Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity.

Wait, based on some news articles I've read lately, I thought non-celiac wheat sensitives were a bunch of wilting prima donnas intent on eating an annoying hipster diet that excludes wheat, an important nutrient that people have been eating for a really long time or something like that. And since their diet excludes sandwiches and pizza, they must be UnAmerican. 

But in the medical research community, there is growing recognition that non-celiac wheat sensitivity is a real thing that affects quality of life and even mortality risk when it leads to intestinal inflammation. Stephan Guyenet posted about the last promising study.

This new study is very interesting, but highlights some limitations in dealing with problems like this. This study was on patients who already had been through the wringer test-wise and all had

• IBS-like symptoms (Rome II criteria)
• Negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA) IgA antibodies (the common blood tests for celiac)
• Negative duodenal histology (absence of intestinal villous atrophy)- requires a biopsy
• Negative IgE-mediated immuno-allergy tests to wheat (skin prick tests and serum-specii c IgE — RASTs).
• Resolution of the symptoms on gluten-free diet and their reappearance on double-blind placebo controlled wheat challenge, which means neither the person nor the patient knew whether or not they were giving or receiving a placebo

Um, how many people here with IBS have ever been offered this standard of care? Anyone had a doctor who offered to supervise a double-blind placebo controlled wheat challenge? Maybe things are different in Italy. 

Once they were in this study, these patients got more tests including biopsies of the duodenum and colon, HLA genotyping, as well as skin-prick and blood tests. Then these people had to eat a minimum quantity of wheat daily as they were observed. Then they did a regular elimination diet that excluded wheat, cow's milk, eggs, tomato, and chocolate. Then they got to do a fun exciting double-blind placebo controlled wheat challenge again.

Wheat challenge was performed administering a daily dose 13 g of flour, equal to about 20 g of bread. A total of 12 capsules daily were given subdivided in three times daily, away from meals.  DBPC for cow’s milk was performed by administering capsules coded as A or B containing milk proteins (casein from bovine milk, lactoalbumin, lactoglobulin – daily dose 6 g, equal to about 200 ml of cow’s milk) or xylose, respectively. A total of 6 capsules daily were given subdivided in three times daily, away from meals.

Patients used a survey to track their symptoms. They used celiac disease and IBS patients without wheat sensitivities as controls. 

Among those who were wheat sensitive, a high number of them tested positive on the cytomteric basophil activation test, and many also tested positive for serum IgG and IgA AGA tests. Many of these patients suffered from anemia and weight-loss. Biopsies showed eosinophil infiltration of the duodenal and colon mucosa.
, despite not having the type of villous atrophy damage associated with celiac. 

There seemed to be two groups of IBS wheat-sensitive patients- those with wheat sensitivity alone and those with wheat sensitivity AND multiple other sensitivities to cow's milk and other foods. The later group was also more likely to also have other types of allergies (non-food allergies, skin allergies, etc.) and a family history of allergies.

Further studies will have to look more into the mechanism in which wheat causes damage in these patients. The researches propose one mechanism in their conclusion

Obviously, other hypotheses must be considered; experimental  models have demonstrated that gluten sensitization of DQ8 mice increases acetylcholine release by the myenteric plexus and this can lead to consequent in vivo dysmotility ( 27 ). In this model, gluten did not cause villous atrophy, but there was evidence that coexistent triggers, e.g., intestine-damaging drugs or dysbacteriosis, can lead to a more severe intestinal impairment ( 28 ). Clearly, wheat  antigens may also act in a similar manner.

Acetylcholine is responsible for ahem, moving things along, so it might explain why wheat causes diarrhea in some people. 

Also, it is notable that this study used wheat rather than gluten, so it might be other components of wheat like fructans that are responsible for the symptoms. 

The researchers say

the very high frequency of self-reported wheat intolerance, which we observed in our patients, should induce clinicians to pay full attention to patient suggestions

I wonder how long it will take the average doctor to catch on? 

 The internet is full of vegetarian and vegan websites claiming meat is bad because it "rots" in your colon. This is actually a very old idea, tracing back in the United States to neo-puritan vegetarian movements obsessed with the uncleanliness of the colon. According to folks like John Harvey Kellogg, the colon, like the genitalia, was a source of uncleanliness, so it must be bombarded by as much harsh fiber as possible and regular enemas to keep it "clean."

