Wednesday, March 26, 2014

Copper and wrinkles

I assume that you, like me, do not wake up looking your best.  So here's interesting news from Korea via Prevention Magazine in cooperation with Bergdorf Goodman. 


That which keeps our skin firm and fresh are two proteins--collagen and elastin--and a substance called hyaluronic acid.  Collagen gives structure to the skin and promotes the foundation in which elastin provides elasticity (e.g. the ability to spring back to smoothness after being smushed all night against the pillow) while hyaluronic acid cushions and moisturizes.  Sun exposure, smoking, dry air, pollution, facial expressions, and sleep positions along with aging hasten the loss of these three substances and the progression of lines to wrinkles to furrows and folds.


Apparently copper oxide can be absorbed by intact skin wherein it facilitates the process of making these structural proteins and stabilizes them within the sub-surface structure.  Korean dermatologists took these copper characteristics and ran with them, theorizing that sleeping on pillowcases made of copper-saturated fibers could reduce wrinkles(1).  61 volunteers were recruited to snooze perchance to lose their bags and sags. They were graded and measured by 'expert graders' as well as with an objective skin wrinkle measuring device called the 3D Image Analysis GFM PRIMOS.


A significant decrease in crow's feet as well as in 3 'roughness parameters' was both observed and measured at 4 and 8 weeks into the study in the copper-pillowcase group but not in the usual bed linen controls.  That translates into shallower wrinkles and better overall appearance! An earlier study (2) noted these same improvements after a mere 2 weeks of nighttime copper exposure.


So here's where BergdorfGoodman.com comes in.  You can order a coppery pillowcase for $60.  I was so-so on the prospect after reading the news in Prevention and somewhat more interested now that I've read the study.  It does seem like the perfect 'milestone' birthday gift, but I'm unsure if I'm ready to buy one myself.  Let me know if you give it a try!
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1) Baek, JH et al.  Reduction of facial wrinkles depth by sleeping on copper oxide containing pillowcases. http://www.ncbi.nlm.nih.gov/pubmed/22938003
2) Borkow, G et al. Improvement of facial skin characteristics using copper oxide containing pillowcases. http://www.ncbi.nlm.nih.gov/pubmed/19467028







Thursday, October 24, 2013

What else should I take besides calcium for my bones (Part V of "Should I take calcium")

Calcium is necessary to build and maintain strong bones, but it is not necessarily sufficient.  To focus in on calcium supplements as a top priority solution to the prevention and treatment of osteoporosis is to lose sight of the complexity of bone-building and maintenance, and to risk the unwanted consequences of too much of a single good thing.

Vitamin K, as mentioned in Part IV of this series, is essential to the modification of proteins integral to blood-clotting and the proper use of calcium.  Vitamin K1, available from plants particularly of the leafy green variety such as kale, is the K form involved with normal blood coagulation.  People are rarely deficient in K1 insofar as clotting is concerned. At times, individuals who have experienced problems such as deep vein thrombosis (clot) in leg veins or pulmonary emboli (blood clots traveling to the lungs) are put on warfarin (aka Coumadin) which partially blocks the function of K1 thus preventing future unwanted clot formation.  Unfortunately, people on long-term warfarin are known to be at greater risk for arterial calcification.

K1 can be converted to K2 by intestinal bacteria.  While there is dispute as to whether or not bacterial K2 is available for absorption into the body through the gut wall, it is known that women with high intake of K1 are less likely to sustain hip fractures, and lettuce intake--a good source of K1--was inversely proportional to future incidence of hip fractures in the Nurses Health Study(1).  Those medical professionals eating lettuce once or more daily had a nearly 50% hip fracture risk reduction compared to those downing one or less salads per week. 

It is difficult to take in enough K1, however, to meet your K2 requirements.  Researchers from The Netherlands compared the efficacy of K1 to K2 in the MK-7 form with respect to the production of proteins essential to proper bone calcification and found the K2 more effective and far more long-acting in its bone-forming functions(2).

Therefore, in order to build strong bones AND keep unwanted calcium out of your blood vessels, daily intake of K2--especially the MK-7 molecule--is absolutely the answer.  Besides the Rotterdam study cited in my previous post, multiple other clinical studies correlate K2 intake with long term vascular health. 

While calcium is good and necessary, vitamin K2 is essential.  Vitamin D, of course, is also crucial as are multiple other micro-nutrients.  In the sixth and final installment of this series, I'll give you my best advice as to "Should you take calcium" and what you should be taking as well for optimal bone and vascular health.
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1) Feskanich D et al.  Vitamin K and Hip Fractures in Women, a Prospective Study.  Am J Clin Nutr vol. 69 no. 1 74-79. 
2) Schurgers LJ et al. Vitamin K–Containing Dietary Supplements: Comparison of Synthetic Vitamin K1 and Natto-derived Menaquinone-7. Blood vol. 109 no. 8 3279-3283.                                    

Wednesday, October 09, 2013

The Calcification Paradox (or Part IV of Should I Take Calcium?)

As I mentioned in Part III of this series, there is an inverse association between decreased bone calcification and increased vascular calcification, neither of which is a good thing.  In other words, those who shrink and crumble into the osteopenia/osteoporosis thing are also those most likely to deposit unwanted calcium in their aging blood vessels.  The heart of this supplemental calcium controversy (do I take it or not?) lands squarely here: how does our body calcify that which holds us upright while also preventing calcium build-up where it does not belong? What matters here is not just the necessity of incoming calcium to balance calcium loss but also an ongoing incoming supply of the known co-factors needed for proper calcium use.

