My interest is the molecular basis of inflammation, how inflammation is triggered and how inflammation contributes to numerous diseases. I try to expose the inflammatory underpinnings of various diseases by initially linking a disease to inflammation and then unraveling the molecular events that lead to and make up the disease.
How Do I Link a Disease to Inflammation?
My first task is to check the biomedical literature to see if there are research articles that support anti-inflammatory interventions that prevent or limit the disease. I just do a PubMed search the disease name plus anti-inflammatory treatments, e.g. omega-3 fish oils, vitamin D, NSAIDs, etc. It is also possible to see if a disease, such as diabetes, that produces chronic inflammation is a risk factor for the new disease being examined. It is shocking to me that omega-3 fish oils (EPA/DHA) or even flax seed oil, have been found to be effective treatments for numerous diseases that range from allergies, arthritis, inflammatory bowel diseases, depression and even septic shock and multiple organ failure. Aspirin has been used to treat infertility and post partum depression, and at high levels to treat cancer.Dietary Suppression as Prima Fascia Evidence of Inflammatory Cause
If I find that omega-3 oils have been used successfully to treat a disease, then I attempt to link inflammation to the molecular events that initiate the disease. The biomedical literature is of minimal help here. [Biomedical research is usually limited to assessing the impact of drugs on the symptoms of diseases, so the biomedical literature typically does not provide information on the cause of diseases or ways to cure diseases. Causes and cures do not receive research funding.] I have to learn the basic workings of the organs involved and the alterations of function associated with the disease. I have also found by long experience, that major molecular components are systematically missing from typical explanations of function.
Heparan sulfate/heparin Is Missing in Action
Heparan sulfate proteoglycans (HSPGs) dominate the extracellular environment and yet they are systematically excluded from biomedical research. On this blog, I have provided dozens of examples of the essential role played by HSPGs and disruption of these roles by heparin. The majority of cytokines, growth factors, clotting events, complement cascades and even lipid transport (LDL) act via HSPGs. Leaking of proteins into the urine, across the intestines or the blood brain barrier is controlled by HSPGs, is reduced by inflammation and can be partially repaired by heparin. Autoimmune and allergic diseases are initiated by disruptions in HSPG metabolism. Viral and bacterial pathogens bind to human cells via HSPGs. Cancer cells reduce their HSPGs and start to secrete heparanase in order to metastasize. Mast cells secrete heparin! HSPGs and heparin are major players in tissue function and yet the major cell biology text book does not even discuss them. HSPGs are not mentioned in medical school training even though heparin is the most commonly administered drug.
One of the insights that I bring to my conceptualization of diseases is the role of heparan/heparin in cellular physiology. It explains a lot.
Check for Inflammatory Symptoms by Trying the Anti-Inflammatory Diet
If your symptoms are due to inflammation, there is an easy way to find out. Since diet is the biggest source of inflammation and most of the cells of the immune system congregate in your intestines, it makes sense to check to see your health problems are rooted in inflammation by making simple changes in your diet. Since this is just a test, don’t worry about whether or not this is diet for the rest of your life. Just stick to it for a week and see if it changes your life.
The Basic Anti-Inflammatory Diet and Lifestyle Guidelines are here.
(Vitamin D and omega-3 fish oil amounts are minimal levels. More severe examples of inflammation will require higher levels. Vitamin D up to 10,000 IU per day has been found safe. Some individuals require up to 12 fish oil capsule per day to experience relief from symptoms. Increases should be gradual over weeks of time.)
Try it for a week and let me know if your symptoms disappear. The prevalence of diet-based inflammation, makes me confident that you will be glad that you tried these simple, healthy changes. For immediate relief of pain, see my articles on capsaicin, castor oil and menthol/Vicks.
This is not medical advice and is used only in appropriate support of primary medical care.
15 comments:
First, thanks for posting your thoughts online. They are fascinating, and I'm glad somebody is thinking them.
BTW, the link in your article to "The Basic Anti-Inflammatory Diet and Lifestyle Guideline" seems to be broken. (Looks like there's an extra "http" in there.)
You mention that "some individuals require up to 12 fish oil capsule per day to experience relief from symptoms." Do you know if there is any research on a safe upper limit for fish oil consumption? Are any kinds of fish oil known to be more effective (or less contaminated) than others? For example, some people claim krill oil to be superior to fish oil. From an anti-inflammatory point of view, are such claims justified?
Thanks again for your blog, and keep up the good work with your research and writing. It's great that this information is finally coming to light.
