Friday, June 11, 2010

The Hypothesis

The Hypothesis

In my travels through life and the internets, I’ve recently had a bunch of people ask me exactly what it is I’m doing, and why I’m doing it. Looking back at my initial explanation post, I realize that it doesn’t really do any scientific justice to my thoroughly unscientific experiment, at least not when it comes to explaining and justifying my course of action through the statement of a hypothesis for testing.

So here‘s the hypothesis:

By eating no starch and no fiber, I will put my Crohn’s Disease into clinical remission by reducing or eliminating the activity of Klebsiella Pneumoniae in my gut.

Ok! But what the hell does that mean? Why do I think this will work? What’s the end game? Let’s start with the most compelling piece of theoretical science, move to the only significant tests of that science, and then on to how (and why) to test it yourself if you have Crohn’s, Ulcerative Colitis or IBD/IBS.

Theory

(In the spirit of credit where credit is due, I must thank AJ for telling me about Ebringer’s work and taking the time to talk to me about the implications. I owe him a great debt of gratitude! AJ is also attempting a low starch diet with success in treating his Crohn’s.)

Alan Ebringer, a professor of Immunology at King’s College, London, lead a research team studying ankylosing spondylitis (AS), which is a condition of auto-immune arthritis of the lower back. They discovered that patients with AS tended to have anti-bodies in their bodies to a ubiquitous bacterium called Klebisella Penumoniae (KP). KP is present in everyone’s intestines, but if everything is working properly your body’s immune system should not be required to control it. In AS patients, something was wrong with the way their guts and immune system were handling this bacteria.

Ebringer and his team eventually developed the following hypothesis. I am probably simplifying this through my ignorance of the full meaning of the terms in the papers, but I think I have the gist correct:

90% of their patients with AS produced the HLA-B27 antigen. KP produces a particular enzyme to break down starch for digestion which happened to partially mimic the structure of the HLA-B27 antigen, as well as the structure of several types of collagen in your body. When you eat a large bolus of starch, not all of it will be digested before your KP has a chance to eat some. The KP will merrily eat and reproduce until the starch is gone, at which point they slowly die back until the next meal.

If you have good gut permeability (that is low gut permeability), and little damage to your intestines from your diet, chances are that the products of bacterial action will never cross the tight junctions in your gut and into your body. If, however, you are at all sensitive to gluten, lectin, or any of the other common allergens in the modern diet, or you have recently suffered trauma to your gut, you may have a compromised gut which will allow minute amounts of KP and KP byproducts to by pass the gut wall. Your body’s immune system will respond like it does to any foreign protein – it will being producing anti-bodies which are coded to attack that protein.

But that’s the catch. If you are HLA-B27 positive, your immune response may be confused and attack not only the foreign proteins, but any protein which mimic them. You are now experiencing an auto-immune response, and in AS patients, this manifests itself as chronic inflammation of the spine and pelvic joints.

Ebringer and his team noticed an association between AS and IBS, so they decided to see how Crohnies fared in terms of KP anti-body counts. They discovered that Crohn’s sufferers also had very elevated KP anti-body activity, but they were predominately HLA-B27 negative. So they went looking and discovered that KP also mimics several kinds of collagen which are helpfully present in your intestinal wall: right where you get the colitis that characterizes Crohn’s! They concluded that people who are HLA-B27 positive have a high propensity to develop AS if they compromise their gut, while people who are HLA-B27 negative would get Crohn’s, Ulcerative Colitis, and the other inflammatory bowel disorders.

Ebringer and company developed what they call the “low-starch diet” and prescribed it to their AS patients. Unfortunately, funding for their research appears to have dried up and Ebringer himself has retired. Presumably someone will be along to pick up this line of inquiry, but until then we’re in limbo in terms of further theoretical advances, at least that I’ve seen. I make no claims to being all knowing and all seeing so maybe I’m pleasantly mistaken and there is a full blown clinical trial going on somewhere!

In the absence of that miracle, however, we are left with no published clinical tests run by Ebringer to establish whether or not the low-starch diet would work for AS or Crohn’s patients. Which leads us to the next question.

Testing

There are two “tests” of this theory available, one strong, one weak. I’ll lead with my low card here.

