Sunday, November 1, 2009

Inflammation and Oxidation

Inflammation and oxidation contribute to many, if not most, diseases.

Based on this observation one would suspect that anti-inflammatories and antioxidants should prevent many diseases. Indeed, there is excellent data that anti-inflammatories can help prevent many diseases. However, support for antioxidants is more limited.

First, antioxidants.

There are a number of antioxidants that one must consume (e.g., vitamin E, vitamin C, zinc, and selenium). There is a lot of mileage in making sure that one is not deficient in any of these antioxidants. However, there is decent evidence that, in general, after sufficiency is attained, more is not better.

The body also has a number of in-house antioxidants, known as endogenous antioxidants (e.g., superoxide dismutase, glutathione peroxidase, alpha lipoic acid, catalase and coenzyme Q10). Many external, or exogenous, antioxidants (like the vitamins and minerals mentioned above) are necessary to maintain proper levels of these all-important endogenous antioxidants. Moreover, many exogenous antioxidants also happen to have other biological effects aside from reducing oxidation (e.g., some have anti-inflammatory effects and some are polyphenols with diverse effects)

And, that might very well be all there is to exogenous antioxidants -- they're important, but perhaps not because of their (direct) capacity to reduce oxidation...

And now, inflammation.

Inflammation generally starts with injury (e.g., acid or bile injury in the case of esophagitis). The body responds to an injury by sending lots of blood to the area to address the underlying problem. The body's response is modulated by a cascade of signaling molecules designed to cause the inflammatory reaction.

On a molecular level, the signaling cascade starts with omega 3 and omega 6 fatty-acids. These fatty-acids, made from dietary polyunsaturated fat, are turned into signaling molecules called eicosanoids. Two families of enzymes catalyze fatty acid oxygenation to produce the eicosanoids: (1) cyclooxygenase, or COX, which generates the prostanoids (Cox-2 generates PGE2) and (2) lipoxygensase, or LOX ( 5-LOX generates the leukotrienes).

It turns out (and this is a bit of a simplification) that there are two broad types of prostanoids and leukotrienes: (1) inflammatory prostanoids and leukotrienes and (2) anti-inflammatory prostanoids and leukotrienes. Significantly, omega 6 fatty acids are the precursors to the inflammatory prostanoids and leukotrines while omega 3 fatty acids are the precursors to the anti-inflammatory prostanoids and leukotrines.

Almost all modern people eat way more omega 6 than omega 3 fatty acid (some eating 50 times more). Unfortunately for us, most people for the last 2 million years ate a fairly even ratio. Sounds like trouble...

With such an over-abundance of omega 6 in our tissue, there generally aren't enough omega 3 precursors present to be made into anti-inflammatory signaling molecules. Chronic inflammation, inflammation that outlives its biological purpose, seems to be the result.

Tissue highly unsaturated fat (omega 3 and omega 6) has a two-year half-life on average. That means that it takes two years for your body to replace half this fat in your body. In addition, omega 6 oil is ubiquitous in our food supply (vegetable oils, corn/soy fed animal, nuts & seeds). Thus, replacing all that tissue omega 6 with tissue omega 3s takes a long time and is hard to do. That said, I am currently in the process of doing it because it is the actual cure rather than the band aid.

In the meantime, NSAIDs can help to stop chronic inflammation by inhibiting the Cox-2 enzyme and/or by inhibiting the 5-Lox enzyme (by the way, it might be ideal to inhibit both Cox-2 and 5-Lox at the same time). Turmeric, ginger, green tea, french pine bark, and numerous other natural compounds inhibit both enzymes. In addition, aspirin is a potent inhibitor Cox enzymes and boswellia is a potent inhibitor of 5-Lox.

In the context of the chemoprevention of esophageal cancer in people with Barrett's esophagus, there is very good epidemiological data for aspirin. Indeed, aspirin is currently the subject of a placebo-controlled trial in England, which should produce some preliminary data in 2011. However, aspirin's effect on cancer progression, if any, might be due to mechanisms other than Cox-2 inhibition (as suggested by a trial, albeit a small & short one, in which selective a Cox-2 inhibitor didn't perform so well). For instance, aspirin also promotes cellular adhesion. (I believe that the authors of the U.K. trial also share my suspicions about aspirin as the dose they are using, 300mg, is well in excess of the dose required to effectively inhibit Cox-2, suggesting they are interested in exploring some of the other benefits of aspirin.)

