Eating Wheat Gluten Causes Symptoms in Some People Who Don't Have Celiac Disease

Irritable bowel syndrome (IBS) is a condition characterized by the frequent occurrence of abdominal pain, diarrhea, constipation, bloating and/or gas. If that sounds like an extremely broad description, that's because it is. The word "syndrome" is medicalese for "we don't know what causes it." IBS seems to be a catch-all for various persistent digestive problems that aren't defined as separate disorders, and it has a very high prevalence: as high as 14 percent of people in the US, although the estimates depend on what diagnostic criteria are used (1). It can be brought on or exacerbated by several different types of stressors, including emotional stress and infection.

Maelán Fontes Villalba at Lund University recently forwarded me an interesting new paper in the American Journal of Gastroenterology (2). Dr. Jessica R. Biesiekierski and colleagues recruited 34 IBS patients who did not have celiac disease, but who felt they had benefited from going gluten-free in their daily lives*. All patients continued on their pre-study gluten-free diet, however, all participants were provided with two slices of gluten-free bread and one gluten-free muffin per day. The investigators added isolated wheat gluten to the bread and muffins of half the study group.

During the six weeks of the intervention, patients receiving the gluten-free food fared considerably better on nearly every symptom of IBS measured. The most striking difference was in tiredness-- the gluten-free group was much less tired on average than the gluten group. Interestingly, they found that a negative reaction to gluten was not necessarily accompanied by the presence of anti-gluten antibodies in the blood, which is a test often used to diagnose gluten sensitivity.

Here's what I take away from this study:

1. Wheat gluten can cause symptoms in susceptible people who do not have celiac disease.
2. A lack of circulating antibodies against gluten does not necessarily indicate a lack of gluten sensitivity.
   
3. People with mysterious digestive problems may want to try avoiding gluten for a while to see if it improves their symptoms**.
4. People with mysterious fatigue may want to try avoiding gluten.
   

A previous study in 1981 showed that feeding volunteers a large dose of gluten every day for 6 weeks caused adverse gastrointestinal effects, including inflammatory changes, in relatives of people with celiac disease, who did not themselves have celiac (3). Together, these two studies are the most solid evidence that gluten can be damaging in people without celiac disease, a topic that has not received much interest in the biomedical research community.

I don't expect everyone to benefit from avoiding gluten. But for those who are really sensitive, it can make a huge difference. Digestive, autoimmune and neurological disorders associate most strongly with gluten sensitivity. Avoiding gluten can be a fruitful thing to try in cases of mysterious chronic illness. We're two-thirds of the way through Gluten-Free January. I've been fastidiously avoiding gluten, as annoying as it's been at times***. Has anyone noticed a change in their health?


* 56% of volunteers carried HLA-DQ2 or DQ8 alleles, which is slightly higher than the general population. Nearly all people with celiac disease carry one of these two alleles. 28% of volunteers were positive for anti-gliadin IgA, which is higher than the general population.

** Some people feel they are reacting to the fructans in wheat, rather than the gluten. If a modest amount of onion causes the same symptoms as eating wheat, then that may be true. If not, then it's probably the gluten.

*** I'm usually about 95% gluten-free anyway. But when I want a real beer, I want one brewed with barley. And when I want Thai food or sushi, I don't worry about a little bit of wheat in the soy sauce. If a friend makes me food with gluten in it, I'll eat it and enjoy it. This month I'm 100% gluten-free though, because I can't in good conscience encourage my blog readership to try it if I'm not doing it myself. At the end of the month, I'm going to do a blinded gluten challenge (with a gluten-free control challenge) to see once and for all if I react to it. Stay tuned for more on that.

Japchae (with soba noodles)

"Got Kimchi?" was the headline a this article on Korean cooking in the September, 2010 issue of Women's Health magazine. And pictured on the first page was Japchae. Described as a word that means "mixture of vegetables", my mouth watered with all the yummy veggies and noodles piled together.

