Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Saturday, February 6, 2010

Arthritis, Autoimmunity and Arginine Deimidation

Celiac and Antibody Production Against Tissue Transglutaminase as a Model

Arthritis is an autoimmune disease in which the immune system attacks and degrades the connective tissue of joints.  Antibodies against modified amino acids, arginine converted to citrulline, and proteins commonly found in joints, mediate the arthritis disease process.  The development of arthritis mimics the development of gluten intolerance, celiac, in which another enzyme, transglutaminase ( tissue transglutaminase, tTG or TG2) modifies the major gluten protein, gliadin, and antibodies are produced against both modified gliadin and TG2 autoantigen.

Arthritis of Joints Is Like Coeliac of Intestines;  Autoantibodies to Protein Modifying Enzymes

In other articles, I outlined the pathology of gluten intolerance:
  • The major protein of wheat gluten, gliadin, contains long stretches of glutamines.
  • An intestinal enzyme, TG2, converts the glutamines to glutamates by deamination.
  • As TG2 works it binds to gliadin.
  • In celiac, the TG2-gliadin complexes are internalized and fragmented to stimulate antibody production against both TG2 and gliadin.
  • I think that the internalization and processing for antibody stimulation is dependent on the basic triplet found in TG2.

Arthritis Is Mediated by Autoantibodies to Peptidylarginine Deiminase and Citrullinated Proteins

Parallel to the celiac example, in some forms of arthritis, antibodies are produced against an enzyme that modifies proteins.  In arthritis, the enzyme involved, peptidylarginine deiminase (PAD) removes the terminal nitrogen from arginine (deimination) to produce citrullinated proteins.  Antibodies are produced to both PAD and citrullinated proteins.

PAD Also Has a Triplet of Basic Amino Acids for Internalization

I of course wondered if PAD had the same triplet of basic amino acids, e.g. RRK, that I had found on all other autoantigens and allergens.  Examining the sequence of human PAD in the NCBI sequence databases and comparing to other sequences, I found the basic triplet near the carboxy terminus.  The same or an alternative basic triplet was found in PADs from other mammals.

Autoantigens and Predicted Basic Triplets of Amino Acids Reveal the Cause of Arthritis

Arthritis is an inflammatory disease.  That means that without inflammation, arthritis cannot start and if inflammation is inhibited, arthritis cannot progress.  It is likely that arthritis is the result of chronic inflammation plus a precipitating event, such as joint injury or joint infection.  Alternatively, in a manner similar to Hashimoto’s thyroiditis, in which celiac produces anti-TG2 antibodies that attack the TG2 also produced in the thyroid gland, arthritis may be produced by autoantibodies stimulated in the inflammation of other tissues and spreading to the joints.  Celiac is also a risk factor for arthritis.  Trauma-based inflammation of a joint can also result in migration of Clamydia pneumonia (Cpn)-infected macrophages to the site of inflammation.  Cpn could contribute to joint inflammation and promote immunological presentation of autoantigens and autoantibody production.

reference:
Stenberg P, Roth B, Wollheim FA.  Peptidylarginine deiminases and the pathogenesis of rheumatoid arthritis: a reflection of the involvement of transglutaminase in coeliac disease.  Eur J Intern Med. 2009 Dec;20(8):749-55. Epub 2009 Sep 19.

50 comments:

William Trumbower said...

Art What a wonderful post! My younger sister has celiac. I do not even though we both have the HLA DQ2 genetic type. I was smug for many years, however I became gluten free several years ago after reading sites such as yours. I recently had bilateral knee replacement for oteoarthritis. I agree that I had celiac of the knees. At my last highschool reunion I had pizza and beer and had bloody stools for a week. I guess I should not have been so smug for so long.

Steven Low said...

Art,

Is this all arthritis or just rheumatoid arthritis?

I can definitely see how it can be both given that they are all synovial joints, but some aspects of osteoarthritis seem to be wear and tear and some other factors.

Dr. Art Ayers said...

Steven Low,
I think that there are about a hundred different types of arthritis and I think that it is a mistake to think that arthritis is a result of wear and tear, or aging of joints. The cartilage surfaces of joints are dynamic and are being continuously eaten and synthesized by chondrocytes that mine the articular cartilage. My prejudice is that any ongoing damage to joints, say the constant abuse of gymnastics or martial arts, which I did in high school and college, is due to inadequate repair due to inadequate diet and gut flora. The contribution of aging is basically the same, i.e. poorly managed chronic inflammation.

The attack on the joint connective tissues varies depending on the pathogenesis of the various forms of the disease. It is autoinflammatory as well as autoimmune. The attack of the innate and adaptive components of the immune system on connective tissue spreads to other joints, but many of the initiating defects are in the gut where T cell development occurs in response to gut flora and diet.

Thanks for your comments.

Dr. Art Ayers said...

William Trumbower,
It seems to me that so much suffering could be eliminated by actually treating the causes of diseases instead of just symptoms. The gut is a major contributor to most diseases and yet it is seldom treated.

Genetic predispositions are treated as if they are inevitabilities and yet their contributions to disease are minimal compared to diet. An anti-inflammatory diet can avoid most of the negative consequences of genetic predispositions.

Celiac is a very intricate disease. The HLA associations are fascinating, because those are the proteins that display the antigen fragments for T cell receptor recognition. Those involved in celiac have strong heparin-binding domains along the surface that interacts with the T cell receptor. It is interesting that inflammation and degranulation of mast cells (that coat the gut with heparin) reduces heparin availability.

