THE INTERVIEWS OF EVOLUTAMENTE.IT: Ian Spreadbury

Alessio: Can you give us a brief excursus of your career?  I think that your explanation of the metabolic havoc around us is the most fascinating, logical and comprehensive one so far, that conciliates all the pieces of the complicate puzzle. We just published an article about it. However, can you give a brief explanation about the nitty gritty of your research and how you got here? We would love to hear it directly from you.

Ian:
I was a neuroscientist by training, patch clamping ion channels on cochlear hair cells, nicotinic acetylcholine receptors in cultured cells, neurotransmission in brain stem slices and finally the primary afferent neurons that project to the colon as part of my 9 year stint working on IBS and IBD at the Gastrointestinal Diseases Research Unit at Queen’s University in Kingston, Ontario. I’d always had a habit of finding negative data, so was never going to be a professor or have my own lab. As such I was able to occasionally look at scientific problems a little more abstractly, without that laser-focus on the personal practicalities of securing my own future or funding – since I was already finished in that regard(!). I’d troubleshot my own health issues via diet, and found by a process of progressive trial and error that a real food paleolithic-style approach clearly worked best. That had really got my attention, and I was constantly thinking hard about a practical mechanistic explanation for this, but always ran into the theoretical limitations of the low carbohydrate theories – and in any case a higher carbohydrate approach was working just as well for me personally. With my exposure to GI diseases research, I was aware of the power of the gut microbiota over metabolic and inflammatory health, but the penny really dropped when I was reading Cleave’s ‘The Saccharine Disease’, and he mentioned an idea involving the gut microbiota and the suggested effects of cellular plant foods versus powdered carbohydrate upon diverticulitis and appendicitis incidence in the pre-nutrition-transition developing world. Since we now knew so much more about the power of the microbiota, I realised that this intuitively obvious ability of gut microbes to spot living vs powdered foods could be the missing link in obesity and inflammatory conditions. The longer I thought about it without finding any good reasons why it couldn’t work, and the more ramifications it seemed to explain, the more I thought it might actually be broadly correct. Eventually I saw an article in the news that the UK government was seriously advocating that people needed to get their babies to exercise more to tackle overweight in early childhood; this absurdity was the straw that broke the camel’s back, the point when I knew that I had a moral obligation to write the idea up as best I could and publish it somewhere. Sadly, the practical necessity of maintaining that focus on funding meant that no-one at Queen’s was about to shift their carefully-planned research roadmaps to look at the idea, especially since the nuances of nutrition weren’t something anyone was working on at GIDRU. Those at Queen’s who were looking at nutrition weren’t about to line up behind a fringe idea like ancestral diets. Now I’m in Montreal retraining as an MD, which is a wonderful new opportunity to do something useful and worthwhile with life. I’m hoping by the time I finish my medical training the large change going on in the public and scientific perceptions about nutrition will have moved things to the point where the public guidelines and research interests are being influenced more by ‘real-food’ approaches. Here’s hoping!

Alessio: Did you have to change your mind or adjust anything from your first publication?

Ian
Surprisingly little. Every time I thought I’d developed a new angle, I’d later read the paper again and realise I’d already included it. In a way, I wish I’d written it a year later, to be able to include Alan Cooper’s group’s work on skeletal human oral microbiota, as that’s a nice bit of evidence consistent with the idea. My first paper on the hypothesis is not an easy read, I wish I’d been able to write it in plain English, not as a dry scientific text, but I had run into some criticism at peer review during an early attempt to publish the idea in Nutrition Reviews. Apparently, many scientists view it as inappropriate to attempt to explain a new and complex idea to a broad audience, so I reverted to a more standard scientific and inpenetrable style for the subsequent submissions.

One subtle shift in emphasis I’d now include is of course to clarify that a simple linear relationship with LPS levels in the blood is unlikely to be the main driver – which I did already say in the 2012 paper, but in a slightly understated diplomatic way. Of course at the time the people looking at inflammation, gut microbes and diet were all very LPS-centred, and I figured they’d likely be doing the peer-review for the paper. Hence I included a lot of references to the metabolic syndrome and ‘endotoxemia’ research, hoping to make things a little easier in that regard. Not everyone has since spotted that I qualified that with a citation indicating low fat diets would work much better if it was as simple as that. The microbiota – immune – vagal interaction is likely to be pretty complex, akin to periodontitis in the mouth perhaps.

