Sunday, October 12, 2008

HLA-B27 and Ebringer

This review [EDIT: the review has gone pay only and the abstract is yet to arrive on pubmed so I'll link to this when I can] was forwarded to me off blog and makes some very interesting reading. It's also a great excuse to post this picture:



Now, this might look like a plastic sausage in a plastic bun, forming a plastic hot dog, all from my son's toy cooking set, but to an immunologist (my wife) it's obviously an MHC molecule presenting a peptide. The sausage is the peptide, it's not to scale! The primary function of MHC class I molecules is to signal to the immune system that something is very wrong inside the cell, something represented by the peptide fragment, and the organism would be better off without that particular cell. Usually immune cells with a CD8 receptor get in and do the killing when MHC class I molecules present peptide.

The paper links a broad array of arthritic conditions to gut inflammation, much of which is subclinical (ie the person has arthritis and gut problems but considers their state of gut dysfunction to be "normal") and spends rather a lot of time discussing the role of HLA-B27 in this process. HLA-B27 is one of those buns, an MHC class I molecule. Your genetics determine whether you carry this particular MHC bun/molecule or not. The identity of the sausage is skirted around in the paper and never mentioned, except it is considered to be derived from the gut bacteria. The rat model used to prove this has to have the human HLA-B27 gene inserted. Err, but not just one or two copies the way HLA-B27 occurs in humans. More like 55 copies! You have to wonder about the cause of some of the problems these rats develop (clogged endoplasmic reticulum for a start) and how typical of the human condition they are!

To summarise the paper: there's something in common between gut and joint problems. We don't know what. But the answer will lie in tinkering with the immune system (an aside, does anybody remember Northwick Park? TGN1412 was looking to cure problems like ankylosing sponylitis, something of a high risk stratagem it seems).

I had a look through the references and the main citations, especially about HLA-B27, are by Mielants, who looks to be the group leader of Jacques and Elewaut (review authors). Nothing wrong with citing your boss. Mielants is also an author on the recent consensus report on evidence based management of ankylosing spondylitis, an Opinion Leader.

Jacques and Elewaut didn't mention Ebringer. Who is Ebringer? If you go to pubmed and search on "Ebringer" "HLA B27" you will get the idea of the size of the hole in the Nature paper. Ebringer's first HLA-B27/AS paper was published in 1980. Jacques and Elewaut must know this.

But Ebringer is a maverick, as far as I can see. He is the main proponent for the role of klebsiella pneumoniae, a gut bacterium, as the origin of the peptide in the HLA-B27 bun. There are a number of groups who have worked with him on this, but I suspect Mielants and his group represent the mainstream view. I've yet to see personal exchanges of the type seen between Nottingham neurologists and Sheffield neurologists, but Ebringer is not going to get a mention in a conventional review. He just doesn't get rated.

This is a pity.

Carol Sinclair wrote a book based on Ebringer's work. The book is not perfect but it will get remission of GI and arthritic problems for a lot of AS/IBS sufferers. In it she recounts the anecdote she heard from Ebringer, about how he found the dietary treatment for AS. The episode has a lot in common with my own experience.

Ebringer was managing a patient with AS using conventional drugs. The patient wanted to loose weight. Ebringer gave him advice derived from the low carbohydrate approach (shows how dodgy he is!), possibly influenced by Yudkin who was London based around the time that Ebringer would have been coming through medical school (I'm guessing the dates). The patient went LC and his AS went in to remission. The standard medical approach to this sort of phenomenon is to ignore it (prime example was my relative handing her beta blockers back to her cardiologist, he was uninterested). Ebringer didn't do this. He went on to fix more people using the LC diet approach, modified to a low starch approach.

Why low starch? The whole situation relating to HLA-B27, klebsiella and AS is horribly complex, but at the core is the enzyme pullulonase, which provides the peptide sausage which fits the HLA-B27 bun. I've been trying to find exactly which sugar triplet pullulonase degrades and it's not clear from Wiki. What is clear is that the triplet is present in starch and the enzyme pullulonase is produced whenever klebsiella meets starch. The enzyme is surface mounted on the bacterium and is in an ideal position to be seen by the immune system. If an HLA-B27 carrying white blood cell kills a klebsiella microbe it will easily produce the short peptide from pullulonase which fits the HLA-B27 molecule on its surface. That signals to both the innate and the adaptive immune systems to become active and (a) attack and (b) make antibodies against the peptide fragment. It's a bit unfortunate that the antibodies made against pullulanase, presented by HLA-B27, also fit the collagen around your spine, knees and often fingers. This labels the collagen as foreign, as well as doing a few other things. Result: ankylosing spondylitis, plus gut problems from the local damage.

