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, March 14, 2009

Enteroviruses, Autoimmunity, Diabetes

Insulin-producing cells of the pancreases of diabetics have been found to harbor viruses common to the gut. Antibodies to the virus coat proteins also bind to pancreas proteins.

A recent paper, referenced below, shows that in a collection of samples from the pancreases of individuals that had been diagnosed with type I diabetes less than one year prior to the sampling, insulin producing cells are also infected with enterovirus. The same association between enterovirus infection was found to a lesser extent in type II diabetics, but not in non-diabetic controls.

Enteroviruses have been repeated associated with diabetes over the last decade and antigenic determinants of the enterovirus protein coat also bind, i.e. cross react, with antigenic determinants of human cellular proteins.

I examined the enterovirus coat protein, VP1, and found the same three amino acid sequence (three basic amino acids, lysine [K] or arginine [R], highlighted) that I also found in all allergens (peanut, ragweed, dust mite, bee venom) and autoantigens of autoimmune diseases (lupus, MS), and is associated with heparan sulfate-based internalization and presentation of protein immunogens. This observation is consistent with my hypothesis that inflammation plus the presence of one of these proteins, results in production of B and T lymphocytes specific for antigenic determinants on the surface of the immunogen protein. Note that the antigenic determinants usually do not include the three basic amino acid sequence, e.g. RRK, that is involved in uptake and presentation of the protein.

VP1 [Human enterovirus B]
HVINYHTRSESSVENFMGRAACVYIAQYATEKVNDELDR
YTNWEITTRQVAQLRRKLEMFTYMRFDLEVTFVITSSQR
TSTTYASDSPPLTHQVM

reference:
Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. 2009. The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia. Mar 6. [Epub ahead of print]

34 comments:

Stephan said...

Hi Dr. Ayers,

Is a 3- amino acid sequence enough to provoke an immune response? It seems like any 3- amino acid antigen would be repeated numerous times throughout the proteome, statistically speaking.

Dr. Art Ayers said...

No. The three amino acid sequence merely means that the protein will be dragged into a cell for presentation to the immune system. The protein will then be fragmented and the peptides will be presented on the surface of the cells in MHAs for action by T cells. The three basic amino acids don't even end up being presented. If you check proteins, you will only find three basic amino acids in nuclear proteins (also autoantigens in lupus) and in proteins, such as heparanase or HIV TAT, that are exported and then internalized. That is also the case with the cytokines that have this sequence. In the cytoplasm, four basic amino acids or two close pairs is a nuclear localization signal.
I was just looking at bee venom and the major bee allergen is Melittin the sequence: GIGAVLKVLTTGLPALISWIKRKRQQ.
Note the four basic amino acids, KRKR.

Dr. Art Ayers said...

Another example of a couple of amino acids that provides molecular recognition is the twin arginine transport system in bacteria. Only proteins that are dumped outside the cell have two arginines together. You can check to see if a bacterium has that transport system by the exclusion of two adjacent Rs from all of its other proteins. Even DNA binding proteins, that frequently have adjacent basic amino acids will lack RR.

Stephan said...

Thanks. I understand that within a proteome, short peptide sequences are enough to mediate recognition, but you're saying that's also true of the immune system recognizing foreign proteins? So if I understand correctly, that three a.a. sequence you mentioned is enough for a cell to recognize a protein as foreign and present antigens to the immune system? I'm asking naively because my immunology knowledge is rudimentary.

On another topic, I remember you mentioning that you're skeptical of anti-lectin antibody tests because antibodies are glycoproteins. Is that because they use lectins in their detection assay? It's an interesting idea. So are you skeptical of gluten sensitivity tests based on anti-gliadin IgG/IgA then? I wonder if gliadin binds the sugars on IgA/IgG glycoproteins.

Wheat lectins (both WGA and gliadin) bind glucosamine, which I've speculated might be the real reason why glucosamine helps some peoples' arthritis symptoms.

Dr. Art Ayers said...

The distinction between foreign and self is very complex and based on both deletion of self-responding components and active suppression, tolerance to antigens associated with self. Mistakes become disease, i.e. infections or autoimmunity.

I am just identifying a general system used to internalize proteins, three basic amino acids, e.g. RRR or RKR or KKR, that is apparently used or abused during protein processing for the immune system. In inflamed tissue the proteins processed by this system should be foreign and the subsequent immune response should be beneficial. If self, cellular antigens are swept in by mistake, then autoimmunity can result. If innocuous foreign antigens are swept in, then allergy can result.
The question about lectin being used in antibody-based systems was, I think, related to the fact that the antibodies are glycoproteins and the lectins might bind to the antibodies. In that case, the antibodies would have no specificity for the lectin.