Cheers,
Tom
Tom,
Sorry about the link.
I think that fish oil is well tolerated and I would expect that the amount needed to keep symptoms under control is less than is needed to initially stop them. There are lots of claims about contaminants in fish oil. I don't think that it matters what the contaminants are for the first bottle, but it may make sense to find some refined EPA/DHA after you see if it is effective for you. From what I have read, getting omega-3s from oily fish is safe, because the selenium in the fish minimizes the heavy metal impact. Capsules are easiest to test.
The krill oil also has astaxanthin, which is touted as an antioxidant. I think that it is also an anti-inflammatory compound in its own right, but its target of action has not been identified. Krill oil is more potent than fish oil DHA/EPA. It is one of those things where different people will get different results.
In the diet, I think that vitamin D is most important, followed by carb control, decreased omega-6, increased omega-3, vitamin C, etc. Gradually increasing vitamin D and then omega-3 fish oils, should eliminate most inflammatory symptoms.
Don't miss my previous 100+ articles.
Thanks for your comments.
Art
Cristian,
That article (JPEN J Parenter Enteral Nutr. 2009 Jul-Aug;33(4):380-9. Epub 2009 Apr 14) illustrates my point of the intimate role of inflammation in disease symptoms. Also note that whey, used in the CYSPUFA diet, is rich in lactoferrin, a potent antibacterial agent. Lactoferrin is hydrolyzed to lactoferricin, an antibacterial peptide, by stomach enzymes. The supportive role of gut flora is also suggested by the successful inclusion of prebiotics. PUFAs have also been used in people and they reduce sepsis deaths by half.
Thanks for the recent article.
Art
Dr. Ayers,
Hi, your recommendations for the anti-inflammatory are excellent. Recently, I came across other grain articles which seem to also suggest (thank you Don) the effects of modern agriculture and cereal grains (wheat, gluten, corn, rice) on lowering serum vitamin D concentrations.
What are your thoughts?
If grains may be triggering immense perturbations on potent hormone systems like the vitamin D system and its metabolism (and intrinisically related hormone systms... PTH, T4 T3 TSH, elevating estrogens E1 E1S E2 (man-boobs *haa*), insulin (truncal obesity), testosterone, eicosanoids, desaturases, etc), then... may environmental estrogenic-compounds (plastics, bisphenol, pesticides, etc) have a potential for burdening a system that is quite taxed already by extreme hormonal imbalances?
Sorry so convoluted...
Personally over the last 12mos I've had progestin excess from a drug LNg. My main difficulty waiting to get it out of the system b/c it appears stuck in the adipose. Synthetics hormones appear as evil/toxic as omega-6 PUFAs! LNg in the literature raises hsCRP, 2nd phase insulin, glucoses, heart rates, BPs, fluid retention, and a host of hormonal derangements... I think exposure to ALL unnatural hormone-like substances are best avoided if possible for the ultimate anti-inflammatory lifestyle.
Thank you kindly again,
G
MacAuliffe T, Pietraszek A, McGinnis J: Variable rachitogenic effects of grain and alleviation by extraction or supplementation with vitamin D, fat and antibiotics. Poultry Sci 1976;55:2142-47.
Hidiroglou M, Ivan M, Proulx JG, Lessard JR: Effect of a single intramuscular dose of vitamin D on concentrations of liposoluble
vitamins in the plasma of heifers winter-fed oat silage, grass silage or hay. Can J Anim Sci 1980;60:311-18.
Sly MR, van der Walt WH, Du Bruyn DB, Pettifor JM, Marie PJ: Exacerbation of rickets and osteomalacia by maize: a study of bone histomorphometry and composition in young baboons. Calcif Tissue Int 1984;36:370-79.
Clements MR, Johnson L, Fraser DR: A new mechanism for induced vitamin D deficiency in calcium deprivation. Nature
1987;325:62-65.
Cordain, Loren -- unpublished, he reports of scientists showing that cereal grains lower serum vitamin D via increasing the rate of inactivation of vitamin D in the liver
How does an anti-inflammatory diet and supplements (fish oil, Vit D, Astaxanthin, etc.)impact muscular inflammation as a result of strength exercising? Since the muscular inflammation is part of the healing repair and muscle growth process, would an anti-inflammatory diet, supplements slow the healing process?
Cristian,
Thanks for the article summaries.
[Please post just your comments with the PubMed ID number or citation and not the whole summary.]
