Gearing up for a gluten challenge

I know I haven’t been around much lately.  I haven’t had much I’ve felt like writing.  And I’m trying to get both some school and personal projects done (I’ve yet to be successful with those either).

But one thing I did discuss with my doctor the last time I saw her was the possibility of doing a gluten challenge so that I can finally get diagnosed with celiac disease.  It’s been hard to really work through why I really want a celiac diagnosis.  There is a little voice that lives in the back of my head that questions this whole gluten free thing.  Wonders if I really need to do it.  Wonders if a little wouldn’t hurt.  I’d like to attempt to quiet that voice.  Since my dad is diagnosed as celiac, and I fit two out of the five criteria for having celiac disease, I likely have it too.  Now to make it official.

The hard part however has been scheduling when to do this gluten challenge, as I’m sure it will impact my ability to function, and answering the question of just how much gluten I need to eat for how long to get an accurate diagnosis.  On this last one, the doctor and I didn’t agree.  She said to eat “some” every day for two weeks, and then come in for the blood work.  That set off warning bells in my head, so off I went in search of papers on the subject.

So far, there is only one paper that addresses this question specifically:

Pyle G. G., B. Paaso, B. E. Anderson, D. Allen, T. Marti, C. Khosla, and G. M. Gray. 2005. Low-dose gluten challenge in celiac sprue: malabsorptive and antibody responses. Clinical gastroenterology and hepatology 3:679-86.

pubmed link

The gist is that 8 diagnosed nonsymptomatic celiac patients ate gluten daily for 21 days.  Four of them had 5 g a day, the other four had 10 g a day.  While all the patients had an increase in symptoms and all the patients performed worse on a few of the malabsorptive tests (which aren’t incredibly accurate), NO ONEs antibody levels changed.

So I’m still left wondering how to handle this.  This paper was helpful in that I know 10 g a day for 21 days is insufficient.  But I don’t know if I’ll just need to eat more or longer, likely both.  And as 10 g is roughly equal to two slices a day, I’ll definitely be blowing that portion right out the water, as I plan on consuming gluten like a ‘normal’ person, at pretty much every damn meal.  Now the question is for how long will I need to suffer?  And hope that this will all be worth it in the end.


Is gluten intolerance real?

If you are around the alternative health blogs at all, or really many mainstream health sources these days, you might have seen mention that ‘perhaps a gluten free diet can help you too!’ But if you don’t have celiac disease, is going gluten free of any use? Are there gluten issues other than celiac disease and a true gluten allergy? Is gluten and wheat intolerance real? What I think this really gets to is, if we don’t medically understand something yet, is it real? I’ve heard many people argue that gluten intolerance simply isn’t real. Either you have celiac disease or you don’t. It’s not a stance I agreed with, especially after reading this article.

All I know is, some people do report that they feel better when they eat gluten free. While I call myself a celiac, I actually count myself as one of those who don’t really know. If you’ve been here long enough, you know I went gluten free long before I realized there was a test for this whole thing. But between a vast improvement on a gluten free diet and the fact that my father has in fact tested positive for celiac disease, I figure I have it too. And finally, some groups are putting some research time into this. This is the first major study that I’ve seen that actually attempts to do Good Science:

Biesiekierski J. R., E. D. Newnham, P. M. Irving, J. S. Barrett, M. Haines, J. D. Doecke, S. J. Shepherd, J. G. Muir, and P. R. Gibson. 2011. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. The American journal of gastroenterology. 1-7.

The authors had two main aims: do non-celiacs react to gluten and if so, what is/are the mechanism(s)? While there are some things that need to be worked out, we know quite a bit about celiac disease. There is modification of the gliadin portion of gluten by a molecule known as tissue transglutaminase causing them to be presented to immune cells, but only in patients who have at least one of two different genes (HLA-DQ2 or HLA-DQ8). 99.4% of patients express the gene products from one of these genes. This process results in the symptoms we see in celiac patients.