The gliadin system is another complication and immunological confusion, because of all of the proteins that are being internalized for the wrong reasons. I think that the gliadin is present as part of the plant seed defense system against herbivores. The plant could produce large, negatively charged molecules and these would be a problem to digest. There would also be a charge repulsion problem to package in seeds (like packaging DNA in the nucleus or secretion of heparin by mast cells -- charge neutralization is required.) The plant produces proteins containing glutamine instead of glutamic acid to avoid the charge problem. The intestines produce transglutaminase to remove the amines, but the enzyme process leaves the gliadin bound to the enzyme. The net result, is that both the gliadin and enzyme get swept into the immune system, are chopped up and presented, and antibodies to gliadin and transglutaminase epitopes are produced. Subsequently, these antibodies participate in celiac flareups in the presence of wheat.
Your speculation about glucosamine, lectins and arthritis sounds good to me. I doubt if just a single interaction is involved. It is complex and that is why the research data are controversial. I still think that most of the reactions with glucosamine take place in the gut, that the gut is very important as part of both the immune and the nervous system, and that the symptom relief is real. Glucosamine modifies glucose metabolism, lectin interactions (wheat, bacteria, viral), gut flora communication and the AGE (advanced glycation endproducts) response system. The only thing that doesn't make sense with glucosamine supplements is altering GAG metabolism in joints. That would be the same as saying that eating gelatin will help your fingernails.

Anonymous said...

Sorry for the off-topic nature of this comment. It concerns a post from October of last year, where you mentioned that glucosamine would be useful in cases of asthma. What amount would one take, and which would likely be more effective, the hydrochloride or the sulphate form? Also, would it be more effective to take the glucosamine on an empty stomach or with food? You also mentioned in a different post the possibility that arginine supplementation might be useful for asthma. What amounts would you suggest, and again, would you take it on an empty stomach or with food?

Thanks so much for your help and or your informative and useful blog – the first time I found it I ended up reading most of it in one evening!

Dr. Art Ayers said...

Asthma is a complex acute and chronic immunological response to environmental molecular signals. The tissues of the lungs have been restructured. Treatment and cure require reversal of aberrant development and elimination of inappropriate immunological responses.

The foundation of asthma is inflammation. The cure requires elimination of all of the inflammatory inputs.

This does not mean focusing on avoiding allergens. It means shifting to an anti-inflammatory diet and lifestyle. I have given the general outlines for this approach and explained various aspects throughout this website. In brief: low carbs, low omega-6, high omega-3, high vitamins C (1000mg) and D (>2000 iu), high plant anti-oxidants, high glucosamine (1000 mg). mg = milligram

High glucosamine means taking a large, 750 mg pill with each meal.

Arginine supplementation to compensate for suspected nitric oxide depletion is speculative. The point of the discussion was that chronic inflammation with superimposed acute production of NO would deplete arginine and rebound into an NO deficiency. Compensating for this depletion would be difficult to estimate. I would recommend using typical supplement recommendations, until some studies have been done. I don't know anything about the toxicity of arginine.

The most effective treatment for asthma that I have read about is helminth therapy. Parasitic intestinal worms suppress inflammation and produce more appropriate tolerance. That may be a bit too much too swallow, but it shows the impact of the gut in asthma and points toward a need for probiotics as part of the treatment.

I am not a medical doctor, so I cannot give medical advice. My focus is showing how disease reveals the molecular basis of living systems.

Angela said...

Hi Dr. Ayers,

I just found your blog and it's like a gold mine. I wish all of the things I have to learn for med school would be so supported by real evidence.

I would love to have your opinion on my case -- of course if you have a moment to look at it.

I am a 25 yo medical student (-i know-) with multiple sclerosis, rosacea, story of recurring hypoglycemias, many -itis, familiar hypercholesterolemia, familiar history of Alzheimer's, cardiovascular disease and osteoarthritis (not single cases).

In two years I have gone from i-don't-need-anatomy-carts-i-can-see-my-muscles leanness to overweight because of depression (used to be very active and then everything went down).

I feel like I am the poster girl of inflammation. I have tried everything, from mcdonald's low in sat fat (which i feel it made everything worse because of all the carbs) to a more paleo-like Best Bet Diet... But you just have to look at my face to know something's not working.

I suffer a bit from paralysis by analysis. I don't know what to watch out for is it - saturated fat? trigger proteins in dairy and grains, lectins from legumes? dairy -- but what, proteins or lactose? nightshades? sugar, to avoid insulin spikes?

