Friday, February 27, 2009

Can NSAIDs prevent Alzheimer's Disease?

Alzheimer's disease (AD) gums up the brainworks with tangled neurons and protein plaques. Much of the damage occurs, however, as a result of an inflammatory response to these changes. Scientists theorized that the regular use of anti-inflammatory drugs such as Advil, naproxen, or Celebrex (also known as non-steroidal inflammatory drugs or NSAIDs) could slow down or prevent this degenerative disease.

The Alzheimer's Disease Anti-inflammatory Prevention Trial(1) enrolled over 2,000 seniors aged 70 years and older and followed them through 7 years of life correlating the use of NSAIDs (naproxen 220 mg. twice daily, Celebrex 200 mg. twice daily, or a look-alike placebo with no anti-inflammatory properties at all). All participants had a family history of AD and were thus considered to be at increased risk for developing the disease.

Made no difference what the septuagenerarian subjects took--naproxen, Celebrex, or no drug at all--with respect to their subsequent tendency to drift towards dementia. In fact, there was 'weak evidence' for a detrimental effect of naproxen.

The problem, however, is that this really wasn't a preventive trial at all. By the time old folks enter their eighth decade, they may well already be on the road to AD. Chemopreventive studies--i.e. those research trials seeking substances that actually protect against the development of AD through a neuroprotective substance-- would need to be undertaken on younger subjects over a longer period of study, an approach that is prohibitively expensive. The studies that suggest that NSAIDs are indeed useful in AD prevention are largely observational and/or retrospective; large populations are quizzed as to their health habits and medication usage, and these reports are correlated with present or future health outcomes. And if you've ever quizzed an old person about their drug use now and in the past, you may well wonder as do I how accurate those self-reports really are.

While the jury's still out as to whether NSAIDs are useful against AD, there is evidence that they may lower the incidence of cancer, and they certainly are good for pain. On the other hand, a recent study(2) showed a strong link between their use in patients also on anti-depressants such as Prozac or Lexapro (aka SSRIs) and gastrointestinal bleeding. Those on this pharmaceutical duet were 4.8 times more likely to bleed from their upper GI tract.
1. ADAPT Research Group. Cognitive Function Over Time in the ADAPT: Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Arch of Neur. 2008;65(7): 896-905.
2. deAbajo FJ, et al. Risk of upper GI tract bleeding associated with SSRI and Venlafaxine therapy: Interaction with NSAIDs and effect of Acid-suppressing agents. Arch of General Psychiatry. 2008;65(7):795-803.

Tuesday, February 24, 2009

Kefir and breast cancer

(thanks to Dr. Jacob Schor once again for bringing yet another health topic to my attention; check out his web-site at to subscribe to his newsletter)

Human beings have a self-preservation mechanism in the gag reflex; when something unexpectedly unpleasant in taste or texture hits the mouth, the entire upper digestive system reacts quickly and violently to eject to the offender. The first time I learned about this survival mechanism, I had just taken a large mouthful of buttermilk with my childhood friend Jean's encouragement. She raved about how tasty it was when, in fact, it was vile. I laughed hard and gagged simultaneously, sending the buttermilk through my nose.

Decades later, I accepted a small jar of homemade kefir from my patient V who took a bottle of the worthy stuff to work every day along with a container of home-cooked stew. As she is absolutely one of the healthiest people I know and care for, I was eager to start a kefir habit of my own. But oh heavens, it's surprisingly tart and foul, worse than buttermilk, and I spit the stuff out. New research suggests, however, that it may be the latest and greatest chemopreventive agent against breast cancer. Maybe chocolate syrup can enhance the taste. Check this out:

Canadian nutritionists cultured human breast cells--both cancerous and not-- in the lab, then fed the little colonies extracts of kefir, yogurt, and plain old pasteurized milk in various concentrations and checked out who thrived and who died(1). Kefir depressed tumor cell growth in a dose dependent fashion--the more kefir present, the fewer the cells. A .63% kefir extract dose (now perhaps even I could handle that) decreased tumor cell numbers by 29% and the 2.5% formula felled those cancerous bad girls to 56% their pre-kefir numbers. The yogurt also suppressed tumor growth, but less vigorously than the kefir. And the milk stimulated both lines of breast cells--normal and malignant--at concentrations as low as .31%!

Do I want to wait for more info, more studies? I think not. I'm calling V tomorrow for her kefir recipe. After all, if I fully expect it to taste sour and slightly carbonated, I can overcome the urge to cough it out through my nose.
(1) Chen, C et al. Kefir extracts suppress in vitro proliferation of estrogen-dependent human breast cancer cells but not normal mammary epithelial cells. J Med Food. 2007 Sep;10(3):416-22.

