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 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

May News Round-Up

In_the_News_May· Potatoes and hypertension
· Antibiotics, depression and phages
· Gluten debate
· Low-carb diets good for diabetes
· Salt does not raise BP (yet again)
· Medical errors – high death toll
· Vitamin D & sunshine
· 50y of changing UK food habits

Potato consumption linked to raised blood pressure

The Guardian (17th May) covered this story as well as any, after a study found that those who ate potatoes four or more times per week had a small, but significant, increased risk of hypertentsion (high blood pressure) compared to those eating them less than once per week. This link applied to boiled, mashed or baked potatoes and chips (aka French fries), but weirdly, not to crisps (aka potato chips in the USA). The study authors, suggest the effect is caused by the high carb content raising blood sugar. Interestingly, they point to trials that show high protein and high fat diets lower blood pressure. (See BMJ paper here).

Grass-Fed Nation: Book Review

The Telegraph (26th May) reviews a new book by Graham Harvey, script writer of The Archer’s agricultural story lines and one of the excellent speakers at our Grass Fed Meat Revolution in 2014.

Unfortunately, British dairy farming is moving in the opposite direction with the creeping introduction of US style mega-dairies (now numbering 100+), where cows are raised permanently indoors. The Telegraph (1st June) reports on this disturbing trend.

Antibiotics, depression and resistance – Phages to the rescue?

The Mail (24th May)  reports on Israeli research showing that just one course of antibiotics is linked to an increased incidence of depression, probably due to changes in gut microbes.

Even more depressing is the news that a woman in the US was found to have a bacterial infection that is resistant to colistin – the antibiotic of last resort (BBC News, 27th May).

The belated fightback by British doctors, however, is starting to bite with The Telegraph (25th May) reporting that GPs have slashed their use of antibiotics in the last 12 months. Was this due to their growing awareness of over-prescription and a public spirited determination to tackle the problem? Or was it because the government brought in financial incentives to encourage them? Oh… the latter. Well I never.


Phages attack a bacteria (Wikimedia)

With few new antibiotics on the horizon, research is turning to alternative means to treat infections, including bacteriophages – viruses that target and kill specific bacteria. The Independent (26th May) reports one such advance, with a phage found in a pond which attacks a type of multi-drug resistant bacteria. Interestingly, phage therapy was widely developed in the former USSR during the cold war, as they did not have access to western antibiotics. Phage therapy is still widely used in Russia, Georgia and Poland. You can read more in this 2014 Nature article.

Gluten controversy

The gluten-free ‘fad’ comes in for criticism with headlines such as “Gluten-Free Diets Are Not Necessarily Healthier, Doctors Warn” (Live Science 25th May, ). Yes indeed, gluten-free bread, biscuits, cakes and other simulacra are often chock-full of additives in an attempt to recreate gluten’s unique glutinousness. Additionally, gluten-free flours (like rice and corn) can be high in heavy metals such as arsenic, which has resulted in at least one recorded case of arsenic poisoning. So, yes, we concur: avoid all grains and don’t go shopping down the gluten free aisle! Eat more fish, meat, fruit, nuts and vegetables, i.e. real food as opposed to ‘products’ or as I like to call them ‘food like substances’.

The Mail (16th May) reports that supermarket gluten free bread is high in fat (shock horror), suggesting that this is a problem. To my mind, it’s not the fat you should worry about (although I wouldn’t reckon on the quality of their industrial oils), it’s the grain and chemical concoctions that are dodgy. My coconut keto-bread recipe is mega-high fat and grain free. Alternatively, my almond bread is versatile, delicious and can be toasted and made into sandwiches. Both are low GI, nutrient dense alternatives, not fake food.

In the same Mail Online article is a video reporting on links between gluten and depressions. Worth a click:


High-fat, low-carb diet takes on the mainstream – round two, ding ding!

The National Obesity Forum came out fighting this month with “Official advice on low-fat diet and cholesterol is wrong, says health charity” the Guardian (23rd May). They argue (as do I), that type 2 diabetes can be better managed on a low-carb diet, rather than the recommended low-fat approach. However, this has lead to a string of pugilistic condemnations from the nutritional orthodoxy. Public Health England weighed in calling the report “irresponsible” while The British Dietetic Association, warned that advising people to eat more saturated fat “could be extremely dangerous”. (The Observer 28th May)

However, we think The Telegraph (31st May) gets in the final knock-out punch with “Low-carb diet helps control diabetes, new study suggests”.