I also don't know if I have to be very radical about it (don't dare look at the ice cream never again! don't touch that tomato) or if I will have some room once I control inflammation.

I am supplementing with omega 3 (8 g/day). I am considering other supplements (vitamin D, B complex, magnesium, zinc), but living in Spain makes it a bit difficult. For example, it is very hard to find vitamin D in gel cap form, there's only tablets... And spanish customs stop everything from outside the EU.

Intermittent fasting (14 hours a day) really helps my periodontal disease.

I am not on any medication as I don't think interferon or glatiramer acetate can offer something I can't get from a healthy lifestyle... Plus I have seen the secondary effects they have (had one uncle with MS). Plus I am too young (my brain scan showed old MS lesions when I was 15, so it probably started when I was a child), and my MS is not *that* bad. Right now I don't have any complains from it other than some tightness sp in hip flexors -- and the fact that I am very out of shape (used to compete in taekwondo during my teens).

Do you have any dietary advice from me? Any recommendation on supplements? As for lifestyle, I am taking it easy in medical school (the greatest pain in the *** is having to study so many idiothic things in the name of Evidence Based Medicine), I try to have plenty of sleep and am slowy increasing my activity levels.

Thank you very much in advance.

Anonymous said...

Hi Dr A,

I just found this site. It's very interesting. I noticed you treated your dog with glucosamine. I'm a veterinarian and recommend it often for client's animals. For an enhanced effect, I augment with Adequan, an injectable polysulfated glycosaminoglycan.

Recently I developed lateral epicondylitis in both elbows and plan to treat myself with adequan injections. It's a painless, subcutaneous injection.

kevin

Dr. B G said...

Hi Dr. Ayers,

From a pharmacological perspective, your posts are eye-opening! I love your BLOG.

What are your thoughts on our immune system producing MBLs (mannose-binding lectins)? Like Stephan's hypothesis that glucosamine is effective by being a 'surrogate' target of a dysregulated immune system, it appears to me that mannose from let's say cranberry juice may be effective for Gram-neg (like E.coli) UTIs by providing mannose, in this case, by providing more 'surrogate' immune targets, heightening the bacterial triggered immune response (?).

Fructose and mannose are both carried on the outer membranes of invading bacteria and prokaryotes and programmed to be sensed by our sentinel immune system. Excessive fruit consumption (and HFCS, soda, juices) appears particularly detrimental to Autoimmunity, Diabetes and other inflammatory conditions (like wheat/gluten). I'd love to hear your thoughts...!

(have to admit my immunology needs help)
Thank you!
G

Anonymous said...

Hi Dr. Ayers,

I just found your blog yesterday and am working my way through all of your previous posts. I look forward to reading any future postings. This has been a fantastic find for me. Thank You.
steveyyz

Dr. Art Ayers said...

Angela,
Sorry I was so slow in getting back to you.
Your symptoms do make you sound like the inflammation poster child.
I would suggest to focus first on vitamin D. You may be so inflamed that you have compromised your solar production. I would start with 5000 IU/day and take it throughout the day with meals (phytoantioxidants). I think that as much as 10,000/day is without side effects. This should also help oral health.

Dental problems are obviously major contributors to inflammation. Good oral health is essential -- brushing, flossing, etc. It sounds like you have more serious problems. Listerine with menthol, thymol, eucalyptol, etc. (blue) should be a big help. It is also anti-inflammatory.

Vitamin C -- It sounds like you have a big load of oxidation stress. I would expect that to lead to vitamin C depletion and deficiency. This would give you oral health problems. You might try increasing your vitamin C until you get bowel symptoms. That would mean trying 4000 mg/day to see if you can tolerate that much and then adjusting up or down.

Probiotics -- You have probably messed up all of your gut flora by producing food allergies as a result of high chronic inflammation. This will also mess up your B vitamin uptake. Start enjoying simple whole fat yogurt without sweetening. You can make very tasty Indian lasi drinks using a hand-held blender to mix yogurt and fresh/frozen fruit.

Your fasting is a master stroke, because it induces anti-inflammatory cytokines and lowers your blood sugar. Unfortunately, coming off your fast, even lower sugar meals will cause a big insulin boost. I would expect you to have trouble regulating your blood sugar. Low carb is the only approach. Switch to more small meals. Avoid starch, fruit juices, sugar. Enjoy meat and lots of spices -- turmeric, red pepper, black pepper.

Avoid all vegetable oils except olive oil. Try cooking with coconut oil and butter. Enjoy wild salmon frequently -- just broil with pats of butter and lemon juice.
Supplement with fish oil. You are already doing this, but are not benefiting, because of all of the other sources of inflammation.

