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 .

Thursday, November 12, 2009

Psoriasis, IL-17, Cathelicidin, TLRs, NFkB, Inflammation and Heparin Therapy


Host DNA Released by Keratinocyte Apoptosis Binds LL-37 and Activates Dendrocytes

Psoriasis is an inflammation of the skin that leads to overproduction of keratinocytes resulting in a thick crust.  Skin inflammation, in this case, is considered a result of autoimmunity, but an autoantigen has not been identified.  It is more likely that psoriasis results from an autoinflammatory condition, in which inflammation produces a complex of self molecules that mimic bacterial DNA and trigger TLR/NFkB inflammation signaling.  And of course, if this is going to be interesting, it has to involve heparin.

Vitamin D Binds to a Transcription Factor Receptor that Controls Antimicrobial Peptides
A significant component of the innate immune system is a group of antimicrobial peptide  (defensins, cathelicidins, e.g. LL-37).  These short polypeptides owe their natural antibiotic activity to numerous basic (positively charged, arginine and lysine) amino acids.  The transcription factor that controls the expression of these peptides is the vitamin D receptor.  Thus, various forms of vitamin D influence the amount of antimicrobial peptides produced in the mouth, skin and crypts of the intestinal villi.  Oral vitamin D3 would be expected to directly improve defensin production in the gut and LL-37 production in the skin.

IL-17 Stimulates Skin Inflammation and LL-37 Production
A specific group of lymphocytes, called T helper 17 cells, produce IL-17.  These Th17 cells accumulate in some sites of inflammation, such as psoriasis and their secretion of IL-17 is associated with ongoing inflammation and may contribute to LL-37 production, as well as apoptosis of keratinocytes in the thickening skin of psoriasis plaques.
http://www.ncbi.nlm.nih.gov/pubmed/19623255?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_PMC&linkpos=2&log$=citedinpmcarticles&logdbfrom=pubmed

Th17 Cells Are Produced in the Gut in Response to Segmented Bacteria
One of my readers brought to my attention an article that shows that one of the hundreds of species of gut bacteria, segmented filamentous baceria, stimulates the gut to develop T helper 17 cells that subsequently migrate to sites of inflammation.
http://www.medpagetoday.com/Gastroenterology/InflammatoryBowelDisease/16472
This emphasizes the link between the gut and inflammatory diseases and parallels other examples of gut influence on disease, such as the ability of Helicobacter pylori to affect asthma or parasitic worms to tame Crohn’s disease, allergies and asthma.

Inflammation Lowers Heparan Sulfate Production and Spreads LL-37
One of my students induced inflammation in cells in vitro and showed by quantitative PCR that genes involved in heparan sulfate proteoglycan production are selectively silenced.  This observation explains in part the loss of heparan sulfate in kidneys and intestines that contributes to the leakiness of these organs in response to inflammation and the partial repair of these organs by heparin treatment.  Decrease of heparan sulfate that normally coats cells and binds antimicrobial peptides, such as LL-37, would explain the enhanced movement of LL-37 in psoriatic skin.

LL-37 Binds to Host DNA and Triggers Toll-Like Receptors
DNA is released from keratinocytes in psoriatic skin and this host DNA binds the antimicrobial peptide cathelicidin LL-37.  The LL-37/DNA complex mimics bacterial DNA and triggers the Toll-like receptors (TLR) on the surface of immune cells, dendrocytes, to activate NFkB, the transcription factor controlling inflammation.
http://www.ncbi.nlm.nih.gov/pubmed/19050268?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed

Heparin Treats Psoriasis
It seemed obvious to me that the heparin binding domains (Look at all the basic amino acids in blue in the illustration of LL-37.) of LL-37 were involved in DNA binding and the reason the LL-37 was binding to host DNA, was that heparan sulfate had been depleted as a result of local inflammation.  It also seemed obvious that topical heparin should eliminate psoriasis plaques.  So I did a Google search of psoriasis + topical heparin and got a hit on a 1991 patent application that claims a broad applicability for heparin use in curing symptoms of a wide variety of diseases, including psoriasis.
http://www.patentstorm.us/patents/5037810/description.html
The only topical form of heparin that I know of is Lipactin (available in Canada and Europe?), a treatment for coldsores, which makes sense because herpes viruses use heparan sulfate to infect cells.

57 comments:

coolbus18 said...

I have both P and PsA, so I'm always searching for info. Have you contacted The National Psoriasis Foundation? If not , please do. Great article, great study.Nice to follow you.

E said...

So ... this means avoiding oral Vitamin D3 .. ? //Erik

Dr. Art Ayers said...

E,
The way that I read it, oral vitD3 should improve the production of antimicrobial peptides (AMPs) and augment innate immunity. In most cases, decreased AMPs is a problem. In rosacea, where the typical skin AMP, LL-37, is cleaved to produce shorter peptides that contribute to the inflammatory symptoms, then vitD both increases symptoms and attacks the bacteria that are part of the problem. Thus, it appears that in some cases vitD3 is needed in addition to appropriate inhibitors of inflammation.

These are complex diseases that can't be cured by just manipulating symptoms with drugs.

Thanks for your comments and questions.

Krissie said...

So fascinating. I just did a quick google search on heparin and psoriasis and found a bunch of articles/anecdotes/studies about the positive effects of heparin on psoriasis - dating back to 1954!
SO what is with the treatment...is there a side effect that they can't use it? (I guess the obvious is bleeding?)
Can you increase heparin in your body using Dr. Art's anti-inflammitory diet?
Maybe eat turkey intestines (wiki mentions them as a heparin source)?

Dr. Art Ayers said...

Krissie,
I don't think that there is a down side to topical heparin therapy. Long polysaccharides of heparan sulfate are secreted attached to membrane bound proteins on most cells. Those molecules drag across the surface and are taken in again (half life = six hours). The heparan is degraded, the membrane proteins are recycled to the Golgi and new heparan is attached. The point is that other proteins with heparin-binding domains, as well as other heparin are also dragged in and reprocessed. This reprocessing is why heparin injected into veins is quickly removed and must be replenished to suppress the clotting enzymes that all have heparin-binding domains.

