Frontiers’ Bread Madness

The journal Frontiers in Human Neurosciences now published a paper titled: “Bread and Other Edible Agents of Mental Disease“. It is authored by two psychologists, Paola Bressan and Peter Kramer from the Department of General Psychology at University of Padova in Italy, and claims “in non-technical, plain English” that mental diseases such as schizophrenia and autism are caused by bread (yes, you read right, bread). In their “review article” Bressan and Kramer claim to provide evidence that bread gluten makes “holes in our gut”, thus activating an immune response, and is degraded into opioid substances (“some of them resemble morphine extremely much”). The casein in milk has allegedly exactly the same effect, and cure for “schizophrenia, bipolar disorder, depression, anxiety, and autism” is possible by adhering to a strict bread- and milk-free diet. In fact, other staple foods might make you mad as well, as authors conclude:

“Bread is the very symbol of food, and learning that it can threaten our mental wellbeing may come as a shock to many. Yet bread is not alone; like it, other foodstuffs, such as milk, rice, and corn, release exorphins during digestion”.

Though the paper appeared on March 29th, it was meant seriously and not as an April 1st joke.

As psychologists, Bressan and Kramer apparently feel fully qualified to address all possible aspects of biomedical sciences: microbiology and genetics, but also gastroenterology and immunology, like with their latest paper. In fact, the authors straight away postulate that it is the other sciences, the”gastroenterology, immunology, toxicology, and the nutrition and agricultural sciences” who are “outside of their competence and responsibility”. And the two Italian multispecialists came to their right journal: the Editor-in-Chief of Frontiers in Human Neurosciences, Hauke Heekeren, psychology professor at the Free University of Berlin, is very open to unconventional science by field-boundary defying colleagues. As I previously reported, Heekeren published in his Frontiers journal several research papers on parapsychology, where clairvoyance, mind-reading and life after death were dealt with as scientific facts. Now, when I attempted to phone Heekeren about the “bread makes mad” paper, he told me: “I have no interest in speaking with you”.

Also the handling editor Rajeev Krishnadas, consultant psychiatrist at the University of Glasgow did not reply to my email. His research follows a rather unconventional theory that inflammation is the cause of mental disorders like depression, a clinical trial is already scheduled. Krishnadas invited the “bread derangement” paper as part of a collection titled “Inflammation and the brain, in the context of mental health and illness“, where also a hypothesis paper by a US gynecologist appeared, claiming autism might be caused by the rubella virus. Luckily, not the vaccine against it, as Wakefield claimed.

But back to the bread lunacy. This Frontiers paper was spotted by the microbiologist Elisabeth Bik, research associate at the Stanford School of Medicine:

Bik then set on to batter the bready nonsense. She commented on my site:

“In this paper, bread is presented as a food item that will cause damage to the intestinal lining in all people, not just people with gluten intolerance, eventually leading to mental health problems. This paper is presented as a Review, not a Hypothesis, suggesting that the statements of this papers are factual. Although an interesting hypothesis, this paper makes several ill-founded statements that lack citations or support. It also has a sensational and fear-evoking tone to it that does not belong in a scientific and peer-reviewed paper“.

Also, Bik shared her views on her microbiology blog, as Storify and on PubPeer. Among her detailed criticisms are:

• “The text is a mixture of true statements backed up by science, mixed with bible quotes, musings, speculations and gross extrapolations. It is very hard to tease apart where science ends and wild ideas start”.
• “Several key statements in paper don’t have a citation. Eg “gluten is broken down into fragments some of which resemble morphine” – citation was needed here”
• “One of the references is to an “Ancestral nutrition” YouTube video presentation from a conference – presumably not peer reviewed“

Willem van Schaik, professor for medical microbiology at UMC Utrecht, reacted quite distinctly after learning of bread-induced psychosis:

The chemistry lecturer at University of Glasgow, Haralampos Moiras (aka Harry Miras) described the”bread makes mad” paper on Twitter as “bullshit”.

Finally, while Frontiers editors were convinced that two psychologists are fully qualified to do research on gastroenterology, immunology and nutrition, here is what some proper field specialists say.

