Sunday, March 30, 2008

Helicobacter and glucose

Helicobacter is a bad bug. Really bad. So bad that in the recent consensus conferences, like this one, the plan is clear. Hunt, find, kill. Sounds like the cholesterol consensus to me. The only good cholesterol molecule is a dead cholesterol molecule. Oops, getting a bit random there. Back to reality:

"The consensus conference boldly recommended population-based screening and treatment for H. pylori in particularly high-risk population settings"

Anyway, some time around 60,000 years ago humans walked out of Africa in to what is now the Middle East and kept going. Taking their Helicobacter pylori with them. Yes, H pylori has been around the human gut for a long time. There is a nice neat diagram and discussion of human/helicobacter co-expansion on this person's blog. The basic idea is that you can get some idea of the spread of humans by looking at the genes of their H pylori. Presumably the hunter-gatherers were dying like flies from gastric carcinoma along the way.

So, the consensus plan is to eliminate a bug which has been with us on a timescale of up to 100,000 years, and this will stop gastric cancer. Truly a bold recommendation.

If you go back to the early accounts of the missionary hospitals tending to native populations before the introduction of Western lifestyles, cancer was very very very rare. Stefansson summarises it rather well in his 1960 book Cancer: Disease of Civilisation. It's hard to get hold of a copy and rather expensive too, but it makes an interesting read. Cancer searches came back negative. I'm willing to accept that H. pylori wasn't causing cancer in human hunter gatherers, although they were all "infected", if that's the right word for a gastric commensal.

So why does helicobacter cause cancer in humans nowadays? Some light was shed on the problem by the Japanese who noticed that elevated fasting plasma glucose levels are associated with gastric cancer, but only in those patients who carry helicobacter.

Helicobacter is quite a specialised bug. This paper has some interesting snippets. H pylori appears to love glucose. It will do both aerobic and anaerobic metabolism with it, but look at this:

"Under aerobic conditions acetate was the major oxidation product from pyruvate; no evidence was obtained for tricarboxylic acid cycle activity"

H. pylori doesn't appear to use the tricaboxylic acid cycle! Certainly not in this set up. Pyruvate is converted to acetate without acetyl CoA entering the TCA. This looks to me as if fermentation might be producing the bulk of its ATP. In fact if you look further you find that helicobacter does actually run a TCA cycle of sorts, but it runs it in reverse, and it's non cyclical and it runs as a reducing system, non oxidative... I'm not sure how much this set up could do with a fatty acid! I get the impression that glucose might just be the preferred fuel...

Back in the big world there is a mass of anecdotal evidence that LC eating "sorts out" many cases of dyspepsia. I can't find any specific studies since Yudkin's open cross over diet trial detailed in chapter 12 of Pure, White and Deadly, where LC eating worked for many, but not all, dyspepsia patients.

I think it's a reasonable speculation that anything which increases blood glucose might just encourage helicobacter to have a field day and do some cancer generating. Dropping blood glucose might just do the opposite. Actually, maybe just eating the glucose non-stop is a bad idea! Certainly a LC diet might have a better long term outcome for those people currently dependent on ranitidine or omeprazole for control of the extremely unpleasant effects of dyspepsia.

Or of course we could just kill all the Helicobacter pylori in people at risk of gastric cancer, and stop them ever getting infected again. That's the consensus.

Ha ha ha.

Peter

26 comments:

Chainey said...

"H. pylori doesn't appear to use the tricaboxylic acid cycle ... Pyruvate is converted to acetate without acetyl CoA entering the TCA."

And here was I thinking that was just an old wives' tale.

Peter said...

Bin readin' too much Power, Sex, Suicide.

Ooooh, looks like I bought the last copy! Must be selling like hot cakes...

Racy.

Peter

Paul said...

Peter,

I'm picking up bits and pieces about the Optimal Diet as I read this blog, but still missing some big picture stuff. There seems lots of evidence that excess carbohydrate is unhealthy (like this paper), but OD also puts limits on protein intake - correct? Why is that?