As with most good medical studies, the authors went about this by doing a double-blind, randomized, placebo-controlled trial. They took 34 people; 30 female, 4 male, ranging in age from 29-59. All reported problems that labeled them as having ‘IBS’. They responded well to a gluten free diet, but tested negative for celiac disease. 19 were placed into a gluten eating group and asked to follow their regular diet along with consuming two provided pieces of gluten containing bread and a gluten containing muffin. 15 were placed into a gluten free group and asked to follow their regular diet along with consuming two provided pieces of gluten free bread and a gluten free muffin. They were followed for 6 weeks. 56% of them had either one or both of the genes associated with celiac disease (HLA-DQ2 or HLA-DQ8).

Now, as with many medical studies, sometimes they seem to miss obvious things. The patients they recruited had to have been adhering to a gluten free diet for only 6 weeks. I don’t know about anyone else who is gluten free, but it took me much longer than 6 weeks to really get this diet. Hell, even at 8 years I still sometimes make mistakes. I think this is a major weakness of their study, despite the food diaries they asked patients to keep.

The set up was that in the 2 weeks prior to the study, patients kept a 7 day food diary. They were also asked to maintain their gluten free diet throughout the study, with 2 food diary checks in between, expect that they were to eat the two provided pieces of bread and the muffin every day for the entire 6 weeks of the study. If they were consuming the gluten containing products, this was 16g of gluten, well above the threshold for getting a response in celiac patients. Every week, and for 3 weeks after, patients symptoms were evaluated. At the beginning and end of the study serum, urine and stool were also collected for testing.

Here’s where I think things get pretty neat in a nonscience way. These researchers were crafty. To control for potential differences between gluten free and gluten containing products, they had their own muffins and breads made. The only difference between the two was that the gluten containing products had added wheat gluten. Why is this crafty? Some people have a reaction to FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), and wheat is a food that falls under this category. So by making sure these were not present in the bread products, they ensured that they really were testing the presence of the gluten, and not any of these other compounds that might also cause symptoms not related to the gluten. And according to them, 10 normal people couldn’t tell the difference based on taste or texture between the gluten free and the gluten containing products. Crafty mofos!

Also a problem with medical studies, you don’t often get as many people as you think you need. And then some drop out. The authors estimated that they needed 30 people in each group to get good reliable statistics. But out of the 300 who applied, and the 100 that they screened, only 39 met the criteria to be included. And then 5 dropped out. Such is science.

So that leaves us 19 in the gluten group and 15 in the gluten free group. Of the 19 in the gluten group, 6 withdrew after only a week because symptoms were intolerable. 3 in the gluten free group withdrew for the same reasons after 2 weeks. Of the 19 in the gluten group, 13 (68%) reported problems on the gluten diet, while 6 of the 15 in the gluten free group reported problems (40%). While these numbers seem pretty shitty, the authors state that for the gluten eating group, even after just a week, they reported worse overall symptoms, more pain, bloating and tiredness, along with problems with their stool consistency. However, importantly, the antibodies that signify active celiac disease were not induced in either group. They also found no significant difference between those that had the celiac associated genes and those who didn’t.

Their conclusion, and one I agree with based on the study design and their data, is that non-celiac gluten sensitivity does indeed exist. While this study isn’t perfect, they have the stats to back up that 68% feeling shitty on a gluten containing diet is enough to say that there is indeed a problem. They do note, the biggest difference between the two groups was that the gluten eating group reported feeling more tired (I wonder if you can have celiac disease AND whatever this issue is, as I remember feeling incredibly tired). While they also had more problems with bloating, pain and the stool form, it was really tiredness that explained the biggest difference between the two groups.

The bad news? They have no clues as to the mechanism of the problem. C-reactive proteins, a marker for systemic immune activation, were not elevated in either group. Fecal lactoferrin levels, an indication of intestinal inflammation, were also not different between the two groups. They also measured general intestinal permeability to see if it was an issue of intestinal injury, but that too was negative. They do go into some hypotheses at the end that could explain what is happening that they did not or were not able to test for, but I don’t understand them enough to summarize here. But suffice it to say, it looks like non-celiac gluten intolerance is gaining some traction as a real medical issue.