Back, once again, to an evolutionary perspective.  In Part II I mentioned our Ice Age ancestors who ate a high-calcium diet of plants and insects and little or no grain--a food source both low in calcium and high in phytates (substances that bind calcium thus preventing effective absorption).  Now let's go back even further to our remote water-based relatives who spent their lives swimming about in calcium-rich seas.  Early evolutionary pressure, therefore, required the development of mechanisms to prevent widespread calcification through their soft, fishy tissues. The ability to survive and thrive depended--still depends!--on the limitation of calcium deposition solely to skeletons be they external shells or, much later, internal bones. Elaborate regulatory mechanisms developed over eons that promote calcium phosphate crystallization in the right place and prevent it elsewhere.

The central actors in strong bone production are cells that package mineral matrix--a mixture of calcium, phosphate, enzymes, and proteins--and then deposit it along collagen fibers also produced by these cells.  This can happen in the right place (in bones that are growing as in children or repairing as in adults) or the wrong place as in aging aortas or arteries.  Cells that can turn into osteoblasts (bonemakers) are not only found within the skeleton but also in the walls of blood vessels.  The most important protein responsible for bone mineralization is osteocalcin which is dependent on vitamin K2 for proper function.  The most important protein responsible for the prevention of mineralization outside of bones is matrix gamma-carboxy glutamic acid which is also dependent on vitamin K2 for proper function.  Do you see where this is going?

I am here to tell you that I had no idea why I've been taking vitamin K2 regularly for the past year except for a vague notion that it was good for bone health.  I'm certain that I learned nothing about this in medical school decades ago when the importance of vitamin K to proper blood clotting was emphasized but no one mentioned its importance to mineralization. For those of you who haven't spent hours studying the literature on vitamin K as I have while writing this series, there are two main forms of K: K1 important to normal blood clotting function, and K2 which is integral to the deposition of calcium in the body.  More on that in Part V.

Recent studies abound on the benefits of K2 with respect to cardiovascular health.  The Rotterdam Study, published in 2004, found that persons with the highest levels of K2 were less than half as likely to die of coronary heart disease or develop severe aortic calcification over a seven year period than those with the lowest levels, and almost 75% less likely to die of anything in that same time period. 

Wow, if you haven't got K2, get some!
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1) Geleijnse, J et al.  Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. J. Nutr. vol. 134 no. 11 3100-3105.  

Monday, September 16, 2013

Blood Vessel Calcification (or Part III of Should I take calcium?)

Here's the heart of the calcium supplement debate. Does taking extra calcium for prevention and treatment of bone loss associated with aging hasten the calcification of blood vessels, a process which is also associated with aging. That which is normal and healthy for your skeleton, namely the incorporation of calcium crystals into its structure, is neither normal nor healthy within your arteries.  Studies of aging humans and their whole body CT scans suggest that virtually all men and women have some demonstrable vascular calcium by age 70.(1)  Furthermore, the calcification was widespread in 80% of men and 60% of women by that age, and extensive calcification is known to correlate with a high degree of atherosclerosis more commonly known as 'hardening of the arteries'.(2)

This sort of dilemma--a basically good physiological process gone rogue--takes us into a lot of science on calcium, injury, hormones, aging, and inflammation.  The CT scanning study cited above not only confirmed that calcification, and therefore atherosclerosis, is definitely correlated with aging and increases as the years progress, it also, once again, found that menopause with its attendant loss of estrogen is also a time of accelerated progression of vascular disease.  Women under 50 years of age were much less likely than men to have calcium, but the prevalence of calcified vessels greatly increased between 50 and 60, and the gals were as likely as the guys to have calcifications by age 70 (just not as extensive).  Whether or not hormone therapy can slow down this vascular deterioration is another complicated story for another post.

Of note in this discussion, however, is the immune system's response to the presence of calcium crystals in developing atherosclerotic lesions in arteries.  Cells called macrophages which are first responders to bodily harm show up early in the course of blood vessel injury and set immediately to work eating foreign invaders Pac-Man style.  As they gobble up various harmful substances such as oxidized LDL cholesterol or basic calcium phosphate (BCP) crystals, they send out proinflammatory cytokines which are chemical messenger molecules that further activate an immune response.  This is a good thing with regards to incoming foreign bodies such as bacteria or dirt from the sidewalk when you've fallen and scraped your knee, but not so good when it's an ongoing assault from various environmental insults such as LDL-cholesterol, trans-fats, cigarette smoke, or...too much calcium (more on this later).  The inflammation from BCP crystals in activated macrophages "may lead to a positive feed-back loop of calcification and inflammation driving disease progression."(3)  In other words, once blood vessels are disturbed by calcification, the immune response invites the deposition of more calcium.

Here's one more puzzle to set your head reeling (mine is already so why not join me?).  There is a known clinical association between vascular calcification and osteoporosis.  In other words, those of us dealing with loss of bone mineral density are the very people that need to worry most about gaining unwanted vascular mineralization in the form of calcium in our arterial walls.  This suggests a link between bone and vascular metabolism.  Either vascular calcification promotes bone mineral loss, bone loss hastens vascular calcification, or there's a common underlying pathology to both processes.  The latter seems the most likely scenario, and the underlying normal and abnormal physiology of calcification in the body finally leads to some answers about whether or not calcium supplements are a good idea.

More on that in the next post.


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1) Matthew A, et al. Patterns and Risk Factors for Systemic Calcified Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology.                                   
2) Solberg LA, Eggen DA.  Localization and sequence of development of atherosclerotic lesions in the carotid and vertebral arteries. arteries. Circulation; 1971.
3) Nadra, I, et al. Proinflammatory Activation of Macrophages by Basic Calcium Phosphate Crystals via Protein Kinase C and MAP Kinase Pathways. Circulation Research. 96: 1248-1256.

Friday, August 30, 2013

Should I take calcium? Part II

In Part I of this series of posts, I discussed the science behind calcium intake.  In short, what goes out via intestinal loss (at least 150 mg/day or more) and kidney excretion (at least 100 mg/day or more)(1) must be replaced in order to maintain a steady level of calcium in the extracellular fluid (ECF) including blood.  If calcium out is greater than calcium in, the parathyroid glands release a hormone which facilitates breakdown of bone mineral matrix freeing calcium to enter the ECF. Thus, bone-based calcium is not only an integral part of your skeletal strength but also a readily available calcium reserve in case you're running short.