Good luck and stick to an anti-inflammatory diet. Watch your vitamin D level and try to avoid thyroid problems.

Thanks for your comments.

Erik said...

Fascinating.

What are your thoughts on already-present osteoarthritis?

I ate pretty poorly and played a lot of basketball (both outdoor and indoor) throughout high school and college. I was always in good shape, never overweight, but my left knee was degrading. I avoided the doctor (no insurance) until I had a steady job. Turns out a significant chunk of cartilage was missing - something in the realm of a few centimeters worth. I had arthroscopic microfracture surgery and was sidelined for a few months, during which time I continued to eat paleo (had been eating paleo for about a year up til then).

Doc said the surgery didn't take and I'd need autologous chondrocyte implantation to have any hope of regrowing cartilage. I asked for more time; he agreed.

Went full bore paleo, upped the saturated fat, cut out the omega 6s, fructose, converted to full pastured/organic/grass-fed farmers' market fare, ate more organ meat, supplemented with Vit. D/K2, ditched the shoes, bought some Vibram FiveFingers, and often went barefoot.

Two years out of surgery and I'm now beating squat, deadlift PRs, sprinting once a week, hiking, backpacking, even playing basketball on occasion. No pain, no indication of a cartilage deficiency. I haven't had another MRI to confirm either way, but might my wear-and-tear arthritis be improving on its own? Is this even possible?

Dr. Art Ayers said...

Erik,
Your results are exactly what I would expect. I think that arthritis is a form of juvenilzation of chondrocytes so that instead of synthesizing tough, mature cartilage, they synthesize the expanse-filling initial form that is made when they have good access to the vascular system with plenty of oxygen and nutrients.

Chondrocytes in the midst of articular cartilage live in a cave surrounded by heparan sulfate, which they recycle completely every six hours. They mine adjacent cartilage and eat the polysaccharides (GAGs) and proteins, and synthesize new, tough cartilage in their wake. Torn cartilage tightly juxtaposed will be reknit by chondrocytes eating their way through the break.

Damaged cartilage will repair if it receives the stress necessary to induce the production of tough new cartilage and the embedded chondrocytes do not receive too much oxygen or nutrients. Load bearing exercise and full range of motion is needed during healing. Angiogenesis is also a problem, because properly growing cartilage inhibits growth of blood vessels.

I enjoyed your experience, especially since it confirms my laboratory experience and conceptualization of cartilage formation.

Anonymous said...

Do you subscribe to the nightshades theory about inflammation? I have been eating a low inflamation diet for awhile, I use homemade kefir for gut flora but I still consume peppers and tomatoes and I do have some recurring joint pain I assume form my weight lifting. I was wondering if you thought the elimination of night shades and my adding Glucosmine would help? Thanks.

Judge Holden said...

In the linked article the authors discuss the dangers of vitamin d dysregulation caused by inflammatory conditions (or should I say caused by the bacteria which likely also cause inflammatory conditions) and recommend "extreme caution" when it comes to vitamin d supplementation.

From reading your blog over the last year or so I had believed that vitamin d supplementation was an unqualified good and have been on about 4,000 i.u. daily. I was wondering what your views were on this question of vit d dysregulation?

http://books.google.com/books?id=oSl8VY33634C&printsec=frontcover&dq=vitamin+d&cd=1#v=onepage&q=&f=false

Dr. Art Ayers said...

Anon,
I don't give much credence to the nightshade toxicity idea.

If you still have joint aches I would recommend getting rid of the rest of the vegetable oil, grain and starch in your diet and see if that changes things. If you haven't had your vitD checked, that is another likely problem, even if you are supplementing with 1,000 IU per day and are getting plenty of sun. You can tell if it is residual inflammation by just taking 4 to 8 fish oil capsules per day for a week. If the aches go away, it is inflammation.

Thanks for the comments. Let me know what happens.

Dr. Art Ayers said...

Judge Holden,
The book that you cite was published as a meeting proceedings in 2006. It doesn't seem to have much to say besides very specialized responses to vitD and deficiencies. VitD is complex, because it is used as a hormone, rather than an enzyme cofactor like the other vitamins.

I think that if vitD3 were a patented drug, it would be worth billions of dollars a year. After all, unlike most drugs on the market, it is actually effective and has very few side effects. That can't be demonstrated for NSAIDS, anti-depressants, antacids, laxatives, statins or even vaccines.

I haven't read anything that dissuades me from taking 2,000 - 4,000 IU vitD3 per day.

Thanks for your comments.

Steven Low said...

Thanks for the response Dr. Ayers.

Given the information I'd have to agree.

Going into the physical therapy professional hopefully I'll be able to make some impact getting people to change their diets. :)

Garry said...

This is always such an interesting blog. Thanks Dr. Ayers!

Regarding Judge Holden's linked text, one of the authors is Trevor Marshall, who more or less is the head figure in a movement that runs counter in many ways to the rest of the literature regarding vitamin D. The 'Marshall Protocol', as it's known, recommends people suffering certain conditions actively avoid vitamin D. He has his followers, but he is standing rather alone at this stage of vitamin D research.

Peter said...

Hi Art,

I really like this particular post! Arthritis as coelaic disease of the joints definitely seems to describe a big chunk of arthritis.

