Saturday, June 28, 2008

Tumor necrosis factor

This sounds like a good thing, right? Produced by cells of the immune system, this protein's name implies that it is a sort of cellular "ace-in-the-hole," inducing death in wayward cells and their mutant offspring before a cancerous tumor is formed.

When first discovered in 1975, tumor necrosis factor (TNF) was noted to induce death in malignant cells in laboratory studies. Unfortunately, it is most complex in its actions, proving toxic to healthy cells and actually promoting the growth of certain kinds of cancer. TNF in the wrong place at the wrong time causes unwanted inflammation. This little troublemaker is a destructive party crasher in the joints of persons with rheumatoid arthritis, It also has destructive, pro-inflammatory effects in Crohn's colitis, smoking-related lung disease, atherosclerosis, Alzheimer's disease, and doubtless much more of that which ails us. It contributes to the profound wasting of AIDS and induces fever and shock in the face of overwhelming bacterial infections.

TNF is a good thing if you happen to do battle with a saber-toothed tiger, accidentally drive a Folsom point into your leg, or fall off your bicycle and scrape your knee. TNF is known as an 'acute phase reactant'; as the body's own EMT, it is one of the first responders at the scene of injury or infection. Produced by activated white cells and the endothelial cells that line blood vessels, TNF attracts bacteria-killing white cells known as neutrophils, promotes the passage of these cells through the blood vessel lining into damaged tissues, alerts the liver to produce pro-inflammatory molecules such as c-reactive protein or CRP, suppresses appetite, and promotes fever.

If TNF and company are activated, however, by cigarette smoke, doughnuts, McDonald's french fries, or too much waisted fat, this same immune response sets off a world of trouble in our arteries. Likewise, auto-immune diseases such as lupus or rheumatoid arthritis cause TNF inflammatory responses in joint spaces and other body tissues.

Body balance or homeostasis depends on equilibrium between troubleshooters such as TNF and peacemakers such TNF inhibitors. Therapies directed against TNF have changed the long-term outlook for patients with rheumatoid arthritis. These new drugs include TNF antibodies such as Remicade and Humira, and proteins that fuse with TNF such as Embrel. Early suppression of the joint-destroying inflammation associated with RA can prevent skeletal deformities and pain, markedly improving a patient's quality of life. Unfortunately, blocking a bad actor such as TNF which also has essential immune functions is not without problems. For one thing, TNF has an active role in the body's response to mycobacterial infections. As a result, cases of active tuberculosis have been reported with the use of anti-TNF agents.

Wednesday, June 25, 2008

Optimal vitamin D doses

I thought everyone had heard the news about the widespread deficiencies in vitamin D, yet the majority of people whose D levels I check measure way, way low in this essential vitamin. Even those who take a daily multi-vitamin with 400 units of D per tablet (the current RDA) are failing to top 30 ng/ml, the lower end of the desirable range.

Doctors in Beirut studied two groups of adolescents over 16 weeks. Half took 1400 units of D3 per week (the RDA for this age group is 200 units) and the other half took 14000 units per week. By study's end, the high dose group had a significant upward change in their serum D levels, but, better yet, demonstrated "substantial increments in lean mass, bone area, and bone mass."(1)

Many of my patients take 400 units of D3 per day, the amount present in most multi-vitamin pills. Per Toronto's Dr. Reinhold Vieth and colleagues "Supplemental intake of 400 IU vitamin D/d has only a modest effect on blood concentrations of [vitamin D], raising them by 7–12 nmol/L [2.8-4.8 ng/ml], depending on the starting point."(2) So if you're skidding along in a pasty white fashion, no sun plus one multivitamin pill/day, and your vitamin D level is around 11 (like so many of my patients), adding one more 400 unit D tablet per day will only get you up to 15, still terribly deficient.

Experts recommend supplementation in the neighborhood of 2000 units per day. Studies suggest that fracture risk falls with D levels of 30 ng/ml, and the improved outcomes not only result from stronger bones but also from greater muscle strength.
(1)Maalouf J, et al "Short term and long term safety of weekly high dose vitamin D3 supplementation in school children" J Clin Endocrinol Metab 2008; DOI: 10.1210/jc.2007-2530.

(2)Vieth, R et al. "The urgent need to recommend an intake of vitamin D that is effective" American Journal of Clinical Nutrition, Vol. 85, No. 3, 649-650, March 2007

Friday, June 20, 2008

Dr. Ed Hepworth, Denver, CO

Credit where credit's due. I know that people search for patient reviews of physicians, so here's one from a woman who had complicated sinus surgery with Dr. Ed Hepworth here in Denver:

This guy's incredible. Man, he's good!

Tuesday, June 17, 2008


Here's the new lipocentric news! What is not news, of course, is how lipocentric we're all getting, our fat or lipid-filled midriffs featured front and center in a pregnant abdomen sort of way. Researchers now, however, are theorizing that the fat load we carry as a result of overeating and undermoving is the primary metabolic driver behind the current epidemic of type 2 diabetes. Dr. Roger Unger of the Touchstone Center for Diabetes Research concludes in a recent JAMA editorial that "If this is in fact the case, [high blood sugar] should be corrected by eliminating the lipid overload."(1)

Want the skinny on fat overload? Check out: Lipotoxicity for the details.
(1) Unger, RH. Reinventing Type 2 Diabetes. JAMA, March 12, 2008, Vol 299, No 10.