That study was conducted after an online revolt by patients in which 120,000 people signed up to the “low-carb” diet plan launched by in a backlash against official advice.

By rejecting guidelines and eating a diet low in starchy foods but high in protein and “good” saturated fats, such as olive oil and nuts, more than 80 percent of the patients said that they had lost weight, with 10 percent shedding 9kg or more.

More than 70 per cent of participants experienced improvements of blood glucose, and a fifth said they no longer needed drugs to regulate blood glucose by the end of the ten-week plan. (my emphasis)

KERPOW! Take that British Dietetic Association. WHAM! Stick that in your low-fat pipe National Health England.

U turn on salt recommendations? Probably not…

Further challenges to the orthodoxy were found in Mail Online (20th May) reporting on a study published in the lancet, in which “a global study found that, contrary to past belief, low-salt diets may not be beneficial. Rather, they can increase the risk of cardiovascular disease and death, compared with average salt consumption.”

Of course this led to the usual condemnatory remarks from WHO representatives who labelled the study as ‘bad science’.

My view is that lowering salt may be beneficial for some individuals with hypertension, especially those with genetic SNPs for salt metabolism, but for most of the population their is little evidence of benefit. You can see the numerous conflicting studies linked to salt here, and read our post on salt here.

Iatrogenic deaths

Medical errors have been identified as the third leading cause of deaths in the US, causing over 251,000 deaths annually, after heart disease and cancer, respectively, according to researchers at Johns Hopkins University. (Care2, 5th May, BMJ, 3rd May)

According to the study, “Medical error has been defined as an unintended act (either of omission or commission) or one that does not achieve its intended outcome, the failure of a planned action to be completed as intended (an error of execution), the use of a wrong plan to achieve an aim (an error of planning), or a deviation from the process of care that may or may not cause harm to the patient.” Amazingly, no form of medical error ever appears as a cause of death on a death certificate.

The situation is no less rosy on this side of the pond, with the Mail Online (10th May) reporting “Thousands of heart victims killed by poor care: More than 33,000 people died needlessly over the past few years because of shocking flaws in NHS treatment”. I don’t need telling about the hundreds of patients that have come to me over the years after being so poorly served by an incompetent NHS, indeed my own mother died from heart surgery that ‘went wrong’. Her surgeon humbly admitted to me personally that if he hadn’t done the operation she would still be alive. For all that, he still absconded from the hospital presumably back to Egypt, and I have not pursued that story further!

Vitamin D and Sunshine

Well, we had a handful of sunny days in May, so I suppose we can’t complain…

Our related post: Human photosynthesis – Beyond vitamin-D

Info-graphic of the month: Changes in British food shopping, 1974-2014


The above graph, courtesy of The Mail (4th May), shows changing UK food habits over the last half century. Interesting! What do you think?

Tweet of the month



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

The chemical warfare on your plate

  • Why insecticides in your veg can be healthy (sometimes)
  • SCOOP: The remarkable story of how wheat learned to turn an insect’s immune system against itself
  • Why that might not be so great for us humans

Graphic by K Watson, USING original ‘killer vegetable’ cartoon by Ken Turner

Plants are in constant chemical warfare with the insects, microbes and animals that want to eat them. Unlike animals they cannot run away (although the angry sweetcorn dude in the image above suggests otherwise!) so their only option is to develop chemical deterrents. Consequently plants are chock-full of natural pesticides such as taninns, polyphenols, saponins, oxalates, cyanides, protease inhibitors, lectins and alkaloids to name just a few. Because predators eventually evolve tolerance to these toxins, plants are forced to continuously evolve new compounds to defeat them. So the chemical weapon development escalates.

According to new research, wheat may have developed a particularly clever chemical weapon in this insecticidal battle, and the extraordinary story of how it directly contributes to coeliac disease makes up the second half of this post. However, back to the story…

Most people don’t want pesticides sprayed on their foods, but they can’t avoid the natural pesticides found in the fruit and veggies they eat. Surprisingly, however, those endogenous plant toxins are not necessarily harmful. At normal doses many are harmless, and frequently beneficial – for example the sulphur containing compounds in broccoli, kale and cabbage appear to have anti-cancer properties. At higher doses though, plant insecticides may threaten health – for example the cyanide in almonds, especially bitter almonds, which can sometimes exceed safe limits as happened in the USA in 2014 leading to bags of healthy sounding ‘organic raw almonds’ being removed from the shelves due to their high cyanide content.