Clinical research scientists who regularly conduct studies on every sort of medical dilemma have compiled an enormous amount of data on the benefits of calcium intake. Starting from an evolutionary perspective--my personal favorite--let's first consider our ancestors from 10,000 years ago when life was quite different but the human genome was not. 

Radiologists and anthropologists from Emory University have determined that our ancestors--both human and primate--ate a lot of high-calcium insects and high-calcium plant food.(2)  These experts estimate that our Stone-Age predecessors took in at least twice as much calcium, mostly from plant based sources, along with more fiber, micronutrients, and protein than we consume with our modern diet. They ate virtually no grains which are not only a poor source of calcium but certain varieties including wheat contain phytates, a compound which binds minerals and decreases their absorption. X-rays of our foreparents' fossilized skeletons confirm that the outer layers of their bones were nearly 20% thicker than ours.  Strong Cro-Magnon structure was the result of a whole lot of outdoor hunting and gathering plus lots of calcium.  The authors of this review conclude that the best-for-modern-bone plan would include a return to the "nutritional pattern for which we have been genetically programmed by evolution."

There is an enormous amount written about the effects of calcium supplementation, with or without vitamin D, in a modern population that avoids the sun and doesn't snack on praying mantises.  The evidence is clear that calcium intake can promote a positive calcium balance--more in than out--which in turn reduces the rate of bone loss and may result in an increase in bone density.  What is not clear is whether or not this has a positive effect on fracture risk. Some experts point out that many of these studies were too short in duration to fully evaluate the long-term benefits of better bone. One study out of France(3) featuring 3,000+ old ladies with added calcium, however, demonstrated decreased fracture risk in just 18 months of follow-up! Half the subjects in this investigation received 1200 mg of calcium plus 800 units of D each day and ended up 43% less likely to have broken their hips by study's end compared with their colleagues who took look-alike placebos.

The US Preventive Services Task Force spent a lot of time reviewing this mountain of medical evidence.  They considered "meta-analyses" that pooled data from multiple studies and concluded that there was not enough evidence to support a recommendation for the use of supplements, and declared that smaller doses (less than 1,000 mg/day calcium and 400 units D) made no dent in fracture risk at all.  Because extra calcium intake can increase the incidence of kidney stones in susceptible persons, the USPSTF graded such dosing as Grade D, i.e. don't do it!

Uptodate.com, a 'living' on-line textbook for doctors, also considered the data, last updating the section on calcium supplements on August 28, 2013.  The reviewers agreed that the fracture data was variable, but were particularly impressed with the data from the Women's Health Initiative, the same trial that created headline news about negative health outcomes from the long-term use of HRT.  Over 36,000 women were assigned to take 1,000 mg/day of calcium citrate with 400 units of vitamin D or placebo pills.  Those who were most compliant with the regimen, taking at least 80% of the supplements over 7 years of follow-up, had a nearly 30% decreased risk of hip fracture.  Overall, compliant or not, the calcium/D group had a 12% decrease in fractures.

Uptodate's wrapped up their discussion after considering the latest data as of just two days ago by stating "Based upon the meta-analyses discussed above, we recommend 1200 mg of calcium (total of diet and supplement) and 800 int. units of vitamin D daily for most postmenopausal women with osteoporosis."  And, spoiler alert, they took into account the effect of supplemental calcium on the risk of cardiovascular disease.

More on that in Part III.
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1) Houillier, P et al.  "What serum calcium can tell us and what it can't".  Nephrol. Dial. Transplant. 21 (1): 29-32.
(2)Eaton, SB and Nelson, DA.  "Calcium in Evolutionary Perspective." Check it out for the calcium content of grasshoppers and moths!
(3)Chapuy, MC et al.  Vitamin D3 and calcium to prevent hip fractures in the elderly women.  N Engl J Med 1992 Dec 3;327(23):1637-42.

Wednesday, August 28, 2013

Should I take calcium? Part I



I have been reading up on that which is good for blood vessels versus that which hastens their demise.  In particular, owning a set of bones increasingly fragile with age, I was curious about the effects of calcium supplementation on vascular health.  Recent headline news from the latest medical research suggests that excess intake of calcium tablets results in deposition of calcium in the walls of arteries--not something you'd wish on your hardworking vessels. I used to recommend adequate calcium intake as  an integral part of the prevention and treatment of age-related bone loss-- 1,000 mg/day total (diet plus  supplements) if on hormone replacement and 1,500 mg/day if not. Now the US Preventive Services Task Force says no. In fact they give a calcium plus D supplementation strategy a "D" grade (which is very strong language for the USPSTF) based on the increased risk of kidney stones but mentioning not at all this vascular business.  Uptodate.com--a widely used on-line resource for physicians says yes.
What's an old lady to decide?  Do I recommend extra calcium for myself and for others? 
After two hours of reading, I realized this was a decision so complex that it could not be answered in a single day nor a single post.  I decided to approach the problem according to the 8 components that I believe are the basis for making medical decisions.  In brief,  I think physicians bring three areas of expertise to the process--the science, the evidence from a constantly changing body of medical literature, and their personal practice experience.  Patients (and in this case I'm filling both roles) bring their current situation, their personal medical history, their family history, and their beliefs to the table.  Finally, and unfortunately, the insurance company brings its willingness to pay into the picture.  This is  not important here as calcium and D supplements are not an insurance-covered benefit.