The simple point is that heparin applied to the skin and to a great extent, the gut, is trapped on the surface and metabolized. It is very hard to increase serum heparin levels by eating heparin. Afterall, your gut is coated with it, that is why it is a source of heparin.

Inadequate heparan sulfate is a sign of disease and is suggested by a propensity for blood to clot or for female infertility remedied by heparin injections.

My guess on why topical and oral heparin have not been developed is that they would replace expensive, dangerous patented pharmaceuticals with cheap, safe nutrichemicals. These approaches would eliminate the need for a large part of the health industry.

The Anti-Inflammatory Diet and Lifestyle that I suggest is just a compendium of dietary solutions to most of the sources of chronic inflammation. Relief of chronic inflammation should revive heparan sulfate production.

Thanks for the comments.

peter robinson said...

5 years ago i suddenly developed sensitivity to light on my face, which led to me living a life of isolation in my flat for 2 years in the dark.

Heat and any light would bring about serious inflamation and burning, like a deep burn that would last for days.
Thankfully it isn't as bad and for some reason the symptoms went somewhat. As a long term sufferer of mental health issues including , fear, anxiety, chronic depression, i wondered what effect having come off anti-depressants at the time played a role. Since being back on them my symptoms are less, although recently i have had serious problems with my computer screen again and with sunshine as i did before. At the time and now i seem to have a film of yeast that i can scrape off my skin when in the bath, i also became very sensitive to chemicals as well.
May i also say, from what you say my vegetarian diet does not help. When i take supplements i get a flare up of the skin and i am intolerable to exercise as it leaves me bed bound for days.

Great blog by the way

Dr. Art Ayers said...

Peter,
I think that you should look up rosacea and porphyria in Wikipedia.

It also sounds like you could benefit from some type of anti-inflammatory diet. All of your symptoms are consistent with problems with your gut flora and chronic inflammation. Your gut problems probably also contribute to nutrient absorption difficulty and vitamin deficiency. I would anticipate a very low vitamin D level that is contributing to many of your problems.

It is difficult to get off anti-depressants, but lowering inflammation helps.

I would recommend medical care. You may need to go on high glucose (not starch or sugar/fructose) until some of your symptoms abate.

Let me know how it works out.

John Magee said...

HI - Been dealing unsuccessfully with psoriasis for years. Paleo diet has been good for weight and lipids but no change on the psoriasis. I have been supplement ing with 4000 Vit D3and Omega 3 - going to add alpha Linoleic Acid to this mix too. Is heparin sulphate a cream that is available over the counter.

Thanks for the info
John

Krissie said...

John, how long have you been eating 'paleo' ?

Without getting into long detail about how my psoriasis symptoms manifest (they include psoriatic plaque, itching, joint ache);
I found that after 1 year of eating 'anti-inflammatory' -(>60% fat, low carb, no grains); my symptoms have not progressed at all, and are just now starting to recede. The joint pain is gone completely.

I think there is a long time period for true healing when reading about the SCD and GAPS diets, for example, they both say do the diet for at least one more year after symptoms resolve...and that is expected to be after 2 years (and skin is one of the last things to clear up).

I wonder if using ketosis would help speed things along. I also wonder if going all raw would help speed things along.

as another anecdote, I finally got my mom (who took enbrel for PsArthrits)to try Dr. Art's way of eating... her pain/stiffness majorly improved after 17 days (on the 17th day she woke up better, it wasn't gradual).
She stopped using Enbrel, the pain has come back, but not as bad, and she is successfully using icey hot (from your vapor rub suggestion, Dr. Art).

We are looking for a topical heparin, but would it work on the joints? at least the smaller ones?

John Magee said...

Hi Krissie
I guess since about Feb this year - like many people its sort of a long story of how I got here BUT pretty much everything that was a medical issue before has been getting better with paleo except the psoriasis - I am curious about whether its possible to find a topical version of this heparin sulphate
J

Dr. Art Ayers said...

Krissie and John,
I think that these are very fruitful discussions that test the application of diet-based anti-inflammatory approaches on an inflammatory disease.

Psoriasis is interesting from my perspective, because IL-17 has been implicated and the T17 cells that produce the interleukin develop in the gut in response to a particular gut bacterial species. Thus, changing the gut flora should change the course of the disease.

Changing the gut flora is slow unless some type of fecal transplant is used. Also the existing T17 cells in the skin must be depleted before symptoms will be reduced. This is a problem for all autoimmune and autoinflammatory diseases.

To aid the change in gut flora, lactulose may be useful. It seems to alter the critical bacteria at the end of the small intestines where T17 cells probably develop. I think that it is also important to actually measure serum vit.D. Even 5,000 IU of D3 per day may be inadequate to raise serum levels to >70 ng/ml. Check, supplement and check again to confirm that supplements have raised the serum level. (The majority of patients treated by a physician for vit.D deficiency do not show normalization of serum vit.D following treatment.) Inflammation reduces solar vit.D production and low serum vit.D is inflammatory.

Depression is related to inflammatory cytokine production, i.e. chronic inflammation can lead to depression and depression results in the production of inflammatory cytokines. I also think that going off anti-depressants leads to a rebound rise in inflammatory cytokines. Omega-3 fatty acids can probably be increased until they reduce these inflammatory cytokines.

I have asked pharmacists in the Pacific Northwest and they have not heard of any topical heparin. Lipactin is advertised on the internet, but I haven't pursued it.

Thanks for the discussion.

Anonymous Eponymous said...

This is interesting. I am a psoriasis sufferer. About 11 years ago I was admitted into hospital with meningitis. As part of my recovery, they injected me with heparin daily. The injection site would often be the lower stomach or the upper leg. I left hospital without any psoriasis. I have been taking additional Vit D. The other time I cleared (other than drugs) was at the Dead Sea - sunbathing daily. (I guess Vitd Intake skyrocketed there). The heparin issue is very interesting. I would like to see if heparin may be used as a treatment for psoriasis.

John Magee said...

Thanks for your comments Dr Ayers - I will definitely get Serum D levels checked and I will be taking a close look at my prebiotic and probiotic issues. I have to admit that the biochem / immune system info you talk about on your site is a little over my head - and I teach Bio! - I need to go back and study a little more! But... I was wondering if instead of the heparin there was any merit to using chondroitin sulphate topically? I would be interested in your take on this product - it seems - that they mention chondroitin sulphate as having a similar function to heparin sulphate and imply this compound is in their product .The link is from bioskinbalm.com - here is the piece that got my attention.