The Specific Carbohydrate Diet was created by Sidney Haas in the 1920s in an attempt to address celiac, Crohn’s and other digestive disorders. It was fairly successful, but it was supplanted once the actual mechanism behind celiac was discovered. This probably buried Haas in the footnotes of celiac disease and the effectiveness of the diet for Crohn’s was lost until Elaine Gottschall wrote Breaking the Vicious Cycle. Since the book was published, many people suffering from various bowel disorders have reported success if they were very strict in following the dietary recommendations Gottschall laid out.

I call this my weak evidence because anecdotes are not data. There are also a substantial number of people who fail on the SCD – adherents might say that’s because the failures couldn’t stick to the program, a view which I tend to agree with, but which must be taken into account when applying proper skepticism. SCD also lacks a specific mechanism for how it treats the diseases it appears to alleviate, which makes it less useful when one is trying to synthesize disparate sources into an overall hypothesis or worldview. So the SCD is intriguing, but barring clinical trials will remain only intriguing for the mainstream.

For our purposes, the collective anecdote of the SCD community provides a partial test of the hypothesis. The SCD also allows invert sugar (honey) and nuts in the form of nut flours in the diet. I’m somewhat curious about the nut flours, since many nuts appear to have a fair amount of starch in them, and leery of the sugar for other reasons. I wonder if some of the SCD failures have been caused by people falling into the candy cigarettes trap of trying to fake themselves out with “bread” made from walnut flour.

On to the second test of the hypothesis. Wolfgang Lutz was an early low-carbohydrate diet promoter. He practiced in Austria in the 1970s, and wrote a book entitled Leben Ohne Brot, or in English, Life without Bread. The book is fairly standard low-carb fare until the end, where the authors detail how various medical conditions responded to low-carbohydrate diets.

When I hit this part in the book, I started skimming until I hit the gastrointestinal disorder section. That’s when I discovered a truly jaw-dropping graph for any Crohn’s sufferer. If I weren’t suddenly inspired to obey copyright law, I would reproduce the original here, but instead I’ll just describe the results: Lutz claimed an 80% remission rate after six months of nothing more complicated than low carb dieting.

That’s either complete bull or a very powerful, if overly broad, confirmation of the hypothesis. People following Lutz’s diet are allowed 6 “bread units” a day – basically, the amount of carbohydrate in six slices of bread, or 72 grams – and so one can imagine that the diet of the 80% who were successful contained plenty of starch. If so, then the hypothesis would actually be falsified, since the starch and fiber restrictions would be shown to be irrelevant, or at least overly strict. But that information is not forthcoming in the book and I doubt that it would be possible to obtain the food logs of patients from the 70s at this point.

We can’t fully trust the Lutz results because they were not verified via clinical trial. The patient records of a practicing doctor can be considered very powerful arguments in the justification of a trial, but are not themselves as compelling as the results of a well run trial. So again, we must remain skeptical.

Thankfully, we don’t have to leave it at that.

How (and why) to test this yourself

The essence of science is the testing of ideas by experiment. Here we have an eminently testable idea, one you can test in your very own home. You don’t need a particle collider to change your diet and observe the results. Here’s how to run the test:

1) Start eating according to the low-starch diet outlined by Ebringer. This may not be readily available on the internet so I’ll reproduce the basics here:

a. Eliminate grains, sugar, all starchy vegetables and legumes (basically anything that isn’t green and crunchy), fruits and nuts.

b. Replace the eliminated foods with fatty meat and non-starchy vegetables.

Your goal is to completely get rid of all the starch in your diet. All of it – don’t compromise, don’t wimp out, don’t pine away for an ice cream cone and cheat. Your mindset should be that of a boxer stepping into the ring or a marathoner taking the first step in the race – you are in a fight here, a fight where you don’t get to make many mistakes, a fight which quite literally might determine how the rest of your life plays out.

2) Continue this diet strictly for at least six months. Work with your doctor on your medications; most aren’t too happy if you just drop them cold turkey, and if you are on steroid therapy quitting cold turkey can be very dangerous to your health. I’ll say that again: if you are taking predisone or another steroid, do not quit cold turkey!

3) Let us know how it turned out!

Many people respond to the diet proposed with horror. No more cookies? No more cake? No more bread? Are you insane?