MS results from inflammation that has broken down the blood brain barrier. Doing all of the above simple stuff should be a big help.

Physical activity is also a big help, so force yourself to increase your muscle mass. You need more than cardio.

Glucosamine should also help, once you have reestablished your gut flora -- 1,500 mg/day.

I can only help with this common sense approach. You still need to work with medical people, so find some people who have a clue. Some veterinarians may be more helpful.

Dr. Art Ayers said...

Kevin- the Vet,

I must admit that I have more respect for vets than MDs. You guys are more pragmatic than ideologic.


I have no idea why Adequan would work as an injectible. I am convinced that glucosamine's effects are all in the gut. Gut administration of any of the GAGs (heparin, chondroitin, HA) or their monomers can't have an effect on connective tissue GAGs. Glucosamine is produced in most cells and having more available isn't going to impact GAG production. Besides, chondrocytes actively metabolize the GAGs in which they are embedded -- they burrow like moles. It is these tunnels of newly synthesized cartilage that repair torn or cut cartilage; chondrocytes stitch the cartilage together.

Your tennis elbow may respond better by chemical acupuncture in the form of castor oil. You can add menthol or capsaicin to stimulate the hot/cold sensor. All three work similarly to stimulate pain reduction and lower inflammation. Just coat the whole general area and pain should be gone in five minutes. You should be able to use that pain to monitor your overall inflammation.

I enjoy your comments.

Dr. Art Ayers said...

Dr. B G,

Thanks for your comments.

I started working with lectins in host-pathogen interactions back in the early 70s. I found a glucan that would trigger plant disease resistance. Mannose could inhibit the response. Now supplements with that glucan are used to "stimulate the immune system". This probably means that it induces inflammation. Mannans seem to be anti-inflammatory.

Pathogen detection in mammals takes place in part by innate lectins, such as the mannosyl binding protein. Many pathogens bind to human cells by using their lectins to bind to human glycosyl residues. This makes sense, because sugar binding is a hydrophobic process that can release approx. 20 kcal/mol. Simple sugars are very much less effective than oligosaccharides in binding, so only situation such as the bladder, in which the pathogen will be swept away unless it adheres, will be affected by monosaccharides such as mannose.

Fructose has lots of other actions outside of the realm of lectin interactions. I doubt that dietary fructose has anything to do with lectins. It is much more important in advanced glycation endproducts, in which case it no longer chemically resembles fructose.

I also don't think that wheat lectins or any lectins are involved in celiac and gluten-based problems.

Dr. B G said...

Dr. Ayers,

Again I really appreciate how Asclepius (of Natural Messiah blog) found you!

You are a GEM! Thank you for your explanations!

Dietary lectins may not be involved in fructose toxicity in mammals but how about the role of mannose and fructose in the exterior of viruses, bacteria and fungus? Can innate MBLs distinguish between mannose v. fructose?

I agree, fructose can cause autoimmune problems, like NASH (autoimmune fatty liver), via its damage from AGEs production (? probably accelerated by excessive omega-6 and lack of omega-3 and vitamin ADEK deficiencies?).

We have found that gluten elimination is highly effective in 'cooling inflammation' for CAD and a variety of autoimmune disorders (including osteoarthritis, diabetes Type 2, Hashimoto's, etc) at our heart disease reversal program. The gluten-genetic interaction appears to affect 99% of the population. For my family and I, eliminating gluten has produced immense anti-inflammatory benefits:
--my father-in-laws RA subsided and eliminated knee joint aches (some antioxidants speeded recover -- krill oil/astaxanthin (you've written about), pycnogenol)
--my daughter's vitiligo resolved
--IBS for several family members resolved completely
--my mood is calm
--my children halted ALL tantrums (which were rare anyway)

For my patients I've noticed 5 lb/month wt loss despite lack of exercise, resolution of body/joint aches, reduction in belly fat and decreased insulin requirements (or even complete elimination)!

I think I'll stay away from Mannose for now :)

THANK YOU AGAIN!
g

Dr. Art Ayers said...

Dr. B G,
I grew up with lectins and see them in rather friendly terms. Structurally monomers are not related to the corresponding residue in a polymer, so an enzyme that binds mannose will not bind to a mannosyl residue in an oligosaccharide. Antibodies or lectin specific for mannosyl residues will bind mannose with less than 1% the affinity. Mannose and fructose in the diet will not have an impact on lectins binding to oligosaccharides.

