grains aside from rice are prohibited. Processed cheeses, lunch meats, ham, bacon or other such processed, self-basted or cured meat products are not allowed.
– Justin R Hollon et al, BMC Gastroenterology, 2013

[Now that’s nearer to what I call a gluten free diet!] Of the seventeen patients that stuck to the diet, fourteen had complete resolution of symptoms.

Whilst contamination of gluten-free grains can be a problem, in some cases the persistence of symptoms or intestinal damage is because coeliacs are reacting to other grains such as corn (maize) [ref] or oats [ref], which are considered ‘safe’ for coeliacs as they do not contain gliadin. These grains are common in many of the so-called ‘gluten free’ products, so coeliacs on a standard prescribed GFD may be consuming these in significant amounts.

A substantial fraction of pediatric CD patients seem to not tolerate oats. In these patients, dietary oats influence the immune status of the intestinal mucosa with an mRNA profile suggesting presence of activated cytotoxic lymphocytes and Tregs and a stressed epithelium with affected tight junctions.

Sjöberg et al, Clin and transl gastroenterology (Jun 2014)

The idea that oats and corn can harm some coeliacs is not widely appreciated, yet it is less surprising when one considers that these crops are all part of the same botanical family of grasses – the Poaceae. This is an area that has received little attention from researchers to date, but makes the case for a paleolithic diet – which eschews all grains, not just wheat, rye and barley – all the more compelling.

A gluten-free diet can benefit non-coeliacs

First degree relatives of coeliacs are at heightened risk of developing the disease. However, even relatives who are symptom free may benefit from a gluten-free diet. In a 2014 study, screening for endomysial antibodies was performed on first degree relatives of known coeliacs, and those that were positive, but symptom free, were randomised to a normal or gluten-free diet. Those on the gluten-free diet benefited “as measured by extensive clinical, serologic, and histologic parameters”. The authors point out that:

This randomized approach showed that subjects who thought they were asymptomatic experienced improvement in several objective disease scores upon adopting a GFD. These findings… suggest that the patients may in fact have accepted mild symptoms as normal and recognized them as abnormal only later when on the diet. [Gastroenterology, 2014]

In other words, there are people who are not classified as coeliac, yet have been living with gluten related health problems, but are unaware of their symptoms. They only realise once they try a gluten free diet and find they feel better.

Patient Case 3 – A relative of a coeliac who benefited from a gluten-free diet

A young woman with severe acne contacted me as she wanted to bring it under control for her up coming wedding. In taking her medical history I found that her grandmother had been diagnosed with coeliac disease and her mother had Crohn’s disease. She was initially skeptical of the idea that grains could be behind her acne as she did not want to change her diet, which was dominated by bread, pasta and biscuits. However, with the wedding approaching she agreed to go entirely grain free. To her astonishment she had clear skin six weeks later as the wedding photos prove, and she also noted an improvement in her rather volatile emotions. Yes, acne can be a reaction to cereal grains, and this is one of many cases where a grain-free diet solved the problem.

And with this last study, we have left the tip of the gluten iceberg where coeliac disease exists and are beginning our descent into the murky sub-surface world where gluten’s effects spread out into a much larger proportion of the general population.

Next week: PART 2 – Non Coeliac Gluten Sensitivity


  • At least one percent of the population has coeliac disease, and the numbers have increased in the last twenty years. Three quarters of coeliacs remain undiagnosed. You cannot predict if it will be you next.
  • Coeliac is an incredibly complex disease with a high rate of misdiagnoses.
  • The co-morbidities associated with coeliac disease are serious and far reaching indicating multiple pathological effects of wheat, gluten or grains in general.
  • Many people who are excluded from a formal coeliac diagnosis may benefit from a gluten free diet.
  • A grain-free, not just gluten-free diet, is the only guarantee of lifelong protection.