I also came across an ancient paper describing ILGF1 as "sulphation factor" due to its effects on proteoglycan production, before it was characterised properly.

That has me thinking of another swathe of arthritis as insulin resistance of the chondrocytes. Does this seem plausible?

Peter

Dr. Art Ayers said...

Peter,
I don't think that chondrocytes encounter glucose or insulin. Mature chondrocytes are embedded in cartilage and have only distant access to blood vessels, glucose and oxygen. Collagen contains lots of hydroxyproline that uses up even the remaining low levels of oxygen and requires vitamin C -- remember scurvy is a connective tissue deficiency disease. Hypoxia is required for normal connective tissue integrity. [What does that say about rosacea and facial skin integrity?]

A peptide fragment (endostatin) clipped off of a collagen protein as it matures blocks angiogenesis and prevents blood vessels from growing into and weakening cartilage. Blood introduced into the synovial space disrupts surface cartilage.

Chondrocytes eat cartilage and secrete new, tough cartilage. Chondrocytes fed glucose and exposed to oxygen act like fibroblasts and secrete weak, space-filling, repair cartilage. Cartilage also requires mechanical stress to develop properly. Immobility is hard on connective tissue.

Thanks for your comments.

Judge Holden said...

Thanks for the response.

Peter said...

Thanks Art,

That's very informative

Peter

Dr. Art Ayers said...

Peter,
I am still pondering the insulin-like growth factor 1, sulphating factor, proteoglycan connection. I did some work of heparan sulfate proteoglycan expression changes in response to inflammation. Most of the genes involved, including heparanase are controlled by NFkB and most are silenced. Heparanase is turned up by inflammation. Sulfation of some heparans is increased during inflammation and that changes lots of the extracellular signaling.

I think that following the sulfation patterns by examining heparin bound to serum proteins might be a very sophisticated way of monitoring body-wide inflammation. It might tell which tissues are inflamed.

Thanks for your input.

William Trumbower said...

Art Thank you for your comment. I do follow a strict anti-inflamatory diet including vitD 6000u daily. I am hypothyroid (negative autoantibodies) and take Naturethroid 1gr twice daily. I think osteoarthritis is curable and reversible if caught early enough. I am 64 and had developed such a bilateral valgus deformity (knock kneed) so bad that my feet would slip laterally off of my bicycle pedals. My goal now is to continue an anti-inflamatory life style and to strengthen my muscles in order to minimize the wear and tear to my artificial knee joints. I don't want to go thru this again as it is brutal surgery!

Anonymous said...

Hi Dr. Ayers –

I’ve been fascinated by your work on inflammation and believe that your research is helping me get closer to finding relief for my own autoimmune / reactive arthritis.

I have tried using fish oil (as many as 5-7 capsules per meal) but can’t understand why my arthritis (sharp, stabbing joint pain in fingers, hip, and heel) is greatly exacerbated rather than relieved. I have also tried adopting the paleo diet (mostly grass-fed lamb, raw hard cheeses, and plenty of cooked vegetables), but my immune system seems to be so hyperactive that I react within 24-36 hours of eating any food with high fat content, gluten, corn, or animal proteins.

Thus far, the only foods that keep my autoimmune arthritis calm are brown rice, beans, and vegetables. I need to try reintroduce animal proteins to my body again as my current diet is unsustainable due to its low-fat and low-calorie nature (I am 5’11” and 122 lbs. as a result of this horrible starvation diet).

I wonder if oral heparin might be of use in helping my body become accustomed again to animal proteins and dietary fats in general?
I have read through your work on heparin and wondered what your thoughts are regarding the use of a low-dose nonanticoagulant oral heparin (or heparin analogue?) in the hope of suppressing the hyperimmune reaction and “forcing” the tolerance of more foods like meats, poultry, etc. My doctor is quite perplexed at this point as virtually all test results have come back normal. So, I wanted to present some ideas to him on the possible use of heparin (although I couldn’t find out how much was administered in the articles I read online). Also, do you know if any side effects have been noted with the use of oral heparin? Any thoughts you have would be greatly appreciated.

Jeff

Oral heparin in the treatment of rheumatoid arthritis.
Archivum immunologiae et therapiae experimentalis.
Imiela, J & Nosarzewski, J & Górski, A. (1995).

Low-dose heparin: a novel approach in immunosuppression munomodulating activity of heparin.
FASEB J 5:2287-2291. 3.
Gorski A, Imiela J, Norsarzewski J. (1993)

Heparan sulfate proteoglycans in glomerular inflammation
Kidney International (2004) 65, 768–785; doi:10.1111/j.1523-1755.2004.00451.x
ANGELIQUE L W M M ROPS, JOHAN VAN DER VLAG, JOOST F M LENSEN, TESSA J M WIJNHOVEN, LAMBERT P W J VAN DEN HEUVEL, TOIN H VAN KUPPEVELT and JO H M BERDEN
Nephrology Research Laboratory and Laboratory for Matrix Biochemistry, Nijmegen Centre for Molecular Life Sciences; and Division of Nephrology and Division of Pediatrics, University Medical Centre, Nijmegen, The Netherlands

Dr. Art Ayers said...

Jeff,
I think that heparin might be able to suppress some of your symptoms, because heparan sulfate proteoglycans are reduced by inflammation. I don't think that will, however, fix your inflammation.

I think that you have problems in your gut and I would expect that one is gluten intolerance. That means eliminating grain, which would seem to be easy for you.