I get the impression that neither Mielants, Jacques nor Elewaut believe a word of this. That's tough, as the Ebringer/Sinclair diet works pretty well. I used to have a moderate osteopath/chiropracter habit, just a few hundred pounds a year. When I went to Atkins induction I eliminated all starches, essentially by accident. My back pain simply disappeared. I had my first episode of neck pain at about 12 years of age and started with low back pain at about 20 years of age. It persisted through to Atkins induction at 46ish. It fluctuated quite a bit and the sciatica was thankfully very intermittent.

I have learned many of those tricks needed to get dressed without bending your spine. You know, sitting down to get you underpants around both ankles, then using one foot to pull them up to the knees, where you could just about reach them to pull them the rest of the way up. Easy really. You just do it.

Suddenly it all stopped with LC eating. I remember sitting in my car and turning around in the seat to reverse out of the drive, a few yards down the road and then in to a small side road, an "S" shaped reversing maneuver (a necessity of the road layout). Now I could do it, every day, easily, with no neck or lumbar pain. A joy! I used to sit there on the drive and grin at the thought I could turn around and look out of the back windscreen.

So, personally, I have a lot of time for Ebringer. How wacky is he, that the rest of rheumatology would rather not mention him?

This wacky: Does anybody remember Bovine Spongiform Encephalopathy, known as BSE or Mad Cow Disease? This paper shows how Ebringer views the disease. It does not make him popular. Frankly I'm amazed he got it published.

This is the Royal Society for the Promotion of Health. It looks quite respectable to me. The society makes various awards for outstanding work. Ebringer got the 2004 RSPH Gold Medal. From the [original] website:

"This medal is awarded for any major innovation or development which has significantly improved or promises to improve the quality and dignity of human life"

Ebringer got it for his work on BSE. This is the text of Ebringer's acceptance speech and these are the implications of his point of view as regards BSE, taken from that pdf:

[EDIT here's the full text as the RSPH website revamp deleted it]

(1) Consumption of meat is safe and has always been safe.
(2) Culling of cattle was unnecessary.
(3) There will be no epidemic of CJD.
(4) An ante-mortem test for detecting BSE in live cattle is feasible.

It is worth noting that cutting edge researchers in to the prion hypothesis of BSE (currently the mainstream paradigm) are very careful to maintain that their hypothesis is an hypothesis. This subtlety tends to get lost in political decision making. Of course Ebringer may be completely wrong about both BSE and AS and we should be grateful for the cattle cull and TNFA blocking antibodies.

If so I guess my spine problems just went in to spontaneous remission five years ago when I changed my diet, by coincidence. Phew, was I lucky. And so too was my daughter, a few months ago, when she did the same diet change with the same result! Strange, that...

Back to HLA-B27: On an evolutionary basis HLA-B27 would be no problem for a primarily carnivorous hunter gatherer. Probably some degree of intestinal wall damage is needed for the immune system to "see" klebsiella in the gut. So woe betide when grains arrived in the Nile valley, gluten and starch as a continuous combination!

Perhaps you need to build pyramids as your ticket to future happiness because life is currently so awful, there must be something better than the ancient Egyptian everyday arthritis grind. An afterlife would need to be blissful and pain free as a reward for the daily suffering which was life with ankylosing spondylitis.


Peter


PS there's a nice link to this paper about Egyptian arthritis in DrBG's post on "300". I think she likes the film.

44 comments:

Chainey said...

Nice post as always. Sorry I don't comment so much, but I find it hard to make intelligent comment at this high level (but don't dumb it down!) and wisecracks can get tiresome if overdone.

Keep up the good work.

donny said...

