Inflammation is an activated state of a tissue in which inflammatory cytokines, TNF, IL-1, IL-6 are secreted by T-cells and the tissue responds by expressing genes that cause characteristic vascular dilation and accumulation of migrating cells of the immune system. One particular type of blood cell, a macrophage, can also migrate to the site of inflammation and develop, in response to signals from the inflamed tissue and resident bone secreting cells, osteoblasts, into osteoclasts that degrade bone. Thus, inflammation of joints can result in bone destruction and increase in serum calcium.
TNF is p
articularly pivotal in the development of osteoclasts and bone destruction. Thus, drugs, such as thalidomide, that block TNF production, also block the symptoms of arthritis. Antibodies can also be developed that bind to TNF and some of these antibodies have been chemically and genetically modified to make them useful as drugs. Examples are Infliximab and Andalimumab. These are proteins that bind to and inactivate TNF. In a similar alternative strategy, a portion of the TNF receptor was engineer to serving as a neutralizing molecule to bind TNF in inflamed tissue. All of these TNF inactivators can reduce symptoms and provide effective therapy for arthritic joints.
The unanswered question in the use of TNF inactivators is, “What caused the inflammation of the joint in the first place?” Inactivation of TNF can provide a temporary return to approximately normal tissue function, but the symptoms are expected to return.Thus, we come to the unifying question of what causes inflammatory disease mediated by the immune system and directed at normal tissue components. Two obvious candidates are diet and infectious agents.
Food ingredients can exacerbate or ameliorate the symptoms of inflammatory disease, and particular diets determine the risk of acquiring these diseases. Diet is a major factor in inflammation of any source. Bacterial or viral infections frequently precede inflammatory conditions.
The association of infection with inflammation remains controversial, but there is growing evidence that bacteria in particular reside in almost all inflamed tissues. Moreover, there is abundant anecdotal evidence of effective use of antibiotics in numerous inflammatory diseases, including arthritis, inflammatory bowel disease, atherosclerosis and cancers of various types.
I expect that elucidation of the link between chronic inflammation, diet and bacterial infection will provide increasingly effective and simple therapies for most diseases in the near future.
20 comments:
Have you read any of the papers by the late Thomas McPherson Brown? He used low dose pulsing antibiotics in the tetracycline family (plus IVs) to put rheumatoid arthritis disease into remission.
More info in the book The New Arthritis Breakthrough, and at the Arthritis Research Lab, www.tarci.net
Anonymous,
It is hard to tell from the website and very few research articles on the use of antibiotics to treat autoimmune diseases, if the antibiotics are working on the gut flora or on the cryptic bacteria in the affected tissues. The same approach has been tried on CFS, fibromyalgia and rosacea, with similar results.
One of the difficulties associated with these approaches is that each disease is actually multiple diseases with similar symptoms. That means that each individual responds a little differently to treatment.
Another problem with these approaches is that they involve relatively cheap antibiotics, so there is no incentive for drug companies to fund clinical trials that would replace numerous expensive drugs with a cheap alternative.
Still another problem with the use of antibiotics is that if they are successful in killing crytpic bacteria in affected tissues, there is a severe increase in symptoms associated with release of endotoxins from the dying bacteria.
Thanks for the questions.
The Roadback Foundation maintains a list of journal articles here:
http://www.roadback.org/index.cfm/fuseaction/studies.sub/subgroup_ID/17.html
Back in 2008, I developed severe, sudden onset joint pain. I learned of Dr. Brown's work through the book "The New Arthritis Breakthrough" and Harold Clark's work through the book "Why Arthritis?".
I took a set of tests offered by The Arthritis Research Center, and came back positive for one strain of mycoplasma and chlamydia. No strep.
I sought out a MD familiar with using antibiotics to control these types of stealth infections. I started out on 50 mg of Doxy only on MWF. About four months later, I raised the dose to 100 mg MWF.
I feel very fortunate that the joint pain has slowly subsided since beginning the low dose pulsing therapy in 2008. It's been just about two years now, and my joints rarely burn any longer, and most days I forget about the arthritis.
I hope the Doxy will continue to work, and my own immune system will be able to take over and keep this disease in remission. I hope one day I can stop the antibiotic completely, but frankly, I'm afraid to do so, fearing the the arthritis will come roaring back.
I don't have any doubt that four decades full of sugar and flour, plus gluten damage, plus years of avoiding saturated fat wrecked me.