A high carb diet is inflammatory and cereal is a terrible way to start the day.
Tart cherry anti-oxidants:
I wrote an article about my thoughts on antioxidants. Measuring antioxidant potential in food gives an indication of only a minor impact the food components. Chemicals with antioxidant activity also bind directly to hundreds of different proteins with numerous alterations of activities. Eating tart cherry extract and then checking the effects merely shows the sum of all of these interactions and may vary dramatically with gut flora, other diet components, degree of chronic inflammation, etc.
The bottom line is just that some food contribute to chronic inflammation and others tend to reduce it.
Thanks for your continuing interest in my thoughts on inflammation and health.
Art
Anonymous,
Thanks for your question on inflammation and muscle growth in response to exercise.
Several studies show that NSAIDS, for example, lower the inflammation that is produced by exercise and as a consequence decrease muscle growth.
Extreme exercise results in cytokine production similar to infection and then converts into an anti-inflammatory state.
Chronic fatigue is associated with high inflammatory cytokines and benefits from exercise, but in some forms is also associated with abnormal inflammatory cytokine receptor production, making exercise counterindicated.
Older people tend to become increasingly inflamed and also show dramatic muscle growth in response to exercise.
My thinking on anti-inflammatory diet and muscle growth, is that the final level of inflammation achieved by the diet is what is important. Different people will have the same diet, but different levels of inflammation. Exercise will change the impact of the diet.
It seems to me that you will have to develop a simple measure of your inflammatory state and determine the optimum level of inflammation for maximum muscle growth.
My impression is that a few people in the body building community understand the relationship between diet, exercise (chronic inflammation level) and muscle growth. The biomedical community (particularly dietitians) is much less sophisticated.
Thanks for your comments.
Art
Dr. B G,
Sorry that I am so slow. (I was looking at hot springs in the Sawtooth Mountains.)
Your comments on grain and vitamin D brings up numerous points. How do you determine the status of your gut flora and the impact of your diet on your inflammatory status?
I think that we should aspire to self-medication in response to our personal cues of well being (or a painful index finger.) Self-medication should be through what we eat in our next meal and how we exercise before and after that meal.
My personal bias is that hormonal and psychological problems derive from the diet/inflammatory state. (This implies an obvious dysfunction in our nomenclature and inflammation requires a new series of terms.) That means that adjusting the diet can remedy hormonal problems and eliminate much of the impact of environmental estrogens and most other "toxins." This is the flip side of the article that you cite. This means that we need to get over treating the symptoms of hormonal dysfunctions and get down to the cause of the hormonal disruption. My prejudice is that in all cases there will be a substantial dietary contribution to the problem.
Alas, there is no money in treating very lucrative diseases with a printed diet, vitamin D capsules and a bottle of cheap fish oil capsules. The neighborhood nurse could just hand these health kits out to everyone with instructions to use the kit for one week for any health problem. The result would be the collapse of agribusiness and the medical industry, and the elimination of the discussion on the healthcare catastrophe in America.
Thanks for reading my thoughts.
Art
Cristian,
Thank you so much for the Maes link. I am relatively new to the inflammation literature and Maes seems to have made most of the connections that I have been struggling to make over the last couple of years. It seems almost possible to connect the over/under-production of each inflammatory cytokine in the body or brain with a different disease or symptom.
.....
The article is also interesting to me, because it ties in the major inflammatory transcription factor, NFkB with a chronic disease, CFS. My prejudice is that production of transcription factors is set and they are either active or inactive. Producing different amounts is a very different process.
Thanks again.
Art
I'm trying to treat nasal allergies and sinus inflammation with fish oil and your suggested diet. I currently take a tsp a day. Is there any advantage in increasing that dose?
Anonymous,
The dose of fish oil is dependent on the amount of omega-6 fatty acids in the diet, usually from vegetable oils. It is the ratio of fish oil to omega-6 oils that matters in reducing inflammation.
I usually just keep increasing the fish oil until the inflammatory symptoms are reduced. In the case of allergies, the inflammation is more indirect and it takes longer for existing antibodies to dissipate. Gut flora is also important, since the allergies are based on an initial combination of inflammation and disfunction of gut-based immunity.
I would experiment with slowly increasing fish oil each week to see how much it takes to reduce symptoms.
Thanks for the question.