Does your son even know what that plastic hotdog is supposed to be? I can add to the anecdotal evidence that a low carb diet reduces back and especially neck pain. My neck used to freeze up to the extent that I couldn't turn my head without pain. It usually took most of a week to recover.
Now that I'm hard core low carb, the only time I get a sore back is when I've done too many pullups.
I also used to wake up around one oclock many nights, thouroughly bloated, needing to stand up and burp for five or ten minutes before I could comfortably lie down again. That went away too, but comes back on the rare occasion that I eat pizza or peanut butter or too much raw broccoli. Not exactly irritable bowel syndrome, but still I wonder.

Dr. B G said...

Any post of yours -- starting with a weanie in a bun -- gets my attention! Or about medical miracles of self-healing.

Ebringer reminds me of another genius Peter Duesberg (who taught my biochem lab --but that's not why I suck) -- who believed that HIV did not cause AIDS. A highly unpopular stance -- which is true --- not everyone exposed develops AIDS (but the great majority must have some 'co-factor' (?wheat? why not?) that does eventually lead to it).

Would Rheumatologists (and Endo's) even have jobs if it weren't for wheat/gluten/casein?
--SLE, alkylos spondo, OA, DJD, vasculitis, rheumatoid, psoriatic arthritis, etc

Peter said...

Ta Chainey..

Hi Donny,

Squiggs' main use for the toy food is to pour it our of its bag in to a reasonable sized heap on the floor (there's a lot of it) then run through it, scattering it with his feet.... Big grin. He also feeds some to his main teddy bear.

For the neck and back pain I suspect it's easy for us amateurs. Real hard core HLA-B27 positive AS, like rheumatoid disease, may need more than just LC as we practice it. No chips for a start in AS...

Peter

Taka said...

Didn't have a chance to try the LC diet yet but consuming different probiotics such as yoghurt (containing various bacterial strains such as lactobacillus, thermococcus, streptococcus) doesn't do me any good. Tested the hard way after trying to cure my pollen allergy by eating the new L-92 strain yoghurt (designed to fend off allergies) for a cup of months on daily basis ending with IBS and leaky gut. When the nearly half year lasting diarrhea finally ended my osteoarthritis started ...

emil henry said...

Peter,

But potatoes are all right, as they are consumed in small amounts?

Cheers,
Emil.

Peter said...

G,

Duesberg, whether he is correct or not, has my utmost respect. Can I say that Gallo is a crook, when he got off scot free after the incident about the Pasteur Institute HIV sequencing fiasco? Perhaps not, but what the hell, he is.

I have a copy of Bryan Ellison and Peter Duesberg's discussion of the SMON fiasco in Japan, which is easy to track in Pubmed to verify the story. Might be worth a post sometime even if it's drug toxicity rather than nutrition.

Actually clioquinol reminds me of lovastatin and there will be massive litigation once the true problems from the statins become appreciated. It took 15 years to pin down clioquinol as the cause of SMON, so its probably about the right time now for people to realise how toxic lovastatin is...

Peter

Peter said...

Emil, it probably depends on whether you are HLA-B27 positive. My daughter tolerates rice and I am fine with spuds, so I suspect either we are HLA-B27 negative or it might be the luck of the draw on other genes, or perhaps an effect of LC eating with low levels of PUFA...

Hi Taka,

Try starving the bugs out. No fibre, no resistant starches, LC with high saturated fat and eat real food only. The germs I eat are traditional bugs that have made yogurt for the last few thousand years. Generally most "improvements" get bitten by the Law of unintended consequences. It's a big Law.

Peter

emil henry said...

Peter,

Thanks for your reply. I have mild back pains, but they seem to have gone better since going ON.

Should I be worried about vitamin A toxicity? I eat about 100 grams butter, 4-5 eggs, and maybe 0.15 litre of cream each day. That's a lot of vitamin A.

Should I add D3 supplementation?

Still haven't noticed any adverse reaction. My skin is brighter, but that might be due to less inflammation.

Cheers,
Emil.

Connie said...

Thanks again for a highly interesting post.

Way over my head though, I kept reading "kielbasa" for "klebsiella."

They make grass-fed hot dogs here in the US now. I hope they make them with all those non-muscle bits, and what a tasty way to get in organ meat.

One could make the bun with that weird "sponge bread" recipe.

Cardimom said...