Do celiac patients die earlier than ‘regular’ people?

TL;DR: If you have celiac disease, and you continue to eat gluten, you have a significantly increased chance of dying at a younger age than someone from the general population.

Recently, particularly in r/glutenfree, I’ve run into a lot of people who either don’t understand why they should be gluten free if they have celiac disease, or who second guess why I wish I had an official diagnosis for celiac disease. To the first group, I always make the same comment: if you have celiac disease and you continue to consume gluten, you increase your odds of dieing sooner. To the second group, it really is the same answer as the first. If I had an official celiac disease diagnosis, then I’d know that I need to be gluten free for the rest of my life. The flip side is that if I’m not celiac, then my body -might- be okay with small quantities of gluten (ie, if I had a gluten/wheat allergy or intolerance); the research is still out on this, and I haven’t seen anything good recently on this topic.

So the other night, who knows what I was doing, but I stumbled across this paper:
Biagi F., and G. R. Corazza. 2010. Mortality in celiac disease. Nature reviews Gastroenterology & hepatology. 7:158-62.

I always like reading primary literature, but as a graduate student in the sciences, I also know that I need to be mindful of what I spend my time reading. Needless to say, I find the Nature Reviews series helpful, especially when I’m reading for my own interests, versus what I read for my lab work. Generally, these style papers are easy for me to read, and the shorter ones often get the point across without being overly detailed. So while I know that reading the primary literature is important because review authors don’t always get the details right, for something like this, I’m grateful for reviews that give me the overall pictures in a concise easy to read manner.

This is my attempt to summarize what is contained in that review for a more general audience.

It has been postulated for years that celiac patients die at a higher rate than the general population. But the research done has been somewhat diffuse, with many inconsistencies, and no clear overarching story. It’s been known for well over 20 years that a celiac patient who adheres to a strict gluten free diet will increase their average life span. And all of this is about average life spans, or how often we die and at what age compared to the general population.

Lets start off with what celiac patients die of. The biggest killers are gastrointestinal malignancies such as non-Hodgkin’s lymphoma and small bowel cancer. Also high on the list are other autoimmune diseases such as rheumatoid arthritis, ischemic heart disease, and oddly enough, violence. Location also seems to play a part. Celiac patients in Sicily die at a higher rate than those in Finland, for example.

So lets look at some of the nuances when asking how and when celiac patients die. For this, we need to consider that not all celiacs are equal, they can include: actual celiac diagnosis, suspected celiac disease, dermatitis herpetiformis, and refractory celiac disease. To further complicate the picture, we also need to consider if the patient is eating gluten and how well they adhere to being gluten free.

General studies have found that for diagnosed celiac patients, if they adhere strictly to a gluten free diet, they die at the same rate as the general population. This is great news. If you have celiac disease, and you are as gluten free as you can be, your risk of dying earlier is the same as any non-celiac person. BUT, if you are celiac, and you aren’t careful, your likelihood of dying earlier is nearly double. Know you have celiac disease and disregard it to eat gluten any way? Your risk of early death jumps up to six times the general population. While these numbers seem to hold up well, some studies have found that for some patients, even if they adhere strictly to a gluten free diet, they still seem to die at a higher rate than the general population. For those of you with celiac kids, or those of you who were diagnosed as a child, your odds are even better. All those years of NOT doing damage to your body puts your risk pretty damn close to the general population.

Eight of the papers in the review that looked at celiac patients over time found that patient mortality significantly decreases over even the first year. But three other papers found no effect. What gives? Well, if you include refractory celiac patients, they tend to skew the data towards early mortality. Oddly enough, one paper found that even over a 25 year span, celiac patients tended to die more often of things that aren’t as easy to tie to celiac disease: accidents, suicides and violence.

How about healthy individuals who test positive for celiac antibodies?
Two studies showed that mortality was not increased, a caveat though is that these two studies were done in countries (Finland and the UK) who have the lowest general deaths of diagnosed celiac patients. In two different studies in the US and Germany, they found significantly increased mortality of this population.