A steady level of circulating calcium in the fluids and blood surrounding our cells is essential to the proper function of multiple organ systems, especially normal nerve conduction.  Too little can cause spasms, seizures, and abnormal heart rhythm; too much leads to confusion, coma, and abnormal heart rhythm.  As a result, a wonderfully orchestrated system controls serum calcium by balancing incoming sources from both intestinal absorption and internal release from bones with outgoing losses through the colon and the kidneys.  If your serum calcium level is normal on your lab panel, you can thank your intestines, kidneys, bones, and parathyroid glands, but you cannot assume that your calcium intake is adequate nor that your bones are holding up okay. 
In order to maintain that crucial balance, calcium in to the extracellular fluid (ECF) must equal calcium out.  Your parathyroid hormone levels rise in response to decreased ECF calcium which quickly leads to release of bone calcium.  In the short term, only superficial bone layers are involved in the release of mineralized calcium from the bone structure, and this loss is easily replenished.  On the other hand, a negative calcium balance over time, amplified perhaps by vitamin D deficiency or an age-related drop in estrogen and testosterone, can lead to a loss of bone density progressing to osteopenia and osteoporosis.  
So calcium balance is critical to bone density along with many other functions.  There are many conditions which can cause abnormal calcium levels, but what we are considering here is the situation of an otherwise healthy aging person trying to maintain bone health through calcium intake without increased risk to the cardiovascular system.  The next post will cover the evidence with regards to calcium intake and bone health.
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Sunday, August 25, 2013

Beta-blockers and Cancer

Beta-blockers were first released for clinical use in the 1960s to control angina from coronary artery disease.  They became the go-to drug for hypertension, heart failure, cardiac protection after heart attacks or during surgery, and heart rhythm control.  They work through the blockade of beta-receptors found on many different cell types, preventing cell stimulation through the effects of epinephrine (adrenalin) and norepinephrine on those cell surface sites. These "flight or fight" stress chemicals cause a rise in pulse rate and blood pressure and produce the physical sensations of fear.  As a result, beta-blockade is also useful in controlling anxiety and stage fright.  One of my professors in medical school declared "We should all be on beta-blockers.  After considering the following research, I'm inclined to think he had a good point.

A thick stack of studies supports a mind-body connection in disease. Depression and anxiety have been associated with increased risk of both recurrence and progression of cancer in "the worried not-so-well," a term coined by psychiatrists in Philadelphia. Thanks to Dr. Jacob Schor(1), a Denver naturopath, for putting me on to to a recent article regarding outcomes in women with triple-negative breast cancer(2) (a particularly difficult to treat subset of breast cancer types).

Italian investigators located 800 postmenopausal women diagnosed with TNBC and checked their records to evaluate the effect of beta-blocker usage (prescribed for other conditions) on risk of recurrence and death.  74 of the subjects were on beta-blockers at the time of their diagnosis, and, in the five years that followed, the incidence of recurrence or death in this group was less than half that of those without beta-blockade.  

A number of cancer cell types, including breast and ovarian, are known to have beta-receptors on their cell membranes.  The stress chemicals mentioned above activate a metabolic pathway that promotes unbridled growth of these renegade cells.  Thus, beta-blockers could be down-regulating this process, slowing replication and spread of the tumors.

Beta-blockers are not without side effects--some people feel tired and depressed with regular use.  The pulse slows, and the heart rate response to aerobic exercise is muted.  To further complicate the picture, Boston researchers also published a paper this summer that compared breast cancer deaths over 10 years in nearly 5,000 women diagnosed with Stage I-III tumors as related to use of beta-blockers, ACE inhibitors (another blood pressure drug class) and aspirin(3).  While women on either BP med had reduced rates of death, the most dramatic risk drop occurred in those with regular aspirin use.  As many women on BP meds also take aspirin for cardiac health, the study authors postulate that it may be the aspirin that brings on the benefits.

Should we all be on beta-blockers?  That's still up for debate.
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1) Dr. Schor writes an excellent e-mail newsletter.  You can subscribe at   www.denvernaturopathic.com

2) Botteri, E, et al. "Therapeutic effect of β-blockers in triple-negative breast cancer postmenopausal women." Breast Cancer Res Treat. 2013 Aug;140(3):567-75. doi: 10.1007/s10549-013-2654-3.

3) Holmes, MD, et al. "Beta blockers and angiotensin-converting enzyme inhibitors' purported benefit on breast cancer survival may be explained by aspirin use." Breast Cancer Res Treat. 2013 Jun;139(2):507-13. doi: 10.1007/s10549-013-2553-7. Epub 2013 May 7.

Sunday, June 03, 2012

Will walk for feedback

I ask all my patients about their personal exercise routines. They often answer that while they do no exercise, they are "extremely active" all day at work. I encourage them to wear pedometers in order to gauge just how active they are. One dismayed lady tried it out, then wailed in a follow-up email "There are only three steps between my desk and the file cabinet!". Not such a whirlwind at work after all.

Researchers in New Zealand decided to see if sedentary seniors could be persuaded to move more if equipped with encouragement and a pedometer(1). One group of geezers (geezettes too!) were given step-counting gadgets along with exercise counseling and follow-up phone calls to set ever greater step-counting goals. A control group were counseled and called but were not issued any freebie pedometers.

At the end of a year, both groups had significantly increased their leisure walking, proving that mere encouragement and phone calls are useful interventions. The pedometered seniors, however, doubled their extra walk-time compared with the unmetered oldsters. Blood pressures dropped in both groups. No surprise--this step-counting strategy works in middle-aged ladies as well(2).

I've been through multiple pedometers in multiple years. I've lost more than a few--in a cab, a nail salon, into the toilet. I've tossed out several due to inaccuracy; so sensitive to motion, they registered any shift of position. I currently wear a Fitbit designed to remain true to step count even if stuffed in a pocket. It also has a flower that gains more leaves the more active you are.

If the Fitbit is too pricey for you, I encourage you to invest in a mid-range device. The Yamax SW701 Digi-Walker Pedometer has been trial-tested for accuracy.