Alessio: Are you currently going on with your research, and what kind of hurdles do you usually encounter with?

Ian:
No, sadly research cannot happen without funding, and you cannot get funding without an unbroken stream of positive data leading to high-impact publications. My electrophysiology data during my training was almost always unpublishably negative (my findings always suggested the interesting option wasn’t happening), so my career as an independent scientist ended before it began. A combination of ‘publish or perish’ with publication bias ensures that only incremental variations on established wisdom is usually researched, and is also why around 50% of the literature is unreproducible. Science is currently fundamentally broken in that regard. I’d be glad to contribute to research on dietary matters in future, but I’m afraid it would take a considerably different funding paradigm for me to do so as a principle investigator. 

Alessio: How has your research been taken by your colleagues, especially from the stubborn low carb vs low fat worlds?

Ian:
That’s a great question! Of course the low-fat advocates are focused on the shifting evidence base produced now that low-carbohydrate diets are ethically acceptable to fund and investigate. Hence, the low-fat advocates tend to view insulin theory as the idea challenging their dietary world-view, and are largely fighting their corner on ongoing fears of cardiovascular disease or even the environmental angle against meat now that saturated fat and CVD is losing its sting. Meanwhile, the low-carbing / insulin theoreticians are enjoying their evidential triumphs over low fat or caloric restriction, and haven’t yet been forced to acknowledge the shortcomings of their current mechanism of interest. Hence the idea of a microbiota / real food mechnism has managed to fly under pretty much everyone’s radar. I’m assuming this is because too few people are taking either the small bowel microbiota or ancestral diets seriously yet, and this could go on for some time: there’s life in insulin theory yet. After all, low fat survived as the dominant paradigm for at least 20 years without the diet even really working, so insulin theory could hang on for a while. Who knows, maybe in the end it’ll be the the current low-fat advocates that will seize upon a real food – microbiota theory as a more credible way to argue against a need for environmentally unsustainable levels of meat-eating. Stranger things have happened.

Alessio: Aside from carb acellularity, what are the other harmful features of the western diet? What is your perspective about gluten, lectins and caseins?

Ian:
My sense is that lectins and casein are an order of magnitude less important, but may affect individuals sufficiently to warrant being removed from diet for those individuals. I am not currently aware of any evidence for gluten itself being a problem for anyone but those with celiac disease, but since the only real source of it are foods my metabolic health precludes me from eating, I don’t think about it much. I tend to suspect WGA and other candidate molecules in any additional inflammatory or gastrointestinal effects of wheat, rather than gluten.

I still suspect lectins may be behind some of the apparent metabolic and immunological effects of certain foods on some people, but I’m content to wait for much better evidence before it moves out of the realm of ‘a hunch’. Casein is an interesting one, I seem to recall there’s decent evidence that it has effects involving insulin, but some fairly extensive clinical trials to date seem to suggest a protective effect of high fat dairy (at least versus low fat dairy) against CVD. I can’t recall seeing anything compelling suggesting why all dairy ought to be omitted from diet, beyond the acne and migraine angle for people susceptible to those conditions. If there’s anything broader there, I suspect the research simply hasn’t been done yet.

Beyond the dermatology and headaches, I’m still pretty dairy agnostic. Although I do currently think of a nice slab of brie as a form of refined fat. My thoughts on refined fats are that these may well be a problem, albeit one that is less pronounced than refined carbohydrates. However, if refined fats and oils are the last thing unnatural with one’s diet, I’m open to the idea that in time someone may become sensitised to their actions on the microbial ecosystem, and they may need to be stopped to achieve good weight control and metabolic health. This is still a hunch, a stronger one, but I can’t point to anything other than circumstantial evidence to support this one yet(!)  Especially interesting would be research separating out the chemical effects of fats and oils of particular types, versus the effects produced by fats/oils being outside their biological context (i.e. refined).

Alessio: Probably rice is the most tolerated grain because is more “cellular” compared to the other grains and its prolamines are less harmful than gliadin. What do you think?