Next would be to check for vitamin D deficiency and correct that aggressively and check again to confirm a high level > 60 ng/dl.

I think that the fish oil isn't helping because it is not taken with enough saturated fats. The saturated fats are needed for absorption and also to avoid conversion of the omega-3 oils to inflammatory prostaglandins as a result of existing high inflammation. I think your diet is low in saturated fats. You should also try to eliminate vegetable oils and include olive oil, butter and coconut oil.

It doesn't sound like most of your food reactions are allergies, so your gut flora are simply not adapted to them. I would say that your immune system is a little aggressive, because it is lacking T regs, that normally suppress overactivity. That points to a gut problems, since that is where much of the immune system develops.

I would avoid cheese and use probiotics instead in the form of full fat yogurt. You should be able to eats eggs, chicken and pork. It may take a while to get enough fat in your diet to provide enough bile to make fat metabolism work. Olive oil should help.

It sounds like your gut flora is now dysfunctional and needs to be rebuilt before you can take advantage of the anti-inflammatory aspects of a diet. It may take a week to get used to new foods.

You may be getting histamine reactions and an anti-histamine (e.g. benadryl) may help with your food tolerance initially. You may also consider trying to repair your gut with a glutamine supplement. You may also be low on vitamins and minerals in general, because of weight loss and poor digestion. Remember that you can't absorb most of the fat-soluble vitamins from veggies unless they are served with oils/fats (olive oil or butter.)

Also, make sure that you don't have any existing dental problems, since they are major contributors to arthritis and general inflammation.

Fixing your gut flora will go a long way toward addressing you other inflammation problems. In the mean time, you should be able to reduce some of your joint pains by topical applications of castor oil or Vicks Vaporub.

Have you taken antibiotics? Did you read the article on constipation and gut flora?

Try some of these suggestions and let me know how you respond.

donny said...

Hi Doctor Ayers. I got into taking Niacin a few years ago after starting to read Dr Davis at the HeartScan Blog, along with fish oil and vitamin D.
I have a shoulder that bums out, it gets progressively stiffer and sore if I run out of supplements, sometimes travelling up towards my neck, getting to the point where I can barely turn my head. I tended to get lazy, run out of supplements one at a time, it would get bad, I'd run to the store.
I'd thought the fish oil was most of it; when I started supplementing again, it would usually take four days to around a week to resolve, depending on how stupid I was (how long I went without supplements.) I didn't want to wait that long, so I tried a crazy amount of fish oil, two tablespoons. The next day, all symptoms were gone. So there you go. But lately, fish oil doesn't seem to be as effective.
But the niacin seems to work great. I've been using it more consistently then I have in the past, two grams a day for the last month, and my shoulder hasn't felt this consistently good for this long in years. I keep reading your blog, wondering if any of this biofilm stuff applies to my shoulder.
The thing about niacin, at this dose there's no argument for it as a nutrient; it's a drug, and a self-prescribed one at that, which makes me a little nervous. So I'm always trying to find some alternative, by figuring out what the niacin is doing.

Anyways, I found this just now;

http://www.erj.ersjournals.com/cgi/reprint/7/6/1125.pdf
-----------------------------------
Niacin attenuates acute lung injury induced by
lipopolysaccharide in the hamster
-----------------------------------

The title pretty much speaks for itself. That won't stop me from quoting this;)

----------------------------------
Although the mechanism of niacin
protection remains unknown, one explanation for the protective
effect is that deoxyribonucleic acid (DNA) damage
caused by toxic agents leads to the consumption of
nicotinamide adenine dinucleotide (NAD) through the
synthesis of poly adenosine diphosphate (ADP)-ribose,
and that the administration of niacin prevents the depletion
of NAD, resulting in prevention of cellular injury
----------------------------------

Which sort of reads like a very specialized form of niacin deficiency. I have two sisters and two nieces who are celiac, and a schizophrenic mother. One of the sisters is also fructose intolerant. I guess if I have a problem with gut bacteria, and endotoxins leaking through my gut, that shouldn't be totally shocking.
I'm thinking something like the gut biofilm attacking protocol you wrote about in some other posts might be worth trying, followed by some fermented foods. I'm already doing pretty much everything else you recommend, diet-wise.

Ooh, here's another one;

"Nicotinamide is a potent inhibitor of proinflammatory cytokines"

"...It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor."

Maybe this is what's behind Abram Hoffer's claims that niacinamide is effective against rheumatoid arthritis.

So whattaya think?

Dr. Art Ayers said...

Donny,
That's a lot to think about. Thanks.

First off, I think of fish oil as a quick fix for inflammation. In other words, if I notice symptoms that point toward body-wide inflammation, I try fish oil and see if it reduces the symptoms. It it does, then I search for the source of the inflammation. I suspect that you have a source of inflammation.

You need to test a few things. You are already aware of most of the dietary problems so I would suspect:
Dental infections
Vitamin D -- you still seem to need too much suppression of inflammation, so I think that the typical problem is still not reaching a high enough level of functional vitamin D.
Gut flora and gut health. Your family history of celiac is too obvious. You have to stay away from grains (celiac) and starch (for Klebsiella/H. pylori) until you sort this out.

Do you blush with nicotinamide? It doesn't sound like that is a problem for you. Are you aware of the nicotinamide lack of flushing and the association with schizophrenia? This is an indication of a defect in DHA metabolism. Check out my article on the subject.