Thursday, February 19, 2009

Updated colon cancer screening guidelines

When I was an intern, we had a standard 'scut list' of tasks that no one loves but only an intern (or medical student if you were lucky enough to have one around) would do. Every admission, no matter what time they rolled through the ER door, needed a complete work-up by the time morning rounds began, and that work-up included a gram stain of that which they were coughing up if coughing was one of their presenting symptoms. This involved getting a phlegmy sample, teasing out spit from the real deal gunk within, then spreading the mess on a slide and processing it appropriately. Needless to say, it was gross.

What does that have to do with colon cancer screening? Well it's to let you know that I'm okay with digital rectal exams and testing stool samples thus obtained for blood because it's a walk in the park compared to the above. Nevertheless, I welcome the latest screening guidelines(1) from the United States Preventive Services Task Force (USPSTF) that do not include rectal finger probes for those brave souls who get their every 10-year colonoscopy exams.

Colonoscopies are the best cancer screening tests we have with respect to cancers ducked (as pre-cancerous polyps are removed) or cured (tiny cancers found before they spread). That said, they're expensive, time intensive, and not without rare but serious complications. Someday we'll have a better way, but meanwhile they are still on the A list for those over 50 at average risk. On the other hand, the USPSTF says that colon CT scans are not yet ready for prime time screening purposes. More info needed, they declared, to support its routine use because thus far, this easier and less expensive scanning technique produces too many 'false positives' (looks like a polyp but not a polyp just a hunk'a stool clinging to the colon wall).

For those who cannot stomach (or perhaps cannot colon) the thought of a colonoscopy, or just plain can't afford it, the panel supports yearly high-sensitivity fecal occult blood testing (FOBT) or every 5 year sigmoidoscopy with FOBT in between. Used to be that FOBT was about equivalent creepy to sputum gram smears--requiring that the testy testee fish around in the toilet water for their 'specimen,' then to use a junior-sized popsicle stick to apply it a little card, do this three days in a row, then mail the cards off to the MD office where a testy assistant had to open the crusty old card and test it for blood. Now, the MD or patient takes darling little grooved stick from a teensy tube, gently rubs it in the residual stool on the exam glove finger or a used piece of toilet paper (if doing test at home), and reinserts stick in tube. Testing is then carried out with a treated paper strip and no further person/fecal interaction is required.

Alright, that is a wee bit gross as well, but all this colon cancer seeking is important stuff for persons of age.
1) Preventive Medicine 2009: The Annual Meeting of the American College of Preventive Medicine (ACPM). Session 30. Presented February 13, 2009.

Tuesday, February 10, 2009

Breast cancer and hormone therapy

I believe that the most important influences driving our medical decision making process are our personal beliefs, both our worst fears and our fondest hopes. These belief systems are powered by our own medical histories, those of our family, the things that we read, and our personal experience. Sometimes my exam room is crowded to overflowing as Suzanne Somers argues with Dr. Susan Love in the corner as Dr. Andrew Weil tries to get a word in edgewise. Meanwhile my patient's mother and her best friend's cousin are lurking just behind her clamoring to add their opinions on the magazine articles spread out on the desk in front of us.

I would be foolish to discount these many voices; if they're important to my patient, they need to be a part of our discussion. I like to think my worst fears are highly informed ones, yet I am highly influenced by my family history of dementia and completely freaked out by the latest news on breast cancer and HRT in the latest issue of the NEJM(1). Here's the scoop:

The Women's Health Initiative randomized over 16,000 women to receive either combined postmenopausal hormone replacement therapy (Premarin plus Provera) or a look-alike placebo, then followed each group with regard to health outcomes, particularly the incidence of cardiovascular disease and breast cancer. The trial was abruptly halted in the summer of 2002 (what menopausal internist can forget that?) when it was clear that harm outweighed benefit with respect to heart attack, stroke, and breast cancer risk.

The study has come under attack for applying data obtained from a somewhat older group of women (average age 63) many of whom were overweight, hypertensive, diabetic, and smokers to a younger group of women just entering menopause and looking to improving their quality of life with HRT. Several studies, both trials concluded and some still underway suggest that, in fact, this latter group of 50-somethings may actually receive cardiovascular protection from the use of hormones particularly so-called bioidentical estrogen delivered in a non-oral fashion (such as via a skin patch).

I'm good with all that but note please that cardiovascular disease is not high on my to-worry list although I certainly recognize that many of my patients are at risk for same. And as losing my marbles is number one on my future frets, and estrogen is a top neuroprotective agent for aging female brains, I'm choosing to motor on with my HRT choices.

