“All disease begins in the gut.” – Hippocrates

Tuesday, July 13, 2010

Tumor Necrosis Factor (TNF) and Natural TNF Inhibitors for IBD Treatment

OK, so if you are on one of these biological treatment agents mentioned below, please don't take this post personally. I don't mean to degrade people who take the drugs, rather to question the use of them given the price (in dollars, and in health) and all we don't know.

Depending on the level of severity of your IBD, allopathic doctors may make use of steroids such as prednisone, azathioprine (Imuran), methotrexate, or 6-mercaptopurine, or a form of mesalamine. TNF inhibitors are typically recommended when all of the above fail.

What is Tumor Necrosis Factor (TNF)?
TNF is a cytokine (chemical means of cellular communication) produced by your immune system that helps regulate immune cells. It helps induce inflammation, inhibit tumor growth, and keeps viruses from reproducing in your body (and more!)--All good things.

Why should I care?
People with Crohn's and Colitis have been shown to have increased blood levels of TNF-alpha (don't get stuck on the names). So what? So...maybe increased levels of TNF in our blood are causing excess inflammation in our guts. The theory goes, "Decrease TNF levels, decrease inflammation in the gut." A little simple for you? Yea, me too. It turns out that other drugs designed to block TNF-alpha have not worked, and some have even been worse than the placebo in studies. Oops. Must be more complicated than that. Newer drugs are focusing higher up on the immune chain with, for example, activated T-cells.

Allopathic Anti-TNF Treatments:
This theory has led to a suite of biological treatment agents for Crohn's and Colitis (among other inflammatory conditions). These treatments target specific parts of the immune system (in this case, TNF) to decrease inflammation. These drugs (such as Infliximab) have been successful at mitigating symptoms for those with moderate-to severe Crohn's, and has also shown efficacy in Colitis, though not as much as in Crohn's.

What's the Problem with these Biological Treatments? There are several:
1. Depending on your dose, Infliximab can cost you between $19,000 and $22,000 per year. Luckily it's usually covered under major medical insurance! But what if you have a lifetime spending cap on your insurance? Start treatments at 25 years old, live to 75, and you've spent $1.1 million on this one treatment alone. Hope you don't get cancer, or have a child who needs long-term care. Also hope you don't have to change insurance companies...ever (pre-existing condition, anyone?)

2. All of these drugs work to disrupt the immune system. While I understand that IBD is seen in the medical community as an autoimmune disease, we don't understand the full implications of disrupting the immune system over the long-haul. It's just too complex. I take that back, we do know one major implication: If you take these drugs, your immune system will not function the way it was designed. The medical counter-argument is that it's already malfunctioning. Maybe, maybe not. Since we don't know the etiology of IBD, maybe our immune system is doing what it's supposed to do, and if we find the causative agent (such as a bacteria or yeast) we can return things to normal.

3. People who take Infliximab have a much higher risk of cancer (aren't we at a high enough risk already?), and people with background exposure to, for example, TB have actually been infected by TB after starting the drug.

***By tying the hands of our immune system we open ourselves to myriad other health problems. Given the high cancer risk of people (like me) with IBD, shouldn't we want to have an immune system that is able to fight off cancer, virus, bacteria, and other nasties? Have doctors (and patients) appropriately weighed the costs and benefits of prolonged immune suppression for IBD? With all we don't know about the immune system and suppressing it in very specific ways, can we accurately assess them? Are the benefits of (potentially) reducing inflammation (for an unspecified amount of time) worth reducing our body's defenses against, cancer, TB, flu, viruses, food poisoning, etc?

4. Since your body produces antibodies to them, drugs like Infliximab can produce such violent anaphylactic reactions as to endanger your life.

The Natural Response to IBD:
There are a suite of natural treatments for IBD out there (I may someday outline them in one post or a series of posts). It may be true that the only thing that can help you is a TNF inhibitor, but doctors fail in calling TNF inhibition a last resort when they haven't tried or are unwilling to try effective natural treatments such as probiotic therapy, antibiotics (there are natural antibiotics and anti-fungals you can use), and changes in diet first. These treatments are gentle, without side effects, and they cost oodles less than $22,000 per year.  Most doctors are sincere, wonderful people who have dedicated their life to helping people. Doctors, however, are required to practice 'within the standards of the community', so if natural treatments are not the standard of the community it makes it difficult for doctors to (1) find respected, professional training to learn about natural or non-conventional treatments, and (2) it makes it hard for them to be respected in their community if they go off the radar, so to speak.

With that said, there are some natural anti-TNF compounds you can try.

Natural Anti-TNF Compounds:
There is recent, promising research that TNF or the effects of TNF can be inhibited by a number of natural compounds, including curcumin (a compound present in turmeric), and catechins (in green tea). I've included references (in lieu of links) below. I actually take both, curicumin (500-1000mg/day) and catechins in the form of green tea extract (300-600mg/day, catechins).

These natural TNF inhibition agents will not be as strong or as targeted as Infliximab, but they are found whole in our natural food chain, which gives me rest. Combine these with probiotic treatment and the Specific Carbohydrate Diet, and I think you've got a good natural treatment protocol started.

If you are someone who likes to follow the references, start with the Gulcubuk and the Lantz papers.

References for Natural Anti-TNF Compounds:
Siddiqui AM, Cui X, Wu R, et al. (July 2006). "The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma". Crit. Care Med. 34 (7): 1874–82. doi:10.1097/01.CCM.0000221921.71300.BF. PMID 16715036.

Okunieff P, Xu J, Hu D, et al. (July 2006). "Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines". Int. J. Radiat. Oncol. Biol. Phys. 65 (3): 890–8. doi:10.1016/j.ijrobp.2006.03.025. PMID 16751071.

Gulcubuk A, Altunatmaz K, Sonmez K, et al. (February 2006). "Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis". J Vet Med a Physiol Pathol Clin Med 53 (1): 49–54. doi:10.1111/j.1439-0442.2006.00786.x. PMID 16411910.

Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN (June 2005). "The effect of turmeric extracts on inflammatory mediator production". Phytomedicine 12 (6-7): 445–52. doi:10.1016/j.phymed.2003.12.011. PMID 16008121.

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