I doubt that mannose in cranberry juice has any impact on bacteria binding to mannosyl residues of the urinary tract, unless large quantities of mannose are concentrated in the kidney and stored in the bladder. I would still be surprised if gut bacteria were impacted by the dietary mannose during this process.

I think that dietary supplement glucosamine has a metabolic impact on gut flora, but I remain skeptical of any lectin-mediated effects.

The vitiligo interaction is interesting. One of my students developed vitiligo, celiac and a string of food allergies. She is an expert at avoiding gluten, but still has lots of allergies. She recently developed an allergy to DHA/EPA capsules. Clearly her inflammation is not under control and her strange nutrient absorption makes it hard to determine the impact of supplements. What would you recommend?

Thanks for stopping by,
Art

Dr. B G said...

Hi Dr. Ayers,

Thank you for the clarification -- perhaps that explains why some cranberry juice UTI studies show efficacy while others bunk... Lectins are so curious to me -- like auto-antibodies, there are some studies that show lectins bind insulin receptors as well as structures like ovarian cells. Perhaps nature intended some sort of protective 'signal' (hibernation, hyper-immunity, ?) which now is going awry?

(I'm in the camp where 99.5% of the global populace are silent celiac or overt celiac.) Gluten-damage on the intestinal lining responds well to nutrients that boost immunity, removal of dietary toxins (gluten, sometimes casein) and replacing fat soluble vitamins (which are not absorbed while the gut is 'leaky' and damaged).
-Zn Se Bo Iodine Chromium etc
-Magnesium to keep blood levels 2.2 -2.3mg/dl
-B vitamins, folic acid, TMG, B6, sublingual B12, etc
-vitamin D (enough to bring blood to 25(OH)D 70 ng/ml or higher)
-vitamin A E K1 K2
-vitamin C
-EPA DHA fish oil (maybe try liquid Carlson's? tastes yummy, like lemon pledge, j/k)
-saturated fats (lauric acid, MCT, coconut oil, meat/fish, yolks, butter oil, etc)
-co Q10, alpha lipoic acid, carnitine, taurine, etc
-low carb, insulin-controlled diet

The role of digestive enzymes (to replace what the gallbladder is probably too damaged to make) and probiotics is highly beneficial as well. (Fungal overgrowth is sometimes a HUGE problem. Yeast die off can be an issue too.)

It's hard -- hope she feels better soon!

-G

Anonymous said...

Dr. Ayers,

I'm curious as to your take on this paper, "Vitamin D: the alternative hypothesis," to be published in Autoimmunity Reviews, and available at http://autoimmunityresearch.org/transcripts/AR-Albert-VitD.pdf. It suggests that vitamin D might supplementation might be counterproductive in autoimmune conditions. What should we make of this?

Dr. Art Ayers said...

That is a great article. It provides a skeptical perspective on the new vitamin D deficiency bandwagon (that I support.) It basically sets up a choice between the vitamin D deficiency and pervasive chronic infections as the basis for autoimmune diseases. Supplementation with vitamin D would be a disaster, if the infection model is true, because it would lead to an initial obscuring of symptoms followed by more severe relapse.

I find the article flawed by its characterization of the deficiency model as a simple switch triggered by vitamin D (forms) binding to the vitamin D receptor transcription factor and turning on innate immunity genes. I think that there are numerous vitamin D activated proteins, since the binding structure is very common and many extracellular proteins have beta-sheet jelly doughnut like structures that might bind steroids. So I fall into the stereotype of black box biochemistry that says that too little vitamin D leads to dysfunctions that trigger chronic inflammation and autoimmune diseases start from there.

That said, I also give credibility to the chronic infection models and the triggering of hibernation-like responses. Thus, some treatments with antibiotics may make sense for some autoimmune diseases, cancers, etc. We don't know enough for these treatments. After all, high dose aspirin has also been effective in some cases.

The article also makes reference to gut flora and I find that aspect very important as well.

So, the bottom line is a vague support for my general prejudices. The article says to beware of cures lacking clear explanations of the causes. That advice would eliminate the whole drug industry. I tend to avoid pharmaceuticals and lean toward sensible diet and exercise. At 60+ I can still do handstands and practice karate without joint pain or stiffness (as long as I stay on an anti-inflammatory diet.) If I eat American, I suffer just like everyone else.

AngelaN said...

Dr Ayers,

Thanks you for your -very comprehensive- response. I was absolutely focused in food allergies, instead of bringing balance to inflammation.

The truth is that I don't think the "complete elimination of X, Y, Z" was making any difference and I am coming to a point where I may develop allergies for everything that I eat (as confirmed by ELISA tests... Lots of false positives, I know, but every time I do one of them more and more things will come back positive).