"Glycosaminoglycans (GAGs), Antibiotic Peptides & Skin Regenerating Triggers

Snail secretions include sulfated glycosaminoglycans (GAGs), present as strongly acidic protein-free polysaccharides.

GAGs-binding and the control of a large number of ligands and receptors are crucial intermediaries of normal cell and tumor cell functionality. They can oversee behaviors such as their growth, differentiation, expansion, and adhesion. The specific composition of GAG chains and their binding proteins influence tumor cell growth, metastasis, and cancer progression. GAGs such as heparan sulfate, heparin, dermatan sulfate, chondroitin sulfate and hyaluronic acid serve as vital biological response modifiers by functioning as (1) stabilizers, cofactors, and/or co-receptors for growth factors, cytokines, and chemokines; (2) controllers of enzyme activity; (3) signaling molecules in answer to cellular damages, such as wound healing, infection, and tumorigenesis; (4) targets for bacterial, viral, and parasitic virulence factors for adherence, invasion, and immune system; (5) controllers of neurite outgrowth; and (6) anti-inflammatory agent that limits oxidative corruption after tissue injury.

Thanks
John

Tanya said...

Dr A--your comment about antidepressants and a cytokine flare got me to thinking I need to check my timelines from last year. I weaned myself off Cymbalta, and perhaps it was after that the upper body aches attacked. Off to hunt down the dates...Depression is also related to Progesterone...so am looking down that angle more of late. Thanks.

Dr. Art Ayers said...

Anonymous Eponymous,
Your observations on heparin and vit.D/sunshine resolving psoriasis are great. The same effect should be achieved, more gradually by eliminating chronic inflammation (to raise heparan sulfate body-wide) and supplementing with vit.D3 until serum levels rise to >70 ng/ml.

What is needed is a measure of serum saturation of heparin-binding proteins, such as CRP. Note that of the dozens of serum proteins that interact with heparin, only clotting functions are measured and the amount of heparin that needs to be injected to achieve a desired level of clotting suppression has to be determined empirically, because the existing heparin saturation is not measurable.

The heparin saturation would be a measure of inflammation and would also reveal the status of treatment for numerous inflammatory diseases, such as psoriasis or IBD. A direct intervention of many of those diseases may be directly adjusting heparin saturation by heparin injections. Oral and topical heparin would also be very useful. Clotting complications are minimal, because most cells readily utilize heparin for metabolism.

Thanks for the great comment.

Dr. Art Ayers said...

John,
The discussion of GAGs is what would be found in any source, e.g. Wikipedia. Snails produce some type of GAG and sulfated GAGs are abundant in all mammalian connective tissue, e.g. beef.

Hypersulfated chondroitin sulfate was the additive in the adulterated Chinese heparin drug scandal. I assume that most of the eaten GAGs are digested by gut flora as fiber in the lower gut. Only short GAGs would penetrate any distance into the skin. Most sulfated GAGs can slightly compete with heparin.

If you want to try an alternative molecule that should work better than GAGs and is relatively non-toxic, that would be polyethylene glycol. It is available is a variety of molecular weights/sizes and the smaller versions should penetrate skin more effectively. I think that they are also available in many skin care products (and as a laxative.) I would expect that PEG would also be effective in reducing viral infections (It would be interesting to test as a lubricant with antiviral properties against some STDs.)

As a dark humor note, PEG is routinely used to make protein crystals for the gold standard of molecular structure determination, X-ray crystallography. So many of the structures of proteins interacting with heparin sulfate and other polysaccharides are systematically incorrect.

Thanks for the comments/questions.

Julian S said...

This is all very interesting. I'm pretty fit, and only have two (known!) health problems--psoriasis on my elbows and the occasional cold sore. Could these be connected, I wonder? I've noticed that occasionally when I've got a cold sore, the psoriasis lessens.

Lipactin, anyway, sounds like it is worth a try. I've also started on a 'primal' diet, so fingers crossed...

Julian S said...

Another note: I went and googled heparin and psoriasis together and found that a Louis G. Jekel tried it out on psoriasis patients way back in 1953. He explains why he tried heparin:

"The idea of using heparin in the treatment of psoriasis stems from combining the older theories of the etiology of psoriasis as a disturbance of fat metabolism with some new observations made by Gofman and his co-workers.
That psoriasis is associated with a faulty fat metabolism is a theory held by a number of dermatologists. Quantitative studies on the total lipids in the blood, or on cholesterol, or cholesterol ester levels have given conflicting results. Therefore the idea is entertained that the disorder may be qualitative as well as quantitative basically."

I've just been reading Taubes' "Good Calories, Bad Calories", so the mention of Goffman and faulty fat metabolisms was fascinating to me.

Jekel had success with three patients. A follow-up study was done by Paul LeVan in 1954. He summarizes his results:

"In all, 12 patients were treated, 7 of whom showed improvement and 5 of whom failed to improve. Six control subjects receiving isotonic sodium chloride showed clinical improvement, while two showed no improvement.
From the foregoing, it is our conclusion that heparin has no specific effect in the treatment of psoriasis. The improvement noted in both the heparin-treated and control groups may be attributed to the psychological effect of receiving injections and the benefits of hospitalization.
It woud seem that this information should be made available to avoid the widespread use of heparin in the treatment of psoriasis."

That's our answer to why heparin was never much tried: LeVan's study said it didn't work. Of course, we might have our doubts about exactly what those 12 tested patients prove or disprove...

But when I look at a 2008 article by Rahat S. Azfar and Joel M. Gelfand entitled "Psoriasis and metabolic disease: epidemiology and pathophysiology", which states there is now a "broad literature linking psoriasis to metabolic disorders", I start thinking that maybe Jekel and his fellow 1950s doctors weren't so wrong in noticing that something screwy was going on with the (fat) metabolism...

Julian S said...