I know this sounds like a broken record, but vitamin D also promotes cellular adhesion, probably better than does aspirin.

Thursday, October 22, 2009

Incomplete Reversal of Barrett's Esophagus

Does ablation of non-dysplastic Barrett's esophagus make sense?

According to one recent study and another ten-year old study, squamous islands, created during the incomplete ablation of Barrett's esophagus, may still be genomically unstable and prone to carcinogenesis.

The creation of squamous islands (i.e., islands of normal esophageal cells in the sea of Barrett's esophagus cells) can occur as a result of prolonged PPI therapy. The simplest hypothesis is that normal squamous cells grow over or grow out from under the Barrett's cells once conditions in the esophagus return to normal due to acid suppression. The potential creation of squamous islands is promoted as one of the successes of PPI therapy.

However, a study way back in 1999 found that these squamous islands possess abnormal biomarkers (e.g., Ki-67, p53 abnormalities) that suggest genomic instability and continued risk for cancer progression. I am not aware of any follow up studies showing that such squamous islands progress to cancer at higher rates than other tissue, and suspect the implications of this finding are not fully understood yet.

Interestingly, the recent study cited above showed that incomplete photodynamic abaltion produces similar results -- abnormal biomarkers, including Ki-67, cyclooxygenase-2 (COX-2), and p53 staining.

The moral of the story is that if you get photodynamic therapy, don't be one of the 30%-50% of people whose doctors do it wrong... The more serious moral of the study, is that it might not be a good idea to get photodynamic ablation unless you already have dysplasia.

I just don't know whether the 1999 finding is a good enough reason to stop PPI therapy. I guess I have some faith that, since this has been known for 10 years, somebody would have noticed if those "lucky" people with squamous islands were dropping dead faster than those without. Perhaps the abnormal biomarkers are just a temporary sign of genomic instability in the good sense -- i.e., caused by the reversion to neo-epithelial cells -- and not a genomic instability that leads to cancer?

In any case, I suspect that eating and supplementing in a manner that promotes genomic stability should help. Vitamin D seems to be one powerful weapon in this fight. There are others that I will discuss in future posts.

Image from here.

Tuesday, October 13, 2009

Pure L-Theanine

As I mentioned in an earlier post, theanine, an amino acid found in green tea, should help reduce reflux by increasing GABA levels in the central nervous system. Because green tea also has caffeine, which inhibits GABA release, I decided to take pure L-theanine, available in pill form, to see if it would help my reflux.

I took 100mg L-theanine about 5 times (when I had reflux) over a period of two weeks. I stopped the experiment early because L-theanine seems to make me anxious and/or give me heart palpitations. It's not supposed to do that at all, so I'm not sure it wasn't just coincidence or imaginary. But, to be safe, no more L-theanine for me. Besides, based on my limited experience with it, I don't think it helped my reflux that much.

I'm going to move away from anti-reflux measures for a little while to focus on some core Barrett's esophagus chemopreventation strategies. I will return to anti-reflux measure after I complete a few more experiments. Stay tuned.

Wednesday, October 7, 2009

Does Reflux Matter?

Most cases of esophageal adenocarcinoma start with Barrett's esophagus and most cases of Barrett's esophagus start with reflux. Does it follow that stopping reflux can halt the cancerous progression of Barrett's esophagus? I'm not so sure.

As you would expect, reflux isn't made up of just acid. It includes partially digested food, bacteria, stomach acid, and bile, among other constituents. And, it seems that both acid and bile reflux play important roles in the development of Barrett's esophagus.

It is not as clear that reflux causes Barrett's esophagus to progress to cancer as it is that reflux causes Barrett's esophagus to develop in the first place. For example, surgical correction of the lower esophageal sphincter doesn't seem to be better than acid suppression at reducing the risk cancer in people with Barrett's esophagus. Likewise, consumption of substances, like alcohol, that increase reflux don't seem to be significantly associated with the progression of Barrett's esophagus to cancer. On the other hand, excessive consumption of alcohol in early-life (presumably before the development of Barrett's esophagus) is strongly associated with having Barrett's esophagus later in life.