Ole Haagen Nielsen is clinical professor at the University of Copenhagen (and one of the 31 former Frontiers medical editors who were sacked for their demand of editorial independence, as I reported).  Nielsen specialises in the molecular biology of inflammation  in patients with gastroenterological syndroms.  So, what the psychologists Bressan and Kramer claim to have studied in their leisure, is actually his very field of research. Nielsen judges:

“When I read their article it appears as if they “bend the truth” into a direction that fits with their opinion. In recent years, there has been much focus on nonceliac gluten sensitivity (cf. article by A Fasano), but the delimitation to irritable bowel syndrome (a functional disorder) is rather difficult. […] Immediately, I believe that the text of Bressan & Kramers’ article seems tendentious or maybe the word “religious” is even more appropriate – and at the same time it is from your second mail [my hints to peer review issues, see below,- LS] questionable how Frontiers managed the editorial process prior to publication.

Today I am happy I left Frontiers a year ago“.

Michael Müller, professor of nutrigenomics and systems nutrition at the University of East Anglia, stated:

“I am unfortunately not a real expert on this topic as I am a molecular nutrition/metabolism researcher but clearly have more expertise than these authors. The problem (and this is a scandal) that the topic is too complex and needs insider information to discuss it in such a review. These authors are no experts (food scientists, nutritionists) at all and therefore this paper should have been rejected. Most of the statements are nonsense and the references likely used in a very selective way. When I look at some of their other “papers” e.g. “Belief in God and in strong government as accidental cognitive by-products”  know enough. So from God to Bread……It is a shame for Frontiers but even for their own profession Psychology. I hoped that Human Neuroscience is a more exact science as exemplified in this Frontier article“.

Says “Nein!”: Bernd das Brot (Bernd the Bread), the sceptical German children TV character. Image source: KIKA.

Finally, also the peer review process of the “bread insanity” paper was heavily compromised by conflicts of interest (COI):

The reviewer declaring this strangely acceptable COI is  Paul Whiteley. Though he apparently has a PhD, he is not a scientist, neither academic nor even industrial, but commercially associated with an obscure group called “espa research” which claims to be researching “gluten- and/or casein-free diets for people with autism”.  Whitely also has other business interests in promoting bread-free diets to cure autism and has published in 2013 a Frontiers in Human Neuroscience review article, about treating autism through a gluten- and casein-free diet.

The other reviewer, Jessica Biesiekierski, postdoc at KU Leuven, published a controversial clinical study which claimed that “gluten may induce depression as a consequence of changes in brain serotonin, gluten exorphins or changes in gut microbiota“.

I attempted to engage an Associate Editor of an (unrelated) Frontiers journal, namely Rich Boden, lecturer at University of Plymouth, into commenting on editorial process and reviewer choice. Was Frontiers’ own peer review compromised, given the information from the reviewers’ Loop profiles? Boden denied this information was sufficient; the overall discussion was not at all productive, this is why I corrected the previous text version. Here are however some answers:

Good scientists on one side against bad scientists on the other? Maybe it is not that simple. One of the co-authors of the respectable 2015 Fasano et al study “Nonceliac Gluten Sensitivity” in Gastroenterology, which Bressan and Kramer were seemingly misinterpreting to support their wonky claims, was the Neapolitan Anna Sapone. She co-authored a 2011 paper in Hindawi  (a publisher I discuss together with Frontiers here), titled: “Autism Spectrum Disorders: Is Mesenchymal Stem Cell Personalized Therapy the Future?“. Yes , they did propose that “mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease”. Where is one to start at criticising this outrageously ill-informed and potentially highly dangerous nonsense?

Until the “bread madness” issue is objectively and competently resolved by Prof. Heekeren in Berlin and the highly qualified Frontiers journal managers in Lausanne, we all are probably best advised not to eat any bread or milk products. One is also safe to assume that the Italian researcher duo Bressan and Kramer are sustaining their sanity on a healthy diet of eggs, bacon, sausages and spam.