Always looking to cook new kinds of foods using new ingredients, I couldn't wait to give this one a try. I had to visit the Asian market to get the hot pepper paste and enoki mushrooms, but I was able to find all the other ingredients at my local grocery store. In fact, you don't really need the enoki mushrooms, but they are fun. I'm not sure they add much flavor, but they do make this dish look super fancy.

Go ahead and make this one evening and save leftovers for lunch the next day. The flavors combine more and it even tastes great cold!

I did a little research and discovered that this dish is usually made with cellophane noodles but I like that this version is made with soba noodles because they are healthy for you and one of my favorite noodles.

Japache Serves 4 2 Tbsp sesame seeds 3 Tbsp low-sodium soy sauce 1 Tbsp + 1 tsp sugar 2 tsp hot pepper paste (kochujang) 1 Tbsp sesame oil ½ lb soba noodles 2 tsp vegetable oil ½ medium yellow onion, thinly sliced 1 large carrot, cut into matchsticks 3 cloves garlic, minced 3 green onions, thinly sliced 1 red bell pepper, thinly sliced 5 oz baby spinach 3 oz enoki mushrooms, ends trimmed

In a dry skillet, toast sesame seeds over medium heat until golden brown, stirring frequently. Remove from skillet and set aside.

In a small bowl, combine soy sauce, 1 tablespoon sugar, hot pepper paste, and sesame oil; set aside. Prepare noodles according to package directions.

Meanwhile, heat vegetable oil in a wok or large skillet. Add yellow onion and carrot; cook for 4 minutes. Add garlic, green onion, red pepper, spinach, 1 teaspoon sugar, and salt and pepper to taste; cook for 3 minutes. Stir in noodles and sauce; heat for 2 minutes. Serve topped with enoki mushrooms and toasted sesame seeds.

Nutritional information per serving as provided in magazine:
332 cal, 9 g fat (1g sat), 57 g carbs, 889 mg sodium, 4 g fiber, 12 g protein

Does Dietary Saturated Fat Increase Blood Cholesterol? An Informal Review of Observational Studies

The diet-heart hypothesis states three things:

1. Dietary saturated fat increases blood cholesterol
   
2. Elevated blood cholesterol increases the risk of having a heart attack
3. Therefore, dietary saturated fat increases the risk of having a heart attack
   

To evaluate the second contention, investigators have examined the relationship between blood cholesterol and heart attack risk. Many studies including MRFIT have shown that the two are related (1):

The relationship becomes much more complex when you consider lipoprotein subtypes, density and oxidation level, among other factors, but at the very least there is an association between habitual blood cholesterol level and heart attack risk. This is what you would want to see if your hypothesis states that high blood cholesterol causes heart attacks.

Now let's turn to the first contention, the hypothesis that dietary saturated fat increases serum cholesterol. This idea is so deeply ingrained in the scientific literature that many authors don't even bother providing references for it anymore. When references are provided, they nearly always point to the same type of study: short-term controlled diet trials, in which volunteers are fed different fats for 2-13 weeks and their blood cholesterol measured (2)*. These are the studies on which the diet-heart hypothesis was built.

But now we have a problem. Nearly every high-quality (prospective) observational study ever conducted found that saturated fat intake is not associated with heart attack risk (3). So if saturated fat increases blood cholesterol, and higher blood cholesterol is associated with an increased risk of having a heart attack, then why don't people who eat more saturated fat have more heart attacks?

I'll begin to answer that question with another question: why do researchers almost never cite observational studies to support the idea that dietary saturated fat increases blood cholesterol? Surely if the hypothesis is correct, then people who habitually eat a lot of saturated fat should have high cholesterol, right? One reason may be that in most instances, when researchers have looked for a relationship between saturated fat intake and blood cholesterol, they haven't found one. Those findings have essentially been ignored, but let's have a look...

The Studies

It's difficult to do a complete accounting of these studies, but I've done my best to round them up. I can't claim this post is comprehensive, but I doubt I missed very many, and I certainly didn't exclude any that I came across. If you know of any I missed, please add them to the comments.