One manner in which reflux may contribute to the cancerous progression of Barrett's esophagus is by causing damage to the esophagus that results in chronic inflammation. Acid suppression seems to reduce this chronic inflammation, which is why I take a PPI every day. There are different viewpoints on whether acid suppression is cost-effective chemoprevention for esophageal adenocarcinoma - for example, see this. Having studied both sides of the debate, I suspect it's wise to suppress acid at least enough to control chronic inflammation. Unfortunately, there have been no placebo controlled trials on the efficacy of PPIs for chemoprevention of esophageal adenocarcinoma, so we don't know for sure and are unlikely to know for some time.

Beyond contributing to chronic inflammation, I suspect that reflux plays a relatively minor role in the progression of Barrett's esophagus to cancer. Instead, my guess is that once a person gets Barrett's esophagus, the Barrett's cells that have formed are on march towards cancer that is principally modulated by (i) inflammation, (ii) diminished genetic stability/cellular adhesion, and (iii) poor immune response.

That said, I still worry about reflux for three reasons:

1. Since I only have short segment Barrett's esophagus (about 1 cm), there are still many more cells in the vicinity of my dysfunctional LES that could "go rogue" (i.e., become Barrett's esophagus cells). Since the the chance of progressing to cancer seems to depend, to some extent, of the amount of Barrett's cells one has, I would like to have fewer Barrett's cells if possible.

2. Acid suppression doesn't do much to prevent bile reflux, and bile reflux may contribute to inflammation.

3. There's a chance that reflux is a player (beyond its effect on inflammation) in the progression of esophageal cancer after all.

Tuesday, October 6, 2009

Green Tea; Theanine, Caffeine, and GABA

Among its many health benefits for people with Barrett's esophagus, green tea also seems to reduce reflux by tightening the lower esophageal sphincter. Green tea's effect on reflux is caused by the caffeine and theanine in it, both of which affect the CNS control of the LES. Caffeine decreases the amount of GABA in the Vagus nerve while theanine increases the amount. More GABA in the Vagus nerve produces a tighter LES, and a tighter LES produces less reflux. Since the theanine in green tea has a more potent effect on GABA than caffeine, green tea should, in general, reduce reflux. Indeed, it does just that for me.

Since caffeine undoes some of theanine's good deeds, it might be nice, especially at night, to brew a cup of high-theanine, low-caffeine tea. I know that most of the caffeine is released from tea leaves in the first 30 seconds or so, but I can't find reliable information on the release of theanine from tea leaves. Decaffeinated green tea may offer a solution as it seems that supercritical CO2 decaffeination (a method used for all organic decaf green teas), leaves in most of the theanine. Also, I believe there's more theanine in high quality loose leaf tea than in teabag tea, so I would generally recommend loose leaf teas.

A post on theanine supplements coming soon....

Wednesday, September 23, 2009

Central control of reflux; the Vagus nerve

The body has two safeguards against reflux, the diaphragmatic sphincter and the lower esophageal sphincter. Both are supposed to remain shut unless you swallow, burp, or vomit, but sometimes they malfunction and cause reflux. Typically, there are two kinds of malfunctions: (i) transient lower esophageal sphincter relaxations and (ii) weakness in one or both of the sphincters.

The first type of malfunction, transient lower esophageal sphincter relaxations, is basically a brief (i.e., a couple of seconds long) relaxation of the sphincters. Many things can cause these relaxations, including stomach distention, certain food items, and stress. Transient esophageal relaxations are likely the cause of most cases of GERD.

The second type of malfunction, sphincter weakness, is a more prolonged defect in one or both sphincters. Many things can cause such sphincter weakness, including stomach distention, abdominal pressure (such as from weight lifting or straining to go the bathroom), certain food items, certain medications, irritation of the esophagus, and stress. This type of malfunction seems to result in more serious GERD, especially when lying down at night.