One more post before I get accused of spamming: it seems heparin has been tested a fair bit: more searching turned up tests that have been done in India, the Czech Republic, and Russia. Results have been mixed:

Good:

The use of a heparin ointment in combination with dimexide in treating psoriasis
Authors: V V Evstaf'ev

Journal: Vestnik dermatologii i venerologii
Thirty-five male patients with psoriasis en plaques, persisting for 2-5 years, resistant to routine therapy, were treated with official heparin ointment with 15% dimexide under an occlusion dressing. Positive results were achieved in 41.2 +/- 5.9 days of the ointment application. Complete resolution of the rash was observed in 19 (54.3%) patients, partial regression in 14 (40%), no effect in 2 (5.7%) patients. This ointment is recommended for active therapy of patients with local psoriatic plaques with a stable course of the condition, torpid to routine antipsoriatic therapy.
Vestnik dermatologii i venerologii. 01/02/1989

Not so good:
Title: Heparin in psoriasis
Author: Chacko Maria ; Mathew Thomas ; Sugathan P ; Nair Laxmi
Abstract: Ten patients with chronic stable psoriasis of more than three years duration were treated with injection heparin 2500 IU subcutaneously twice a day for 7 days. Six patients showed aggravation. Three showed no response and one patient improved and went into remission after 6 months.
Journal: Indian Journal of Dermatology, Venereology and Leprology
Year: 1998
Volume: 64
Issue: 6
pages/rec.No: 273-274

Dr. Art Ayers said...

Julian,
The use of heparin is not straightforward. Inflammation alters heparan sulfate proteoglycan (HSPG) production, so since most cells produce HSPGs, the level of inflammation in that cells tissue will determine its HSPG production. At the same time, mast cells release HS fragments, heparin, when they are triggered. Heparin can block the action of HSPG, which is used in most signaling outside of cells.

In the blood there are dozens of proteins that bind heparin and some of those are involved in blood clotting. Depending on the level of inflammation, each person would require a different amount of heparin to alter blood clotting.

The same variability will be true for trying to use IV or tissue injected heparin or topical heparin to alter signaling involved in a disease such as psoriasis. The results of the experiments would make a lot more sense, if test subjects all had the same level of inflammation or responded equivalently to the heparin.

These studies remind me of the hundreds of experiments done to determine if fish oil could treat mental symptoms. Unfortunately, all of the tests were useless, because dietary omega-6 oils and other sources of inflammation were not controlled.

Thanks for looking into the literature on heparin and psoriasis.

Tanya said...

As posted earlier, I did check my records for the anti-depressant timeline. However it was a year before the aches set in. So, my new thought and would like your opinion/thoughts Dr Ayers, is could the onset of the pain be related to my weight loss (40# at that point in a bit less than a year). What vitamins/hormones could be stored in the fat that were depleted with the weight loss (not that my body fat is abnormal now) that could have affected inflammation levels?

Dr. Art Ayers said...

Hi Tanya,
Extra weight is generally inflammatory and weight loss, especially if steep, is generally anti-inflammatory. Weight loss is generally associated with relief of aches and pains.

It is possible, I guess to lose weight and also decrease inflammation, but still have problems with your gut flora that compromise your immune system.

And aren't you a recovering Lymer? Perhaps you have some load of cryptic bacterial endotoxin that was released with the loss of weight. And you also had the hole in your heart, which may have been inflammatory by causing flow/oxygen problems. And some vit.D/calcium resorption issues. These symptoms speak of complexity in your vitamin D metabolism that may have caused inflammation associated with vitamin D or A deficiencies. And both of these vitamins are fat soluble. I also previously observed when doing structural studies on collagens, that the tips of these and many other extracellular modular proteins have domains that fold into crushed jelly donut like structures, where fat-soluble molecules can bind. These structures could be body-wide storage areas that are exploited during weight change.

Perhaps the fat-dissolved toxins are bacterial lipopolysaccharides. I doubt that they are the usual candidates of man-made chemicals/pesticides. My ignorance of hormone interactions also tempts me to dismiss hormone issues. There are many possibilities and limited data.

Thanks for the questions.

Tanya said...

The Lyme tests were never followed up with the 'right' tests to determine if it truly was/is lime etc. So, it is hard to know. Again, doing all the good things and then bam worse, and then bam the stroke. Lots of unknowns.

I had hoped the surgery on heart would have reaped benefits by now if it was hypoxia. I know the only pain free time was after a major massage and a jacuzzi soak. I am hoping it is structural and easing into excercise when I am allowed/able will help. My IT band in hip however is another story and only aspirin seemed to help it as the excercises don't...and most with IT issues have only been helped by more surgery...not interested!

I found the comment about sores in the nose interesting. Mine have recently recurred...and I am taking 15000 Vit D per day...I don't know where to find coconut oil here...I use the antibiotic ointment for cuts on mine, something an old doc told my Grandpa to do 30+ yrs ago. I have heard it is staph infxn.

I upped my zinc and magnesium again and it seems to help but since my symptoms cycle, it is hard to know.

Thanks as always.

Dr. Art Ayers said...

Tanya,
What happens with your IT pain in response to:
castor oil/Vicks/capsaicin topical
hot baths
increased fish oil capsules
vit.D3 supplements

Lyme disease would explain a lot of diverse symptoms.

Tanya said...

To answer your question, Dr Ayers,...
castor oil/Vicks/capsaicin topical--honestly haven't done it long enough to help (stroke interupted my plans and I am slow at starting new habits since then...brain is still in slow motion) would be an easy thing to try. Vicks helped my neck when it was acute, but never got it to completely relieve symptoms/tetany

hot baths-no change or only very temporary

increased fish oil capsules--still trying to get my liver working so I can take the fish oil, although pre-stroke high doses for most of first year post 1st surgery had no noticeable affect when stopped

vit.D3 supplements--taking 15000 units daily before/after aspirin use period, and no change

Inactivity/rest works until I use it again! :-) It got worse after third surgery...thinking there is scar/adhesion also

For the person with candida...I used grapefruit seed extract successfully to treat thrush embedded in my breasts/milk ducts. I took it for over a year just to be sure it was gone!

Dr. Art Ayers said...

Tanya,
Notes:
Liver inflammation + omega-3s = more inflammation,
Liver inflammation is calmed by saturated fats.
Liver inflammation can be cured by saturated fats with omega-3s

Make sure that you have adequate vitamin A with your D3 supplements

It is interesting that you took grapeseed extracts (high in omega-6s?) for yeast, since yeast produces anti-inflammatory resolvins from omega-3s. The resolvins block neutrophil attack.