I had a terrible bout with inflammation that went on for 8 years. I thought it began with tendenitis in my wrist but now I realize that my metabolism had been spiraling out of my control into insulin resistance before the tendenitis appeared. Long story short, after a number of years of searching for information I found (among other helpful sites) Level One Diet (Or Level1Diet), where after some study I realized that omega3 might be the key to reducing my own inflammation. Again long story short, I wound up ingesting 8 capsules per day, about 4,000 mg combined epa/dha, and my joint pain subsided (immediately at that level) as long as I took every last pill every day. If I didn't, I began to suffer accordingly, quickly.
Last year I found a doctor who really did offer help rather than prescriptions, and on my own I found the the Drs. Eades book PROTEIN POWER LIFEPLAN whose diet I adhere to today, and probably always will. I began on the low-carb plan last fall and quickly lost 25 pounds. My blood tests showed that my blood sugar still is slightly high but I wonder if that's from the omega3. I am taking a high level of vitamin D along with a diebetic multivitamin and some other supplements. I'm 66, feel better than when I was 26.
I knew before I found your site that inflammation is the the cause of human disease and that it's the inflammation that we have to pay attention to. I also understand the inflammatory nature of grains and other foods we're commonly exhorted to eat. I'm through with that. I can move so freely without pain, am so comfortable in my body, and feel so good that I will never again listen to any diet dictocrat who prattles about the healthfulness of the sugar that is referred to as carbohydrates.
Thank you for this amazing website. I'll be working my way through it bit by bit, sending links to friends who are miserable because they are depending on doctors who only offer prescriptions and no real help.
Is it any wonder that our national health care bill is out of control?!
Best wishes.Stay healthy.
Have been very sick most of my life (gluten intolerance) but didn't know it. Most recently, with no help from several docs, I began to read and suspected metabolic syndrome. Discovered PROTEIN POWER LIFEPLAN (Eades) and with its help lost 45 pounds. Now HDL is high, triglycerides are low and everything else is right too. I now have the energy I've never had and actually want to run...well, maybe jog. Tried it and nothing fell off or dislocated so will be doing it 3 days per week, starting slowly with a jog one minute/walk one minute routine.
Ah, life is so sweet, but I digress.
Without 4,000 mg of epa/dha per day my whole inflammation thing becomes active again. X-rays proved (to my endocrinologist) that my hands and feet are riddled with arthritis. My neck crackles and snaps, so do knees, spine, shoulders, but as long as I take enough omega3, I feel wonderful and have no pain, which must mean that the inflammation is held in check. If I cut back by even one 500 mg capsule I soon feel the effects.
I'm still on low-carb diet (more or less the Dr. Bernstein plan) and will be for the rest of my life. I need to keep my carbs at around 21 grams per day or I cannot function (and cannot continue to lose body fat). I'm very grateful that I found the Drs. Eades and their book, Gary Taubes and his books, Volek and Phinney and their book, this blogsite and many many others that assisted me to become more self-aware and more aware of my cell chemistry and understand the wonder and implacable demands of my biochemical body. If we eat right, all will be well. Believe it.
Dr Ayers,
I understand there is a huge prevalence of diet-based inflammation in our culture. You address this very thoroughly here on your blog.
What roll does stress play in inflammation? Does it negatively affect our gut flora? I know stress can be very subjective and difficult to measure, and can be emotional, mental, physical or relational in nature, even good stress, and bad stress. But as I understand it, our bodies don't know the difference, so it is all the same, really. It is still stress.
Does the gut flora disruption come first and then the stress, or the stress result in gut flora disruption. All I know is that when I am under a lot of stress, I have many more aches, pains, and inflammatory symptoms. Is there an explanation for this? And in this light, should reduction of stress be on the lifestyle recommendations, for people like me whose health feels negatively affected by stress? Or is this what the vagal nerve stimulation is getting at?
Thank you,
SD
Dr. Ayers,
What is your opinion regarding the impact of inflammation on the body's susceptibility to chronic infection? Or vice versa?
A quantitative Marcons test (Multiple Antibiotic Resistant Coagulase Negative Staphylococci) yielded a high level of staph in my sinuses. I have a strong suspicion that this bug is what is contributing to whole body inflammation.
I've read that Vitamin D acts as a natural antibiotic (BTW, my level is low at 17 ng/dl) and that Vitamin D activates a cell receptor that activates cathelicidin, which is involved in killing of intracellular bacteria.
Theoretically, could increasing Vitamin D levels thwart off this opportunistic bug by strengthening the immune system? So tired of trying anti-microbials, which seem to fail me, without a strong immune system in place to begin with.
Thank you
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