ErinPharm Gazette July 2008
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Extending lifespan with calorie restriction gains attention, sirtuin research advances, treatment of pre-hypertension in younger people is important, obesity rates are rising to an alarming extent in the general population, statin users are found to have a reduced rate of cognitive impairment while simvastatin (zocor) has been associated with a more than 50% reduction in dementia and Parkinson's disease, significant longer lifespans for those receiving early antiretroviral treatment for HIV infection, diabetics urged to lower blood pressure and accept treatment for cardiovascular risk factors, heated milk is safe for children with milk allergies. We celebrate the long life (to age 99) of Dr. Michael DeBakey, and celebrate the life of Frank Calloway, who
at age 112 is still alive, creating art works, and is
about to take his first airplane ride. Tea drinkers can derive satisfaction that they are gaining cognitive protection.
A review of July 2008. A selection of topics.
This web page is one of a number of ErinPharm web pages designed by me as a synopsis of topics that interest me as well as being a quick reference page for my newsletter subscribers and myself. I have no affiliation of any kind to any pharmaceutical company or medical group. The opinions expressed are my own. I welcome communication and debate. I am an optimist. I look forward to the future with wonder.
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The first comprehensive map of Genomic copy number variations has been developed. Such copy numbers influence genetic diversity and susceptibility to disease.
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Are you trying to lose weight and have been misled by the multi-billion dollar industry selling pills, potions, and 'magic cures'? You are not alone. A survey backed by a commercial drug company reports that approximately 70% of American dieters have tried scientifically unproven methods to lose weight. That's an astounding number of people who have tried dietary supplements in the form of pills and powders. About half of survey respondents incorrectly think supplements are approved by the federal Food and Drug Administration, while about two-thirds believe such products must carry warning labels for side effects. All that happens is maybe temporary loss of weight and the emptying of your pocket. Resist the temptation to believe in those seductive commercials. The only way you can lose weight and keep it off is by a commitment to a change in lifestyle. I recommend lifestyle changes.
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Readers of ErinPharm Gazettes are among those aware, motivated, and seeking to take advantage of knowledge generated on the expanding frontiers of medical/scientific research. It is important to recognise that while we are privileged to be part of this future coming rapidly toward us we also live on a planet where the majority of our fellow human beings suffer under a burden of disease overwhelming and horrifying. One such disease is malaria. It threatens half the world's population, will strike up to half a billion people this year, at least a million will die, most of them under age 5, the vast majority living in Africa.
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Coming on vacation from overseas? Taking out membership with the Life Extension Foundation means you can shop at the LEF Retail Store in Fort Lauderdale, Florida, and get blood drawn for a comprehensive test analysis the same day. No appointment for a blood draw is necessary. Just arrive before 2:00 pm.
As of March 31, 2008, Abbott Laboratories has already submitted an NDA (New Drug Application) to the US FDA for TriLipix as monotherapy and in combination with a statin.
In an intriguing and very thought provoking publication in Nature Medicine (14, 767-772, 2008), online June 29, 2008, evidence is presented that treating progeria syndrome mice with a mix of a statin and an aminobiphosphonate substantially extended their longevity. This is reminiscent of the Scottish study of coronary disease patients taking a statin who appeared to have a reduced rate of telomere shortening in their leucocyte blood cells. Is it just barely possible that some on high dose statin treatment are inadvertently reducing their rate of aging? This speculation is of course outrageous and has the aura of science fiction but many discoveries in medicine have had humble beginnings.
However, realistically, at the present time there is only one way of extending lifespan. That method requires calorie restriction; eating less. It is a sad irony that at this time in world history, when inadequate supplies of food ravage humankind living in desperately poor regions of the world, when obesity from excessive consumption of food afflicts the developed regions of the world, when international crises on the use and distribution of crops and livestock constantly fill the news media, that calorie restriction by the amply endowed could extend their lifespan. It is also a sad commentary on human nature that we cannot adjust to a periodic incidence of calorie restriction and even sometimes near starvation routinely part of life for our paleolithic ancestors or the minimum nutrition experienced by hunter gatherer societies. We have become habituated to copious amounts of calorie rich food. There is even more irony that current pharmaceutical research is directed toward discovering safe molecules that will mimic the effects of calorie restriction as seen by the acquisition of Sirtris by GlaxoSmithKline as we reported last month.