Thanks again and please keep it up with your blog, it's a great resource for both patients and scientists.

Best regards

Kevin said...

Hi Dr A,

I read your March 29 article on estrogen and prostate inflammation. I was recently diagnosed with BPH. I read Shippen's book ten years ago, saying pretty much what your article says. Maybe it's simplistic, but suppressing estrogen through tamoxifen-type drugs makes sense. So why are drugs like Proscar used more commonly? And why would it cause estrogenic side effects, such as gyncomastia? Not looking for a medical opinion, just your personal opinion on these questions.

TIA,

kevin

Dr. Art Ayers said...

Kevin,
Prostate cells have lots of interesting receptors, e.g. testosterone, estrogen, TRPM8 (cold/menthol). Testosterone-based inhibitors have been used, because prostate development is male-specific and so these inhibitors are logical. They work, temporarily, until the selection pressure results in testosterone independent growth.
Estrogen receptors (everywhere) is a new idea, so it wasn't tested. My impression is that this is a hot new area for pharmaceutical development. Soon, all boys will be getting rectal exams and be treated with the next big drug.
The moral of the story is that prostate problems are modern and related to diet and lifestyle.
Prostate problems point to inflammation and that is why older men have more prostate problems, because inflammation increases with age.
Symptoms of aging are mismanaged chronic inflammation.
The good news is that if you adjust your lifestyle to fix your prostate, you will age more slowly.
Art

Bengt said...

Seems like your blog spot is becoming more and more popular, good job Dr. Ayers =)
Interesting that you are talking about vitiligo. I just gave a project presentation involving c-kit receptor and a key regulating transcription factor of pigmentation called mitf. Affected skin areas from vitiligo patients show a significant downregulation of both c-kit and mitf protein. I am not very well read in the mechanisms behind autoimmune disease and how it is related to vitiligo but reports show that transcription factors (SOX9 & SOX 10) directly upstream of mitf are reactive to autoantigens found the serum of patients with hereditary disorder autoimmune polyendocrine syndrome type I.
Don't know if this fits into your area of research but I found it interesting how everything is connected.

Anonymous said...

Hi dr, i am a medical student with great interest in neuroendocrinology and immunology. Apart from that i have a chronic cytomegalovirus and enterovirus-coxsackie B infection and i am searching for different ways to combat it, especially the latest enterovirus infection that has caused a very difficult enteric inflammation and dilatation.
Do you have any ideas how could i approach a potential treatment?? My immune system is deteriorating and i cant figure out what to do, there is no direct anti-enteroviral drugs, and im trying some immunemodulators which are really strong on my body and dont see any results. large quantities of vitamin C shows some very very small improvement but nothing important.

I am looking for some natural or herbal or antivirals or some other anti-interleukins or receptor fusion treatment or modulators

Axel said...

If anyone have more suggestion for vitiligo please let me know.

Would you suggest testing for celiac?
Multivitamin but no D3 high dose?

Thanks

Anonymous said...

Axel,
My sister has vitiligo and she had very good results with relatively high dose vitamin D supplementation. She weighs approximately 145 pounds and was taking 8,000 to 10,000iu per day. Her serum 25 OH D level reached the 65 ng/ml area. She started seeing improvement in her pigmentation after 4 weeks. I'm sure there are likely multiple causes and vitamin D may not help everyone, but if you are deficient or quite low anyway, the potential health benefits of getting toward that 65~70 ng/ml area may be a good idea for general health in many people.
On a related note, about 6 months ago, she had an allergic reaction to something and decided to discontinue all of her supplements just in case any of them were the cause. After about two months of no vitamin d supplements and little if any sun exposure, her vitiligo started to reappear although not nearly as bad as it had been. By that time she had recovered from her allergic reaction and restarted her vitamin D again. Shortly after that her vitiligo started to go away again.


Art

Axel said...

Thanks Anonymous for the info oan vitiligo and D3.

What I find strange is that people with vitiligo avoid the sun but treatments use UV light.

Anonymous said...

Axel,

If it has any significance to you, I remember my sister saying that she could not go out in sunlight prior to taking vitamin d as she would have an allergic type reaction. She could only tolerate the very early morning sun for a brief period of time.
I remember now, that is the reason I had suggested supplementing with vitamin D to her because I felt that if she could not go out in the mid day sun and was not taking vitamin D, then she must surely be deficient.
Once she got her serum 25 OH D level up, she was able to tolerate sun exposure better.

Art

Hip said...

This allergen amino acid sequence you found in the enterovirus VP1 protein is extremely interesting!