Hmmm, I immediately saw the plastic hotdog as a dog's squeaky toy, but I see the world through glasses fogged with a double coat. Low carb/whole foods certainly is a huge part of what's working for me. Rheumatoid arthritis, plus a big dose of stress in my life right now, and I am walking/hiking for an hour every few days, running sprints every few days, and strength training, not to mention training/competing in agility trials with my dogs. None of which I would have believed possible for me a year ago; the pain was too much to maintain even low levels of activity. Of course, I'm still injecting a TNF blocker once a week, but I was on a TNF blocker this time last year as well, and steadily going down hill. I was also dx'd with IBS (symptoms started many, many years before RA symptoms) around the time I was diagnosed with RA. Excellent post, as always!

JohnN said...

Peter,
The Acinetobacter connection mentioned in Erbinger's address is provocative (correlation Vs causation?), and so is his proclaimed safety of beef with BSE.

I'm not convinced Stanley Prusiner's Nobel prize in medicine is well-deserved either but here is some counter evidence to the BSE/CJD bacteria connection/hypothesis:
1. The Fore of New Guinea who contracts Kuru from consuming human brain lives with Acinetobacter everyday while practicing a "traditional" diet.
2. The well-documented case of the Venetian family with Fatal Familial Insomnia seems to point to a genetic component.

Have you read Paul Ewald's "new germ theory"?

By the way, the advice to starve the bugs is spot-on. Think of your overgrown gut microbiota as a vineyard afflicted with phyloxera. You need to yank out the old vines, replant with better root-stocks and go biodynamic.

Peter said...

Hi Johnn,

So Ebringer is certainly provocative... And it's pretty obvious that awards, Nobels included, are not always markers of a correct hypothesis. The BSE thing is very interesting. Personally I tend to disregard the genetic problems such as Fatal Familial Insomnia as it clearly doesn't represent a model for the UK BSE outbreak. The Fore in New Guinea are more interesting. Any idea how widespread brain eating was in New Guinea and how well it correlates geographically with Kuru? Just curious.

I did email Ebringer once about the more clear cut case reports, where about a gram of brain tissue orally to each of a group of monkeys gave a 100% BSE incidence. No reply. It was a very small study and didn't seem well done, but...

Ebringer views BSE/CJD/MS/vaccine encephalitis as a spectrum of the same disease. I'm not so sure that he is correct in all of this, but I struggle with the prion hypothesis too. The misfolded proteins remind me so much of the beta amyloid plaques in Alzheimers. I think they're like shrapnel, nasty when it maims you but it's only a part of a world war.

It would be ironic if Ebringer's diet was right (starve the bacteria) for the wrong reasons (HLA-B27/klebsiella hypothesis).

And one has to pull in the Kitavans too, eating their yams and sweet potatoes... But, as always, no gluten on Kitava. Starch without IBS... Unlike ancient Egypt.

Groan, is Paul Ewald another author to read? My bookshelves are bending and there's no more wall space!

Peter

Peter said...

Hi Emil,

Don't forget the liver you should be eating. Masses of vit A there. These seem perfectly reasonable doses to me and I don't worry re A, though I do try to maintain a decent vit D intake too. Mea culpa, I don't measure blood D though...

Peter

JohnN said...

Hi Peter,
Paul Ewald thinks pathogens are behind every disease (CHD, DM, cancer, etc.) and for our own benefit, any intervention undertaken by us should guide their evolution toward a less virulent form.

A few examples in this line of thinking:
a) Nuking the bugs with antibiotic causes it to be more nasty - bad idea.
b) FFI (Fatal Familial Insomnia) could be a form of infection within the stem cell causing certain heat shock protein to be non-functional (my wild speculation not Ewald's).
c) A bug is responsible for the HLA-B27 antigen. Find it and treat it.
d) The apparent health of the Kitavans may be seen as a successful coexistence between the microbiota and its host in a well-isolated environment.
e) Th1 pathogens dysregulate VDR (vitamin D receptor) and cause chronic inflammatory disease.

Proponents of this theory think that taking on more secosteroid to correct the perceived deficiency without addressing the root cause is a worrysome development.

John

Taka said...