It sounds like you have a lot of leads on how to compensate for some physiological problems.

Let me know what you figure out.

Anonymous said...

Thank you Dr. Ayers for your response! I will start trying some of these and let you know how I do.

Jeff

donny said...

Thanks for answering. Something I neglected to mention. My Dad also takes niacin. If he goes off it for a week or so, he has to go down to very small doses and then work his way up, because of the flush. I do flush, but it doesn't take me nearly as long to work up to the larger doses as it does for him. I also deal with social anxiety, and had a prolonged psychotic episode fifteen years. (Hearing voices, but I wasn't crazy-- I knew they weren't real.)

Dr. Art Ayers said...

Donny,
I wonder if niacin flushes would be minimized by increasing saturated fats. The flush seems to be related to omega-3 adequacy. So maybe it is similar to the exacerbation of inflammation by peroxidation of omega-3s and that is minimized by saturated fats.

Art

merrybee said...
This comment has been removed by the author.
Dr. Art Ayers said...

Merrybee,
I see arthritis as a typical autoimmune disease that starts with chronic, usually diet-based, inflammation and a disruption of the gut-associated lymphatic system ( GALT, the part of the small intestines that leads into the colon.) The net result is an inappropriate antibody attack on body tissue that is not suppressed by immune cells that would be produced in the GALT.

Probiotics help support the gut flora around the GALT and are needed for development of a healthy immune system.

It sounds like your gut flora were damaged by the vegetarian diet and that was the source of chronic inflammation and damaged GALT that resulted in an immune reaction to common meat components. I will write an article today on the major antigen, Neu5Gc, that is also involved in milk allergies in infants.

I think that you are suppressing attack on your joints by keeping GALT disfunctional by disrupting normal gut flora with a restricted diet. You may also have intestinal candidiasis or Helicobacter pylori infection in your stomach. If you have used lots of NSAIDs, then you also have leaky gut and plenty of bacteria, e.g. Clamydia pneumonia, distributed throughout your body at sights of local inflammation.

Your symptoms are consistent with significant gut dysbiosis that frequently also produces constipation.

The typical response for inflammatory and autoimmune diseases is to follow the basic guidelines for the anti-inflammatory diet that I recommend.

Test your serum vit.D, supplement to >70ng/ml by followup test.

Eliminate grain/starch/sugar.

Eliminate vegetable oils (use olive, coconut).

Increase saturated fats and start supplementing with omega-3 fish oils to reduce symptoms.

Check your vit.C tolerance by finding out the minimum amount of vitamin C supplement needed to produce diarrhea. If this is higher than 4grams/d, then you also have oxidative stress and should supplement with acetylcysteine.

Try to see if temporary relief from pain in hands and feet can be achieved with menthol (Vicks) and/or castor oil topical applications. Test the impact of vagal stimulation exercises on symptoms.

Start to build up your gut flora with probiotics and prebiotics (pectin and inulin-rich veggies.)

This approach should help to reduce sensitivity to triggering foods and start rebuilding gut flora as indicated by normal stools (no constipation) and tolerance to a broad range of veggies.

Let men know how you do.

merrybee said...
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Anonymous said...

Dr. Ayers, what do you consider a starch? Potatoes seem obvious. What else?

Thank you.

merrybee said...
This comment has been removed by the author.
Dr. Art Ayers said...

Merrybee,
Constipation doesn't actually come and go. I would say that you have eliminated most of your gut bacteria and the small amounts of stool that remain are determined by undigested material. That is the way that most people incorrectly view gut function. Normal stools are not made up of undigested fiber, but rather bacteria, gut flora.

I doubt that past episodes of honey or vitamin C or major dietary changes contributed to your loss of gut flora. The simplification of your gut flora probably came as you simplified your diet in response to increasing food intolerances.

In short, your gut flora is dysfunctional, but can be fixed by persistence in increasing the variety in your diet and recruiting the missing bacteria.

Acetylcysteine (NAC) is one of many synonyms (check Wikipedia) for this nutritional chemical that is available over the counter or in health food stores. Oxidative stress is a symptom, is not hard to avoid, but is due to dietary problems or disease. It does not occur naturally, nor is it environmental. It is directly related to inflammation, which is also just a management issue.

I think that you should keep track of the possible intestinal yeast infection, since most of your symptoms could result from intestinal candidiasis.

Serum 25(OH)D is a blood test done by a doctor. Most people with symptoms of inflammation, such as you, are low in vit. D. You are taking very low levels of vit.D in your cod liver oil. I would recommend using vit.D3 capsules instead. You will probably have to take very high levels for a short time to bring your serum 25(OH) test levels up to about 50ng/ml. The high initial doses are needed to overcome inflammation, that interferes with the ability to produce vit.D by sunlight on your skin. Subsequently, you can take 2000-5000 IU/day of vit.D3. Be forewarned, that most people test low for vit.D, then supplement and still remain low, because they never got over the initial inflammation caused by the vit.D deficiency.

You situation is certainly treatable. I would also say that many people are in the same situation with respect to their disrupted gut flora/constipation, but they just have different symptoms.

Keep me updated.

Dr. Art Ayers said...

Anonymous,
Starch is a polysaccharide made of a series of glucose molecules linked together in long chains. It is the only polysaccharide that can be digested by the body's enzymes in saliva and intestines. Starch in food is present in crystals that dissolve quickly in hot water to make thick gels, e.g. gravy or sauces.