Both types of malfunctions also seem to be under some form of central nervous system control via the Vagus nerve, with the result that reflux may be modulated, to some extent, by tweaking the neurotransmitters and receptors of the Vagus nerve. As I mentioned recently, cisapride seems to tighten esophageal sphincter pressure, likely by increasing the amount of acetlycholine in the Vagus nerve. Unfortunately for cisapride (and many other drugs in its class), it also increases the amount of acetlycholine elsewhere and can lead to some bad side effects (like cardiac arrhythmias).

Transient lower esophageal sphincter relaxations seem to be modulated by wide vareity of neurotranmitters, including GABA, glutamate, nitic oxide, and substance P, Cannabinoids. Melatonin, zinc, cholecystokinin, gastrin, atropine, and opioids may also play a role.

As you can see, there are many potential targets that could affect reflux. I will experiment with a number of substances that I know to affect one or more of these targets and that I consider safe. I am not interested in gambling (especially against the odds), so I am confining myself to only those foods & supplements that have been used well for long periods of time by large numbers of people. Results from these experiments will be the subject of numerous future blog posts.

Anatomical picture above is from here.

Tuesday, September 22, 2009

Swine Flu

In addition to having a regimen for Barrett's esophagus, I also have a regimen for swine flu. So far, not that much is known about prevention of swine flu, so my swine flu regimen is based on extrapolations from other data (i.e., studies about colds & regular flus or the immune system generally) . Nothing below is proven to prevent or cure swine flu and I am not selling anything whatsoever.

The goal is to promote the immune system while inhibiting a cytokine storm. If you have any questions about why I've included a particular item in my swine flu regimen, feel free to ask because I don't plan on explaining the regimen in future blog posts.

Over the past two days, I have conducted a test run for my anti-swine flu regimen. The timing was perfect as I had just started to feel the first effects of my wife’s cold. However, after unleashing the full power of my regimen, I emerged unscathed while she is still slightly sick.

Here's the regimen:
vitamin D 5000IU
vitamin C 6 grams (500mg every half hour)
green tea 5 cups
coconut oil 2 tablespoons
selenium 50 mcgs
zinc 25 mg
resveratrol 250mg
quercetin 200mg
sulforaphane 100mg
vitamin E 30IU
whey 2 tablespoons
glutamine 4500 mg
heavy cream 2 cups
turmeric 400mg
pomegranate extract 2 tablespoons
melatonin 6 mg
cimetidine (tagamet) 800mg (in divided doses)
I also use a neti pot.

Wednesday, September 16, 2009

Oatmeal and Ayurveda

Recently I posted on colonic fermentation induced reflux. If you followed the links, you saw that the idea seems to be that the bacterial fermentation of carb by-products (what's left over after your digestive system absorbs what it can) produces something (maybe just gas, maybe something more complicated) that causes reflux.

One thing I discovered on my own is that if you go very low carb for a while (say 80% fat) and then have a bunch of carbs for lunch one day (oatmeal in my case), you might have a very burpy night. In my case, the experience went well beyond what I would normally expect from oats. So what happened?

I think that some of the good bacteria inside of me (probably the bifido ones) died of starvation during my 4 day long whipping cream binge. Then, when I ate Irish steel cut oats for lunch, the only thing left to ferment them were the more gas-producing bacteria. I guess the moral of the story might be to not eat whipping cream for 4 days straight. Or if you do, take a probiotic while you do it and introduce the carbs back gradually. I'll let you know if that works.

As a side note, after my oatmeal lunch, my reflux was so bad at night that I thought I should try to shut it down. I tried some strong decaf green tea, but that didn't help enough. So, I resorted to ashwaganda, an Indian herbal supplement known as an adaptogen (anti-stress medicine). In addition to promoting sleep, ashwaganda also inhibits acetylcholinesterase, an enzyme that degrades the neurotransmitter acetlycholine. Turns out, more acetycholine around (as a result of disabling that enzyme that degrades it) means less reflux because acetycholine helps to keep the LES closed.