The earliest and perhaps most interesting study I found was published in the British Medical Journal in 1963 and is titled "Diet and Plasma Cholesterol in 99 Bank Men" (4). Investigators asked volunteers to weigh all food consumed at home for 1-2 weeks, and describe in detail all food consumed away from home. Compliance was good. This dietary accounting method was much more thorough than in most observational studies today**. Animal fat intake ranged from 55 to 173 grams per day, and blood cholesterol ranged from 154 to 324 mg/dL, yet there was no relationship whatsoever between the two. I'm looking at a graph of animal fat intake vs. blood cholesterol as I write this, and it looks like someone shot it with a shotgun at 50 yards. They twisted the data every which way, but were never able to squeeze even a hint of an association out of it:

Making the most out of the data in other ways- for example, by analysis of the men very stable in their diets, or in whom weighing of food intake was maximal, or where blood was taken close to the diet [measurement]- did not increase the correlation. Because the correlation coefficient is almost as often negative as positive, moreover, what is being discussed mostly is the absence of association, not merely association that is unexpectedly small.

The next study to discuss is the 1976 Tecumseh study (5). This was a large cardiovascular observational study conducted in Tecumseh, Michigan, which is often used as the basis for comparison for other cardiovascular studies in the literature. Using the 24 hour dietary recall method, including an analysis of saturated fat, the investigators found that:

Cholesterol and triglyceride levels were unrelated to quality, quantity, or proportions of fat, carbohydrate or protein consumed in the 24-hr recall period.

They also noted that the result was consistent with what had been reported in other previously published studies, including the Evans county study (6), the massive Israel Ischemic Heart Disease Study (7) and the Framingham study. One of the longest-running, most comprehensive and most highly cited observational studies, the Framingham study was organized by Harvard investigators and continues to this day. When investigators analyzed the relationship between saturated fat intake, serum cholesterol and heart attack risk, they were so disappointed that they never formally published the results. We know from multiple sources that they found no significant relationship between saturated fat intake and blood cholesterol or heart attack risk***.

The next study is the Bogalusa Heart Study, published in 1978, which studied the diet and health of 10 year old American children (8). This study found an association by one statistical method, and none by a second method****. They found that the dietary factors they analyzed explained no more than 4% of the variation in blood cholesterol. Overall, I think this study lends little or no support to the hypothesis.

Next is the Western Electric study, published in 1981 (9). This study found an association between saturated fat intake and blood cholesterol in middle-aged men in Chicago. However, the correlation was small, and there was no association between saturated fat intake and heart attack deaths. They cited two other studies that found an association between dietary saturated fat and blood cholesterol (and did not cite any of the numerous studies that found no association). One was a very small study conducted in young men doing research in Antarctica, which did not measure saturated fat but found an association between total fat intake and blood cholesterol (10). The other studied Japanese (Nagasaki and Hiroshima) and Japanese Americans in Japan, Hawai'i and California respectively (11).

This study requires some discussion. Published in 1973, it found a correlation between saturated fat intake and blood cholesterol in Japan, Hawai'i but not in California. The strongest association was in Japan, where going from 5 to 75 g/day of saturated fat (a 15-fold change!) was associated with an increase in blood cholesterol from about 175 to 200 mg/dL. However, I don't think this study offers much support to the hypothesis upon closer examination. Food intake in Japan was collected by 24-hour recall in 1965-1967, when the diet was mostly white rice in some areas. The lower limit of saturated fat intake in Japan was 5g/day, 1/12th what was typically eaten in Hawai'i and California, and the Japanese average was 16g, with most people falling below 10g. That is an extraordinarily low saturated fat intake. I think a significant portion of the Japanese in this study, living in the war-ravaged cities of Nagasaki and Hiroshima, were over-reliant on white rice and perhaps bordering on malnourishment.

In Japanese-Americans living in Hawai'i, over a range of saturated fat intakes between 5 and 110 g/day, cholesterol went from 210 to 220 mg/dL. That was statistically significant but it's not exactly knocking my socks off, considering it's a 22-fold change in saturated fat intake. In California, going from 15 to 110 g/day of saturated fat (7.3-fold change) was not associated with a change in blood cholesterol. Blood cholesterol was 20-30 mg/dL lower in Japan than in Hawai'i or California at any given level of saturated fat intake (e.g., Japanese eating 30g per day vs. Hawai'ians eating 30g per day). I think it's probable that saturated fat is not the relevant factor here, or at least it's being trumped by other factors. An equally plausible explanation is that people in the very low range of saturated fat intake are the rural poor who eat an impoverished diet that differs in many ways from the diets at the upper end of the range.