But his philosophy, which seems quite dysfunctional today, was a reaction to another idea that was popular during this time: that the colon was a useless vestigial remnant used to store garbage before clearance. Taken to its extreme, it led to a brief fancy by surgeons like Sir William Arbuthnot Lane to simply just remove the colons of people who suffered from constipation, believing it was nearly useless anyway. Colon removals are still performed today, but mainly in truly serious cases of damage such as severe inflammatory bowel disease.

Kellogg also believed it was a garbage dispenser, but he thought it was very important to keep it as clear and clean as possible, ideally eliminating after every single meal. 

The truth is that the colon is not a garbage dispenser, it is a rich and biodiverse ecosystem in which much of the intestinal microbiota resides. And nature abhors a waste, so if a food makes it into the colon, there will probably be something eager to eat it. I suppose "rot" could be an uncharitable way to view it, as these remnants are degraded by bacteria, producing a variety of harmful, harmless, and beneficial byproducts that can play important roles in human health. If we are going to view things in such a negative light, it's worth thinking about how when you die and your immune system flat-lines forever, this bacteria will be on the front lines for rotting you. But for now, it's our very own internal composting system. 

our colon is more like a composting bin than a trash can

Being a rich, full ecosystem, some bacteria in the colon even feed primarily on the byproducts of other bacteria in the colon, which is known as cross-feeding.

These bacteria will consume basically anything that the small intestine does not absorb. In humans compared to other primates, the small intestine is enlarged and the colon is diminished, indicating that humans evolved to consume more foods that are readily absorbed by the small intestine. In other primates, like the gorilla for example, the small intestine is much smaller and the colon is much much larger. Gorillas, who eat a diet of mainly rough leaves and pith that the small intestine would not be able to absorb, get most of their energy (around 60%) from bacterial degradation to short-chain fatty acids (SCFA) in the colon. 

Humans can also get energy from SCFA, probably as much as 9%, though this data suffers from the fact that most of it comes from Western populations. Recent studies on more diverse populations shows that other groups of people have very different gut bacterial populations, which might allow them to extract more energy from colonic fermentation. Overall, in humans SCFA are less important as an energy source, but retain an important role in controlling inflammation and gut integrity. 

In the opposite circles of the "meat will rot in your colon" crowd, there is the idea that if you remove carbohydrates, particularly complex carbohydrates, from the diet you can avoid some of the more noxious types of fermentation in the colon that may produce flatulence and diarrhea. 

This works for some people, but fails for others, particularly over time. This is a testament to the plucky nature of our microbiome. There are plenty of bacteria in the colon more than eager to chomp on excess dietary iron and amino acids, among many other things which are present on low-carb diets as well. 

This problem can be exacerbated when the small intestine is damaged, allowing nutrients that should be absorbed mainly by the small intestine into the colon. This seems to be a reason that iron supplementation sometimes fails to improve anemia and instead causes gastrointestinal problems. It is also perhaps the mechanism in which heme iron could lead to inflammation that is connected with colon cancer.

Small intestine dysfunction can also be caused by the overgrowth of bacteria that really belong in the large intestine and colon, known as Small Intestine Bacterial Overgrowth (SIBO).

On the other side, there is a worry that low-carb will lead to inflammation due to lowered SCFA production. Lucas Tafur has written that perhaps these studies did not last long enough for the ecosystem to adjust and cross-feed in order to produce SCFA.

There is also a need for more studies on different people from different cultures in order to fully capture the full capacities of the human microbiome. For example, some people have cellulose-degrading bacteria, others do not. In the future, perhaps a scan of individual gut biomes could help people figure out what diet is best for them. 

So yeah, lots of things "rot" in your colon. And that's not a bad thing at all. That's exactly how the colon is supposed to work. It's not supposed to be squeaky clean and scoured with wheat bran, it's supposed to be a jungle. It's controlling the "bad" bacteria and their byproducts, as well as selecting for good bacteria and maintaining the integrity of the gut lining and the "gut brain" (our second brain) that really matters.

If you enjoyed this post, you'd probably like my series on the colon.

 In a weird turn of events, I have had two ancient-Roman inspired meals in the past month. It started when my friends and I decided to have a dinner party inspired by Apicius, an ancient Roman cookbook considered by some to be the first real cookbook. A translation is available for free online.