I've been off gluten for 3 years now, and have recently embraced a near zero sugar, nutrient dense, low refined carb way of eating.
I do take probiotics regularly (Natren's Healthy Trinity) and consume homemade yogurt daily. Although gut damage does concern me, I'm afraid I won't be able to control my disease without the antibiotics.
Brown is somewhat of a hero to me. One of the good guys. Successfully treated nearly 10,000 arthritis patients.
No question, really. I'm enjoying your blog Dr. Art, and wanted to share my experience.
Be well.
Anonymous,
The only problem with the bulk of the literature on antibiotic treatment of autoimmune diseases is that the vast majority are just on whether antibiotics decrease the symptoms of the disease. As with much of the biomedical literature, there is little or no discussion or study of the causes or cure of the diseases. Few molecular mechanisms are examined and no distinction is made between antibiotic effects on the tissues involved or indirectly through gut flora.
Most of the studies would be consistent with the antibiotics damaging the gut-associated immune system, so that it can no longer attack the tissues showing symptoms. That approach avoids discussion of the disease process, causes and cures. It just makes the disease chronic, but in remission.
I would prefer to understand the molecular biology of the disease to provide a way to avoid and cure it. If cryptic infections in the affected tissue is involved, I would like to kill them off with antibiotics and then reconstitute the gut flora for a complete cure.
How much of your gut flora is spared by the selective quality of the antibiotics used? Do the antibiotics + probiotics still produce constipation/gut dysbiosis? What about food intolerances? Can you eat any foods you wish?
Thanks for the comment.
I wish I understood more about the disease mechanism myself.
For anyone who might be interested, the Roadback Foundation has a lot of information on its site.
This article explains the idea behind low dose pulsing antibiotic therapy:
http://www.roadback.org/index.cfm/fuseaction/education.display/display_id/104.html
I wish I had the knowledge base to talk science with you, Dr. Art!
I don't doubt that the roots of rheumatoid disease are in the gut.
Anecdotally, I had a ruptured appendix at the age of 13. About a year and a half later, I was hospitalized for acute sepsus arthritis. I had a staph infection concentrate in my sacroilliac joint. That required a 30 day hospital stay, plus nearly six months on antibiotics. Nary a probiotic, and the on the typical SAD.
I suspect the resultant gut dysbiosis set me up for years of "minor" health problems, culminating in the arthritis.
I'm working hard to get this train back on the track.
Oh, one more thing, interestingly, one MD told me I could put the disease into remission using East Park Research D-Lenolate (olive leaf extract) instead of Doxy. He said it is more expensive, but is less disruptive to the gut flora.
Best.
I would prefer to understand the molecular biology of the disease to provide a way to avoid and cure it. If cryptic infections in the affected tissue is involved, I would like to kill them off with antibiotics and then reconstitute the gut flora for a complete cure.
How much of your gut flora is spared by the selective quality of the antibiotics used? Do the antibiotics + probiotics still produce constipation/gut dysbiosis? What about food intolerances? Can you eat any foods you wish?
Dr. Ayers,
I find your articles interesting, along with all the comments. I was diagnosed with RA 2 years ago (age 49). My fraternal grandmother had RA also. Before RA, I rarely ate processed foods and cook all my meals with lots of spices and everything from scratch. Right now I am taking Cimzia every 7 weeks. I supplement with fish oil, turmeric pills, vitamin D, and I eat 4-6 Tbs. of hemp seed a day. I lift weights 3x a week and do a spinning class 3x a week and during Spring, Summer and Fall I play golf. Right now I am in remission but I can't get my doctor to take me off the Cimzia. He told me he would reevaluate me in April (after seeing him in December). Any other suggestions you have for me that will "cure" me for good. Thanks Mary Beth
Mary Beth,
My impression is that the Cimzia, antibody against TNF, wipes out the signaling for inflammation and severely compromises the immune system and the normal development of tissues that require TNF.
Antibiotics wipe out various parts of the immune system by killing the gut bacteria that are essential for development of immune cells in the lining of the gut.
Both anti-TNF antibodies and antibiotics decrease the symptoms of arthritis, because they eliminate autoimmune attack on joint tissue. These are perfect medical treatments, because they manage the disease and result in additional side effects that are treated with more drugs.
As you indicate, the cause of the autoimmune disease is the gut and the damaged gut flora that is causing immune dysfunction. Absence of an appendix to provide a stock of functional gut flora is a further problem.