It would be so perfect, but playing around with neurotransmitters makes me a little nervous because not enough is understood at this point. What's good in the short term may be very bad in the long term, especially in this area. Acetylcholinesterase inhibitors may have short term side-effects as well. In particular, acetylcholinesterase inhibitors can contribute to cardiac arrhythmias in some people. Likewise, Cisapride (a drug approved to treat GERD by increasing LES pressure) was pulled from the market over similar fears -- it's not an acetylcholinesterase inhibitor but does increase acetylcholine nonetheless via agony of 5HT4 (serotonin) receptors. So, can ashwaganda also contribute to cardiac arrhythmias? I have no idea, but I would guess it's unlikely as most of these things are dose dependent and I don't think ashwaganda is a particularly potent inhibitor of acetylcholinesterase. Also, people take ashwaganda and it's not known as the drop dead supplement. So, long story short, I took it and slept like a baby, without reflux.

EDIT: I tried Ashwaganda again and do not think it helped my reflux. In addition, it might have given me heart palpitations. Maybe psychological, maybe not. I have had palpitations before, but mostly after a hard night of boozing... The point of the update is to record that my ashwaganda experiment is officially over.

Monday, September 14, 2009

H Pylori

Some people infected with h pylori get reflux. This type of reflux may go away after eradicating the offending infection.

If you have a definitive diagnosis, you might want ask your doctor for a prescription for antibiotics. However, if you want to try a natural remedy before resorting to the harder stuff, there are a number that may help. For example, kombucha tea, apple cider vinegar, manuka honey, and d-limonene all seem to have some natural antibiotic potential against h pylori. Coconut oil, green tea, and suforaphane (found in cruciferous vegetables, especially brocolli sprouts) also seem to help. The problem with these remedies is that h pylori may return after you stop using them (total eradication seems to be difficult to accomplish). That said, I'm not sure I would use some of the more caustic remedies on a long term basis, especially with Barrett's esophagus. (I don't consider green tea, coconut oil, and broccoli sprouts to be caustic).

You might also try to starve off the h pylori by taking a probiotic supplement as the good bacteria may compete for food with h pylori. Also, as discussed in the last post, a low-carb, low-sugar diet will also help (they actually test for h pylori by giving sugar water before measuring for bacteria exhalations). Also, by chewing food very well, you can start the digestion process sooner and absorb more of your food, leaving less to the bacteria. Lastly, you could try not taking sips of water between bites of food (something I used to do). This practice lowers stomach acidity, which is good for h pylori and bad for digestion.

I don't have h pylori so I'm not going to write much about it in future posts. This post was just an information dump for some of what I picked up about h pylori along the way. Many people push kombucha tea, apple cider vinegar, manuka honey, and d-limonene as all-purpose reflux remedies, however, so it is important to recognize that they may have a more limited utility.

One final note, if you do have h pylori in addition to Barrett's esophagus, you should definitely keep up on your endoscopic surveillance because the h pylori puts you at risk for stomach cancer as well.

My reflux does not originate with low stomach acid or H pylori. Rather, it comes from having a weakened diaphram/hiatal hernia. Thus, not everything mentioned on this blog will have applicability to h pylori reflux (though many things will).

The next few posts will be about ways to tighten the lower esophageal sphincter ("LES") and theories for why EAC has increased 500% in the last few decades. As discussed in the last post, a low carb diet is one weapon to combate LES relaxations. There are others.

Bacteria Food and Reflux

If you spend a few minutes on the internet trying to figure out what one with BE should eat, you will likely find a recommendation that you should eat a low fat diet. There are a few reasons why this recommendation is typically made. First, it is thought that high fat meals delay gastric emptying (turns out, high carb meals do too). Second, it is thought that high fat diets result in more bile production (turns out, high carb meals do too). Third, certain kinds of fats may result in more bad bile acids (will do a full post on this soon). Lastly, there is some evidence from epidemiological studies (i.e., the kind of studies that should never be relied upon) that high fat diets are associated with higher rates of esophageal adenocarcinoma.