I would be surprised if the year of grapeseed extract would eradicate yeast. It may still be a persistent problem.

It sounds like you still have substantial inflammation and I would not be surprised if it was not related to the spirochete of Lyme. Or perhaps you have Cpn that has migrated to your inflamed connective tissue/joints and is now causing its own inflammation and pain. The surgery may also have damaged some of the nerves that normally produce anti-inflammatory signals during vagal stimulation.

The response to massage and (hot?) whirlpool probably indicate that some of the anti-inflammatory nerve signaling is still intact, and that is why I suggested the Vicks. Hot wax treatment, a la arthritis treatments, might also help with the pain and inflammation.

What about trying the vagal stimulation exercises/treatments?

What about your antioxidant levels? How much vitamin C can you tolerate before you get loose stools, indicating overload into the gut? You may have overwhelmed your glutathione with surgery and other traumas. That could be a problem for sulphur amino acids, B12, SAM.

By the way, are you sensitive to the seasons and day length, e.g. SAD. Related to SOD and sensitivity to high carb diet.

Just some thoughts.

Tanya said...

I took grapeFRUIT seed extract, which is antifungal and antibiotic. I have a friend I buy it for now...if she doesn't take it she gets scaly psoriasis? on her hands. When she takes it, it is gone.

I eat high sat fat and have been taking liver function supplement from chiro for two months. When I get back from Mayo clinic I will be out of them and then start on the fish oil again and see where it goes. That test I mentioned on another post did show poor 3/6 ratio so I am hoping it will help if my liver is ready. :-) But still don't know why my ratio is so far off since I don't eat any 'bad' oils...

I guess my biggest question mark for a systemic issue is why my pain is isolated to my bad hip and neck/shoulders. If it was lyme or fibro or whatever, shouldn't my whole body hurt?

I am taking 2000 vit C everymorning with my baby aspirin to protect my belly and sometimes at night when I remember. I had ramped it up even higher at times and my tolerance was very high...I took 500-1000 every hour during the day which helped with my tooth pain but did not ever get bowel response until pain dropped off. I haven't tried that since my tooth got better to see if it will help my leg.

I am a belly breather (musician in the past) already and my husband will look at me funny when we are watching TV or whatever and he hears me doing the breathing..it makes him think there's something wrong!

I took MSM (sulfur)and felt fabulous for two weeks until the rash came on! Not brave enough to try again as even dropping to low levels made my legs itch...

Guess my biggest problem is probably consistency and committment. :(

RE: SAD My issues are monthly cycle not really daily. The neck pain came on in JulyAug last year when I was out on the water a few days a week and taking Vit D. too.
My bowels were better before the stroke than now, as they again change with my cycle (my eating pattern is pretty consistent and variety may be an issue but where I live it is a fact of life due to access/availability, and a brown thumb!)

Appreciate the thoughts...I am resolved to patience at this point and doing things despite the pain. Life is too short and it is not keeping me down like it has in the past so it is better if you look at it that way.

Dr. Art Ayers said...

Tanya,
Your high tolerance of vit. C says to me that you have a lot of oxidation stress. That probably also means that you have glutatione depletion. I don't think that MSM is a good choice for sulfur amino acid deficiency treatment. A better choice would be acetylcysteine.

I don't think that the sidedness of your symptoms says anything about possible Lyme disease. The Lyme would merely provide a systemic trigger for your established areas of inflammation. Leaky gut promoted by NSAIDs will provide a continual supply of bacteria migrating to sources of inflammation as well as an elevation of system-wide LPS.

It becomes imperative for you to find a way to eliminate your sources of oxidative stress/inflammation, so that you can eliminate use of aspirin and heal your gut. You also need to focus on the health of your gut mucosal immune system to help suppress your total inflammation load.

Omega-3 suppression of inflammation is useful temporarily to demonstrate chronic system inflammation by suppressing symptoms. In the long haul, large amounts of omega-3s are not a good idea, because they could aggrevate liver inflammation or support resolvin-based fungal infections. That suggests that it would be good for you to normalize your omega-3/6 ratio, but not bother to go beyond compensating for your omega-6 intake.

I just read an article on the adenine-based signaling of acupuncture. I think that the same system work for topical pain treatment by menthol/capsaicin. That suggests that the extent to which these systems relieve pain/inflammation is dependent on the functionality of the adenine signaling. Inhibitors of adenine, inhibit acupuncture. The opposite should be true of adenine enhancement. I don't know how this is supplemented, but it would be useful in your case to permit topical application of a pain reliever/anti-inflammatory to permit you to do the exercise that you need to rehabilitate. Now, the aspirin will prevent the benefits of exercise, because some omega-6 based prostaglandins are needed for building connective tissue.

The estrogen-related components of your symptoms also point to inflammation, because of the estrogen suppression of systemic inflammation.

I was referring previously to seasonal affectation disorder that is based on melatonin, because melatonin is implicated in some inflammation syndromes, e.g. acne. If you had depression in the winter and not in the summer, SAD, then I would take that as an indication of melatonin issues. Melatonin is suggested to act via superoxide dismutase, and that also relates to your oxidative stress. The oxidative stress would make you prone to insulin resistance in the presence of a high carb diet.

I am still concerned that some of your symptoms are paradoxical and suggest fungal infections.

Let me know if these thoughts yield any benefits.

Tanya said...

This guy is the fungus guru...
http://knowthecause.com/Resources/tabid/56/articleType/ArticleView/articleId/184/categoryId/55/What-is-the-Phase-One-diet.aspx His diet (I have the three fungus books of his) should seem familiar. He is anti grains and starches. His reasoning for the same diet you recommend is to fight fungus, while yours fights inflammation, but with same results. He however likes beta glucans and recommends them highly, along with caprylic acid or other antifungal (like GSE that I took, nystatin, etc.).
I was following him until I found your blog (lucky you!) and the inflammation theory made more sense.
I was most leary of higher dose vit c because of kidney stones (had one once and don't EVER want to go through that again) but I read an article tonight citing a study that shows no connection. So, guess I'll ramp up the C first, then add in the vicks on my leg and neck again, and search out the adenine issue. I am wondering though if it is still leaky gut (too much Celebrex in my past?!) after almost 2 yrs of eating low carb etc, that perhaps I will also pursue the low dose naltrexone treatment to help repair.