The answer is to reestablish a functional gut flora and to focus on the colon, where new studies show that numerous Clostridium species control development of the Treg cells that are needed to block autoimmune disease.
You need new sources of gut bacteria, e.g. in soil clinging to local produce, that are not provided by probiotics that focus on bacteria that grow higher up in the GI tract where there are higher levels of oxygen. Autoimmunity is a disease of excessive hygiene and limited access to soil bacteria.
I hope that this helps. Keep in touch.
Dr. Ayers,
You wrote"Absence of an appendix to provide a stock of functional gut flora is a further problem." I have my appendix so that is not one of my problems. So how do I go about reestablishing a functional gut flora and to focus on the colon? I would not call myself excessive in hygiene.
Also are you indicating that if I were to go off the Cimzia that my RA will come roaring back. That it is just being masked by the use of the drug.
Thanks for your help.
Mary Beth
Mary Beth,
Sorry that I confused your history with another post. I guess it was a senior moment. Maybe I had better eat a few more fish oil capsules.
Others have experience with adding lots of different foods and avoiding excess washing and cooking of greens to maximize the transfer of new bacteria and support those bacteria with diverse plant polysaccharides/soluble fiber. The first too obvious sources of soluble fiber are fruits with pectin (apples) and green veggies with inulin (leeks).
I think that most people are too clean, by the practical standards of maintaining good gut flora health.
I think that Cimzia can aid in healing inflamed tissues and help damage repair. It does not, however, address the causes of arthritis, so I would expect symptoms to start to recur, unless sources of chronic inflammation are eliminated. The anti-inflammatory diet that I recommend should be an excellent start to avoid relapes.
Let me know how you do.
Mary Beth,
My experience with RA might help you. I was diagnosed 7 years ago at age 58 and my mother also had RA.
I refused drugs and instead put myself in remission with an elimination diet (took 3 years). So we also have remission in common.
Last summer I discovered this blog and realized I had unwittingly weakened my immune system further and left myself vulnerable to many other diseases in spite of achieving remission. You appear to be in a similar situation even though your remission is drug induced.
The key hinges on the fact that some gut flora (bacteria) requires other flora to be present before it can establish itself. If you are missing flora for any reason (antibiotics, elimination diets, lack of breast feeding as an infant, overgrowth of bad bacteria, etc.), you need to cultivate your gut flora "garden" to build it back to good health/strong immunity. If you decide to go off drugs and find you have food intolerances which trigger flareups, it merely indicates missing gut flora. Sounds daunting, but building up tolerances is easy - just eat a diverse diet, try any "trigger" foods again (repeat if necessary since some other food's flora may need to be present first) until you have tolerance. It only took me 2 weeks! Now I can eat anything with no RA.
As I understand it from reading this blog, the immune system is the central part of the intestines and is strengthened by diversity of foods/flora. Strong plants like herbs/spices/peppers are best (because they are resistant to pests and parasites Dr. Ayers explained recently). Soil also contains good bacteria (as well as parasites so eating handfuls of soil is not recommended by Dr. Ayers). "Dirty" vegetables straight from the garden are encouraged however so I browse my herb garden eating them unwashed, I eat wild berries when hiking, and I eat "dirty" unpeeled carrots for example.
As Dr. Ayers says, your best defense against toxins, parasites, disease and aging is a strong immune system so don't worry so much about food sources and cleanliness.
Best wishes,
Mary
Mary,
I hope you will be reading this blog today. I so want to know about your diet!! I went on a gluten free diet to see if that had any effect on my RA. I didn't notice any difference. I can't really say that any foods trigger my RA. I consider myself a healthy eater. I cook a lot of Indian, Thai and other ethnic foods. I use mainly EVOO, butter, ghee and Grapeseed oil. I have always made my own salad dressings and eat lots of salad. Well I could go on but will stop here. In order to boost my gut flora would it be beneficial to take a pill form. But if so how do I know what is the best one? I would really love to hear from you.
My first RA doctor basically told me I would be on drugs for the rest of my life. Never encouraged me to do anything to improve myself.After 2 months I searched for a new doctor. My current doctor listens to me but I still get the feeling he thinks I'm a bit crazy for thinking that I can keep myself on remission with diet and exercise.
I look forward to hearing from you Mary. And Dr. Ayers, you are a godsend!
Mary Beth
Mary,
Grapeseed Oil is high in Omega-6, and may be promoting your inflammation. You may want to try eliminating it from your diet and see if this helps.