Paul.

p.s. You might like Good Germs, Bad Germs by Snyder Sachs if you haven't yet come across it.

migraineur said...

Peter - for those of us who flatter ourselves that we are relatively intelligent but haven't had any biochem beyond what was taught in high school bio (at a good school with a good textbook) - could you recommend a good general biochem book? I work for a textbook publisher and have been thinking of trying to snag one from work, but haven't been able to lay my hands one one. Every time I read an article on your blog like today's, I wish I knew more of the basics.

Peter said...

Hi Paul,

Protein beyond our needs is primarily converted to glucose, slowly, over several hours, but it's still glucose (and some ketones). It's a metabolically complex process, why bother seems to be the answer...

Peter

Peter said...

Hi Migraineur,

I found this one useful

It seems quite expensive at £20ish for a paperback but that's medical texts for you. I've got the 1998 edition which has the added advantage of featuring a motorcycle rather than a car. You might find it less expensively on a second hand search. My one was actually written by Sarah Benyon.

Peter

Chainey said...

"My one was actually written by Sarah Benyon"

My study of low-carb has shattered so many illusions. For instance, I always thought that books were written by one person and then copied thousands of times. But I can testify to Peter's observation that this isn't so, as I've read two books called The Great Cholesterol Con, one by Malcolm Kendrick and one by Anthony Colpo.

The lesson to take away from this is that you can't just grab any old copy of a book at the bookshop.

Actually, this may also explain why reviews are so startlingly divergent on any given title.

Anna said...

"Every time I read an article on your blog like today's, I wish I knew more of the basics."

Phew, so it's not just me. I have my hubby as a biochemistry reference, but he's getting a bit dog-eared with all my questions.

G said...

'dog-eared'... !!

I always feel bad asking Peter too many questions.. I try to ask the most relevant... but turns out the irrelevant get good clarification too!!

I can't find an article... but i'll locate it soon. Peter -- I think you're absolutely right about the carb connection with cancer and of course specifically gastric cancer.
here's two that really emphasize it and there actually is a good epidemiological connection with the introduction of fructose into the American (and I'd assume British diet) and gastric cancer/H.pylori (but I can't find it).
(refined sugar=all carbs to me)
http://www.ncbi.nlm.nih.gov/pubmed/2170250?dopt=Abstract

http://www.ncbi.nlm.nih.gov/pubmed/15033662

man, are you hitting it all on the nail... after all that Power, Sex, Suicide! *ha haaa*

migraineur said...

Thanks for the recommendation, Peter. Interestingly, the book costs just about the same on Amazon's US website - I was sort of expecting it to cost more, because textbooks are outrageously priced in the US. Please don't tell my employer I said that.

G said...

It's not gastric ulcer, the article links carbs to esophageal cancer (which is more deadly)...

http://www.ncbi.nlm.nih.gov/pubmed/17986316

G said...

Less fascinating, but a prospective trial showed symptom improvement of GERD with a VERY low carb diet. It makes me laugh!

http://www.ncbi.nlm.nih.gov/pubmed/16871438

G said...

Also, along the lines of the link you gave for the evolution of man and H.pylori, there is evidence that H.pylori is in fact 'protective' in pts with NERD (non-erosive reflux disease). NERD appears to have neuropsych origins (like IBS, anxiety). I think it's all fish oil, vit D and vit A deficiency...

I had no idea that lard had SOOOO MUCH vitamin D. that makes sense!! Chinese people eat a LOT of lard...

Chainey said...

Not sure if this advances the discussion, but browsing Mike Eades' blog I noticed a post here: Heartburn Cured that reviews and links to a book that supposedly tells the whole story.

Peter said...

I'd buy bacterial overgrowth as a cause, in general bacteria love glucose. Whichever direction they spin their tricarboxylic acid cycle. Just H. pylori is special as doesn't need you on omeprazole to be happy in your stomach.

Peter

G said...

