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]:
- Typical symptoms of coeliac disease
- Serum coeliac autoantibodies at high levels (anti-tissue transglutaminase; anti-endomysial antibodies)
- Human leukocyte antigen HLA-DQ2 or -DQ8 genotypes
- Coeliac enteropathy shown by small bowel biopsy
- 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.
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.
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
Patient Case 1 – Late diagnosed coeliac with multiple early symptoms
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:
- Neurological effects: Increased Neuropathy Risk in Celiac Disease
- Hormonal effects: Increased rates of pregnancy complications in women with celiac disease
- Skeletal effects: Bone Microarchitecture Impaired in Active Celiac Disease
- Cardiovascular effects: Impaired aortic function in patients with coeliac disease.
- Gastrointestinal effects: The coeliac stomach: gastritis in patients with coeliac disease.
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:
- dermatitis herpetiformis
- 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
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.
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.
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
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.