Erinpharm celebrates the life and magnificent work of Dr. Michael DeBakey, who died at age 99 at The Methodist Hospital in Houston, Texas. His work was a lifetime of innovation and visionary progress. The surgical procedures he pioneered, open-heart surgery, artificial hearts and heart pumps, invention of many different surgical instruments, are now routine in major hospitals throughout the world. Read this hyperlink about his work. It documents an era of profound change which began when nothing could be done about heart disease to this time when surgical intervention has given decades of life to tens of millions of patients who would have died in years prior to his energetic and dedicated pursuit of his vision.
In a heartwarming story printed in CNN online we hear about Frank Calloway, a 112 year old man who has lived most of his life in state mental health centers in Alabama. His home is in the Bryce Hospital in Tuscaloosa where he occupies himself for seven to nine hours a day creating his art drawing visionary scenes from his memories of when he was younger. He has charm, an engaging personality, and his work has attracted the attention of art experts. Soon he will take his first airplane ride to Baltimore for an exhibition of his work expanding on day trips he already takes frequently. Congratulations Frank.
In his article in the New York Times Nicholas Wade gives us an excellent perspective on the current status of sirtuin research. In his meeting with Dr. David Sinclair, a co-founder of Sirtris, recently acquired by GlaxoSmithKline, we find that two molecules are being investigated for extension of a healthy lifespan. The first, SRT501, is a formulation of resveratrol which gives much higher plasma levels than resveratrol alone. This drug has passed safety tests and in small scale trials has reduced patients' glucose levels. It is pointed out that for practical reasons these molecules need to be investigated as agents to resolve a disease such as diabetes. Extension of a healthy lifespan could then be viewed as a fortunate side effect. The second molecule under investigation is a thousand times as potent as resveratrol and safety tests have begun. The theory is that these sirtuin activators stimulate the production of an enzyme that modulates a 'famine reflex', a biological inheritance we have from ancient times when in times of famine our metabolism switched from reproduction to tissue maintenance. Although there is much discussion about this hypothesis there is no doubt that calorie restriction has been proven to extend healthy lifespan across a range of different species and helps protect animals against a range of diseases that normally would result in mortality. Extension of healthy lifespan with pharmacological agents has come of age as a subject worthy of serious investigation.
Although we are accustomed to thinking of hypertension as a problem mainly for older people it is becoming clearer that younger people below age 35 should be checked for prehypertension since evidence is accumulating that a resting blood pressure above 120/80 increases the risk of calcified plaque buildup in the coronary arteries and thus the risk of heart attack and/or stroke later in life. The risk of course is related to lack of awareness and socioeconomic status. The solution is as simple as using blood pressure measurements to urge the individual to use the risk factor as an impetus to adopting healthy balanced and nutritious eating patterns and a lifestyle of regular daily exercise. As a warning marker this correlation is strong so therefore taking blood pressure measurements even in the younger person should be taken seriously and further reason to have a home blood pressure monitot.
Obesity in the general population is rising to unprecedented levels with surveys showing that up to one in four people is afflicted with this health risk. The media is full of advice, much of it hyping one nostrum or another, fad 'diets' , pills, potions, and erroneous 'facts' ; misleading and confusing many in this scramble to extract commercial advantage from the public, emptying pockets and doing little to guide individuals to a healthy way of life. Amid this commercialization it is comforting that WebMD has an online Health and Diet Center which is freely available to those who wish to know the sensible facts of reaching a reasonable weight without being exhorted to pay for dubious products from those who have more interest in taking your money than in your future optimal health.
For those needing guidance on starting an exercise program WebMD also provides information on the 7 most effective exercises.
Are you aging in a healthy manner?
Although decades of information about the healthy benefits of increasing vegetable and fruit consumption by the individual are well established there has up to now not been a definitive biomarker link to that health bernefit; with studies based upon population groups and trends. Now Dr. Anne-Helen Harding of the University of Cambridge, UK, and her colleagues from the European Prospective Investigation of Cancer-Norfolk study have provided solid information that higher plasma vitamin C levels are associated with a substantially decreased risk of type 2 diabetes. In their study, reported in the July 28 issue of the Archives of Internal Medicine they report on a total of 21,831 participants evaluated from 1993 to 1997 with a follow-up through until December 2005. It was found that plasma vitamin C levels were strongly inversely associated with diabetes risk. This study provides a solid foundation for increasing vegetable and fruit intake with a reason for those having difficulty in changing to such a healthy lifestyle to add daily vitamin C supplementation to their nutrition.