Before moving on, a quick word about the epidemiological findings. First, these types of studies very often get causality wrong -- for instance, these studies typically also find that high fat/meat/junk-food eaters also die in accidents at higher rates. Nobody thinks that fat causes car crashes, so why assume it causes cancer? These studies provide hypotheses to be checked by more direct methods. If there were valid mechanistic reasons why fat should cause Barrett's esophagus and esophageal cancer, I would be worried. However, the mechanistic reasons discussed above cannot be valid because they also apply to high carbohydrate diets. For example, high carb diets cause more reflux, result in the same amount of bile production, and also delay gastric emptying. So why not focus on carbs?

One idea is that high fat diets worsen the composition of bile acids (i.e., more deoxycholic bile acids). First, I don't think this is the theory behind much of the advice (it's just too esoteric). Second, I would guess that high carb diets do the same thing (though know of no studies on the topic). Lastly, I believe the result depends on what type of fat you're eating. For example, fish oil and coconut oil don't seem to produce more deoxycholic acid while corn oil may. Animal fat may be more risky, but I don't worry for a number of reasons that I will cover in a full post on this topic (coming soon).

Even if these epidemiological studies are detecting something causal in part, perhaps they are just picking up the fact that in a western society, most people who eat high fat diets eat a lot of processed vegetable oils. These bad oils are known to worsen the composition of bile acids (more deoxycholic) and the excess of omega 6 fatty acids found in these bad oils significantly promote inflammation!! Ok, don't eat vegetable oils if you're concerned about the epidemiological studies. I certainly don't, for this and many other reasons. I eat a lot of saturated fat instead. Regarding the effect of a high saturated fat diet on cardiovascular and general health see this, this, and this for a lot of background. From my personal experience, I can tell you that after 6 months on a 70% fat diet (mostly saturated), my HDL went from 41 to 54, my LDL went from 88 to 90, and my triglycerides went from 140 to 62. I also take fish oil and vitamin D daily, which may confound the results to some extent.

What is often ignored, however, is the many ill effects of high-carbohydrate diets. Filling up on sweets, grains, and low-fat yogurt increase bacterial fermentation in the colon. Basically, the bacteria eat what you don't adsorb. Add in a touch of lactose intolerance or fructose malabsorption (problems which many people have without knowing it) and you might end up with irritable bowel syndrome to go along with your Barrett's esophagus. So what's wrong with colonic fermentation from a GERD perspective? It causes it, that's what. High-carb diets over time also open the door to metabolic syndrome, something you don't want, especially if you have Barrett's esophagus.

By eating a very low-carb diet (i.e., meals of all meat or, my favorite, organic heavy whipping cream and whey protein powder), one can prevent GERD, probably by depriving the bacteria of their food. The idea is not to kill the bacteria; after all, the healthy ones protect you from the bad ones. Rather, the idea is to deprive them of the undigested sugars they love to ferment, fermentation which causes you heartburn.

Even though bacteria may play a role in reflux, I still take a probiotic (good bacteria) supplement on most days to make sure the "good" ones are crowding out the "bad" ones. That said, on my diet, I avoid feeding even the good ones very much. To this end, I also avoid prebiotics (polysaccharides that bacteria ferment). People take them to help the probiotics take hold better (by providing food for them). I avoid them completely for the same reason that I generally avoid excess intake of carbohydrates; it is bacteria food that may cause reflux.

This will not be the last post on fat. Indeed some of the concerns listed above, do carry some water with me (though not much). However, even putting the science aside, I just experience less reflux when I eat more fat.

Friday, September 4, 2009

Vitamin D

In the last post, I mentioned placebo controlled trial showing that 1100 IUs of vitamin D3 resulted in a 77% reduction in all-cause cancer over a 3 year observation period. There is also a
mountain of epidemeological evidence that vitamin D protects against cancer (and just about everything else). However, the placebo trial is significant because it is the gold standard of evidence, making it very hard to dismiss or debunk.

However, the study has nonetheless been subject to some criticism. The most potent criticism that I have seen is that the rate of cancer in the control group was higher than government statistics would have suggested for the demographic tested. In response to this cirticism, the study authors noted that their study was randomized and the results had a p value of less than 0.005. The study authors also noted the mountain of epidemiological evidence on their side. I think that's a winning argument. Anyway, even if the government cancer statistic was used, vitamin D supplementation still reduced the rate of cancer by about a half in this study.