H.pylori is protective (by PREVENTING GERD) in people with NUD. Sorry, error... got my NUDs and NERDs mixed up ;)

NUD is non-ulcer dypepsia -- when H.pylori (if it happens to be there) gets eradicated, then those people end of with BOTH new-onset GERD A-N-D dypepsia!

thanks for the book link!
Peter, thanks for the new entry!!

Bruce K said...

"(refined sugar=all carbs to me)"

Not to me. I think we should take a study at face value. If they used a particular food, we should base our conclusions on that food only. Find other valid studies, if you want to talk in generalities. To equate all carbs with refined sugar is kind of like saying "margarine = butter" or "corn oil = macadamia oil." It just doesn't wash and is totally biased.

Dr. B G said...

Bruce K -- you're totally right -- I oversimplify often. I actually do believe and prescribe the glycemic index and all that jazz.

I actually have a question for you -- you posted once (I forgot where -- I seem to follow you!) about fish oil or excessive something lowering the immune system. Did you mean the oils that DHA+EPA come packed in fish oil capsules? Or did you have some studies that indicated immune depression with certain 'antioxidant's'? I'm really curious! Thanks in advance!

g

Bruce K said...

Check out Ray Peat's articles about fats, oils, lipids, Vitamin E, and things like that. Didn't Stefansson write that the Eskimos had very low immunity when exposed to infectious disease? Perhaps one of the reasons they ate decayed meats was to build their resistance to pathogens. I am convinced that PUFAs in general are immune-suppressive. They are given to transplant patients, to prevent rejection. It's interesting to note one study Peat cites that an organ from animals eating low-PUFA diets isn't rejected even when recipients are not immune-suppressed. So, low PUFA intake not only makes animals more resistant to disease, it stops their tissues from being rejected, when transplanted. This has broad implications for allergies and all kinds of things like that.

Peter said...

Hi Bruce,

I've googled assorted combinations of search terms to find the particular study on rejection you mention, but the volume of hits on Ray Peat's writing is too high to pick it out. It's interesting to know my organs might be more acceptable on a transplant basis.

Peter

Tiger_Lily said...

i take it that the H.pylori commented on is the same H.pylori that causes stomach ulcers as well??

i happen to have my medical records leading up to my dx with diabetes, when i started treatment for diabetes (type 1, with insulin, most likely LADA from the reports in my file before the dx criteria for diabetes was tightened down)

as SOON as i started on insulin, ALL acid reflux, ulcer pain, and general 'stomach problems' abated

completely

anecdotal information of one person, but years ago i put together lowering my bg levels with NO MORE STOMACH problems

Peter said...

Hi Tiger Lily, yes, my assumption is that glucose feeds Helicobacter to allow it to produce ulcers. LC eating is the most effective way of sorting out acid reflux for most people, though gluten and sometimes casein avoidance is also needed by a few...

Peter

rherman said...

With your emphasis on glucose control, I'd be interested in your thoughts on the Indian herb gymnema and whether you think these types of externals are effective at glucose moderation.

Peter said...

Hi rherman,

I tend to think plants hate us. Some of us are herbivores, at least partially. Asking a plant to help us out seems strange when we could just put the sugar in the bin...

Peter

Jack said...

Hi Peter,

What are your thoughts on H Pylori and Active Manuka Honey? 1 year ago, I switched from SAD to LC and developed heartburn and unsettling feelings in my chest. Been checked out by a Doc extensively (a very discouraging rigmarole). After months of battling it, I finaly tried Active Manuka Honey 15+. It seems to help within days. I stopped taking it months ago, and sometimes my heartburn is back. I am well learned from the likes of Stephan Guyenet, Chis Masterjohn, Chris Kresser, Kurt Harris, Mark Sission etc etc. So I eat well. Anyway, do you think the Active Manuka Honey is a worthwhile way to combat H Pylori? Here's a link for some interesting info on it.

AMH

Thanks,
Jack Kronk

Peter said...

Hi Jack,

I think Helicobacter is a normal human commensal and whatever antimicrobial effects come from components of the honey they are hitting other bugs. Bugs matter a great deal, I doubt we know exactly what we are doing when we alter the microbiome...

Peter