So how can these plant-made insecticides ever be good for us?

The answer: hormesis.


Hormesis can be summed up by the phrase a little of what is bad for you does you good. Hormesis works because the body reacts to low levels of toxins such as those found in plant foods by upregulating cellular detoxification and anti-oxidant pathways. One of the most significant of these pathways is the Nrf2 antioxidant ‘master switch’ (ref) which stimulates our own most powerful antioxidant glutathione.

Whilst many compounds in plants are increasingly  toxic at higher doses, at low doses those same compounds may be beneficial. For example recent studies indicate that resveratrol (found in grape and red wine) protects heart cells at a low dose but kills them at higher doses. [ref]

Upregulating our own antioxidants via hormesis appears much more effective than taking supplementary antioxidants. Over the last thirty years trials of antioxidant supplements have often lead to disappointing results, with either no effect or in some cases an increase in harm (e.g. see our post on vitamin A from animal sources). Many researchers, including nobel prize winning James Watson (co-discoverer of the structure of DNA) now believe that unless you are actually deficient, additional dietary or supplemental antioxidants actually promote disease.

Instead, scientists are increasingly ascribing many of the benefits of eating fruit and vegetables to the hormetic effect caused by their toxins rather than to their antioxidants.

“Hormesis is what makes fruit and vegetables healthy, not antioxidants”, Mattson Mattson & Calabrese, New Scientist 2008

The key to maximising the hormetic benefits from fruit and vegetables is to eat as wide a range as possible so that you do not get excess of any one toxin. The recommendation to eat a wide variety of different coloured fruit and vegetables comes from the idea that the different colours indicate different phytochemical compositions.


A rainbow of chemical weapons… The different colours in fruit and veg are supposed to indicate different phytonutrient content. This is rather simplistic as many phytonutrients are colourless, but as part of the ‘healthy eating’ marketing message it probably succeeds in encouraging people to eat a greater diversity of plant foods.

Studies of contemporary hunter-gatherers show that they eat many more plant species than their farming counterparts which may be one reason that they are invariably healthier. For example a recent study compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence farmers. The hunter-gatherers consumed 130 food species (inc. 80 wild plants) whereas the farmers consumed only 63 species (and only 4 wild plants) and their eyesight declined faster with age.

So here’s a question: How many species do you consume? How many wild foods? The shocking answer for the world as a whole is provided to us by the United Nations:

The world has over 50 000 edible plants [yet] just 15 crop plants provide 90 percent of the world’s food energy intake, with three –  rice, maize and wheat – making up two-thirds of this.  United Nations, FAO

The role of agriculture

During the past 10,000 years of agriculture farmers have selected crops with high pest resistance. In some cases this has led to increased levels of certain plant toxins in the diet. High levels of gluten in wheat being an example.

Simultaneously, our preference for more palatable foods has led to the production of agricultural varieties that contain lower levels of bitter, sour or acrid compounds – for example modern salad lettuces are a lot less bitter than their wild counterparts, and apples are sweeter than their astringent crab-apple ancestors. This has reduced our exposure to the original diversity of plant compounds in the human diet.

Further changes caused by agriculture are due to selecting for high levels of sugars, starches and juiciness (water). The end result is a dilution of the phytochemicals in fruit and vegetables, requiring us to eat more of them, along with more simple sugars in the process, to gain the same quantity of plant micronutrients. A modern paleo diet, therefore, recommends eating berries – which are closer to their wild counterparts – rather than, say, apples and grapes, as they deliver more micro-nutrients per calorie consumed.

Furthermore, our reliance on a limited number of high yielding staple crops such as wheat and potatoes means that compared to our paleolithic forefathers we are exposed to a much lower diversity of phytonutrients, but much higher levels of the toxins and anti-nutrients they contain.

World's 30 top food crops

When measured by dry weight fruit and vegetables hardly figure among world crop production, which is massively dominated by grains. Image by Rosemary Cottage Clinic, after Cordain 1999

An example is the plant anti-nutrient phytate (phytic acid) which is found in its highest levels in cereal grains and nuts. It binds dietary iron, zinc, calcium and magnesium in the gut, reducing the quantities that can be absorbed. In developing countries where diets are limited with a high dependence on cereal grains phytate is a leading cause of mineral deficiency, especially in infants.

one third of world’s population suffers from anemia and zinc deficiency, particularly in developing countries.  Phytic acid is known as a food inhibitor which chelates micronutrient and prevents it to be bioavailabe for…  humans, because they lack enzyme phytase in their digestive tract – Gupta RK et al (2015)

In more affluent countries phytate is less problematic as the diet is more varied, but with grains typically making up 25% of the calories consumed in developed countries it still contributes to the risk of mineral deficiencies. For example last year a paper from the University of Texas examined how phytates in grains were responsible for zinc deficiency among US Mexican-American children, and US premenopausal women. On the other hand some possible positive effects of dietary phytates have been identified, including some anti-proliferative and anti-inflammatory actions. Small amounts in a varied diet, then, probably does some good and little harm.