Whether vitamin D protects against esophageal adenocarcinoma specifically is unclear. There is a study from Italy finding that it protects against esophageal squamous cell carcinoma (SCCE). On the other hand, in a study conducted in a poor and polluted province in China, where almost everyone studied was actually vitamin D deficient, slightly higher, but still deficient, levels of vitamin D were associated with slightly more SCCE. Between the two study populations, I think the Italian study has more to do with me. Of course, SCCE is a different disease than adenocarcinoma anyway. For these reasons, I don't think the China study is worth worrying about at all.

Also, now there is even a good reason why vitamin D protects us from cancer.

From March through July, I took 2500IUs of vitamin D3 per day in a gel cap and my levels rose to 45 ng/ml. After my test, I increased my D to about 3000IU per day hoping get a tiny bit higher.

Supplement Philosophy

Not many supplements have done well against the placebo. Part of the problem is that there haven't been that many placebo controlled trials of supplements in humans. Another problem is that the supplements that have been tested, likely used incorrect doses or forms. That said, one cannot ignore the failure of E, C, beta carotene/A, selenium/E, and zinc against the placebo.

Also, one cannot ignore the findings of thousands of epidemiological studies finding inverse associations between cancer/other bad health outcomes and intakes of various nutrients. One way to thread the needle between the supplement studies and these nutrient studies would be to eat a healthy, whole food diet that is high in nutrients and take no supplements (aside from vitamin D, as discussed below). This approach can't be too far off the mark and might indeed be the most sensible.

However, this is not my approach. I suspect that the reason most supplement trials have failed is because they tested megadoses (and perhaps in the wrong nutrient forms). In the supplement world, more of something good is not better, after a point. In scientific lingo, this concept is known as the U-shaped dose response curve. My goal is to move myself closer to the sweet spot of the U-curve for those nutrients that are most associated with cancer prevention, specifically esophageal adenocarcinoma. To this end, I take low doses of most of my supplements, doses generally even lower than those found in most multivitamin pills. I also avoid certain nutrients that I think are better obtained solely through food (i.e., because I get enough from the many eggs I eat and because higher amounts have associated with worse health outcomes). I also base my decisions, in part, on the nutritional strengths and weaknesses of my particular diet, which can be determined using the chron-o-meter.

Vitamin D is a special situtation that warrants a separate discussion. I do take megadoses of vitamin D3, about 3000 IU per day or 7.5 x the RDA. We used to get vitamin D from the sun, but now we work inside all day, live in northern polluted cities, and generally avoid the sun. The current RDA is almost definitely too low. For instance, recently, a study showed that 1100 IUs of vitamin D3 per day resulted in a 77% reduction in risk of all cancers. I will discuss this study and vitamin D generally in the next post.

Thursday, September 3, 2009

My Regimen

Before reading on, please be aware that I am not a doctor or a scientist. If you see something below that interests you, I encourage you to do your own research and to consult your doctor.

I have organized my regimen conceptually in accordance with the intent of each intervention. Some of my interventions belong in more than one category.

1. General health and anti-cancer protocol (the interventions I would do even if I didn't have Barrett's esophagus)
Low-carbohydrate, with most fats from dairy, omega 3 eggs, grass-fed beef, and coconut oil and
most carbohydrates from starch (potatoes and rice) or fruits and vegetables. Lots of fruits and vegetables, to drink only water or unsweetened, freshly brewed green tea, served warm (not hot), mostly organic, limited grains, sugar, and vegetable oils (except coconut and some olive), low AGEs (advanced glycation end products), meaning (for now) limited charred meats, many spices in cooking, and limited fructose/lactose.
Supplements. (in low doses, except D3).
Vitamin D3 (3600 IUs per day), vitamin A, folic acid, B-12, zinc, B-6, selenium, magnesium, EGCG, curcumin, fish oil (high EPA), pomegranate/blackcurrant extract, probiotics
Cardio on weekends and strength training during the week (avoiding intense strain that could worsen my hiatal hernia).