How about patients with dermatitis herpetiformis?
Four papers looked at death in this group, two from the UK and two from Finland. Mortality does not appear to be increased in this group.

How about patients with diagnosed celiac disease that does not respond to being on a gluten free diet (refractory celiac disease)?
There are two types, type I and type II, though I don’t really understand the difference between the two. The authors were clear though that Type II is more severe. For type I, the 5 year survival rate is 80-96%, but for type II it is 44-58%. And “The survival rate dropped to 8% in patients with refractory celiac disease type II who developed enteropathy-associated T-cell lymphoma.”

So why don’t we have a clear picture of mortality for compliant celiac patients, undiagnosed celiac patients, and refractory celiac patients?
Part of the problem is the different methods and assumptions of the different groups who did this work. The other problem seems to be the base these patients start at. The authors of this review hypothesize that the amount of gluten consumed prior to diagnosis is indicative of how much problems a celiac patient will have, even after going gluten free. “Indeed, there seems to be a relationship between standard mortality rate and pasta and bread consumption in the six countries where symptomatic celiac disease has been studied.” We know “The quantity of gluten that is sufficient to trigger celiac disease is known to be very small.” But it appears that there might be some sort of lifetime threshold for celiac patients where if they go gluten free before that amount, they will be relatively ‘fine’. But if they either get diagnosed too late, or continue to consume gluten, they are significantly more likely to die earlier of untreated celiac associated disease. The authors have coined it the ‘lymphoma triggering amount of gluten’ and define it as “the sum of gluten ingested before and after the diagnosis of celiac disease.”

For me, this confirms what I’ve thought, and how I’ve started to live my life the past two years or so. When I first went gluten free, I wasn’t incredibly strict, going so far as to eat gluten at weddings (that was my ‘cheat’). But about two years ago I put the pieces together: I am better on a gluten free diet and my dad is a diagnosed celiac. This likely means that I too have celiac disease. Maybe next summer I’ll be in a place where I can get an official diagnosis. It is something I would like to know at some point, it’s simply been a manner of having health insurance at the same time as being in a place to possibly be incapacitated and still be functional.

On being allowed in my head by myself

I love when different areas of my interests overlap. Mental health? Physical health? Science? Check!

An article that came out in last weeks issue of Science, A Wandering Mind Is an Unhappy Mind, really caught my attention. We know quite well that people who exercise are supposedly happier. Something or other about endorphins. I’ve also heard it mentioned often that praying and/or meditating can increase serenity. And if you believe others, you just need more sex to be happier.

The authors of this paper though reach the conclusion that with very few exceptions, it is what we think about that effects how we feel, not what we’re actually doing. At least they say that’s what their data reflects. Using an iphone app (how’s that for a data collection instrument?!?), they asked people at some interval what they were doing, how they felt while doing it and how much their mind was wandering. If you look at their little bubble figure, it is negative mind wandering that correlates with not being happy. But making love and/or exercising are on the flip side, with happier associated scores. So while the authors conclude that happy(ier) (or more neutral) thoughts result in a better score of happiness, I have to disagree a bit. When you look at tasks where you mind can’t wander as well, these tend to be tasks you are fully engaged in, and you tend to be less focus on anything else, happy or not. Like exercising or making love. I would gander that if you spent more time fully engaging your mind (reading, cooking, taking a walk, making love), you wouldn’t have the mental space to mentally wander nearly as much.

But I guess perhaps my bigger issue is that I’m not sure happiness is the end all and be all of life. When I find myself aiming to be happy, it just doesn’t work. If anything, I end up with a wandering (unhappy) mind. So overall, I don’t aim to be happy. I aim to be useful and productive on some level, and achieving that is what puts me in a better state of mind. But maybe that’s just me. I have been known to need a chaperon inside my own head.