Ian:
I haven’t looked into the protein make-up of rice to be honest, I’d merely thought of it as having a waxier more cohesive nature to its starches than is seen in industrially milled flour’s powder. Hence, the reported effects of food texture on energy homeostasis (see Desmarchelier’s paper on food texture on mouse chows) and the lower carbohydrate density of rice both seem consistent with it’s less strong perturbation on weight control, if acting via upper gut microbial means. In terms of fewer inflammatory effects I have tended to put that down to the absence of wheat germ agglutinin and other wheaty nasties in rice. Of course all of this is merely a working model based on the slim available evidence, we really need more researchers to start taking the apparent downsides of our most popular grain seriously, and start investigating the mechanisms and the alternatives – including rice or even alternative preparations of some Frankengrain that avoids the problems by design, if possible(!).

Alessio: Is the current research about microbiota getting overhyped? Do you think it may have anything to do with the billionaire business behind it?

Ian:
Overhyped? – yes and no. I’m more concerned that they’re looking in the wrong place (colon, not upper gut), and thinking about the wrong food components (fibre, not powdered carbohydrates and refined fats). I think the conclusion that the microbiota is hugely important is correct, and of course as a new, powerful angle on health it’ll be a source of all manner of snake-oil, from companies large and small. We can only hope that the smart research money continues to drift toward the upper gut and real food interventions, before the fibre and probiotic salespeople overplay their hands and cause a loss of faith in the concept as a whole when people realise a designer roughage pill isn’t going to change their world.

Alessio: What role probiotics and prebiotics may actually have, in light of the fact that it seems that we still don’t know what is a true “healthy” microbiota and we are not completely aware about the actual complexity of the gut ecosystem?

Ian:
Exactly. And in the long term the food we eat everyday is also likely to override any changes we attempt to make with pre and probiotics. Over time we may find that in certain situations after dietary changes, certain facets of an unhealthy ecosystem remain ‘locked in’ for some people, and perhaps a supplement of some sort (or more likely a more complex ecosystem in its entirety) will be used therapeutically to assist the adjustment – assuming the new way of eating is maintained of course. But we’re so far from that, at the moment surely everyone’s just fishing. 

Alessio: What do you typically eat during the day?

Ian:
Today for brunch I ate an apple, a banana, a pear, two raw carrots. I drank an instant decaf coffee (all ground coffee ultimately upsets my stomach in the end, even the decaf, so I use instant now) and also some water. In the evening I cooked a ground lamb / beef mix in a wok pressed into a patty and then chopped up when cooked (all in its own juices), added about 70 ml of lamb bone broth and added fenugreek, chervil, cayenne pepper, powdered jalapeno, chili powder, cilantro, salt, pepper, a jalapeno, spring onions, tinned lentils / pink beans, half an endive sliced, a microwaved potato sliced up, sliced up rapini and then cooked the whole lot until the broth was reducing nicely. Oh, and I had a side dish of baby clams I had left over in the fridge. Dessert was another apple and banana. The day’s food has to be fit around the school timetable, so I can’t say I’d structure the meals like this if I wasn’t having to be in a lectures all day.

Alessio: Do you think that one day we will manage to get rid of carb vs fat vs protein debate and focus more on real vs fake food, or we are doomed to be stuck in this endless war?

Ian:
I certainly hope we’ll be able to move on! Science tries to simplify and quantify things, so it’s going to be hard to fund work and write scientific nutrition articles focused on meals of real foods without trying to quantify everything at a chemical level, and then try to explain it using those chemicals. How do you even quantify processing of foods right now? How would you graph that? Peer reviewers are going to argue strongly for macronutrient and caloric quantification, as it’s the science everyone has been working on up until this point. At some point the body of “it’s the foods not just the chemicals” literature is going to reach a critical mass, then things will move forward more quickly. I hold out hope that between the zeitgeist in Scandinavia and Brasil, and the growing clamour from nutritionists and physicians for a real food approach that a much better appreciation of the factors that really matter about diet will enter the public awareness, and the public health dietary guidelines. Look how far we’ve come in the last five years, we have to have hope.

A SINCERE THANK YOU  Ian for your kindness and your willingness, we really appreciate it!

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