Starch in foods such as cereal, pasta, rice, bread, potatoes, bananas, baked goods/pastries (see Wikipedia) is very quickly degraded by saliva amylase to produce sugar fragments that release glucose into the stomach and upper parts of the intestines.

Starch should be considered a simple sugar for its rapid impact on blood sugar. Starch produces a rapid rise in blood sugar, followed by a rapid rise in blood insulin that causes the blood sugar to be converted into fat. The result is a rapid drop in blood sugar that produces hunger and lethargy.

Starchy foods make you hungry for more starchy foods. Many low fat foods contain high amounts of starch. It is very hard to lose weight with starch as the major calorie source and that is why a diet that replaces the starch with saturated fats makes it easier to maintain a healthy weight. Starch is not needed.

Other dietary polysaccharides (carbohydrates) in plants are digested by gut bacteria and are called fiber. The bacteria use these carbs to produce short chain fatty acids that feed the colon.

Thanks for the question.

merry bee said...
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merrybee said...
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Tanya said...

Regarding glutathione and NAC

I read that whey protein is a greate source of glutathione...so combined with Dr. Ayers other comments about the 6 wk cure, I ordered the book. I will say I have tried whey protein powder and it was yucky. I am hoping there are different brands that don't taste like chalk.

I bought some NAC but haven't taken it. One of the side effects I read was irreg. heart rythym, which is one of the possible complications of my recent heart surgery, so am reluctant to try it on that account.

I'll let you know how the 6wk deal goes once we get going. I am going to try and get my husband to do it also, but since he has troubles with milk (gallbladder I think?) I am not sure how the whey will go for him. He's so miserable now I hope it will help and not make it much worse so he will keep going with it.

I have resorted to taking aspirin and alleve, and it has helped enough that I can function and the dizziness is reduced. I hope the 6 wk cure will be so I can get off them and be well.

Dr. Art Ayers said...

Tanya,
As far as I know, milk doesn't contain much glutathione, but rather has a good supply of cysteine, the sulfur amino acid in glutathione. So eating milk products, e.g. whey, is a good way to supplement your glutathione supply.

Whey is just a bunch of proteins, so like tofu, it doesn't have much taste. That is why the 6 Week Cure diet uses it in the form of whey shakes with cream and various flavorings. It is just the cheapest form of protein without many carbs and with lactoferrin. It is just for temporary consumption as a cheap, somewhat natural medication to adjust gut flora while shifting away from carbs as an energy source.

Is your husband's gall bladder problem related to eating too little fat? If so, after he adjusts, the new low carb diet should be a big help.

Thanks for the comments/questions.

Tanya said...

Thanks for clarifying how the whey and glutathione are connected.

My husband has an intolerance for chicken fat and milk fat. He eats all the fat with his steak, and that doesn't bother. But his recent onset of chest tingles/pain that he feared was cardiac has now been diagnosed as reflux...has small hiatal hernia. Only thing that helps is valium and he only takes it when it is unbearable. Gallbladder has been my working theory with him from a long time ago because of no better solution. It may just be bad gut flora, although he as a rancher is exposed to lots of flora and fauna. His vit d was 15 but he won't take any...he says he gets enough sun but he wears long sleeves and pants and long hair (to protect his neck) so the only sun in on his face/neck and hands...not much D there..and he's always more red than anything...can you say inflammation????

I have been reading the book, and as you have also said, the diet shift should help him if we can get through the initial unpleasant stages. His soda consumption and chewing tobacco are habits that need to change as well. He has severe neuropathic reaction when he quits chewing, even using the slow cutback method. It will be a couple weeks before we start, as I need to cut back my coffee intake and have to travel ~100 miles to get the protein, more veggie varieties etc, as our small town doesn't offer that.

Dr. Art Ayers said...

Hi Tanya,
I think that inflammation is the issue. Vit.D production by the skin in sunlight is blocked by inflammation. He needs to supplement and then retest his serum level. Low vit.D is inflammatory.

Diet is the major source of inflammation, but dental problems are a close second.

My impression is that most gall bladder problems stem from insufficient dietary fat. In other words, to keep bile flowing both the source of the bile, dietary fat, and the stimulus for bile release, dietary fat, must be adequate.

GERT is sometimes caused by inadequate stomach acid production -- inadequate to trigger closure of the valve into the stomach. Evening eating, close to bedtime, contributes to the problem.

I hope that your gut flora adjustment helps.

Anna said...

Tanya,

You said, ""100 miles to get the protein, more veggie varieties etc, as our small town doesn't offer that."

May I make a suggestion in regards to your distance going to town for groceries?

Have you considered keeping a garden for veggies, as well as some chickens for eggs and meat? Keeping rabbits also come to mind for a meat option. You also indicated your husband is a rancher, so to me that suggests you probably have the space and no doubt, the DIY ability to set up a protected chicken run, coop, and simple raised garden beds (I esp like Mel Bartholomew's Square Foot Gardening method for easy crops with minimal effort and time investment. Straw bale gardening is another option. Many no-till methods can be investigated online, at the library, or in magazines such as Acres USA, Mother Earth News, and Permaculture. There are so many innovative no-till methods of producing delicious healthy home-grown produce that is both space- and labor-saving - not even requiring a shovel, let alone tilling and back-breaking hours hoeing the rows.