ALso, Indian diets do not necessarily mean healthy. While they do use plenty of spices, Indians also eat plenty of starch. You may also want to try reducing the starch.
Asim,
Okay, I just threw out the Grapeseed oil and will just use Coconut oil, ghee and EVOO. I realize starch is a no no but not all Indian food contains starch and it uses an abundance of spices.
Mary Beth
@Mary Beth
Jumping on the diet bandwagon, I would recommend checking out this website http://www.kickas.org/as_dietary_primer.shtml if you aren't familiar already. I've not been diagnosed with RA or AS but I have an inflammatory reaction to many of the foods that should be avoided. There's a small area on the forum which deals with RA as well as one for diet specifically.
Mary Beth (Part I),
I'm so glad to help so ask away (I read this blog daily - it's my favorite!).
As I said, I DEFINITELY don't recommend elimination diets to put RA in remission because they weaken the immune system further which makes you more vulnerable to other diseases.
So I'll assume you are asking about my current diet which is just as Dr. Ayers recommends. My elimination diet was pretty much Dr. Ayers' anti-inflammatory diet and I had moved to low-carb so I was close to a cure, but still had major flareups from anything bovine (because it needs supporting flora to be present) and black pepper (for probably the same reason). Nightshade vegetables: tomatoes, potatoes, peppers, eggplant and tobacco are routinely eliminated on an RA diet, but they are some of the strongest plants available so include them. Bovine responded well to fruit being added back in (use in moderation as fructose/glucose is another threat to your health) especially tomatoes which are technically a fruit. As Asim said all "seed oils" are not OK for the reason he gave.
I eat NO grains although I love buckwheat which is technically a "fruit" and not a grain. I tried soaking buckwheat groats and then fermenting them before making pancakes (twice: plain and with blueberries) per Stephen Guyenet's recipe here:
http://wholehealthsource.blogspot.com/search?q=buckwheat
I experienced a glucose spike both times so I gave that up - not saying I wouldn't use some buckwheat flour or groats in moderation though.
I recently made a low-carb almond pound cake (twice: once as written but adding the lemon juice and again with an orange and poppy seeds) for a "bread" like experience. Again, I do everything in moderation now to encourage diversity and keep my weight down. Here's the recipe:
http://diabeticmediterraneandiet.com/2011/01/10/low-carb-almond-pound-cake/
I do however think nuts should be eaten in moderation due to the Omega 6 factor. However, I'm not a scientist and read from a wide variety of sources so these are just my opinions from my reading.
These examples are just to illustrate that there are LOADS of low-carb, paleo and primal recipes out there.
I've really gotten into cooking now and routinely deglaze my pans with a splash of wine (I don't drink it) and add creme fraise (Trader Joes) or butter. Sauces really elevates a meal to five star in my opinion and capture all the fats and nutrients you might otherwise discard. I do a roast once a week (usually lamb), and slices of cold roast can be "warmed" and enhanced greatly by reheating the sauce and just pouring it over the cold slices.
Both my husband and I sometimes eat a square of baker's chocolate (no sugar) and have come to love it on its own, but you can add unsweetened cocoa powder to full fat Greek yogurt (the best available commercially) for a "melted" chocolate ice cream experience. Chocolate is anti-inflammatory, but again, should be eaten in moderation from what I've read.
I think absolutely everyone should give up wheat (and gluten: wheat, rye, oats, barley) and here's why:
http://heartscanblog.blogspot.com/2010/10/dwarf-mutant-wheat.html
and:
http://heartscanblog.blogspot.com/2010/11/why-does-wheat-cause-arthritis.html
I'll post this and start another post as you can only post so much at once.
Mary
Mary Beth (Part II),
I must say I don't use the artificial sweeteners stated in the recipes I linked to - I use ONE tablespoon of local honey (or less) instead. A tip I learned is to taste the batter after sweetening to see if it's sweet enough for you.
You asked about probiotics. I take two because my husband does (for insurance I guess) although I also eat 4-8 oz of either full fat Greek yogurt or kefir daily.
The probiotics we take are Ultimate Flora Senior Formula and Thorne Research Lactobacillus Sporogenes.
Probiotics can't heal your immune system on their own however. You really must eat a diverse diet to do that according to this blog and my beliefs.
You said you noticed no gluten intolerance and have no food triggers. I imagine this would be true on your medication, but I'm sure food intolerance is responsible for your initial RA symptoms and would cause your RA to come "roaring back" if you quit taking the medicine (as the underlying cause has not been dealt with).
