Gluten-free January Participants: Take the Survey!

Matt Lentzner, Janine Jagger and I have designed a survey for participants of Gluten-free January, using the online application StatCrunch. Janine is an epidemiologist who studies healthcare worker safety at the University of Virginia; she has experience designing surveys for data collection so we're glad to have her on board. The survey will allow us to systematically gather and analyze data on the results of Gluten-free January. It will be 100 percent anonymous-- none of your answers will be connected to your identity in any way.

This survey has the potential to be really informative, but it will only work if you respond! The more people who take the survey, the more informative it will be, even if you didn't avoid gluten for a single day. If not very many people respond, it will be highly susceptible to "selection bias", where perhaps the only people who responded are people who improved the most, skewing the results.

Matt will be sending the survey out to everyone on his mailing list. Please complete it, even if you didn't end up avoiding gluten at all! There's no shame in it. The survey has responses built in for people who didn't avoid gluten. Your survey will still be useful!

We have potential data from over 500 people. After we crunch the numbers, I'll share them on the blog.

The Diabetes Epidemic

The CDC just released its latest estimate of diabetes prevalence in the US (1):

Diabetes affects 8.3 percent of Americans of all ages, and 11.3 percent of adults aged 20 and older, according to the National Diabetes Fact Sheet for 2011. About 27 percent of those with diabetes—7 million Americans—do not know they have the disease. Prediabetes affects 35 percent of adults aged 20 and older.

Wow-- this is a massive problem. The prevalence of diabetes has been increasing over time, due to more people developing the disorder, improvements in diabetes care leading to longer survival time, and changes in the way diabetes is diagnosed. Here's a graph I put together based on CDC data, showing the trend of diabetes prevalence (percent) from 1980 to 2008 in different age categories (2):

These data are self-reported, and do not correct for differences in diagnosis methods, so they should be viewed with caution-- but they still serve to illustrate the trend. There was an increase in diabetes incidence that began in the early 1990s. More than 90 percent of cases are type 2 diabetics. Disturbingly, the trend does not show any signs of slowing.

The diabetes epidemic has followed on the heels of the obesity epidemic with 10-20 years of lag time. Excess body fat is the number one risk factor for diabetes*. As far as I can tell, type 2 diabetes is caused by insulin resistance, which is probably due to energy intake exceeding energy needs (overnutrition), causing a state of cellular insulin resistance as a defense mechanism to protect against the damaging effects of too much glucose and fatty acids (3). In addition, type 2 diabetes requires a predisposition that prevents the pancreatic beta cells from keeping up with the greatly increased insulin needs of an insulin resistant person**. Both factors are required, and not all insulin resistant people will develop diabetes as some people's beta cells are able to compensate by hypersecreting insulin.

Why does energy intake exceed energy needs in modern America and in most affluent countries? Why has the typical person's calorie intake increased by 250 calories per day since 1970 (4)? I believe it's because the fat mass "setpoint" has been increased, typically but not always by industrial food. I've been developing some new thoughts on this lately, and potentially new solutions, which I'll reveal when they're ready.


* In other words, it's the best predictor of future diabetes risk.

** Most of the common gene variants (of known function) linked with type 2 diabetes are thought to impact beta cell function (5).

Two Wheat Challenge Ideas from Commenters

Some people have remarked that the blinded challenge method I posted is cumbersome.

Reader "Me" suggested:

You can buy wheat gluten in a grocery store. Why not simply have your friend add some wheat gluten to your normal protein shake.

Reader David suggested:

They sell empty gelatin capsules with carob content to opacify them. Why not fill a few capsules with whole wheat flour, and then a whole bunch with rice starch or other placebo. For two weeks take a set of, say, three capsules every day, with the set of wheat capsules in line to be taken on a random day selected by your friend. This would further reduce the chances that you would see through the blind, and it prevent the risk of not being able to choke the "smoothie" down. It would also keep it to wheat and nothing but wheat (except for the placebo starch).

The reason I chose the method in the last post is that it directly tests wheat in a form that a person would be likely to eat: bread. The limitation of the gluten shake method is that it would miss a sensitivity to components in wheat other than gluten. The limitation of the pill method is that raw flour is difficult to digest, so it would be difficult to extrapolate a sensitivity to cooked flour foods. You might be able to get around that by filling the pills with powdered bread crumbs. Those are two alternative ideas to consider if the one I posted seems too involved.

Blinded Wheat Challenge

Self-experimentation can be an effective way to improve one's health*. One of the problems with diet self-experimentation is that it's difficult to know which changes are the direct result of eating a food, and which are the result of preconceived ideas about a food. For example, are you more likely to notice the fact that you're grumpy after drinking milk if you think milk makes people grumpy? Maybe you're grumpy every other day regardless of diet? Placebo effects and conscious/unconscious bias can lead us to erroneous conclusions.

The beauty of the scientific method is that it offers us effective tools to minimize this kind of bias. This is probably its main advantage over more subjective forms of inquiry**. One of the most effective tools in the scientific method's toolbox is a control. This is a measurement that's used to establish a baseline for comparison with the intervention, which is what you're interested in. Without a control measurement, the intervention measurement is typically meaningless. For example, if we give 100 people pills that cure belly button lint, we have to give a different group placebo (sugar) pills. Only the comparison between drug and placebo groups can tell us if the drug worked, because maybe the changing seasons, regular doctor's visits, or having your belly button examined once a week affects the likelihood of lint.

Another tool is called blinding. This is where the patient, and often the doctor and investigators, don't know which pills are placebo and which are drug. This minimizes bias on the part of the patient, and sometimes the doctor and investigators. If the patient knew he were receiving drug rather than placebo, that could influence the outcome. Likewise, investigators who aren't blinded while they're collecting data can unconsciously (or consciously) influence it.

Back to diet. I want to know if I react to wheat. I've been gluten-free for about a month. But if I eat a slice of bread, how can I be sure I'm not experiencing symptoms because I think I should? How about blinding and a non-gluten control?

Procedure for a Blinded Wheat Challenge

1. Find a friend who can help you.

2. Buy a loaf of wheat bread and a loaf of gluten-free bread.

3. Have your friend choose one of the loaves without telling you which he/she chose.

4. Have your friend take 1-3 slices, blend them with water in a blender until smooth. This is to eliminate differences in consistency that could allow you to determine what you're eating. Don't watch your friend do this-- you might recognize the loaf.

5. Pinch your nose and drink the "bread smoothie" (yum!). This is so that you can't identify the bread by taste. Rinse your mouth with water before releasing your nose. Record how you feel in the next few hours and days.

6. Wait a week. This is called a "washout period". Repeat the experiment with the second loaf, attempting to keep everything else about the experiment as similar as possible.

7. Compare how you felt each time. Have your friend "unblind" you by telling you which bread you ate on each day. If you experienced symptoms during the wheat challenge but not the control challenge, you may be sensitive to wheat.

If you want to take this to the next level of scientific rigor, repeat the procedure several times to see if the result is consistent. The larger the effect, the fewer times you need to repeat it to be confident in the result.


* Although it can also be disastrous. People who get into the most trouble are "extreme thinkers" who have a tendency to take an idea too far, e.g., avoid all animal foods, avoid all carbohydrate, avoid all fat, run two marathons a week, etc.

** More subjective forms of inquiry have their own advantages.

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.

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.