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1) Kolt, GS et al. Healthy Steps Trial: Pedometer-Based Advice and Physical Activity for Low-Active Older Adults. Ann Fam Med May/June 2012 vol. 10 no. 3 206-212.

2) Hultquist CN, Albright C, Thompson DL. Comparison of walking recommendations in previously inactive women. Med Sci Sports Exerc. 2005;37(4):676–683.

Tuesday, October 04, 2011

Of Dreams and Dendritic Cells



"His dream was to use his discovery to cure cancer and infectious diseases like HIV and tuberculosis. It's a dream that's pretty close." Michel Nussenzweig on his fellow researcher Ralph Steinman.

When my mom was newly diagnosed with lung cancer, I brought her a bunch of "Conan the Barbarian" balloons with an encouraging note calling on her immune cell to rally to the job of eliminating the cancer (which she ultimately bested, living on another 18 years!). At the time, however, she was less than amused and huffily informed me that "There is nothing wrong with my white cells."

Immunotherapy, wherein a patient's own immune cells are primed to attack their invasive cancer, is a rapidly advancing area of cancer research. Due to a wide array of ploys with which cancer cells hide from the immune system coupled with various host deficiencies in mounting the appropriate defense, cancer therapy has for years centered instead on chemotherapy. These toxic chemicals are designed to be more lethal to the rapidly dividing cancer cells than on normal tissue. Unfortunately, normal often falls along with the malignant.

One of the giants among researchers in immunotherapy is Ralph Steinman who ironically died September 30th, three days before winning the Nobel Prize in medicine earlier this week. In a further twist of fate, he died of pancreatic cancer, living much longer than most unfortunate souls with this disease perhaps because he applied his own discovery to his personal case.

Dr. Steinman's contribution to this important research was the identification of a unique little player in the immune cascade that he dubbed a dendritic cell due to its tree-like branching configuration reminescent of the dendrites of neurons. The dendritic cell is one of the initial workhorses of the immune system, processing foreign material such as viruses and then presenting it to T cells which are activated in turn to attack the unwelcome invaders.

Dr. Steinman isolated his dendritic cells, exposed them to his pancreatic cancer cells, and thus instructed his T cells to recognize those bad boys as unwanted visitors. A former student, now a collaborator, had this to say, "We'll never know [whether it worked] ...but one thing is for sure: he was able to make T-cells specific for his cancer. It obviously didn't cure him, but it may have prolonged his life."

Saturday, August 27, 2011

Walking across Virginia

Wondering where I've been? Well, busy for one, very busy. For those of you who didn't get the mailing, we've moved our office. From our vintage little office building that was originally built by my pediatricians in 1949 to sleek revamped office digs on the old Children's Hospital medical campus. If you can get through on the phones and find the darned office (still a few glitches to work out!), I think you'll be pleased to see that Adele and I are business as usual under the auspices of Exempla Healthcare here in Denver.

In my spare time, however, I've been walking across Virginia. Well not really walking across Virginia which would doubtless be even hotter than Denver and logistically problematic. I'm talking traversing in a virtual sense. I urge my patients to find an exercise activity that engages their interest as well as their heart. Used to be Jazzercise for me, step aerobics too, but that was years and a lot of knee cartilage ago. Walking with a dog is a personal joy, but I've got no pooch on-site with whom to mosey. So instead, I'm walking solo across the United States with an eye on the West Coast by 2020.

Wanna' come along? Check out the TransAmerica Trail (aka Tools to keep you active) at http://exercise.lbl.gov/index.html. Sign me up as your partner--they'll put you on my map and me on yours at the same starting point. I'm walker number 65471 about to enter Kentucky but happy to join you back on the Virginia coast.

Sunday, March 06, 2011

Sesame oil may be some kind of cure-all!


This just in from my favorite naturopath, Dr. Jacob Schor. This news is particularly important for persons who are hypertensive, have high cholesterol, are diabetic, carry weight around their middle, or travel that overweight road to all of the above.

According to an article penned by Dr. Schor in the current issue of Natural Medicine Journal (1), just a spoonful of sesame oil (actually 2.4 tablespoonfuls/day) makes the blood pressure/cholesterol levels/blood sugar/waistline go down. He cites results from a group of scientists from India's Vinayaka Missions University about the remarkable results of daily sesame oil use in a group of 60 diabetics followed over 2 months. One third downed oil alone, one third used oil plus a diabetic medication called glyburide, and the remaining subjects took glyburide alone.

While those on drugs plus oil did best of all, the oil-alone group fared fairly well as well. The glucose-lowering effects of combo therapy were downright remarkable with blood sugar dropping by 36% and HbA1c (a value that reflects an averaged blood sugar over the prior three months) by 43%! All oil-users also had significant drops in total cholesterol, LDL-cholesterol, and triglycerides plus a bonus rise in HDL-cholesterol.

The Vinayaka group conducted a similar study on locals with high blood pressure who took one of two commonly used anti-hypertensive drugs--hydrochlorothiazide or atenolol. Over a study period of 45 days, the subjects used sesame oil for all their cooking needs and blood pressures dropped to normal. The next 45 days were spent sans sesame supplementation, and blood pressures rose to pre-study levels. Body weight, body mass index, and waistline measurements dropped as well.