2. Healing the esophagus
a. Avoiding additional injury.
(i) Acid suppression. 40mg of Nexium 30 minutes before breakfast.
(ii) Reflux at night. Avoid food & beverage for 3 hours before bedtime. Elevate head of bed by 6 inches.
(iii) Thermal injury. Avoid hot food & beverage. (Ice cubes in tea before drinking.)
b. Mucosal Defense.
(i) Healing time. I avoid my inflammation inhibitors (see below) periodically for short intervals (24-48 hours), especially after experiencing significant reflux. On these occasions, I instead take 6 mg of melatonin 45 minutes before bed (and usually take an additional 1 mg sublingually upon waking during night). I am still investigating melatonin's effect on PGE2 and oxidation.
(ii) Better saliva. I occasionally chew B-Fresh gum (xylitol and calcium) to stimulate saliva and raise its ph. I am currently investigating licorice extract to stimulate PGE2 and mucus (for use on melatonin days).
(iii) Closing the lower esophageal sphincter. I avoid major LES relaxation triggers, which for me seem to include chocolate, hot peppers, peppermint oil, and too much liquid food (e.g., big soups). At night I also avoid minor triggers, which for me seem to include caffeine, alcohol, tomatoes, citrus, garlic, onions, leeks, and asparagus. High fat meals do not increase reflux for me; in fact, after a few days on a high-fat diet, my reflux gets much better. I drink decaf green tea at night to help close the LES. I am currently also investigating various pharmaceuticals/supplements that may help close the LES, including cisapride (pulled from market), ashwaganda, and baclofen/L glutamate.
c. Enhance Bile Composition of Reflux. I attempt to reduce the concentration of deoxycholic bile acid (which might be carcinogenic) with curcumin, fish oil, and probiotics. I am currently investigating ursodeoxycholic acid treatment. Also, I am currently investigating the effect of a high fat diet on bile acid composition.

3. Preventing oxidative injury
a. Exogenous antioxidants
Anthocyanins (wild blueberries, blackcurrant extract), curcumin, EGCG, carotenes (from vegetables), vitamin E (30IU supplement per day), selenium, zinc, and vitamin C (from fruit). I am currently investigating (both for BE and general health) reseveratrol, quercetin, Pycnogenol, and others. In the meantime, I am experimenting with them periodically.
b. Endogenous antioxidants. (The idea is to upregulate the body's natural antioxidants)
Sulforaphane, selenium/vitamin E, whey.
Exercise, short cold/heat shock (hormesis in the shower?).
Curcumin and green tea.
I am currently investigating glisodin, sodzyme, & Extramel and NAC (not sure it does more than whey does more safely).

4. Disrupt chronic inflammation.
Inflammation inhibitors: (i) enteric aspirin (300mg) (ii) curcumin and/or ginger, (iii) 5-Loxin (boswellia), and (iv) Pycnogenol.
I try to get under 2% of my calories from omega 6 fat and to get at least 1-2% of my calories from omega 3 fat (especially EPA).
Vitamin D3.
Green tea.
No gluten.

5. Anti-proliferative/pro-apoptopic/misellaneous anti-cancer
Some acid reflux may actually be anti-proliferative. I think I take care of that at night... :(
Low leptin/IGF levels by eating a low-carb diet.
IP-6/inositol (1.5 grams every other day) on empty stomach.

Tuesday, September 1, 2009


Welcome to Barrett's Blog, a blog about Barrett's esophagus. Although I have no medical or scientific background, I have been interested in health and nutrition for some time. When I found out I had Barrett's esophagus, I become a little obsessed with finding ways to reduce the risk that it progresses to cancer. Thankfully, these days even a lay person can obtain research papers on Google Scholar, access which dramatically increases the returns to being a little obsessed with your own medical conditions.

Based on of my research on Barrett's esophagus and on general health and nutrition, I have developed a personal diet and supplement regimen that I hope will both reduce my risk of esophageal cancer and maximize my overall health.

I will describe my regimen in the next post and will update that post with any changes I make to the regimen in response to new information, with the result that the regimen I describe in the next post will always be more or less current.

The point of this blog is to post articles explaining my reasoning for each aspect of the regimen in the hopes that the process will help me to (i) organize my thoughts, (ii) attract expert critique of my regimen, and (iii) to share my research with you.