The most recent study was the Health Professional Follow-up study, published in 1996 (12). This was a massive, well funded study that found no hint of a relationship between saturated fat intake and blood cholesterol.

Conclusion

Of all the studies I came across, only the Western Electric study found a clear association between habitual saturated fat intake and blood cholesterol, and even that association was weak. The Bogalusa Heart study and the Japanese study provided inconsistent evidence for a weak association. The other studies I cited, including the bank workers' study, the Tecumseh study, the Evans county study, the Israel Ischemic Heart study, the Framingham study and the Health Professionals Follow-up study, found no association between the two factors.

Overall, the literature does not offer much support for the idea that long term saturated fat intake has a significant effect on the concentration of blood cholesterol. If it's a factor at all, it must be rather weak, which is consistent with what has been observed in multiple non-human species (13). I think it's likely that the diet-heart hypothesis rests in part on an over-interpretation of short-term controlled feeding studies. I'd like to see a more open discussion of this in the scientific literature. In any case, these controlled studies have typically shown that saturated fat increases both LDL and HDL, so even if saturated fat did have a small long-term effect on blood cholesterol, as hinted at by some of the observational studies, its effect on heart attack risk would still be difficult to predict.

The Diet-heart Hypothesis: Stuck at the Starting Gate
Animal Models of Atherosclerosis: LDL


* As a side note, many of these studies were of poor quality, and were designed in ways that artificially inflated the effects of saturated fat on blood lipids. For example, using a run-in period high in linoleic acid, or comparing a saturated fat-rich diet to a linoleic acid-rich diet, and attributing the differences in blood cholesterol to the saturated fat. Some of them used hydrogenated seed oils as the saturated fat. Although not always consistent, I do think that overall these studies support the idea that saturated fat does have a modest ability to increase blood cholesterol in the short term.

** Although I would love to hear comments from anyone who has done controlled diet trials. I'm sure this method had flaws, as it was applied in the 1960s.

*** Reference cited in the Tecumseh paper: Kannel, W et al. The Framingham Study. An epidemiological Investigation of Cardiovascular Diseases. Section 24: The Framingham Diet Study: Diet and the Regulation of Serum Cholesterol. US Government Printing Office, 1970.

**** Table 5 shows that the Pearson correlation coefficient for saturated fat intake vs. blood cholesterol is not significant; table 6 shows that children in the two highest tertiles of blood cholesterol have a significantly higher intake of saturated fat, unsaturated fat, total fat and sodium than the lowest tertile. The relationship between saturated fat and blood cholesterol shows no evidence of dose-dependence (cholesterol tertiles= 15.6g, 18.4g, 18.5g saturated fat). The investigators made no effort to adjust for confounding variables.

Dr. Fat

A blog reader recently made me a Wordle from Whole Health Source. A Wordle is a graphical representation of a text, where the size of each word represents how often it appears. Click on the image for a larger version.

Apparently, the two most common words on this blog are "Dr" and "fat." It occurred to me that Dr. Fat would be a great nom de plume.

Paleolithic Diet Clinical Trials, Part V

Dr. Staffan Lindeberg's group has published a new paleolithic diet paper in the journal Nutrition and Metabolism, titled "A Paleolithic Diet is More Satiating per Calorie than a Mediterranean-like Diet in Individuals with Ischemic Heart Disease" (1).

The data in this paper are from the same intervention as his group's 2007 paper in Diabetologia (2). To review the results of this paper, 12 weeks of a Paleolithic-style diet caused impressive fat loss and improvement in glucose tolerance, compared to 12 weeks of a Mediterranean-style diet, in volunteers with pre-diabetes or diabetes and ischemic heart disease. Participants who started off with diabetes ended up without it. A Paleolithic diet excludes grains, dairy, legumes and any other category of food that was not a major human food source prior to agriculture. I commented on this study a while back (3, 4).