Also, from what I've read gluten causes leaky gut which allows food into your blood stream where it can lodge in your joints and cause infections which are difficult to dislodge so beware of gluten.
I go to doctors for their opinion/diagnosis, but I always make my own decisions and I take no drugs.
My husband was initially wary of me following Dr. Ayers' advice, but I figured I knew how to put myself in remission so I'd take a chance and try a tolerance diet as elimination diets are very bland and boring. I'm soooo glad I did give it a try because it only took 2 weeks to cure myself of RA as Dr. Ayers indicated it would. To say I'm grateful is an understatement!
You said your diet is healthy and it certainly sounds like it - especially the spices. It sounds like your diet contains a lot of rice (and wheat?) though. I love rice like I love candy so I don't buy it as it turns quickly into sugar in my system, but I do eat it in moderation if it's offered to me. I've read wild rice is OK though. I think Dr. Ayers would approve of it in moderation - see his guidelines.
At 65, I'm concerned about glucose issues as Alzheimer's runs in my family and is now widely thought to be Type 3 diabetes. I've also read that if we live long enough we will all get diabetes. As a lay person, I just watch my reactions to foods instead of measuring things rigorously. We are all different and respond differently to our environment so the decisions/choices are individual.
When I first found this blog, the scientific terminology was daunting so I try to explain my experience in lay terms hoping that it will help someone else to take a chance on this advice.
The important thing is to read Dr. Ayers' articles to grasp the principles so that you can then use your own head about how to implement them.
If you have any other questions, I'm more than happy to help.
Mary
Sorry this second part took so long, but I didn't copy it before sending so of course it was too long and therefore lost and had to be reconstructed - argh!
Mary,
Thanks so much for all your information. Right now it is all so daunting. I must say giving up gluten is hard for me. I am a big baker. Rice, I can live without. Right now I cook brown rice but love to cook sticky rice with Thai food! If moderation would be the answer I would have no problems. I don't have weight issues, 5'3" and 107 lbs. So I don't have to count calories. I need to go fix dinner, Turkish chicken kabobs with yogurt and tahini but I guess I will have to forgo the flat bread! ;) I know there are other questions and will get back to you!
And to Rainarana, thanks for the website. I have a lot of reading to do!
Mary Beth
Dr. Ayers,
Do food allergy tests work to help find what one should eliminate from their diets? thanks
Mary Beth
Re my January 21, 2011 two-part comment to this article about my diet:
First, I had a difficult time finding this article again because it has no "arthritis" tag. I even Google searched using:
[keyword]:http://coolinginflammation.blogspot.com/ without finding it. Thankfully, it came up today in "Recent Comments".
My recent adventures in "low-carb" baking have left me obviously confused from too many carbs judging by my comments on the 21st. I definitely do not advocate potatoes and tobacco (and don't even eat eggplant), and it took 4 weeks, not 2 weeks, to cure my RA following Dr. Ayers' advice.
I've returned to the best diet for me which is a lower low-carb diet best explained in Gary Taubes book "Why We Get Fat and What To Do About It".
Sorry for the confusion.
Absolutely fascinating.
I'm an APer - use of abx to control the disease - and am fascinated in the use of diet to possibly elicit a cure. I have a form of RA; Palindromic.
I think I can answer the question on inflamed tissue. Most AP doctors encourage use of NSAID's in the beginning of treatment because abx cannot reach CWD bacteria if there is too much inflammation. After treatment begins, and the Jarish-Herxheimer reaction settles (surviving toxin die-off) then NSAID's are discontinued.
There are 2 protocols for AP - the Harvard Protocol (200 mgs Minocycline daily) and the Brown Protocol (200 mgs MWF). The second protocol has less gut disruption and less of a chance to breed resistant microbes.
The problem is identifying co-infections. For example, I tested positive for c. pneumonia as well as strep. Each requires different abx. Treating with only one abx is bound to fail as titers on the other microbe will rise.
I disagree that we're 'too clean' and think that the Hygiene Hypothesis has been sufficiently disproven by both mainstream and alternative science. I do love the ideas of how gut repopulation could conceivably 'cure' the diseases.
As far as I can tell, there is only a theory on the appendix and nobody has proven that the gut-resetting microbes are in there. Yet.
Dr. Art - like a real MD? OMG, you are probably brilliant as you've put a lot more together than most!
I've got to see if I can subscribe to this. Found it by accident.
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