May I ask a question: in addition to diabetes, would you say this finding has import for chronic fatigue syndrome (ME/CFS), which is strongly associated with enteroviruses?

Enterovirus VP1 protein is persistently present in ME/CFS patients, and is found much more commonly in these patients than in health controls. Reference: 1 2

And 50% of ME/CFS patients have autoantibodies to the M1 muscarinic receptor, which is found in the parasympathetic nerves (and these autoantibodies may conceivably be responsible for the disturbed autonomic nervous system function found in ME/CFS). Ref: 1

Also, some very recent clinical research has found that ME/CFS can be put into remission by deleting a patient's B-cells, using the arthritis drug rituximab. This fact further suggests that ME/CFS has an autoimmune basis. Ref: 1

So might this enterovirus allergen amino acid sequence be driving the autoimmune processes that may be present in ME/CFS?

Unknown said...

Hi,

I listed to your talk on Jimmy Moore's Show and read 25 of your posts over this past weekend. Finally, I feel I have read content that makes sense.

I have vitiligo - a skin condition that is linked with Type 1 diabetes. I am quite thin so have never been tested for diabetes. I had no idea vitiligo was related to diabetes until this weekend. I have had the condition since I was 2 years of age.

About three years ago, I developed rosacea - an inflammatory skin condition in the insulin resistant family of illnesses which you have written extensively about.

Dr. Ayers, thank you so so much for this blog. I have learned so much and now know that the paleo-diet I am on is key. I have taken vitamin D on and off, never realizing it was a key factor in my complex array of gut flora breakdown.

I have always had a bowel movement daily and would never have considered myself constipated. That said, I have read that people with rosacea have low orocecal transit time and I am now beginning to see that the Time foods spends inside me is longer. I am also starting to note that although I've been eating seared almost rare beef to heal my intestinal walls, I believe that causes me to be infrequently constipated. It's so frustrating trying to carry out a science experiment on myself while also attempting to live and enjoy life.

I have contacted 2 doctors to investigate getting a fecal transplant. I have gone from incredulous, to sold in a weekend of research. It makes SO much sense to me, I could almost cry for the past three years I have spent banging my head against a wall of limited information to determine how to truly heal inflammation.

Can you offer any comments on the potential links (obvious or not) between roasacea and vitiligo? I am about to cut fruit out of my diet due to their insulin causing effect.

Again, *thank you* for offering your insights.

Dr. Art Ayers said...

Unknown,
I would be very surprised if the cause of all of your problems wasn't celiac/gluten intolerance. It is a major contributor to autoimmune diseases, typically starting with thyroiditis and producing either too much or too little thyroid hormone. I think that when you changed diets, you reduced the celiac symptoms and thereby reduced chronic inflammation.

Your vitamin D is still probably low even though you supplement. Your gut flora, as you recognize, seems very damaged and is a major contributor. I think that you would also be wise to feed your gut flora with plenty of soluble fiber and avoid grains.

I think that a fecal transplant would be a good idea, but you would also have to immediately change your diet to maintain the new gut flora, since your current diet would kill it.

Keep in touch with your progress and questions.

Clare said...

Dr. Ayers,

I updated my profile, so I am the Anon from above...

Yes, you are correct; I have a wheat allergy/intolerance and have cut that out for almost 2 years now. I occasionally get contaminated when I eat out and am weary of anything that may have soy sauce in it.

Two things you wrote that caught my attention: thyroiditis and my diet. My mother had her thyroid removed when she was a child, and has taken thyroid supplements all her life. How did you infer thyroiditis with rosacea/vitiligo? I haven't read anything that correlates the two, yet have a parent with a compromised thyroid. Would that have affected me? and hence be related to rosacea and vitiligo?

Secondly, you said that once I get an FMT that I would have to change my diet immediately. Is a paleo diet not essentially the Anti-Inflammatory diet? Is how I am eating still causing inflammation? Well, it is as I still have break outs, but what am I not seeing?

I eat meat, vegetables and almond milk. I fill my plate with 1/2 to 2/3 vegetables, the rest meat. No starchy vegetables. I cook with ghee and am generous with ghee (fat). Ghee has cooling properties, has a high smoke point, acts like Coconut oil. I am taking Vitamin D (increasing my does to 10,000 IU), O-3 fish oil and L-glutathione. And no fruits for the next year. Can you expand on what caused you to remark that my current diet would kill the new gut flora?

Thank you!


Dr. Art Ayers said...