One of the most intriguing findings in his 2007 study was the low calorie intake of the Paleolithic group. Despite receiving no instruction to reduce calorie intake, the Paleolithic group only ate 1,388 calories per day, compared to 1,823 calories per day for the Mediterranean group*. That's a remarkably low ad libitum calorie intake in the former (and a fairly low intake in the latter as well).

With such a low calorie intake over 12 weeks, you might think the Paleolithic group was starving. Fortunately, the authors had the foresight to measure satiety, or fullness, in both groups during the intervention. They found that satiety was almost identical in the two groups, despite the 24% lower calorie intake of the Paleolithic group. In other words, the Paleolithic group was just as full as the Mediterranean group, despite a considerably lower intake of calories. This implies to me that the body fat "set point" decreased, allowing a reduced calorie intake while body fat stores were burned to make up the calorie deficit. I suspect it also decreased somewhat in the Mediterranean group, although we can't know for sure because we don't have baseline satiety data for comparison.

There are a few possible explanations for this result. The first is that the Paleolithic group was eating more protein, a highly satiating macronutrient. However, given the fact that absolute protein intake was scarcely different between groups, I think this is unlikely to explain the reduced calorie intake.

A second possibility is that certain potentially damaging Neolithic foods (e.g., wheat and refined sugar) interfere with leptin signaling**, and removing them lowers fat mass by allowing leptin to function correctly. Dr. Lindeberg and colleagues authored a hypothesis paper on this topic in 2005 (5).

A third possibility is that a major dietary change of any kind lowers the body fat setpoint and reduces calorie intake for a certain period of time. In support of this hypothesis, both low-carbohydrate and low-fat diet trials show that overweight people spontaneously eat fewer calories when instructed to modify their diets in either direction (6, 7). More extreme changes may cause a larger decrease in calorie intake and fat mass, as evidenced by the results of low-fat vegan diet trials (8, 9). Chris Voigt's potato diet also falls into this category (10, 11). I think there may be something about changing food-related sensory cues that alters the defended level of fat mass. A similar idea is the basis of Seth Roberts' book The Shangri-La Diet.

If I had to guess, I would think the second and third possibilities contributed to the finding that Paleolithic dieters lost more fat without feeling hungry over the 12 week diet period.


*Intakes were determined using 4-day weighed food records.

**Leptin is a hormone produced by body fat that reduces food intake and increases energy expenditure by acting in the brain. The more fat a person carries, the more leptin they produce, and hypothetically this should keep body fat in a narrow window by this form of "negative feedback". Clearly, that's not the whole story, otherwise obesity wouldn't exist. A leading hypothesis is that resistance to the hormone leptin causes this feedback loop to defend a higher level of fat mass.

A Gluten-free January

Are You Gluten Sensitive?

Many people are totally unaware of the fact that they react poorly to gluten. Because they've been eating wheat, barley and/or rye products every day for virtually their entire lives, they don't know what their bodies feel like without gluten. In susceptible people, eating gluten is linked to a dizzying array of health problems that stem from an immune reaction to gliadins and other proteins in gluten (1). Are you a susceptible person? How do you know?

The gold standard way to detect a gluten sensitivity is to do a gluten "challenge" after a period of avoidance and see how you feel. People who react poorly to gluten may feel better after a period of avoidance. After a gluten challenge, symptoms can range from digestive upset, to skin symptoms, to fatigue or irritability within minutes to days of the gluten challenge.

With 2011 approaching, why not make your new year's resolution to go gluten-free for a month? A man named Matt Lentzner e-mailed me this week to ask if I would help with his (non-commercial) project, "A Gluten-free January". I said I'd be delighted. Although I don't typically eat much gluten, this January I'm going 100% gluten-free. Are you on board? Read on.

A Message from Matt Lentzner

Hi There.

My name is Matt Lentzner. I'm just some guy who lifts weights on his patio and tries to eat healthy. That's not important, but I have an idea that just might be.