When the WHI data came out, some drug company or other provided me with graphics on this breast cancer thing. One thousand little grey female stick figures were lined up on the top of the page three of whom were colored orange. These unfortunate orange ladies were the number per year of new breast cancer victims in 1,000 post-menopausal ladies not on hormones. At the bottom of the page, another 1,000 skirted sticks queued up, 996 clad in grey and 4 in blue. You've got it: the blues were new cases of breast cancer per year in 1,000 post-menopausal hormone users. The absolute risk was huge; a 33% increase in breast cancer amongst hormone users but the relative risk small, namely one additional breast cancer per thousand users.

BUT...consider that 4th blue lady, her life turned upside down with biopsies, chemo, radiation, and a world of worry even though her chances of actually dying from that cancer are small. And if your worst fear is that cancer-induced world upheaval, then you will choose to discontinue therapy or never start it in the first place.

And now the doctors of the WHI bring us this new news to add to the evidence behind our worst fears, namely that the incidence of breast cancer which nearly doubled in the hormone users over the 5.6 years of the study decreased rapidly in the two years after the study coinciding with a marked drop in the use of combined hormones by the subjects. The busy slide at the top of this post illustrates this in the upsloping solid red line on the left which represents cancer incidence during the study and the soothing downward solid blue line on the right as fewer women got the bad news in the 2 years following the study's end. The black and white graph that follows is the interesting and contrasting data from a Scottish study that also notes the drop in hormone use over a similar time frame (the two plunging lines) but the more or less straight line at the top shows that Scottish women did not experience the drop in breast cancer rate with falling use of HRT.

Argh, what's an aging woman on hormones or contemplating their use to think? Estrogen is a growth-stimulating hormone, and thanks for the boost when it comes to bone, muscle, connective tissue, skin, vaginas, and brain. I love my brain power, I worry often about dementia, and I don't mind the youngish looking skin, so here's to hormones! But, breasts that aren't prepping to feed a developing babe don't like to be stimulated, and the more you goose your breast cells years after pregnancy is nothing but a distant memory, the more likely you are to stimulate a cancer. I don't want cancer, no not one bit, I know one woman who got cancer within 1 1/2 years of starting HRT, so to heck with hormones!

Well, Ms. Suzanne Somers staring out the cover of "The Sexy Years" like you just rolled out of a bed in which you were not alone, what is easy about this decision? Absolutely nothing. Per Dr. Morris Notelovitz, a venerable old menopausal researcher, every year a woman and her doctor should review her hormone therapy decision (and every other medical decision she makes per me!). If she is using HRT, why? If she is not using HRT, why not? What are the experts and your secretary's aunt saying? What do you believe is best for yourself?
(1)Cheblowski, RT et al. Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women. NEJM. Volume 360:573-587 Feb. 5, 2009.

Sunday, February 08, 2009

Pilates, back pain, and Denver's old spines

I see a lot of older women going to ground--their spines telescoping downward and often acquiring notable, painful curves in the journey south. Unfortunately, got one of those backbones myself. I've tried a lot of things to shore it up but none more useful than my lessons with Dana Dreifus, a wonderful Pilates instructor in central Denver. She has an incredible intuition for that which you need to balance and strengthen, and she's quick with adjustments to the standard postures in order to accomodate your ability and level of fitness.

But you don't have to be old and degenerating to enjoy Dana's careful attentions and enthusiasm. If you're new to Pilates or wish ongoing instruction, you could not do better than to call her at: 720-936-3667.

Friday, February 06, 2009

L-carnitine for your hair

Those of you who follow my Menopause Moments blog might already be taking this stuff to boost your brain. So here's good news from that this supplement may stimulate hair growth.

Hair follicles go through cycles wherein hair grows (anagen) and then falls out (telogen). Hair aging badly becomes thinner, finer, and more colorless with each cycle. Progesterone promotes glorious hair (think hair during pregnancy) and precipitous drops in this hormone cause hair loss (think hair after pregnancy or during menopause). Testosterone causes hair loss in a characteristic pattern (those thinning temples and shiny pink crowns of aging men and some women). Minoxidil or Rogaine improves circulation to hair follicles and sort of helps men and women hold onto their hair. So what does l-carnitine do?

When hair follicles were cultured in the lab (if they can grow 'em in a dish, why can't they grow 'em on our heads?) in the presence of l-carnitine, researchers at the University of Hamburg observed several positive things: the growth phase lasted longer, fewer hair matrix cells keeled over dead, and more matrix cells proliferated. At a molecular level, less TGFbeta2 factor, less TGF-beta II receptor protein, and falling levels of caspase 3 and 7 confirmed a more-growth-less-death environment for the hairy little cell community(1).

The German dermatologists summed it up thus: "l-carnitine, a frequently employed dietary supplement, may stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix." Whoa, I would like to use "massively proliferating" and "my hair" in the same sentence. How do you say "Please don't hate me because I have beautiful hair" in German?
1. Foitzik, K et al. L-carnitine-L-tartrate promotes human hair growth in vitro. Exp Dermatol. 2007 Nov;16(11):936-45.