My response is simple: no, I’m not insane. You give up all of those things, but you also might get to throw your pills away forever. You get to take your health back forever. Rather than cycling through flare-ups and getting progressively more disquieting reports on your colonoscopies until you eventually end up with a colostomy bag, you can take control of your future and maybe avoid that fate. You can avoid a huge increase in risk of prostate and bowel cancers. You can avoid the late night sessions sitting cramped on the toilet wondering what the hell is going on and when it’s going to end, and the creeping despair inherent in the knowledge that tomorrow you’re going to have to pop several grams of medication just to stay alive.

I can’t promise anyone that this diet will work. I still don’t know if it will work. I can say with certainty that I do not have any symptoms of Crohn’s – I have no pain or diarrhea, I’m gaining rather than losing weight, I feel great – but even if my next colonscopy is so amazing that doctor thinks I lied about the diagnosis I still can’t say with certainty that the diet did it. I’ll probably live my whole life wondering. But at least that life won’t be lived as a slave to a bottle of pills, and maybe, if I’m lucky, enough people will try this diet and diets like it that the mainstream will take notice.

So if you’re still with me at this point, I sincerely hope you give it a shot. By way of offering support, feel free to shoot me an email and ask for help or let me know how things are going. I'm always interested in hearing from people who have tried a dietary approach - whether it worked or it didn't.

Good luck!

May Weights and Measures

Tenth monthly roundup of measured data and analysis.

Data

Since blogger is annoying in how it handles images, I’m going to upload an Excel (2003) spreadsheet. Here’s a link:

http://www.forefrontpb.com/phildiet/Diet%20Records.xls

The "Weekly Graphs" worksheet shows the weekly average of weight and the weekly average combined BM score and quantity. Also added average frequency.

The "Weight Chart Daily Graph" worksheet shows the daily morning weight.

The "BM Score Daily Graph" worksheet shows the daily combined BM score and quantity.

I'm keeping a food log and notes in a written notebook, which for the sake of putting off an annoying task, I will scan and upload when I'm done rather than every month.

Analysis

So may got interesting!

The pain from my mystery steak buffet illness subsided until it was time for the endoscopy. Of course, at that point I was something of a hypochondriac and I was aware of every burp or stomach rumble, but by that point nothing hurt anymore. As I walked into the center I thought, “Great, do I really need this?” Nothing like wasting money on a medical test you don’t need. But I was there and I hadn’t had an endoscopy in years, and ignoring medical conditions has bitten me in the ass repeatedly, so in I went.

The nurse prepping me asked what I was in for. Eventually he found out that I had Crohn’s and said, “Oh I have that too. How do you manage it?” That put me in the awkward situation of trying to explain this great diet that’s working really great except for that whole two day crippling pain episode. I think he was just trying to kill time though, so I didn’t get much of a reaction.

My gastro arrived and started reviewing the results of my blood tests while I was lying on the gurney. My fasting blood glucose was pretty low (73) and he joked that I should eat a piece of bread. Har har. I am somewhat intrigued by the low reading and I’ll probably get around to doing a glucose meter experiment one of these days.

Then they knocked me out. I woke up and the doctor said, “Doesn’t look like anything significant. We took some biopsies, we’ll let you know how they turn out.” Great! Nothing significant. I had just wasted everyone’s time – outstanding.

I went about my life as usual for the next week or so. I started lifting weights again at the end of April, just squatting. I wanted to see if I could break my previous record and didn’t really care about the rest of the lifts. Of course, that’s “not doing the program”, and I wasn’t eating enough, so all in all it was a moderate to severely stupid plan. More on that later.

I got a voicemail from a nurse at the endoscopy center saying, in total, “We got the results of your biopsy and you definitely have GERD. You really need to be on Nexium. Call us if you need a prescription or if you’ve run out.” Since it was a voicemail I couldn’t respond with, “Wait, the doctor said it wasn’t anything serious. What the heck?”

I did a quick research blitz, which lead me to Jonathan Wright, who claims that low stomach acid is the cause of 90% of heartburn cases. I dutifully tried the acid treatment recommendations: take one betaine HCl pill with a meal, see if you “feel a burn”. Keep adding a pill until you either feel a burn or something bad happens, and then back off one pill. As near as I can tell after three tries, the result of taking a stomach acid supplement was nausea and diarrhea. Since I didn’t have visible heartburn symptoms to begin with, I had no way of evaluating its reflux fighting power. Ok, back to square one.