And I mistyped my comment when I said 'daily' and meant to say seasonally. I have melatonin in the cupboard from one of my earlier theories or advice I'd read. Don't remember why I didn't pursue it, so will research again. I have a friend who takes it and sleeps for twelve hrs because of it!

I don't know what acetylcysteine is, but I will look it up! :-) I have sulfa allergies but it is my understanding that the sulfur and sulfa are different enough that it isn't a problem.

Thanks for letting me dominate the blog...I'll let you know WHEN I make progress (hope is the key!)

krissie said...

I came across this article about 2 months ago:
http://dermatology.cdlib.org/111/fast_track/chondroitin/verges.html

Here is the summary: 'Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling.'

SO, my mom (who already takes glucosomine, too) started taking the chondroitin (using the guidelines in this study). She said after 6-7 weeks her pain decreased dramatically and her one skin plaque disappeared completely.

Interesting, eh?
(I won't take anything because I am breast feeding, but my plaque is clearing up slowly but steadily, using only the anti-inflammatory diet. I would say it is half of what it was a year ago)

Dr. Art Ayers said...

Krissie,
I am glad that your symptoms have improved with a shift to a healthier diet.

I still don't understand chondroitin sulfate as a supplement. The clinical data are very unimpressive, probably because the CS acts through the gut and probably works through the gut flora. The study populations are not controlled for their preexisting gut flora. Hence the lack of consistent results. Perhaps it influences the gut flora like an animal soluble fiber and favors the growth of gut bacteria that influence the immune system and autoinflammatory diseases such as psoriasis.

Thanks for your personal observations.

Dr. Art Ayers said...

Anonymous posted the following (blocked by spam filter):

http://malecare.org/treatments/hormonal-therapy/chondroitin-sulfate/ Art,would you comment on this post please. thanks

I don't think that the article makes any sense, simply because the chondroitin-sulfate that you eat as a supplement or present abundantly in meat, ever gets out of the gut. It is probably digested in the colon and functions as soluble fiber. Dietary CS hasn't been shown to have any impact on prostate cancer.

Thanks for the question.

Josh said...

This is awesome. Have started 100% Paleo (previously 80%) and wasn't getting Psoriasis relief. This post and comments helped. Google found me www.AmeriCanaMeds.com and I ordered some Lipactin (they appear to be shipping to the US). Hoping it helps. Thanks again

Anonymous said...

Josh,

My husband has psoriasis on his scalp and has tried the following: low dose Naltraxone (didn't work and side effects were hard to live with - lack of sleep); Canadian product, Lipactin (didn't work, minor effect at best); New Zealand product, Nizoral 2% cream, an anti-fungal treatment for the skin (didn't work, brief minor effect but only for a couple of days).

Now he is using:

http://www.amazon.com/Oxipor-Psoriasis-Lotion-Solution-4-Ounce/dp/B000HM4LRO/ref=sr_1_1?ie=UTF8&qid=1294968735&sr=8-1

with good success. He says you wouldn't know he even has psoriasis now. Only the "liquid" which is sold as a "lotion" works for him, and it claims to only work on the inflammation (not the flaking), but my husband's experience is that without the inflammation there is no flaking.

Hope this helps!

Anonymous said...

Dr. Ayers,
I just want to mention an experience I had from using glucosamine for my psoriatic arthritis.
I have been using a glucosamine supplement for years to help with my PA, but had recently stopped taking it and my fish oil supplement because my PA seemed to be worsening and I thought that maybe the glucosamine was no longer working. I replaced the fish oil with krill oil immediatelly. I also discontinued my magnesium supplement about the same time because I was starting an experiment with higher dose melatonin(70mg/day). I had to discontinue the magnesium because the added melatonin to my regimen was causing loose stools.
Shortly after discontinuing the magnesium and glucosamine, I started getting new small psoriasis plaques at an alarming rate. I had had relatively good control of my psoriasis for the past two years, just the PA was what seemed to be in poor control.
At first I thought it was the fact that I had discontinued the magnesium that had caused the psoriasis to flair up, so I lowered my melatonin dose to 40mg/day and restarted magnesium at half the dose I had been taking. This was a tolerable dose that kept the loose stool condition at bay for awhile and my psoriasis seemed to slow a bit with less new plaques , but still not controlled.
I decided to go down to 20 mg/day of melatonin and a full dose of magnesium, but this resulted in loose stools again and my psoriasis seemed to slow a bit more , but still no control.
I was trying to figure out why I could not get control again and then I remembered reading your blog and the glucosamine clicked!
I started back on the glucosamine and at about two and a half weeks, I noticed that I was no longer getting new psoriasis plaques or very few, and the existing ones were starting to fade slowly.
I now feel that I am regaining control of my psoriasis again and am essentially back to the protocol I was taking when I had good control with the exception of I am taking half of my usual magnesium dose and the added 20mg of melatonin.
It's a little early to say for sure, but I feel that my PA has improved now, something I can only attribute to the melatonin since that is the main difference between what I was taking and what I am now taking. I am taking much less krill oil than the fish oil I was taking, so I don't think that is the reason for the possible change in PA.
I am also taking vitamin d @ 10,000 iu/day. Zinc gluconate @ 50 mg/day. A multivitamin every other day.Alpha lipoic acid @ 1,800mg/day. A vitamin B-12 lozenge at 1mg/day.
To be clear, I should mention that the glucosamine I am taking does have multiple other ingredients in it that are frequently found in other glucosamine supplements. This is the product label list of ingredients:
......................................................................
Supplement Facts
Serving Size 2 Caplets
Servings Per Container 60
Amount Per Serving %Daily Value
Vitamin C (as Ascorbic Acid) 60 mg 100%
Manganese (as Manganese Sulfate) 2 mg 100%
Sodium 40 mg 2%
Glucosamine HCI 1,500 mg (1.5 g) **
Joint Shield™ Proprietary Blend 1,350 mg (1.35 g) **
Chondroitin/MSM Complex 1,250 mg (1.25 g) **
(Chondroitin Sulfate, Methylsulfonylmethane (MSM),
Collagen (Hydrolyzed Gelatin), Boswellia serrata (resin),
Vitamin C, Manganese, Hyaluronic Acid)
5-LOXIN Advanced™ AKBA 100 mg **
Boswellia serrata Extract (resin)
Boron (as Sodium Tetraborate) 3 mg **....................................................................