I plan to recommend this strategy to my patients willing to give it a try; I'll let you know what results we get. I personally have used sesame oil each a.m. for almost two years in an ayurvedic quest for oral health(4). That morning spoonful theoretically draws out nasty toxins and is meant to be spit out post-pull. Perhaps thereafter, I should consider actually swallowing a swig for the rest of me.
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(1) http://www.naturalmedicinejournal.com/article_content.asp?article=113
(2) Sankar, D et al. Sesame oil exhibits synergistic effect with anti-diabetic medication in patients with type 2 diabetes mellitus. Clin Nutr. 2010 Dec 15. [Epub ahead of print]
(3) Sankar, D et al. Effect of sesame oil on diuretics or Beta-blockers in the modulation of blood pressure, anthropometry, lipid profile, and redox status. Yale J Biol Med. 2006 Mar;79(1):19-26.
(4) Asokan S. Oil pulling therapy. Indian J Dent Res 2008;19:169

Tuesday, November 09, 2010

Sarcopenia or why we install railings by toilets


I attended a funeral last Friday. There was a fair amount of rising and falling to feet and to seats what with religious moments and a standing, whooping, foot-stomping ovation to Megan and her life well-lived. I've written before about funerals, and how I love a good one, but that is not the subject of this post.

My pew-mate was an older woman who carried more than a little extra weight and who struggled mightily to stand each time we were called upon to do so. In front of me sat a skinny woman, still older yet, who did not even attempt to get upright until it was time to leave the chapel. Two elderly friends of Megan, each losing physical ground in her own way, one to excess adiposity and osteoarthritis of knees and hips perhaps, the other to fraility and sarcopenia. The inability to rise from a seated position, however, be it in a kitchen chair, a living room recliner, or a toilet seat, is a big step on the road to dependence and demise.

Aging is filled with -penias as in osteopenia (loss of bone mass short of osteoporosis) and sarcopenia or loss of muscle mass. There are many factors that contribute to this age-related wasting away of muscles some of which not yet elucidated but not the least of which is inactivity brought on by injury, arthritis, and illness which in turn leads to weakness and fatigue which in turn fosters more inactivity.

In order to repair, regenerate, and develop muscles to propel ourselves up out of a chairs and off to the 'frig (or the gym!!), we depend on 'satellite' stem cells that reside on the surface of our muscle fibers. Reduced numbers of such cells coupled with their decreasing ability to do their job is the biological basis of sarcopenia. I've had patients seek out human growth hormone and human chorionic gonadotropin in order to boost muscle mass and reverse aging, but rats and researchers in Washington state and Israel have recently published findings that suggest a simpler, less expensive, more accessible way to get myogenic satellite cells. One word: Exercise!

Rodent models suggest nothing but bad news from aging satellite cells. Satellite cells are usually in a resting state in older animals but can be activated to repair and renew muscles after injury and illness. But satellite cells are more likely to generate fat (the lady next to me!) or fibrous connective tissue (the stringy, skinny lady in front of me!) than muscle fibers as they grow old. So what happens if rats work out instead of veg in front of the TV set?

The researchers confirmed that the older the rat, the fewer the satellite cells on their calf muscles. However, when the four-legged geezers were persuaded to hit the exercise wheel, this aging effect was corrected, and both males and females greatly increased the number of myogenic--muscle producing--cells. Better yet, this cellular change had a visible effect on the old coots with a favorable shift in their lean-to-fat content and on their level of "spontaneous locomotion." Svelte, toned, AND disinclined to sleep the day away in the wood shavings!

One of the ways I assess how my patients are faring is to greet them first in the waiting room. First of all, it's a good way to start the visit, but, in addition, I can watch them rise from their chairs and walk across the room and up two stairs to the hall. I am daily appalled by the way some of my long-time patients increasingly struggle with the task, even moreso by their seeming indifference or inattention to their inability to move with ease. Check out the way you spring from your pew, your toilet, your desk chair. Don't take "can't do it easily" for an answer.
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1) Shefer, G et al. Reduced Satellite Cell Numbers and Myogenic Capacity in Aging Can Be Alleviated by Endurance Exercise. www.plosone.org.

Saturday, October 02, 2010

Swiss chard and lung cancer


If R is you or more specifically your DNA in charge
of cell proliferation, the CH3 or methyl group is your
potential road to ruin.

In the spring of 2008, one of my patients came back from a vacation to Mexico with "pneumonia". But I didn't really think it was pneumonia--the shadow on her x-ray wasn't quite pneumonia-ish, and her symptoms of fatigue and a non-productive cough weren't exactly right either. Anyway, we optimistically tried a course of antibiotics without any change in that infiltrate, and, alas, it was lung cancer after all. Mother of two boys still at home and an ex-smoker for more than a decade, my patient died at home six short months later.

Sometimes rogue DNA--perhaps damaged by aging, smoke, or an errant sunbeam--just gets the best of you despite all that water and veggies and walking at dawn. Still, a person keeps trying to do what she can to avoid the brick wall of mortality, and a recent study in the journal Cancer Research (1) further supports the value of leafy greens. But before we discuss the goodness of greens, a word or two on gene promoter hypermethylation events which are nothing you want occurring in your DNA.

Genes are minute strips of DNA. During a typical 'business-as-usual' day in the life of a normal cell, they are activated by external and internal events and transcribed via RNA to produce worthy proteins that carry on normal activities that include damage repair and control of cell proliferation. If, however, one instructional molecule of the DNA gets permanently tangled up with a methyl group, the entire gene is silenced and its work remains undone. Worse yet, as that cell with its load of methylated DNA replicates itself because no gene product was there to tell it not to, all its offspring cells are also methylated. As a result, an out of control, methylated mass of cells continues to grow unchecked. Sounds like cancer, doesn't it?

So once hypermethylated, can you become demethylated? Such a demethylation process is the dream of scientists looking for chemopreventive strategies. As opposed to chemotherapy drugs which seek and destroy cancer cells, chemopreventive agents act to repair or prevent malignant change. Researchers from the University of New Mexico sorted through sputum from smokers (both current and ex-) seeing if certain dietary strategies were associated with lower levels of methylated genes in expectorated DNA.

Some 1,100 subjects dutifully hawked up their secretions and completed Harvard Food Frequency Questionnaires. As a result, the New Mexican docs were able to identify leafy greens (and we're not talking lettuce here), folate, and multivitamin use as three strategies that correlate with less methyl-generated mess. They proposed that further study might verify these and other agents as ways to reprogram our genome for life without cancer.