Clare,
Celiac is not a typical food intolerance. It causes inflammation, presents antigen and wipes out gut bacteria that are needed to suppress autoimmunity. The result is the development of a series of autoimmune diseases, starting with inflammatory bowel and then Hashimoto's thyroiditis. Vitiligo and rosacea follow and the whole series is aggregated by medical treatment of the symptoms with antibiotics to kill off gut bacteria that are needed for the normal development of the remaining aggressive part of the immune system.

Please comment on your antibiotic history. What about dental health?

Familial symptoms similar to yours do not indicate genetic inheritance, but rather shared gut flora and diet. It seems clear that your mother also suffered from celiac that should have been treated rather than just removing her thyroid..

I think that the diet you just described sounds perfect. I would like to hear that you understand the relationship between gut bacteria and soluble fiber.

My experience of people who already have your symptom progression also have a ritual eating pattern to avoid rosacea flares. You didn't mention the veggies that I noticed, so I feared that you might do the FMT and then starve out the new bacteria with a ritual diet. I was merely waxing hyperbolic to make the point that new gut bacteria and a new diet go together.

From my experience, it is not unusual for someone with rosacea and your history to respond to anti-inflammatory diet changes, such as fish oil, vit.D, with flares. Your gut flora are too compromised. What happens when you eat soluble fiber, e.g. apples or beans? Do they just increase stool volume and transit rate, with a decrease in symptoms as you feed your gut flora on soluble fiber, or do they pass through undigested?

I think that you should be able to turn all of your symptoms around by fixing and feeding your gut flora and avoiding gluten. You should also get a transient repair with probiotics.

Clare said...

Dr. Ayers,
Thank you for this refreshing conversation – so informative and informed.

OK, so I researched Hashimoto’s and Ord’s (I am of British descent) thyroiditis and reviewed the symptoms. Other than bouts of depression, which I tend to deny as I am prone to an upbeat outlook, and fatigue, which I can correlate with times of extreme gut flora malfunction, I waffle concluding that I’ve had thyroid problems. I have had some of the symptoms of hypothyroidism (cold intolerance, constipation, fatigue, depression) but not others (weight gain, low heart rate, decreased sweating, poor muscle tone, etc). I have been checked in the past, and found to be fine, but what tests exactly I cannot say.

My brother was celiac as a child and nearly died. I was not diagnosed as celiac and in hindsight, our family lived with poorly functioning digestion as I was growing up. We ate meat and vegetables and yet starches, grains and sugar were also present.

As a 3 year old, I had plastic surgery for my belly button that stuck out an inch or two. I wondered if that breach in my stomach wall would have started my vitiligo.

Twelve years ago, I travelled to Indonesia for 4 months, got very sick, came home and didn’t fully recover before going to Mexico for 3 months. Needless to say, I had digestive issues for years.

Antibiotics: I know I took antibiotics as a child. I recall painful ear infections until age 10 and am sure I received a few doses. I am guessing I had antibiotics at least 5 times as a child. As an adult, perhaps once in my twenties and then none until, very unfortunately, last fall, I took them for a urinary tract infection. In hindsight, I found this last winter (Pacific Northwest) very difficult. I was lethargic and the sun deprivation brought on a strong depression. I knew it was sun related, was taking Vitamin D, but it didn’t seem to make a difference. As you’ve surmised, my Vit D levels must be very low. I am looking into getting my levels tested.

Thank you for clarifying your comment regarding FMT new flora and new diet.

Until recently, I was eating a 90% anti-inflammatory diet, with the odd gluten-free bread and gluten-free pizza for fun. Not getting full relief from flares, I consulted with an Ayurvedic nutrition consultant, who based on my symptoms and constitution recommended a diet of well cooked soups of grains and beans. Despite my knowledge, I proceeded. Needless to say, after 5 days, my rosacea briefly went away and then flared with a vengeance. I returned to my base diet (vegetables and meat) this weekend, clearly aware that the previous 10% starches in my diet were causing the persistent flares. It was during my research this weekend that I discovered your website and FMTs.

Soluble fibre: I have eaten fruits and not noticed undigested foods. I rarely eat beans as they seem to hard on my digestion. I cannot say I have noticed undigested beans. I will start to note. I have always taken note of my bowel movements, but not made causal connections with recent meals. I am also going to eat some unchewed sunflower seeds to track my transit time – or do suggest something less hard and pointy?

And finally, although I hadn’t made the connection, fish oil and vit D may cause flares. I will cut them both out again, reintroduce separately, and see.

So, thyroid, celiac, vitiligo and rosacea autoimmune diseases run in my family. I have the latter two. Finally not only are points connecting, but a viable achievable solution is clear: soluble fibre and, low to no starches with a focus of growing my gut flora.

I cannot thank you enough for the sanity and intelligence in this conversation.