Research from New Guinea – nuts and carbs

Two articles have come out recently that I’ve seen mentioned in both the regular news and around the blogging world. As a scientist, when I see ‘popular’ media pieces about things like this, I like to go back to original research article. Often what you see reported is a bastardization of the actual research. These two articles are no different.

Hopefully in the next day or two I’ll get to this one:
Revedin A., B. Aranguren, R. Becattini, L. Longo, E. Marconi, M. M. Lippi, N. Skakun, A. Sinitsyn, E. Spiridonova, and J. Svoboda. 2010. Thirty thousand-year-old evidence of plant food processing. Proceedings of the National Academy of Sciences 1-5.

But today I’d like to discuss this one:
Summerhayes G. R., M. Leavesley, A. Fairbairn, H. Mandui, J. Field, A. Ford, and R. Fullagar. 2010. Human Adaptation and Plant Use in Highland New Guinea 49,000 to 44,000 Years Ago. Science 330:78-81.

It doesn’t appear this article is open access. What this means to those of you in the non-science world is that if you want to read this actual article, you’ll have to do some work to get it. The best some of you may be able to do is read the abstract on the journals page. I might be able to hook people up with the pdf if they are interested.

I’m going to attempt to summarize some of the work discussed in this paper and the conclusions and implications it has.

People colonized New Guinea sometime around 50,000 years ago, likely a bit after that. Evidence is not well preserved from this era making work like this difficult. The earliest sites researchers have found are from around 49-43000 years ago. During this time, the climate would have been much cooler, by about 5-10 degrees Celsius. In the sites examined, old tools and starch grains were found.

First, the tools. One major finding were waisted axes. These tools were likely used to clear plant material to either help sunlight reach growing food bearing plants or other useful plants. On some of the tools found, starch grains were found. Translation: some form of agriculture/farming happened in this region.

A word about grains. This is NOT referring to grains in the common usage. This is a scientific usage referring to how plants store starches/carbohydrates, as small globular grains (think tiny sand like things, inside the plant cell). Most of the grains they found were identified to be in the yam genus. The researchers also found Pandanus nutshells, known for containing nutritious seeds. Two simple pieces of evidence point to these findings coming from human sources. 1. Proximity to charcoal, bone fragments and tools (all human associated). 2. No rodent gnaw marks on the seeds.

Unlike what you may have read in the common media about this being some evidence for grain consumption and ‘Go ahead, eat bread!’, this is NOT the conclusion drawn by the authors. First, they state “The preservation of food plant species in open sites of this age is remarkable, and the analysis confirms that Pandanus and yams were used for subsistence in this valley from the time that the earliest colonists arrived”. This does NOT translate to ‘We ate bread’. It translates to – we ate nutrient dense nuts and complex carbohydrates from yams.

The last paragraph is so interesting to me that I’m just going to copy the entire this here:
“Our data show that people occupied a New Guinea valley at 2000 m above sea level soon after their arrival in Sahul (1). As the climate cooled, the optimal growing conditions for yams would have occurred at lower altitudes. This may indicate that Pandanus was the most important staple at this time and help explain the late Pleistocene abandonment of the highland sites. Foraging into this high-altitude environment would guarantee a high return in plant fat and protein to complement local animal foods, the starch-rich yams from lower altitudes, and those foods not preserved in the archaeological record.”

There are a few things I hope you get out of that last paragraph. The first is that Pandanus was likely a major portion of their diet. They also could only grow yams at lower elevations, so as the climate cooled they had to move further down in elevation. And lastly, yams and Pandanus nuts were PART of their diet. The last part of the last sentence? “… and those foods not preserved in the archaeological record”? That’s really important here. We do know A LOT about our evolution from the archaeological record. But there is a lot we don’t know because not everything preserved well. Think about it. If your people are dying out, is your last thought going to be about preserving your heritage so that future people can study you? No, you’re likely thinking about ways you can help your people survive. If some of your tools and such survive for 50,000, so be it.

What I really want you to get out of this whole article is the simple fact that during this period of human evolution, we ate starch rich foods and nuts. Along with a bunch of other foods. Pretty simple.