Now I'm all for this sort of research as a doctor and an ex-smoker. My problem is that a pile of steamed chard (or kale or greens) is an unappealing mess all its own. Any suggestions of different ways to prepare an appetizing, chemopreventive side dish of greens?
_____
1) Stidley, CA et al. Multivitamins, folate, and green vegetables protect against gene promoter methylation in the aerodigestive tract of smokers. Cancer Res. 2010 Jan 15;70(2):568-74.

Wednesday, September 29, 2010

Best personal trainer deal in Denver

Please note the corrected dates for this program

I have struggled mightily with back pain from scoliosis and degenerative arthritis. Thanks to a program of core strengthening courtesy of two knowledgeable young women--one a Pilates instructor with a strong background in physical therapy and yoga, the other an athletic trainer with a gift for modifying her workouts for older, less flexible non-athletes--my spasms and debility are yesterday's news.

I've put a lot of time and money into this program figuring properly that any bottom line beats crippling pain and decreased mobility. I am pleased to announce now that my trainer Tanya Martelli (Dr. Sykes goes to her too!) has assembled a low cost solution for those of you displeased with your aging spines.

She will be conducting a three class workshop for five participants Oct. 8, 15, and 22 at our office from 4-5 p.m. The focus will be on posture and core power, and at the end of the sessions, each person will have a home program to continue progress made during the class. The cost is $45. If these times do not work for you, Tanya plans another three week session mid-day Tuesdays at the end of this series.

You do not need to be our patient to attend these classes. Interested? Contact Tanya at tlyaskoff@mac.com to sign-up or inquire about future classes. She just designed a home program for me that I took on a recent road trip to California--worked just perfectly to keep me upright and buff while away from home. She could do that for you too!

Sunday, August 01, 2010

Rose Kelly



Rosellen Kelly, 8/20/52-7/31/10

I lost my dear friend Rose yesterday to cancer. Mom, wife, friend extraordinaire, writer, artist, and Assistant Head of School at St. Anne's Episcopal here in Denver, she was a treasure to all who knew her. She collected friends like an endless strand of pearls--like the ones she wore at a time when our generation was mostly through with such traditional adornment.

Gracious, hilarious, and soothing, she told me that she viewed death as "just showing up for my next assignment. An angel in life, she has ample experience for her upcoming gig.

Saturday, May 01, 2010

Window of Opportunity of Estrogen Therapy for Neuroprotection

Those of you who find this topic one of interest should check out the newest post at my other blog: Menopausemoments.blogspot.com.

Friday, April 23, 2010

Fractures and Fosamax

Dang, what was this 60-something year old lady(1) doing that resulted in her femur breaking like a branch across a gardener's knee? The unsettling answer? Nothing. She just felt a "giving away" sensation in her leg and then she gave way and went to ground. Of note, however, she had been taking medications for 17 years to prevent osteoporosis: first Fosamax and then Boniva.

Our bones are in a state of constant turnover. Breakdown of bone matrix by cells called osteoclasts is balanced by a corresponding build-up of bone mass undertaken by osteoblasts--a process that continually replaces old bone with new. In adults, bone formed equals bone broken down as osteoblasts fill areas along the bone surface previously resorbed by osteoclasts. Such dynamic restructuring in response to the forces of gravity and activity is essential to bone strength. In addition, this active bone metabolism repairs micro-traumas caused by everyday wear and tear as well as macro-traumas such as fractures.

As we grow older, we tend to breakdown faster than we build-up (well duh!). Ongoing osteoclastic activity is no longer countered in kind by reciprocal action from aging osteoblasts especially in women who are estrogen-deficient, inactive, on steroids, or deficient in calcium and vitamin D. Now bone resorbed by osteoclasts exceeds bone built by osteoblasts resulting in bones that are not only thinner but also architecturally unsound. As a result, vulnerable areas such as the hip, the vertebrae, and the bones of the forearms lose strength and fracture easily.

One strategy developed to combat this scenario is a class of drugs called bisphosphonates (Fosamax, Actonel, Boniva, Reclast, and others) which inhibit normal bone-remodeling through inhibition of osteoclasts. Since bone resorption triggers bone formation, these drugs are better suited to slowing loss rather than gaining mass. While population studies show decreased risk of fractures in persons using bisphosphonates, disturbing patient histories, such as that from the unfortunate lady pictured above, suggest that extended use of Fosamax and friends may result in bone fragility through the accumulation of microdamage in bones weakened by a loss of the normal reparative functions.

Texas researchers had a look at bone chips from persons who had spontaneous--i.e. no antecedent trauma--fractures while on Fosamax(2) most of whom had delayed or absent healing at the site of the break. Scary stuff on microscopic exam--many of the patients showed "markedly suppressed bone formation" with little or no osteoblastic activity and diminished mineralized bone. Even those patients on concurrent estrogen therapy demonstrated decreased bone formation. While Fosamax was the first bisphosphonate 'out of the gate' and thus most likely to be associated with fractures related to long-term use, scientists believe that this brittle bone thing may well be found with ongoing use of the other agents in this class.

Well yikes, is it time to boycott Boniva? Act not on Actonel? Consider first, this meta-analysis of several bisphosphonate trials.(3) These scientists from four different countries supported by Merck (Fosamax) and Novartis (Aredia, Zolmeta) analyzed data from three large studies looking for risk of fractures of the femoral shaft (considered atypical when compared with the more common fractures of the femoral head) as they were associated with use of bisphosphonates. Most reassuringly, they found such drug-related breaks to be rare, occurring at a combined rate of 2.3 per 10,000 patient-years. In other words, of 1,000 women using a bisphosphonate for 10 years, 2.3 would have an unexpected fracture of their thigh bone. There was no elevated risk of this type of fracture between those on Actonel and those on placebo, and a relative risk of 1.5 for women on Zolmeta (an IV bisphosponate most often used in serious situations such as in women with metastatic cancer where the drug slows down the spread of the tumor through the bones).