One of the first studies on the development of dementia or cognitive impairment in those who are already taking a statin has been reported by Dr. Carynn Cramer and Dr. Mary Haan, of the University of Michigan, in the July 29 issue of Neurology. This small study is observational but nonetheless suggests that statin users are about half as likely as non-users to develop dementia or cognitive impairment without dementa. The study followed 1,674 Mexican Americans, aged 60 years and older, dementia free at baseline in 1998 and 1999, participating in the Sacramento Area Latino Study on Aging. The five year follow-up study found that 452 participants took a statin at some point in the study. These results need much more investigation and should not be a reason to start to take a statin since the biological result, likely the effect of the known anti-inflammatory beneft of a statin, could well be achieved by other means such as dietary change and/or omega-3 fish oils.
Although the risk of rhabdomyolysis for those who take a statin is well established and sound reason for those who take a statin to do so with prudence and under the careful guidance of a good physician there are still incidents such that recently U.S Health officials have had to issue a warning that interaction of more than 20 mg simvastatin (zocor) with amiodarone, used to treat a type of abnormal heart beat, can lead to rhabdomyolysis. So although statins, particularly zocor, clearly state on the label this potential risk, there have been 52 reports of zocor/amiodarone and 6 reports of other statin/amiodarone serious adverse effects since the warnings were promoted in 2002. These numbers are small within the context of the millions taking a statin but they still must be taken seriously. Any relaxation of the surveillance and advice given to those taking a statin is a matter of public concern. As indeed is the benefit/risk ratio of taking any medication.
In a disappointing setback for Alzheimer's Disease researchers a study reports that a vaccine can clear amyloid plaque but does not prevent progression of the disease. The impact of the study implies that vaccine studies should shift emphasis from treatment to prevention.
In a report of interest to parents of children with milk allergy Dr. Anna Nowak-Wegrzyn and colleagues at Mount Sinai School of Medicine in New York have found that seventy-five percent of children with milk allergy can tolerate well heated milk and products made using well heated milk. The exposure to high temperatures destroys milk components associated with the allergy. This initial study was done with 100 children so does need to be confirmed with much larger studies but does imply that a much wider range of consumables could become available to children with a milk allergy affliction.
In an issue to those with diabetes, findings published in the Journal of the American College of Cardiology, July issue, by Dr. Stephen Nicholls and colleagues from the Cleveland Clinic, Ohio, report that patients with diabetes and coronary artery disease have more extensive atherosclerosis and thus less favorable outcomes from heart attack or surgical intervention. This adds impetus to the strong recommendations that people with diabetes should adopt a strategy to follow and modify their lipid profile and other exercise/dietary lifestyle changes, as well as significantly lowering blood pressure as outlined in Erinpharm Central.
Progress in the treatment of HIV infection over the last ten years has now reached the stage where a patient within reach of the latest treatment modalities can now expect to reach a lifespan well into their 60s or 70s if they are infected in their 20s or 30s and have early initiation of treatment with combination antiretroviral therapy. This news comes from an article by Dr. Robert Hogg in the July 26 isue of Lancet. Dr. Hogg and colleagues, at the British Columbia Centre for Excellence in HIV/AIDS in Vancouver, Canada, reviewed groups of patients who had received early initiation of antiretroviral therapy over three time periods: 1996-1999 (19,000 patients), 2000-2002 (14,000 patients) and 2003-2005 (11,000 patients). During that period of time mortality rates were decreasing. This dramatic difference between those capable of reaching early treatment and our distant cousins in the impoverished regions of the world is heartbreaking and illustrates the enormous tasks ahead of our generation of young people who are willing to reach out and work to alleviate the suffering of HIV/AIDS patients in the developing world, particularly in Africa.
A study of the decline in death rates from common cancers between 1993 and 2001 by Dr. Ahmedin Jemal, of the American Cancer Society in Atlanta, makes it clear that even in the United States socioeconomic and educational disparity separate out those who become heath advantaged from those who do not. Dr. Jemal reports that the cancer death rate decline has been primarily confined to those with at least 16 years of education. Thus much more work needs to be done on directing information on prevention, early detection and treatment, and advertising medical advances to the lower socioeconomic sector of our population.
For those who regularly drink tea a report from Dr. Tze-Pin Ng and colleagues, from the University of Singapore, will bring a measure of satisfaction in that regular tea drinking may help protect against cognitive impairment and decline. This study was reported in the July issue of the American Journal of Clinical Nutrition.
In an interesting difference from other statins simvastatin (zocor) has been found to reduce the incidence of both dementia and Parkinson's disease by more than 50%. This remarkable finding, from Dr. Benjamin Wolozin, at the Boston University School of Medicine, Massachusetts, is good reason to consider simvastatin rather than other statins in the treatment of cardiovascular risk factors.
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