In any case, I just wanted you to know that your idea about glucosamine and psoriasis seems to help me! Thank you for your work and ideas!

Krissie said...

Hi Anon that posted on January 31,2011.
Thank you for writing that out, it helps to hear what is working/not working.

A couple thoughts. 1. So the oral Magnesium dose doesn't affect your stools: you can make a magnesium cream (instructions here: http://www.drmyhill.co.uk/wiki/Magnesium_cream_-_how_to_make_it_and_use_it) or bathe in epsom salts. (Here is a site that explains how much you absorb (from recent study at U of Birmingham, UK)http://www.mgwater.com/transdermal.shtml

2. What does your diet consist of, and how long have you been following it?

3. Have you seen Dr. Ayers post on chondroitin sulfate? your glucosamine has that in it...that could be the ingredient keeping your plaques.

4. I am going to do some reading on melatonin...thanks for the info!

4.How long have you been using your supplements? (vit d, etc...)

Anonymous said...

@Anon,
That's a LOT of melatonin! Would you share why such a high dose seemed indicated? Normal dose is 3 mg, and the only research that I'm familiar with came out of Italy using 3 mg.
Thanks.

Anonymous said...

Krissie,
Thank you for the info on magnesium. A friend brought me a topical magnesium gel that he purchased while visiting in Mexico. It is easy to apply and seems soothing to me. It's just that taking the capsules is so easy. I guess I should have stated that I am currently taking a capsule that contains 350mg magnesium oxide, 40mg magnesium citrate and 10mg magnesium aspartate. One a day. I was previously taking two a day.
I take the magnesium for the interplay with vitamin D as well as its anti-inflammatory potential. I guess the magnesium oxide version is not as easilly absorbed.
My diet is poor at best with significant amounts of inflammatory junk foods, but I am trying to very slowly improve my diet toward some of Dr. Ayers suggestions. Those junk food habits die hard though!
I missed Dr. Ayers post on chondroitin sulfate, but did see a quick mention a little ways back in this thread. Can you point me to the post please?
I have read an abstract or two that suggested that it could have a beneficial effect on psoriasis if I remember correctly and that is one of the reasons I chose that particular glucosamine supplement and the reason why I posted the ingredient list.
There is vitamin c in it also, but probably not enough to be of much use on its own.
The boswellia extract/5-loxin/AKBA ingredient does have quite a few studies to more than suggest it is anti-inflammatory at the posted dose and again, another reason why I chose that supplement.
The MSM ingredient is a bit confusing to me. I've tried it individually as well as N-acetylcysteine(NAC) and have never really noticed a difference, however, I should add, I thought the glucosamine was not doing anything anymore either. Sometimes changes in psoriasis are so subtle or so slow that even when you are looking for them, you might miss them.
I have taken at least 8,000 iu of vitamin d for several years now but have more recently increased to 10,000 iu/day.
The supplements I am taking, I have been taking for at least a year with the exception of this recent adjustment.
The melatonin of course is relatively new and based on some recent abstracts I had read.

To Anon, that melatonin dose was used in a human study to test its effect on Duchenne Muscular Dystrophy. The initial results seemed promising and tended to confirm what some recent melatonin studies have shown......improved inflammation and oxidation markers.

http://www.ncbi.nlm.nih.gov/pubmed/20210854

Anonymous said...

Dr. Ayers,

Another week with the glucosamine supplement with the same regimen from my last posts and my psoriasis continues to improve. No new plaques, no new nail involvement, PA seems further improved, existing plaques continue to fade and / or shrink and no redness now. My nails seem relatively clear at the cuticle area and I don't see any new pitting or lifting.
My scalp and head in general, have always been extremely difficult, but even my scalp is flaking less and the flakes seem finer again. "Lumpy areas" are reduced. My ears are flaking less and there is less visible scalp involvement at the hairline. In the past, I have been able to clear almost my whole body, but my scalp has been tough and any clearing has been short lived.

I have been using topical betamethasone to help, but I no longer need to use it, and the discontiuation is not causing a flair. I have replaced the betamethasone with just everyday body lotion.

My diet has been bad this past week and definitely inflammatory, but I am still trying to focus on improving it.

According to the link below, the melatonin also looks like it may aid in repairing some gut issues.

http://www.jpp.krakow.pl/journal/archive/12_07_s6/pdf/23_12_07_s6_article.pdf

Dr. Ayers, Do you have any opinion on what role, if any, the melatonin might be playing in psoriasis/PA?
I thought this link about melatonin was interesting and enlightening to me since I always thought of melatonin as just a sleep aid.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582546/?tool=pubmed

Thank You again for your work and insights/ideas! Watching my psoriasis reverse is a really good feeling! It makes me think that other good things have to be happening to my body.
I wish others would relate their experiences with glucosamine, it could be helpful for others too.

Art

Asim said...

Dr. Ayers,

This may seem like a dumb question, but is the disposition of razor bumps, despite taking precautionary measures when shaving, indicative of some sort of inflammation?

brianlewisdesign said...

Hi Art, do you have knowledge about calaguala (polypodium leucotomos) fern helping autoimmune or inflammatory diseases?

Anonymous said...

brianlewisdesign,

I had never heard of it before, but it sounds interesting.

http://altmedicine.about.com/od/herbsupplementguide/a/Polypodium.htm

Sounds like it is used in Europe, South and Central America, but I have never seen or heard of it in the U.S.
Do you have experience with it?
I didn't see a lot of human studies on NCBI site, but it seems to have anti-inflammatory effects from what I have read so far.
If you use it, where do you get it?

Art

brianlewisdesign said...

I have been taking calaguala (polypodium leucotomos) orally for a couple of weeks. No noticeable results or side effects so far.