The CURU victims eat brains which are very high in the Omega-3 PUFAs. US nuclear tests in the vicinity as well ... The British BSA epidemic coincides with the Chernobyl nuclear disaster and the cows had been fed high PUFA diet as well (sheep brains in the feed). It all looks to me exactly how Ray Peat describes here:

http://raypeat.com/articles/aging/madcow.shtml

i.e. combine the most unstable Omega-3 PUFAs with nuclear radiation and you get the Mad Cow Disease ...

Peter said...

Taka,

I just wish I found Ray Peat convincing. It would be lovely. But I'm just wondering where the Japanese BSE/CJD swathe occurred after the Hiroshima incident which Peat discusses. Who eats more fish than the Japanese and who have been directly nuked? Where is the CJD cluster?

And yes, we fed sheep brains to cows. Via their rumen. How much of the omega 3s get through the rumen? Of that which bypasses the rumen as part of a high protein ration, how much does this change the PUFA content of cattle (brain PUFA is, according to Chris Masterjohn, tightly regulated) Why wasn't there a plume of scrapie across Europe in sheep in the aftermath of Chernobyl if sheep's brain is so high in PUFA as to alter the cattle brain PUFA levels. Have you any idea how small a sheep's brain is compared to a 500kg cow?

I just wish I believed. But I don't.

Peter

BTW Michiko Hachiya's "Hiroshima Doctor" makes very interesting reading if off topic and phenomenally depressing, as do the several accounts of the Chernobyl incident. And the Windscale reactor fire in the 1950s was pretty interesting too.

Peter said...

Hi John,

Wikied Paul Ewald and I have to agree that it is possible to fit his approach in to my own mind set. I was thinking re toxoplasmosis and schizophrenia in addition to Borna virus. I believe there is a certain amount on pubmed about a breast cancer virus.

Genes code the receptors, stuff has to interact with the receptors. Whether there is an infection by a bug using the receptor for access or an auto immune disease working like the AS/klebsiella scenario, the result is disease.

I like to think that decent nutrition decreases the susceptibilty to infection.

This is one possible mechanism for diease/nutrition interaction. Also makes me think of colonic hydrogen and H pylori and ulcers... There is more to it than just the bug. But the bug is accommodatable.

Peter

Dr. B G said...

Ewald certainly has some fascinating ideas -- and I agree bugs are certainly part of the big picture. We do seem to do a lot to make bugs mrre virulent (broad spectrum antibiotics, ?radiation, overtreatment of bugs, growth factors in our meat/fish). I was just reading how H.pylori adapts by making arginase (in addition to what Peter has discussed here) -- arginine is the precursor to NO which is like the 'blast/bullet' from macrophages to kill viruses/bacteria/prokaryotes. (that's why citrulline is more effective for people with Th1 pathogens -- imo; citrulline is a precursor to arginine).

What about epigenetics and the disease-nutrition interaction that Peter speaks about? What if our parents (hard work ethic, no vit D, no fish oil, low protein diet b/c poor) carried us in utero and provided some degree of susceptibility to the environment? Low-protein mother rats give birth and 2 generations are affected -- high insulin -- high diabetes. Rath would say more potential for genetic alterations and mutations to provide perhaps evolution for something better. (or de-evolution to apes)

Are we just killing ourselves slowly? With or without bugs? By poor nutrition, synthetic chemicals, lack of sunlight (the MP fans would not agree). !!Cleopatra baking bread *hee* I'm sorry -- still stuck on pyramids! BREAD... n-6 PUFAs... lack of hard labor... lack of bactericidal/fungicidal immunomodulating F O O D (ie fats -- cholesterol, omega-3, short, med, long-chain saturated fats and triglycerides). Vitamin D has mild bactericidal properties too -- hence why I think we evolved to have such a high concentration in the skin and gut -- our first barriers to the world.

-G

Dr. B G said...

John -- btw those 'proponents' arguing against secosteroids have an excellent point. Not vit D -- but is our innate immunity on hyperdrive? What do you think about lectins in the innate immunity? Lectins/MBLs 'glom' on to anything to try and neutralize: bacteria or fungus or prokaryotes -- uterus, ovaries, insulin, insulin receptors. Why not mitochondria or cytochrome P450s?

Peter -- ideas? Or your beautiful immunologist wife??? (I think NKFb is involved, right?) (Like my biochem, my immunology s*cks.)