In an editorial that accompanies this study(4), Dr. Elizabeth Shane of Columbia University emphasizes that such atypical fractures are extremely rare, and particularly unlikely in persons on bisphosphanates. In fact, she cites studies that show, on average, that these femoral shaft fractures are more commonly caused by osteoporosis than the medications that treat the condition, and high adherence to this drug regimen more often decreases the risk of this type of bone breakage. She concludes: "many more common and equally devastating hip fractures are prevented by bisphosphonates than are potentially caused by the drugs."

Several authors have suggested that women on bisphosphonates be given a drug holiday in order to allow for a time of normal bone remodeling. Bisphosphonates bind to bone and are slowly released by osteoclastic activity. Fosamax is present in the body long after its use is discontinued--one study found bone turnover suppressed for three years after five years of regular Fosamax use. There are no official guidelines to follow with respect to intermittent bisphosphonate use, but one year off does not seem to diminish the positive effects on fracture risk.

What should you do? Talk with your doctor about taking a drug holiday (no, not THAT kind of drug holiday) if you've been on bisphosphonates for more than five years.
_____
(1) X-ray and case history from:
Goddard MS, et al. Atraumatic Bilateral Femur Fracture in Long-Term Bisphosphonate Use. Orthopedics. 2009 Aug;32(8). pii: orthosupersite.com/view.asp?rID=41933. doi: 10.3928/01477447-20090624-27.
(2) Odvina, CV, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar;90(3):1294-301. Epub 2004 Dec 14.
(3) Black, DM, et al. Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur. Published Online March 24, 2010 (DOI: 10.1056/NEJMe1003064).
(4) Shane, E. Evolving Data about Subtrochanteric Fractures and Bisphosphonates. Published at www.nejm.org March 24, 2010 (10.1056/NEJMe1003064)

Friday, April 09, 2010

The changing face of primary care

My medical partner and I are facing big decisions about the future of our medical practice. I urge all of you--particularly our patients--to head over to Denver Doc Online and read about our dilemma and leave your thoughts behind.

Friday, March 19, 2010

Morton's Foot

Dr. Dudley Morton practiced in the 1930's, first describing a number of foot ailments including Morton's foot (aka Morton's toe), and Morton's neuroma. Morton's foot is a common but dysfunctional variant of foot structure occurring in more than 25% of the population. By the time one hits middle-age, however, the instability caused by this condition can lead to pain and an inability to walk pain-free into the golden years.

Check out the sketch below from The Trigger Point Therapy Workbook for a look at Morton's Foot which is also known as short first metatarsal syndrome. The metatarsals are the longish bones beneath each toe, and the first metatarsal meets up with the big toe at a most critical juncture known as the 1st MTP (metatarsal phalangeal) joint which should be one of the primary weight-bearing areas of your foot.

If you've been issued a stumpy first metatarsal (arrow B), your weight is transferred to the 2nd MTP joint (arrow A) beneath your 2nd toe (arrow C). As a result, your weight can wobble inward towards the arch or outwards towards the little toe which has been likened to 'walking on ice skates'. The 2nd toe may extend beyond the big toe in persons with this Morton's business; while some call this long 2nd toe a sign of nobility. In my experience, it's a sign that you may give up walking for exercise.

Then look out, it's like a veritable aging house of cards cascading down your midline. The arches fall, a bunion may pop out, the ankles hyperpronate (see below), your calf muscles start working overtime to hold up your body,your knees knock together in the midline causing arthritis and collapse of your lateral knee joint,


you start to hate walking, gain weight, and plummet into old age way before your time.

So if that info knocked your socks off, check yourself for Morton's foot thusly:By pulling your toes downwards, you'll be able to see the locations where the metatarsals end and Morton's mayhem begins.

Got Morton's? I do. Custom-made orthotics and Pilates have changed my life. If you've been short-changed on your first metatarsal and are starting to hobble with pain, a trip to the podiatrist is definitely worthwhile. For more information, check out Mortonsfoot.com.

Tuesday, March 09, 2010

Milk thistle for liver protection

I had a patient in yesterday whose medical records show a long history of elevated liver function tests. These enzymes, namely aspartate aminotransferase (ALT) and alanine transaminase (AST), are part of routine blood test panels often ordered to screen for disease. Normally present in liver cells, elevated levels in the blood can indicate disruption of the cells by inflammation or disease. Even minor elevations are taken seriously if they persist over time as progressive destruction of the liver from hepatitis or other disease can occur without major changes in the transaminase values.

Further testing indicated she might be suffering from auto-immune liver disease wherein a misguided immune response against one's own tissue can cause damage to the organ. She wondered what she could do to promote liver health while pursuing a definitive diagnosis with a specialist. I recommended milk thistle only to read the following today on the Consumer Lab web-site.

Consumer Lab is an independent organization that tests nutritional supplements for quality, assuring that these products are pure, contain what they claim, and are free of contamination. The nominal yearly subscription fee is well worthwhile if you are a fan, as am I, of supplements. One of their recent reviews covered milk thistle.

Only one brand was found on testing to contain the amount of active ingredient indicated on the label. Furthermore, the evidence that milk thistle changed the course of chronic liver disease caused by hepatitis or alcohol was weak. The research suggesting that the herbal preparation protects against liver toxicity from acetaminaphen and anti-seizure meds was stronger. The active ingredient in milk thistle--silibinin--has been the subject of recent cancer research and seems to have some promise as a chemotherapeutic agent.

I don't feel quite so enthusiastic about my recommendation now. If you're considering milk thistle supplements, have a look at the ConsumerLab site to choose the best brand.