I scheduled an appointment and talked to the gastro. He showed me the biopsy report, which did indeed claim that I had “moderate chronic reflux”. The “chronic” part was surprising, since I hadn’t noticed any reflux or heartburn symptoms at all until that one event. The doc mentioned that some people don’t feel the reflux, and that perhaps I was one of them. He rattled off a few meds I could try, none of which were appealing. He was unimpressed with the acid hypothesis and said that I was too young to have to worry about that. End result: I walked out with a prescription for some drug “if I wanted to try it” and a recommendation for another endoscopy in a year to see how I was doing.

More research. This time I ran across Ricardo de Souza Pereira, a doctor from Brazil who had compared a supplement with a Nexium precursor drug to see which was better at controlling heartburn symptoms. The supplement won hands down. That caught my attention. Dr. Michael Eades (see blog) had apparently come across this before and tried to market it in the US with no success. He’s got a very interesting blog post about that whole process. He also hosts a summary of the study, which helpfully gives the supplement ingredients.

After doing some more research, I discovered that melatonin appears to be the critical ingredient. There’s an anecdote about a woman who was able to control her heartburn with 6mg of melatonin before bedtime. The therapy is founded on the fact that melatonin, often associated only with the pineal gland and sleep, is also secreted by your gastrointestinal tract for unknown reasons. The way it works on hearburn is, in theory:

However, others concluded that the esophagoprotective activity of melatonin against GERD might be related to the inhibitory effect of this indole on gastric acid secretion and due to stimulation of gastrin release, which might attenuate the gastro-esophageal reflux by stimulation of the contractile activity of the lower esophageal sphincter”

A more recent study (quote above) comparing melatonin with omeprazole had some very interesting results. (Sidenote: omeprazole is basically Prilosec, which, when its patent expired, was trivially altered into Nexium, which was then patented again. Gotta keep those patents. So Prilosec is widely used in research as a stand in for prescription heartburn medications.)

The most interesting, and I think important, dichotomy here is the fact that melatonin generated significant increases in LES tone while the omeprazole only created “non-significant” increases. Since reflux is fundamentally a disorder of acid entering the esophagus, melatonin does a better job of treating the fundamentals of the disorder.

In any event, after reading up on that I went to the store and started taking 6mg of melatonin before bed. Again, since I have no obvious heartburn symptoms, this experiment is very difficult to judge. As far as I can tell, the only result has been MUCH deeper sleep. That was a welcome side-effect, since I’m usually the sort of sleeper who will wake up if a mouse farts in the house next door. I’m still looking for studies on the long term effects of melatonin supplementation, but so far I’m happy. We’ll see how it goes.

Since GERD is a clear indication of dietary failure, I went back and reviewed my food choices up until now. My clear reliance on dairy might be a significant contributing factor, but it’s really damn hard to get enough fat without dairy. So I’m not sure if I can give that up as of yet.

I had always been intrigued by the specific carbohydrate diet, which I suppose I am now doing a rather extreme version of, and thought, “Well they eat yogurt. I should see how.” The end result of that line of inquiry was me making homemade yogurt for the first time. It came out pretty watery, but after letting is strain through a cheesecloth for a couple hours it thickened up into some pretty decent (super sour) greek yogurt. I bought a tub of full fat Fage yogurt at the grocery store and my stuff tasted about the same, just a bit more sour. I suspect this was because I fermented mine, or at least tried to ferment mine, for 24 hours, whereas the commercial operations probably only do it for half as long.

If the Klebsiella Pneumoniae connection is true, I really don’t want lactose getting into my large intestine, so I might have to start fermenting my own yogurt from here on out. I need to make some modifications to my system before that’s really a sustainable activity, but it’s actually a pretty simple thing to do.

A final note on weight lifting. It turns out that only working one exercise and not eating a lot of food still results in you stalling. I can’t seem to get 170lbs for 3 sets of 5 on my squat. Since this is a pathetically weak squat for an adult male, I suspect that it just happens to be the weight at which underlying form issues are exposed to the point where I can’t force my way through it. So I guess I’ll be working on form for a while, eating a lot more and doing the damn program.

Ten months down, two to go (holy crap!)