If even no-till gardening isn't an option for you, have you considered sprouting seeds? Micro-gardening with sprouts produces incredibly nutrient- dense veggies that only take minutes of effort and minimal cost, though it does take some attention to establishing a routine to ensure a steady supply. There are a multitude of great sprouting systems available for every level of sprouting production, but my favorite is Easy Sprout: http://www.sproutpeople.com/devices/ez/easysprout.html

Here are some links about keeping chickens.

http://successwithpoultry.blogspot.com
http://www.self-sufficient-life.com
http://www.keepingchickensnewsletter.com/site

I realize there may be other reasons unknown to me why you must rely on store-bought foods, but these ideas came to mind when I read your comment.

Tanya said...

Anna

I appreciate your post. We have looked at the square foot gardening info before actually. But my recent surgeries/stroke sidelined our preparation for it. Also I work full time, and my husband basically ranches full time for his dad and cares for our children most of the time. We also have a business and church offices which take time.

So while we have the space (but poor native soils), water (albeit we pay for it..we are arid here) etc it is not practical for us to grow enough to really be a main stay, canning, etc. Not to mention this year the grasshoppers ate our garden overnight, what little the girls/dad had planted. We are infested this year!

I realize some may say my priorities are out of line but one can't garden in the dark...which is what it is when I get home from work and done with supper/dishes/prep for the next day. I spend my weekends on housework, time with my family, etc. I love to garden, flowers esp, but have had zero success in 15 yrs due to conditions and competition for the time and plants (hoppers!, horses out...etc!!) :-) If life allows, it would be a nice milestone to get a real garden going and growing next year.

We have a grocery store in the town where I work, but it has limited offerings due to distance, volume, etc. There is a farmers market but again limited by our population and climate and the hoppers this year. The nearest chain supermarket is 100 miles. I went Friday and spent $200 at the health food store on the vitamins, protein shakes (what I meant to say when I said 'protein' in my earlier post), etc for the diet, and then ordered another $50 online...and did not get any 'food'!

Don't mention rabbits to my girls...they have been bugging for pet ones forever. And I don't think they, even being farm kids, would take kindly to the eating of them. We know one family that does that and it was not popular (they had played with the rabbits on visits and then they were gone...)

My friend has chickens so we eat fresh eggs, and our own beef. As I said before chicken and my husband don't mesh, and the blood-type diet that had been discussed on this blog states that I am to avoid chicken also, and cured meats. Turkey is encouraged, and when time allows I buy one and roast, make soup, etc. from it.

My daughter and I tried hydroponics for a science fair project and we failed miserably...twice! The sprouted seeds info sound intriguing. I hope to check it out sometime.

My main comments on the diet, Dr. A, would be they still advocate artificial sweeteners, hotdogs, and other things that really make me shake my head. As for my husband, I have no doubt that there is a dental component as well, and that his eating habits are the culprit. I'll let you know how it goes.

Dr. Art Ayers said...

Tanya,
I think that a lot of people would sympathize with the desirability and difficulty of starting and maintaining a garden. I have been focusing on building and tiling a new shower and my garden (and blog) has suffered.

I don't think that the details of the Eades 6-week Cure Diet are as important as the rationales. Unfortunately, I think that the whey shakes, although essentially synthetic and unnatural, are very effective in disrupting gut flora to shift a metabolic set point and to change to a new diet. The artificial sweeteners are just to make the whey shakes more palatable. Most people are used to sweet drinks and essentially all sweeteners are either of questionable safety, carbs or both. The only exception is Stevia, which is a protein, but their is a suggestion that sweeteners of any type may elevate carb responses, e.g. insulin increase, via their taste reception in addition to glucose transporters.

Aside from the health risks of artificial sweeteners, I have a problem with their taste -- the lingering saccharine sweetness.

I don't think that tolerating artificial sweeteners or doing without sweetening, or any of the problems associated with two weeks of a gut treatment diet is a big deal in order to switch to a new diet that is healthy and can be enjoyed and sustained. That basic, anti-inflammatory diet is powerful enough to tolerate all of the other contaminants in our foods. My impression is that most people follow the advice of the medical community, which encourages a disease-causing inflammatory diet, and then those same people obsess over environmental contaminants that have a very minor impact on health.

Thanks for your thoughtful explanation.

Anna said...

I've been giving the protein shakes some thought lately. If one does not have an issue with consuming raw eggs, is there any reason why whey protein powder must be used in the Eades 6 wk shakes (or any version of a protein shake), instead of say, 2-4 raw eggs or several raw egg yolks?

That's how I've been making my "on-the-go" meals lately when the need arises. With just yolks I can use just a fork or spoon to mix them, as the yolks mix smoothly with little effort, but if I use whole raw eggs I use a hand-held blender to break up the thicker egg whites. I got this idea for "real food" shakes after flipping through Aajonus Vonderplanitz' interesting book, The Recipe For Living Without Disease.

To the eggs I add various combinations of other ingredients to achieve different flavors, as well as probiotics, prebiotics, natural fats, fat soluble vitamins, an and so on, such as 1-3 tablespoons raw cream or TJ heavy cream (NOT "ultra-pasteurized"), a "glug" of raw whole milk, a 1/4 whole milk yogurt, some coconut milk, 1-2 tbl MCT oil (NOW brand, not Novartis' $$$ medical version), a heaping scoop of dark Dutched cocoa powder, a shot or two of cold espresso, a handful of frozen berries, and so on. If I used fruit I leave out the cocoa and coffee.