Recently, a particularly interesting aspect of plant v insect chemical warfare has come to light as part of the explanation for coeliac disease. To my knowlegde, the remarkable story below has not been reported in the media or blogosphere before, so dear reader, you will be one of the first to hear of this research. Prepare to be amazed…

How a natural insecticide in gluten contributes to coeliac disease

Insects have a much simpler immune system than we do. They don’t have an adaptive immune system, relying on simpler innate immunity. However, they do have phagocytosis – the ability of certain cells to engulf microbes and then digest them inside the cell. But what do they do if the foreign particle is too large for phagocytosis? Below are mosquito larvae showing how they cope:


Three mosquito larvae (like the ones you see in ponds) showing nematode worm  – the arrows point to the encapsulated worms visible through the transparent body of the larvae (Zohdy et al, Journal of Mosquito research, 2013)

If an insect is invaded by a foreign particle too large for phagocytosis – a parasite or splinter for example – it will encapsulate it instead. This process requires immune cells called haemocytes to form a pallisade (fence) around the invading foreign body, thus immobilising it. The initial cells that bind this foreign body are broken down as further cells rapidly grow extensive sheets to wall off the invader, effectively locking it away in a cage from which it cannot escape. This is what has happened to the nemetodes inside the bodies of the mosquito larvae above. Cells then release glue-like glycose amino glycans (GAGs) which create a tangled water-holding matrix that prevents nutrients reaching the ensnared parasite. It’s an effective strategy for these lavae, but what has this got to do with gluten?

A recent study by Prof Simon Murch’s team at the University of Warwick investigated one aspect of the mechanism of intestinal damage (villous atrophy) in coeliac disease. They were interested in the way that the lower layer – the lamina propria – increases in thickness as the lining of the intestine becomes damaged. What they found was a direct link to insect encapsulation processes.

Perhaps the reason their paper didn’t get picked up by the press is the title: Matrix Expansion and Syncytial Aggregation of Syndecan-1+ Cells Underpin Villous Atrophy in Coeliac DiseaseIt doesn’t sound very promising does it? Yet it explores a  fascinating hypothesis that brings together many of the threads I have been working up to in this post. I will attempt to elaborate below…

celiac_biopsyFirst, a bit of background:

Villi are microscopic projections covering the inside of the small intestine, providing a huge surface area essential for absorption of nutrients. (Upper image: biopsy showing healthy villi)

In coeliac disease the villi are eroded, leaving sections of the intestine that are flat and unable to absorb nutrients. (Lower image: coeliac biopsy showing villous atrophy) How gluten can cause these changes in the small intestine is currently the subject of intensive research efforts.

One little appreciated fact in this process is that the damage to the villi is bottom up, not top down. If you look carefully you can see that the lower layers of cells (the lamia propria) has actually expanded upwards, increased in thickness, and destroyed the structure of the villi above.

Prof Murch’s team investigated the mechanism of this cell overgrowth in the lamia propria. What they found is that it shares many biological features with insect encapsulation.

We hypothesise that our findings, of syndecan-1+ cell syncytial aggregation with excess GAG production, recapitulate core elements of the invertebrate encapsulation reaction, in which insect haemocytes form palisades around an invading pathogen or object too large to phagocytose

Recruited cells are characterised by syndecan expression, required for invertebrate haemocyte binding to laminin and cell cluster formation. Our findings in coeliac mucosa show a similar palisading of syndecan-expressing leukocytes to form syncytial aggregates, together with a lysis of a proportion of these cells, with loss of their plasma membrane. Sulphated GAG including HSPG accumulated around these aggregates in an expansion of the lamina propria.

In insects, the GAG production and matrix expansion is limited by a subsequent melanisation reaction dependent on the enzyme prophenoloxidase, in which haemocyte responses are downregulated by α-melanocyte stimulating hormone (α-MSH). In coeliac mucosa the gliadin-induced IL-6 response is similarly attenuated by α-MSH.