I procrastinated in planning my recipe and realized pretty quickly that this was not going to be particularly easy, since this book was written well before the Columbian Exchange, which brought Europe the gifts of tomatoes, potatoes, and peppers, which I use often in my normal cooking. I was forced to experiment. I settled on a sausage recipe, but being a procrastinator, I knew I wasn't going to be able to make actual sausage or to smoke anything:

LUCANIAN SAUSAGE [or meat pudding] ARE MADE SIMILAR TO THE ABOVE: CRUSH PEPPER, CUMIN, SAVORY, RUE, PARSLEY, CONDIMENT, LAUREL BERRIES AND BROTH; MIX WITH FINELY CHOPPED [fresh Pork] AND POUND WELL WITH BROTH. TO THIS MIXTURE, BEING RICH, ADD WHOLE PEPPER AND NUTS. WHEN FILLING CASINGS CAREFULLY [70] PUSH THE MEAT THROUGH. HANG SAUSAGE UP TO SMOKE.

I also found it rather hard to find savory, laurel, or rue, so I substituted elements from other recipes. I didn't know what "Condiment" was, but I assumed it had to do with the famous Roman "garum," a type of fish sauce made from fermenting fish guts. When I took Latin in high school, I remember thinking that I couldn't imagine eating something so absolutely disgusting. Little did I know I would fall in love with Southeast Asian cuisine and by 25 I would be putting fish sauce on everything. I didn't have to worry about finding fish sauce, because I already had my lovely Red Boat fish sauce, even if it isn't exactly like garum. 

The annoying thing about making up recipes on the fly is that I never write them down, so when I stumble upon something amazing I have trouble replicating it. This is one of those cases, but I will try to remember. 

I had pork belly already from The Butcher and The Larder. I put some cubes of frozen chicken stock on the bottom of the crock pot, put in the pork belly, poured in some apple cider to cover, and then started spicing. I believe I used black pepper (I was pretending to be a rich Roman), cumin, bay leaves, coriander, a small spoon of honey, and quite a bit of fish sauce and a touch of fig vinegar. I cooked it on low overnight. I like to cool it and then slice it thin so I can brown it in a cast-iron skillet, but I didn't have time. Obviously it crumbled with I tried to slice it, but whatever. I heated up some lard, added more black pepper, cumin, and mustard seeds, and browned the belly until nice and crispy, seasoning it with fish sauce to taste. I then reduced the leftover liquid and cooked some pitted sour cherries in it with more of the fig vinegar. For the final dish, I layered on fresh mint and parsley. It was amazingly delicious. 

Obviously, I didn't take this picture. Thanks Jen Moran Photography!

Someday I hope to replicate this dish again, going from the basic premises I always start with, which are: salty, sweet, and sour. It was obviously a little lazy because pork belly is like my culinary trump card, a dish I have been doing over and over again for several years now, so any variation I do is usually good.

The rest of the dishes at the party also had some similar flavors. 

Thanks Jen Moran Photography!

From the couple who brought us egg baos (who need to do a blog post on it and all their amazing recipes *hint hint*), was an incredibly rice risotto made with pine nuts in the foreground. Saffron-spiced chickpeas were also delicious and I was very surprised at how good the eggs with pickled fish sauce were. Even the dessert made with roast peaches and fish sauce was delicious. There were also lamb ribs, cooked lettuce salad, honey roasted nut tarts, and many other wonderful dishes.

Mussels + tiny delicious mushrooms from chef Iliana were another standout. Thanks Jen Moran Photography!

 So when Chicago Foodies announced a dinner at Balena also inspired by Apicius, a bunch of us signed up for that too, particularly since I had read of chef Chris Pandel's experiments with making his own garum.

The dinner was held in a cool wine-cellar looking lair and the chef announced he had pretty much followed Apicius' recipes as closely as possible, with no refined sugar, salt, or flour. All cooking was done in their wood-fired oven. Garum was to stand in for salt. He said he was trying to do a fairly average middle class meal. The drink pairings were pretty interesting too. One was a gruit beer. Gruit was the main bittering option in ancient beers, before hops became widespread. There has been revived interest in gruit, partially because scientists have discovered that hops are probably far more estrogenic than even soy. Some say that hops are an ancient lust-reducing reformation conspiracy. But the German beer laws that enshrined hops came before the reformation and beer usually doesn't have enough hops to make a difference. Either way, there are several gruits on the craft brew market at this point. I have tried the Fraoch Heather Ale and I think some of Dogfish's "Ancient Ales" series are also gruits. I know I've had the Finnish Sah'Tea, which uses juniper berries.

Another drink was a super concentrated wine with amaro, which was diluted with water, since this is also what was done in Rome too. To drink undiluted wine was barbaric. 

The food was interesting to say the least, but there were definitely some things that looked more delicious than they actually were and the lack of salt was kind of off-putting. The gooey sweetbreads and the onion-filled lamb brain "patina", which was like an omelet, were not my favorite offal dishes and it took some wine to get them down. I like my sweetbreads grilled...with lots of salt. Same for the boiled turnips. Turnips just aren't as good as potatoes anyway.