Waterlily said...

Peter:
I don't need any mumbo-jumbo research papers to tell me that I feel 50 years younger and spryer since I ditched those noxious substances called sugars/grains. Not only no pain but my depression has flown the coop now that I feel like a spring chicken.

Keep up the good work young man, I love your turn of phrase.

IFWC said...

Folks,

Ended up in the Emergency Room due to chest pains, discomfort, and almost passing out due to lightheadedness.

Any advice or support is appreciated. My second meal of the day, 4 hours after the first, starts the episodes the past day or two and today it was just too much. Considering dropping the diet...

Peter said...

Well, there's a pair of interesting comments back to back...

IFWC, any numbers re glucose/ketones?

Would you care to put up a couple of day's menus. It's interesting to consider there may be people who cannot eat this way. I've always thought metabolic typing might become less and less important the closwer to the OD you get. Maybe not....

Peter

Peter said...

G,

You're loosing me in some (lots!) of the abbreviations!

I keep trying to fit things like the bug for cancer and the absence of cancer from non modernised natives together. Are the bugs new, have we "improved" them, does sugar depress the immune system (yes) and the bugs are there but harmless (like H pylori) before accultration...?

There has to be some coherence there!

Got to go cut, stitch and chemo.

Peter

Gyan said...

I have been facing viral fever in my family and I wonder what is the recommendation regarding eating in viral fever.

Also regarding the lectin angle and post-fever development of autoimmune diseases, it has been suggested to Starve the Fever by a 3-day water fast or at best some cooked vegetable broth.
But are eggs/meat problematic lectin-wise or otherwise?
Milk is also supposed to be out.

Anna said...

ifwc,

Hope you are feeling better now.

Were gall stones ruled out? I know a number of people who, after years of general low fat diets or shorter term, but more intense low fat physician-supervised calorie restricted liquid diets, ended up at the emergency room convinced they were having heart attacks.

But what they all had were blocked gall bladders because they weren't regularly squirting bile salts in response to fat consumption (lack of bile salt need in a low fat diet), causing bile sludge to accumulate and eventually, form gall stones. Then, when fat is consumed again, the bile is blocked when it tries to quirt out, causing lots of pain and discomfort, often feeling like a heart attack.

BTW, people who have their gall bladders removed often can consume fat normally. Ironicallygall bladder suffers are often advised to stay on a low fat diet, or they do so on their own because eating fat creates discomfort. The abnormality of such a low fat diet is never addressed. And gall bladder surgery is one of the most common surgeries performed, so the medical establishment isn't really interested in promoting diets that keep gall bladder function intact.

Use it or lose it.

If it isn't gall bladder troubles, I hope you find some answers and solutions that feel comfortable and promote your health.

Anna said...

Sorry, that should have been low fat diets OR short term low fat physician supervised low calorie diets.

I need to remember to review and edit before hitting Publish :-)

Anna said...

Hmm, perhaps some digestive enzyme supplements might work to assist your digestion until your own enzyme production can keep up with your new diet?

I rarely get indigestion anymore now that I hardly ever eat really sugary or starchy foods (I swilled antacids for about ten years when I ate a lot of pasta and tomato sauce, though) and eat a lot more saturated fats, but last week I made something with a *lot* of coconut oil and cocoa & a bit of honey and ate too much of it, resulting in an uncomfortable evening. I took some Swedish Bitters in water (very refreshing)before bedtime and that seemed to really calm the heavy GI feeling.

There is a lag time for enzyme production to ramp up in response to a new diet. I know that if I eat wheat flour or potatoes now, even a moderate amount, I get a lot of gas or sleep fitfully because I probably make too little amylase to break it down effectively. I think digestive enzymes for fat and meat are the same. But they come back with regular ingestion of the foods that need them.

Stan (Heretic) said...

What do you think about the Purdy's hypothesis of BSE/CJD (manganese poisoning)?

IFWC said...

Thanks for comments. I've been eating somewhat "normal" the past day or two, part fat part protein part carbs.

Can any of you share comments on the Anabolic Diet? (Type into Google for overviews) It's 60% fat and 40% protein 5 days a week, then carb up on the weekend. Perhaps this would better suit me, so I'd like some of your opinions since, I think for now, I need to avoid high fat 24/7.