The release of GAGs during insect encapsulation, remember, prevents nutrients reaching the parasite. In the lamina propria the GAGs will similarly reduce nutrient uptake – a double whammy for the coeliac intestine – villous atrophy reduces surface area for absorption, then excess GAGs reduce it further!

Another similarity in both insect encapsulation and coeliac disease development is the stimulation of tissue transglutaminase (tTG), which is an enzyme that causes gluing together of tissues.  tTG is a major player in coeliac disease as in the presence of gliadin it can become the target of autoimmunity. (The primary coeliac blood test is for tTG antibodies).

This is all fascinating and points to an evolutionarily conserved mechanism shared by both invertebrates and mammals. However, it begs the question – Why would gluten stimulate a response in the human intestine that is equivalent to what insects do when they are invaded by parasites? The answer to that question is where the true awesomeness of this story lies…

Gluten as a wheat-made insecticide

It is notable that wheat grain has very few insect pests – a fact that made it a good crop to domesticate ten thousand years ago.

A clue as to why this may be is that the few insect species that are able to predate it have all evolved enzymes that can break down gluten. Gluten is very resistant to normal digestive enzymes. That is why many gluten proteins reach the human intestine relatively intact – and why it can set off an immune reaction.

It is notable in this context that the glutenin moiety of wheats provides an effective barrier to predation by most insect species, and there are notably few successful phytophagous predators. Insects able to predate wheat share a common ability to predigest gluten with salivary enzymes, which has evolved separately in species from the northern and southern hemispheres.

The final piece of this story is how gluten pulls off this trick. It appears that the insect immune response to parasites involves the release of two proteins during the early stages of encapsulation. These have been found to have uncanny similarities to some proteins in gluten. The implication is that wheat may have evolved these gluten proteins as an effective insecticide strategy that works by over-stimulating the insect’s own defense system by triggering the encapsulation process inappropriately and presumably fatally! In humans a similar inappropriate triggering is caused by gluten ingestion that can lead to the destruction of the small intestinal villi, via a process which is extremely similar to insect encapsulation.

Cool or what?

Hats off to Prof Murch’s team!

Gluten_free_weevilsimage (c) Rosemary Cottage Clinic 2015

Gluten and Schizophrenia – does it all start in the womb?

Credit: Mary-Claire King, Ph.D., University of Washington [original paper]

Credit: Mary-Claire King, Ph.D., University of Washington [original paper]

  • Research is now identifying how schizophrenia starts in the womb
  • Maternal infections and dietary antigens such as gluten are implicated
  • A key immune molecule C1q has been identified which links schizophrenia, gluten and neuronal development in the unborn child
  • Evidence for dietary factors associated with healthy brain development are considered

Schizophrenia affects one in 100 people at some point in their lifetime. The causes are not understood, but what is known is that it is associated with abnormal networks  of neurones in the brain, specifically, aberrant connections within and between different brain regions. 25 years ago the neurodevelopmental hypothesis proposed that these problems begin in the womb, with disruption to the development of the foetal prefrontal cortex leading to schizophrenia.

Continue reading

Public Talks – 2014 update

Venue: Bassil Shippam Centre, Tozer Way, Chichester,PO19 7LG
Time: Friday, 7:30-10:00pm (doors open at 7:15) Cost: £6.00 inc tea/coffee

Fri 11th July
This not-to-be-missed seminar on one of the hottest topics in nutrition will update our 2013 sell-out talk “Cereal Killers” and fully clarify this vexed  area of food and health science, which currently confuses most people.
The gluten-free diet is the fastest growing dietary trend across the Western world in 2014. Is this just another fad, or is there something in it? We will take a look at the wealth of detailed research emerging on coeliac disease, glutens, grains in general and their staggering implications for everyone’s health.
 ∗ Autumn Special ∗
I am pleased to announce that I have a preliminary booking for:
Dr Malcolm Kendrick
Author of The Great Cholesterol Con

If you have never heard Dr Kendrick speak you are in for a treat: A practicing GP in Macclesfield, he has dared to read and understand the research around heart disease, and made sense of it. His talks are full of wit and humour, are incredibly informative and uplifting. He should have his new book out by then too (not sure what it’s about yet!), so there is a good chance you will be able to pick up a signed copy and with it stay ahead of the pack.
∗∗∗∗∗ Date and venue to be confirmed. ∗∗∗∗∗