One of my favorites is with yolks only (no whites), cream/milk, a touch of honey, and fresh nutmeg - far better than any store-bought egg nog.

If I add supplements, I use inulin powder and/or pectin, a drop of K2 oil, d-Ribose, and sometimes Vit D drops.

I add cold water or refrigerator tea (black, green, and/or herbal) and/or broken ice depending on the temp/ thickness/flavor I am after.

I find these shakes are very fast to mix and clean-up (with practice), the sweetness level is easy to customize, they are much cheaper and certainly less processed than protein powders, and if the fat content is high enough they are very filling. I tend to use little or no sweetening (inulin powder is slightly sweet) for myself, but my son prefers them with a small amount of honey or maple syrup. Personally, I am not opposed to a small amount of Splenda-sweetened flavored syrups, either, but I don't generally use them for myself.

What do you think of making meal replacement shakes with raw eggs/yolks for protein instead of powders?

Dr. Art Ayers said...

Hi Anna,
I think that all of your suggestions are very useful for a low carb, high fat diet. The issue that is being addressed is destabilizing the existing gut flora, not supporting a gut flora appropriate to the new diet.

I think that there is something special about the milk-derived whey protein shakes. Milk attacks most normal gut flora. Milk is adapted to inhibit the growth of all bacteria except the one or two species that stimulates the initial development of the gut and the gut-associated lymphatic tissue.

Raw milk attacks adult gut flora and adult gut flora inactivates the anti-microbial components in milk. That is why a single bottle of formula increases the disease susceptibility of an otherwise exclusively breastfed baby -- the formula permits adult gut flora to take over the gut and inactivate subsequent breast milk.

The point of the whey is to attack the existing gut flora and stimulate ejection of the damaged biofilms by the induced mild diarrhea. The disrupted gut flora are no longer able to contribute to the metabolic set point and change of weight is facilitated. It is also easier to reestablish the gut flora consistent with the new, low carb diet.

To some extent raw egg whites would attack gut flora similarly to whey, but most people don't easily quaff slimy whites. Cooking inactivates most of the enzymes, iron chelators and vitamin sequestoring proteins in egg whites.

So the point of the whey shakes is whey rather than protein.

Note that I am adding a spin on the Eades 6 Week Cure diet that is not presented by the Drs. Eades. I am trying to explain additional reasons why it is effective.

Thanks for the info and comments.

Tanya said...

Dr Ayers...one more question on the diet. They recommend DAG/Enova oil...which apparently is canola oil and soybean oil...to be added to shakes etc. I am figuring on using olive oil instead. I don't even think Enova is on the market anymore...what did you do with that recommendation, and the one about no caffeine!

I don't know which will be harder...no caffeine the first two weeks (I'm going decaf) or no dairly the next two (it is a mainstay for me and so easy).

Dr. Art Ayers said...

Hi Tanya,
I just skip the DAG and certainly don't use canola and soy oils. I just add cream to the shakes. It seems to me that what is important in the first two weeks of the Eades 6-Week Cure Diet is lack of alcohol and other drugs that are hard on the liver, low carbs (especially those containing fructose), no grain and no vegetable oils. That leaves saturated fats in dairy and eggs, and olive oil. The shakes provide whey protein and leucine is added to avoid using muscle protein. Supplements provide necessary vitamins and minerals. There is one low carb meal a day to help the gut flora limp along as it is starved for carbs and gets used to a meat and veggies diet.

Keep me posted.

Jay said...

great blog!

I have no idea if you are still active here or reading these comments but I wanted to ask you something about biofilms and enzymes

If I'm understanding you correctly the enzymes that are most likely to be effective against biofilms are those that hydrolyze polysaccharide. Is that correct?

If so, then wouldn't amylase and cellulase be effective against biofilms?

Dr. Art Ayers said...

Jay,
The fibers or matrix that holds a biofilm bacterial community together is made of polysaccharides that can be different for each major species of bacteria in a biofilm, in the same way that different bacteria synthesize different polysaccharides (LPS) that are the different antigens of the bacteria.

Humans and plants also coat the surfaces of individual cells and tissues with polysaccharides. In the case of humans, the polysaccharides are GAGs (glycosaminoglycans, e.g. heparin, chondroitin sulfate) and in plants they are pectins, xyloglucans, cellulose, etc. In most cases, including bacteria, the matrix is made of acidic polysaccharides.

Humans can only produce enzymes to degrade starch (which is a storage polysaccharide in plants and animals). All other polysaccharides are soluble fibers that are digested in the colon by bacterial enzymes. The bacteria produce short chain fatty acids that are the major energy source for the colon.

Biofilm polysaccharides can be digested only by enyzmes specific to each of hundreds of different polysaccharides. The links between the strands of polysaccharide are, however, made of common materials, either metal ions (calcium, magnesium, zinc, etc.) or proteins. Proteins bind to polysaccharides with a combination of common and unique bonds. The common bonds are typically through hydrophobic interactions between the hydrophobic sides of sugars and hydrophobic parts of protein amino acids, e.g. trytophan, tyrosine, arginine, lysine. PEG can break up these types of bonds and is used in total bowel irrigation prior to colonoscopy.

The bottom line is that amylase won't impact biofilms, but chelators such as EDTA or large amounts of proteases can have some impact. In most cases a careful change of diet and exposure to lots of different bacteria to improve gut flora is a more sound approach to changing gut biofilms.

Thanks for your comment/questions.

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