I am trying to get as many people as possible to go gluten-free for one month - this January 2011.

I've considered this whole ancestral diet thing and I've come to a conclusion. If you could only do just one thing to improve your health then not eating gluten would be it. This is not to say that avoiding other nasty things like fructose or industrial vegetable oil is not important. They are, but you'd get the most bang for your buck from not eating gluten.

"Eat No Gluten" is simple and easy to remember. I think that sometimes the rules get so complicated and overwhelming and people just give up on it. We're keeping it simple here. Even at this simplified level I see that it's difficult for a lot of folks. I think people, Americans especially, tend not to pay much attention to what they're eating - what it is, where it came from, etc.

Getting people to get out of their eating ruts and think a little about what goes into their mouths is a valuable exercise. It sets the stage for better choices in the future. I hope that some success with the simple step will encourage people to further improve their diets.

I have a website at www.glutenfreejan.com. If you want to sign up just send an email with your first name, last initial, and town of residence to glutenfreejan@gmail.com. If you are on Facebook there's a community you can 'Like' called: Gluten Free January. So far I have over 120 people all over the world signed up. If you are already gluten-free then I still want you to sign up - the more the merrier. You can also use this opportunity to spread the word and sign up your family and friends.

Merry Christmas - Looking forward to a gluten-free New Year.

Matt

Sausage and Broccoli Rabe Stoup

I recently decided to give Rachael Ray's new show Rachael Ray's Week in a Day a try. And I confess, I love it! I do like to spend an afternoon cooking and end up with a bunch of stuff I can pick on during the week. But for me it's more about lunches and breakfasts than having dinner prepared in advance. Regardless, I was excited about a bunch of recipes she features.

I have made "stoup" before and love the concept. It's Rachael Ray's cute way of naming a chunky soup - like a cross between a soup and a stew. And I loving making things like this on the weekend, when the house can smell all good while it's cooking, and then taking it for lunch. In addition, this uses broccoli raab which is something I've been trying to eat more of (dark green leafy veggies).

All the flavors come together great in this dish. And in fact, it's a bit spicy! If you are sensitive to heat you may want to cut down on the chili pepper. But for me, it made it even better.

Sausage and Broccoli Rabe Stoup
4 servings

Salt
1 large bundle broccoli rabe, 1 1/4 to 1 1/2 pounds
1 tablespoon extra-virgin olive oil
1 1/4 to 1 1/2 pounds bulk Italian sweet or hot sausage
1 onion, chopped
3 to 4 cloves garlic, finely chopped or very thinly sliced
1 red chile pepper, very thinly sliced
2 tablespoons chopped fresh thyme leaves
1 tablespoon lemon zest
A few grates nutmeg
6 cups chicken stock-in-a-box
2 cups water
About 3/4 cup orecchietti pasta
Grated pecorino or Parmigiano-Reggiano, for topping
Crusty bread, such as ciabatta

In a medium pot, bring a few inches of water to a boil over medium heat, then salt the water. Trim the broccoli rabe and cut it into 1 1/2 to 2-inch lengths. Simmer in boiling water to reduce the bitterness, about 4 to 5 minutes, then cold shock in ice water and drain very well.

Heat a Dutch oven or large soup pot over medium-high heat with extra-virgin olive oil, a turn of the pan. Add the sausage and brown and crumble, 7 to 8 minutes. Add the onions, garlic and chile and cook a few minutes more. Add the thyme and lemon zest, then add broccoli rabe and season with a little nutmeg. Stir in the stock and the water and bring to a boil. Simmer a few minutes to combine the flavors. Turn off the heat, cool and store for a make-ahead meal. Reheat the stoup over low heat and bring to a low boil. Add the pasta and cook to al dente, about 10 minutes. Ladle the stoup in shallow bowls and garnish with cheese. Serve with crusty bread for mopping.

Note: For a milder version, use only 3 tablespoons of chili powder and ½ teaspoon cayenne.




See more hearty recipes for Souper (Soup, Salad & Sammies) Sundays hosted weekly by Kahakai Kitchen.