Peter said...

IFWC,

Can't really comment on these as they're not anything I've tried, others may know more. Hope it works for you.

Peter

Peter said...

Stan,

Well it's hard to decide. I found his OP work early on very interesting, and felt you could possibly tie increased blood brain barrier permeability in to immune mediated neurological damage as per Ebringer. I did a fair bit of searching and there were hints that OPs do increase BBB permeability. Your systemic antibodies need to get in to the CNS to cause disease there.

The Mn3+ and infrasound I found harder to follow the logic to, especially why infrasound effects should largely (but not completely) spare organic farms. Then I noticed that a commercial test system to detect prions uses sub sonic waves to amplify prions to detectable levels, so that took me back slightly. Lost the link to this firm. Found it through Red Flags initially.

I was also interested in the possibility of an excitotoxin based disease, again with OPs improving BBB penetration.

Ultimately I just don't know.

History is littered with non contagious diseases being attributed to a virus, now there is a hyperinfective misfolded protein. Hmmmm.....

Peter

Peter said...

Hi Gyan,

Have a read here:

http://www.ncbi.nlm.nih.gov/pubmed/10205084

The role of both viruses and bacteria in the triggering of auto immune diseases does seem to vary from simple links such as rheumatic fever/streptococcus through to much more complex, with Freed suggesting that the viral neuraminidase exposes sugar moieties which are normally hidden. Quite how this ties in to traditional management of viral problems is wide open... Freed's comments are near the end.

I think mammalian cells use sugar-lectin systems as communication mechanisms. The difference is that these systems are biodegradable by mammalian systems too. Not so wheat germ agglutinin...

Peter

JohnN said...

Dear bg,
"Are we just killing ourselves slowly? With or without bugs?"
Rhetorically or not, it would happen faster (in my view) without the bugs. The environment that we exist in includes the microbiota within and the chemical soup we're swimming in. The former you can do something about but it's clearly not a paleolithic Earth we're living in.

Re. vitamin D: I'm sure we all have anecdotal successes with manipulating its level upward but several issues remain:

Shouldn't the level of circulating 1,25(OH)2D experience the same ebb and flow of the seasons - evolutionaryly speaking?
What is the longterm effect of amping up 1,25(OH)2D year round?
And lastly, shouldn't A & D be considered together the way they exist in food?
Regards,
John

JohnN said...

Peter,
"I like to think that decent nutrition decreases the susceptibilty to infection."

Don't you think decent nutrition (and frequency of its occurrence - fasting) is how we control the bugs?

On prions: the grouping of CJD, DM and AD makes sense (more so than Erbinger's MS and CJD/BSE) since mis-folded proteins seem to be behind the problems.

Dr. B G said...

John,

Neolithic Earth certainly has its challenges. We have to deconstruct F O O D and environmental triggers (ie sunlight/vitD) to manipulate homeostasis.

It appears to me that all traditional cultures consume both vitamins A and D together. For optimum growth, reproduction and prevention of proliferation, A and D appear to work synergistically. Just one example (breast CA) is here. In vivo discussions here and here.

Most cultures prepare brides, mothers-to-be and nursing moms with special diets of rich soup (marrow-derived A and D), cream/milk, and rich meats. (btw my 'anecdotal success' is that this is the formula for GINORMOUS mammaries without requiring surgery). On the walkabout, tribal males/warriors consumed milk and blood; vitamin A is enriched (RBP) in blood.

Makes a whole lotta sense to me too...dunno about the ebb and flow of hormones. I guess there is a purpose? What if I lived in the tropics?

-G

JohnN said...

Hi G,
"What if I lived in the tropics?"
How do you like the Kitavan diet of yam, cassava and fruits? No hyperlipiding there, that's for certain.

Kidding aside, I would seek sun protection as much as possible since that's what the natives do. Those who must work outdoor, the peasants plowing the rice field all day under the sun, you'd see their skin turn as dark as the back of the water buffaloes they walk behind. How much vitamin D do you think they require?

In paleolithic time, sunlight is whatever penetrates through the tropical jungle's thick canopy. Oliver Sack in "An Anthropology on Mars" talks about tribes whose members rarely venture to the edge of the forest. (As an aside, their depth perception is so impaired, by spending the whole life in the jungle, that they attempt to reach out and touch the mountain in the horizon.) Needless to say, their vitamin D production is not as prolific as you imagine.