I was very surprised with how much I liked the boiled honey leeks and raw mackerel, which was very fresh and not fishy like many mackerel dishes. The mushroom cups in garum had a wonderful umami flavor. And you can't go wrong with goat cheese and figs.

stuff quail, the lighting here wasn't good for many pictures.

The next course was stuffed quail, which had an excellent egg-fish sauce topping. I was not thrilled with the mullet in vinegar, which was very fishy. Parts of the boiled pigs head were good, but I did miss the salt. 

For dessert we had sweet sausages stuffed with berries, which were a bit too sweet for me. But the best thing in the meal was definitely the sweet cheese custard with star anise and peaches. 

My dining companions and I all agreed it would be hard to overeat this kind of food. Even though some of the dishes were a bit "Spartan," I respect the chef's choice to not embellish them much to show us what Roman food was probably like. In my own cooking, I was glad I was forced to explore other flavors instead of falling back on tomatoes and peppers. And I really like that the elements of Apician Roman food: organ meats, a variety of meat and seafood, fresh herbs, and fish sauce. 

 I've seen a lot on social media the past week about boycotting Chick-Fil-A because they support organizations that aim to restrict gay rights. This is amusing for me because I grew up in Marietta, Georgia, eating Chick-Fil-A all the time. And I even went to Camp Winshape, which was started by Truett Cathy, Chick-Fil-As founder. Back then I was a fast-food-fried chicken Southern Evangelical. My life has changed since then, but I admit my mouth still waters a little when I think about the Chick-Fil-A fried chicken breakfast biscuit with tater tots. Oh, and the light as air lemon meringue pie. When my family moved north when I was 15, I missed such things sorely and ate at Chick-Fil-A whenever I went back South. But the love affair fell flat when I started cleaning up my diet. I remember I planned on making some exceptions when a Chick-Fil-A opened on the University of Illinois campus. I eagerly devoured my sandwich one bright Illinois morning. And felt absolutely awful for the entire rest of the day. It felt a lot like a hangover. I fell asleep in economics class. I told myself that wouldn't happen again. It wasn't worth it.

But a craving struck when I lived in Sweden. Obviously, it's impossible to get Chick-Fil-A there. So I hit the internet hoping to recreate it in my own kitchen. By then I was a lot more educated about nutrition, so the "top secret" recipe seemed a little horrifying to me. I wasn't about to coat chicken in sugar and flour and fry it in omega-6 garbage peanut oil. Of all the oils to chose, peanut is one of the worst. Extremely high in omega-6, which Americans consume in excessive amounts, it has a more unfavorable fat profile than even canola or soy oil, and is highly allergenic. Omega-6 is also not particularly heat stable and Chick-Fil-A is using it on fried chicken.

 The real recipe also contains a form of MSG called autolyzed yeast extract, making it a super-palatable addictive monster, probably why it still makes my mouth water a decade later. I've written before about how so much meat that Americans eat contains sugar and inflammatory oils. I ended up using almond flour, honey, and lard to make my chicken and it was pretty damn good. But that recipe meant I was never seriously tempted by Chick-Fil-A again. 

Also, god knows where their chicken comes from. I'm pretty sure it's not free-range or even organic. For a company whose ads involve animals pleading to not being eaten, it seems a little sad to think that their meat comes from an industry known for poor animal welfare, as well as community and environmental destruction.

Considering that chickens are excluded from almost all animal welfare legislation, it should be the chickens pleading to be spared. Besides, I'd prefer to not consume arsenic. Or production methods that encourage antibiotic resistance.

So I don't need to boycott Chick-Fil-A for its current stance on gay rights. I already was boycotting it for serving garbage. I mean, nothing says family values like abusing animals, destroying the environment, and addicting people to fast food...right?

It's really disappointing to me to see friends and family members saying they are going to eat Chick-Fil-A to support "family values" and "business freedom." Go to your local farmers market and you will find plenty of farmers with good old-fashioned Christian values. I'm sure Joel Salatin and Cathy would find much to agree on, except Salatin is against using the government to enforce his values while Cathy uses his business to funnel money into groups that lobby the government to shape laws that restrict other people's rights.

As for Chick-Fil-A being a "clean" fast food option, thanks to HACCP (Hazard Analysis & Critical Control Points) plans, food poisoning is pretty rare at any major fast food restaurants. Killing people with acute illness leads to lawsuits, it's perfectly OK to damage their health by serving food linked to chronic long-term health problems.