You can get extract powder pretty cheap in bulk. Pills seem to be quite a bit more.
http://www.kalyx.com/store/proddetail.cfm/ItemID/951926.0/CategoryID/1000.0/SubCatID/2625.0/file.htm

Sunlight or topical steroids seem to be the only thing with quick visible skin results. Both with risk of cancer or other side effects, and probably not addressing the root problem.

Anonymous said...

The root cause would seem to be a bit elusive, but Dr. Ayers seems to have the inflammatory aspect down as a prime candidate to reduce in order to improve heparin status and subsequently control psoriasis.
The anti-inflammatory diet is not as easy to follow for me as I thought it would be.......especially after a lifetime of bad eating habits and consequently I am having to supplement with a combination of anti-inflammatory supplements that I mentioned previously.
Are you considering using the Polypodium leucotomos in a topical application also? I am curious how you chose that substance. There does not seem to be a ton of studies for it.

Art

Anonymous said...

I just got done reading this study that discusses AKBA derived from boswellia serrata and is one of the ingredients in my glucosamine supplement that is noted for its anti-inflammatory abilities in humans. This study however,suggests that AKBA is also a potent antimicrobial against at least 112 pathogens and may also have the ability to breakdown certain biofilms. Interesting reading!
http://www.biomedcentral.com/content/pdf/1471-2180-11-54.pdf

Art

Anonymous said...

I read this small blurb from another website that draws a potential relationship between glucosamine and heparin.The suggestion is that glucosamine indirectly causes an increase in heparin production.That sounds familiar.

'Glucosamine - Doctors at Canadas Brampton Pain Clinic studied 10 people. All suffered and none had been helped by previous standard treatments.23 After they took glucosamine for 4-6 weeks, the volunteers reported a drop in the number and intensity of pain. The researchers theorize that glucosamine works through white blood cells called mast cells to boost the production of heparin, which helps to reduce blood clotting, thus reducing nerve-mediated inflammation and pain. How much glucosamine is required to prevent migraines is unknown, but the therapeutic dose may be similar to that used to support joints (approximately 1,800 mg per day).'

The supplement I take has 1500mg of glucosamine as a daily dose as do many other glucosamine supplements, but I have been taking a bit more, so probably a bit more than suggested by the above.

Art

Anonymous said...

Treatments or therapies that don't destroy another bodily function have the life saving moral place in medical science over meds that eventually kill the person from liver or kidney damage or opportunistic injury. Having an undiagnosed "inflammatory autoimmune disease targeting the cartilage", what is offered in immune suppression is as bad as the disease. God bless those who work avidly on other routes. Lynne on the East Coast.

Anonymous said...

I'm wondering, along with many, what would substitute for Methotrexate or Imuran so generously offered as the only treatment for an inflammatory autoimmune cartilage/connective tissue disease brought on by high stress and abated only by high dose prednisone? Any thoughts? Thank you.

Antonio said...

Hello Professor Ayers,

What's your take on the Low Dose Naltrexone (LDN)? There some "anecdotal" evidence that this drug has improved people's symptoms from their autoimmune disease. There is also a small study using LDN on MS and the study suggested further study on LDN was warranted.

Gavin said...

Dr. Ayers,

Firstly - thanks for such an interesting blog.

I've been eating very low carb for two years, and "paleo" for about 4 months.

As a kid I had regular ear infections. These were always followed by a course of penicillin which was always followed by an extremely severe case of plaque psoriasis. My dermatologist used me as his "demo" piece because I was the worst case he had seen - woop!

My teens and early 20s were pretty clear - but I had a full body breakout of guttate last year - around about the same time as I changed my diet to include a lot more cakes, breads and sugars (I started seeing a new gir)

Since going paleo my skin is 99% clear - I have a fewtiny marks but only noticeable to me.

I read Robb Wolf's paleo book. As well as eliminating ALL grains he advises that nightshades, legumes and dairy are also inflammatory. But you seem to be a lot more lenient towards lectins than he is.

I'm a former biology student and can but honestly can't make enough sense of the data to decide whether I should eliminate dairy, nightshades and legumes from my diet?

I'd really appreciate hearing your thoughts on these three and their role in inflammation?

tack för allt :)

Gavin

Drug Discovery said...

Hello,

Thank you for this useful information for IL-17. This cytokine seems to be important in many inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, asthma and systemic lupus erythematosus...

dextery said...

http://jackkruse.com/the-leaky-gut-prescription/

Dr Jack Kruse has this posting on leaky gut and its relationship to psoriasis...and he has a cure that has worked for a few people on the Leptin Reset Protocol forum going on here. http://www.marksdailyapple.com/forum/thread32345-943.html#post604866 Basically 600mg NAC 2x per day and 1000mg Vit C.

Kobi said...

Its been almost 20 years since I studied chemistry at University....but i understood most of this article! I've been looking for some reputable information about vitamins for psoriasis treatment for a while.

Anonymous said...

There is a new product on the market that may help many with this and other auto-immune disorders. It is a new powerful anti-inflammatory that, unlike any other, specifically targets and modulates NF-kB activity and, apparently little else. Because of that, it causes no side effects in most people, and in those who have them they are mild (slight nervousness) and disappear with discontinuation.

It is so safe that it can be and is sold as a "supplement", but make no mistake: this is not "just another supplement". It is a powerful new "drug".

The active ingredient is anatabine citrate (anatabine is a substance found in plants of the Solanacea family, but in very small amounts, so that one cannot get theraputic benefit from eating them). The product is Anatabloc. Search on it to find sources (GNC, Amazon, and the company itself).

It helps me greatly with rosacea (&/or psoriasis?), asthma, arthritis, and other auto-immune problems that seem to plague me. I hope it may do the same for some of you. Best wishes.

Pip said...

Hi Dr Ayers,

I hope you still read these comments.... I have melasma along with another 7 million women in the USA. I have included the latest research as I am hoping you may provide some insight into finding a resolution to this self esteem robbing, facial disfiguring disorder. I am convinced that inflammation is the root cause of this disease. http://www.jpad.org.pk/Oct-Dec-2011/4.%20Orignal%20artical%20Estrogen,%20progesterone%20and%20prolactin%20levels%20in%20melasma.pdf

Thanks
Pip.

ILoveBarbecue said...

Hello, I have been finding quite a few heparin creams(Lioton) but not heperan sulfate...is heperin ok to use or do we need heperan sulfate?

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