If one bypasses the (self-limiting) control-feedback mechanism intended by evolution when taking D3 supplement, perhaps less is more. It's a potent stuff.

John

Dr. B G said...

For some perhaps the negative feedback loop would present a problem, esp if other hormones were still imbalanced. I can think of a few people 'on the fringe' who would clearly not benefit from vitamin D supplementation -- sarcoidosis (tumor cells over produce 1,25OHD2, cyp 3A4 deviants (hydroxylates D2 and D3), ? others?? probably. There are a few who gain weight (fat, not muscle as expected) who probably have some odd VDR or vitamin D binding protein mutation. Vampires...j/k (I'm reading Twilight -- heavy stuff).

Since the canopy was so dense, perhaps that is why aboriginals consume so much grub? I mean literally... larvae, caterpillars, mealworms, bee babies, insect pupae, etc. These rich little buggers are rich in EPA DHA, vitamin A and vitamin D. Sally Fallon/WAP has discussed as well.

http://www.food-insects.com/
Vitamin PUFA content of Grubs

If it were me *smile* I'd choose a vitamin D/A capsule over a can of worms (as they do in Spain) or turning black/wrinkly as a buffalo's behind.

And a bowl of pork butt, Chinese tripe or blood cubes (YYYUUUMM!) wouldn't get turned down by me either! Asthma would stay controlled as would overall hormesis. Hopefully rickets won't hit my BIM again :)

-G

Anna said...

By the time humans were hunting big game, weren't they often on the savanna/grasslands and out of forest/jungles?

Stephan said...

Hi Peter,

I have two questions about all this. Do you think these intestinal bacteria would be a problem if intestinal permeability is normal? I think I remember you speculating in a previous post that the problem with the Egyptians was a combination of starch and gluten-induced intestinal damage. I wonder if dairy protein might have the same effect. Then of course there's the aspirin and linoleic acid.

Also, I was thinking about how so many cultures ferment their starches. I wonder if that leaves less for the intestinal flora.

Certainly, if you look at traditional grain foods, they're typically a pile of mush that's been soaked, ground and fermented. Cultures often remove bran if they can. I suppose the goal is to maximize absorption so you don't have to many calories hanging around the gut for bacterial overgrowth.

Peter said...

Hi Stephan,

I've been thinking about this and I'm suspicious that having the gene may be quite bad news generally, if you are starch based in your gathering, whatever you do with the starches. The main thing that seems to suggest this is the rarity of the gene, but not it's complete absence, in equatorial areas. This suggests the gene was present in humans before they moved out of Africa. People with the gene did OK the further from the equator they moved. If the gene was neutral under "ideal" conditions (high D, adequate omega 3s etc) there would be no need for it to be rare in starch eating communities and it should be there at a similar frequency as in carnivorous HGs (up to 40% in the Inuit). Hmmm, unless there was some sort of "founder effect"... Less likely as there is a graduation, more frequent B27 as you move north.

I think that grains probably make matters a great deal worse, hence the problems in ancient Egyptian skeletons. I guess a high population density, lots of graves and a dry climate make for lots of archaeological finds too.

Peter

Stephan said...

Interesting. I'll keep that in mind.

Another possibility for the B27 gradient is that it's under selection from something else, maybe a tropical disease. I agree a founder effect seems unlikely if there is a continuous gradient from the equator to the arctic.

Susan said...

So following another thought, the idea that starches (un-predigested as in sourdoughs) are touch on the system and that there are other abuses in the gut, create gut permeability. Klebsiella is then 'leaked' and an anti-body is set out against it. This protein mimics collagen I, III, IV and V which then is attacked where it is present throughout the body. AS, RA, Crohn's strictures.
Also, D needs K2 (in organ meats, blue cheese and natto) to work properly in it's antimicrobial role with the vagas nerve. Primitive people would have eaten the whole animal.
Just some food for thought.

Peter said...

Hi Susan,

I would certainly agree that increased gut permeability is core to most auto immune diseases. The diet derived from Prof Ebringer's work is utterly gluten free as part of the low starch approach...

Peter