Lookin at the HIlls

I look at the local hills every day. After many years here it's still a wonder to wake up and see both of them crystal clear and sharp in the crisp morning air.

But I yearn to meet them again, as a challenge and in an act of outright love.

In a month I plan to leave the ocean shores at the foot of Kilauea and cross over the saddle to the side of Mauna Loa.  I want to summit her once again, (I settle for the North Pit.)  and to do that astonishing face off to the north to see her sister Mana Kea. I would like to walk that slope as well.  But we will see.   We will see.

Fasting as a Method of Life Extension

Dear Reader,

  (I have taken this directly from Patrick Cox's news letter of 7/24)

As a species, we are unprepared for many of the changes technological acceleration has wrought.

Take, for example, the agricultural technologies that have fundamentally changed the human relationship with food. In my lifetime, the cost of basic nutrition as a percentage of household budget has plummeted, as has the acreage needed to produce it.

In less than a century, we have made the transition from caloric scarcity to abundance. For the first time in human history, Western lower-income populations suffer higher rates of obesity than wealthier populations.

Very few people understand what this change means. In fact, most younger people don’t seem to be aware that hunger and malnutrition were commonplace a hundred years ago. The consequences of this unprecedented nutritional bounty in the form of adipose tissue are easy to see.

The costs associated with extra adipose tissue, however, are not so obvious.

I won’t use this space to examine the truly alarming statistics about obesity and disease, but this overview at BioMed Central is a good starting place. Disease rates and medical costs rise dramatically with BMI, while productivity falls. Moreover, measures of body mass index (BMI) increase with age.  Since the population is aging, healthcare costs will continue to rise—until science is liberated to solve this problem.

In the US and Canada, almost one-third of adults are currently obese and about two-thirds are overweight, using the standard BMI definitions. BMI is measured as kg/m² or weight divided by the square of body height. Obesity is 30 or more. Overweight is defined as a lower BMI than obesity, but over 25.

This measure, of course, has its own problems. Athletes with very little fat but lots of muscle often fall into the overweight category. Moreover, some people will suffer the ill health effects associated with obesity without having BMIs over 30.

Until recently, it was believed that Asian populations had much smaller overweight and obese populations, but it seems that many Asians suffer from diabetes and other diseases associated with metabolic syndrome at lower BMIs.

It’s no surprise that the science is confusing or that researchers are only beginning to sort out this new world of caloric plenty. Very few of our ancestors experienced constantly available, inexpensive, and enjoyable food. Our metabolisms are in brand-new territory, and we have adapted neither genetically nor psychologically to the situation.

Solutions Are Coming, Fast

Weight loss drugs continue to improve, though marginally. Down the road, I’m sure we’ll find solutions to the problems associated with higher BMIs. I think regenerative medicine offers the most interesting therapeutic possibility: implants of fat-burning, brown adipose tissue. I’m talking at length about it in my upcoming ebook. (Register here to be among the first ones to receive a free copy once it’s published.)

But right now, there are no “cures,” so many of us are looking for any kind of help we can get.

One of the hottest areas in the area of weight loss isintermittent fasting (IF), which entails not eating for a part of every day or for several days a week. As far as I can tell, interest in this strategy emerged strongest in the UK, but it has spread to North America and beyond.

No long-term research has been done on IF, so I’m not going to describe these strategies, despite the fact that I dropped about 30 pounds some time back while limiting food intake to a six-hour window. At that time, the research indicated that the strategy wasn’t dangerous, though the benefits weren’t clear, beyond those that come from losing weight.

Many proponents claimed that IF provided many of the health benefits of calorie restriction, an extremely low-calorie diet of optimally nutritious foods that has demonstrated life extension benefits in animals. The data, however, didn’t exist.

It still doesn’t, actually, since in order to collect that data, a statistically significant number of people would have to suffer a diet generally described as torturous for decades. On the other hand, really interesting research is emerging.

The most interesting, I think, comes from the field of biogerontology, the study of aging, and specifically from Valter D. Longo of the pioneering USC Davis School of Gerontology. Longo’s most prominent research has been in the field of cancer.

Some years ago, Longo showed that fasting helps animals survive chemotherapy with less severe side effects. He now argues that fasting puts normal cells into a protective mode, making them more resistant to the damage inflicted by chemotherapy drugs. Cancer cells, though, are always growing, so they can’t enter that protective mode. As a result, they are weakened by fasting, making them more susceptible to the drugs designed to kill them.

This protective state triggered by fasting is of interest to many scientists. The NAD+ precursors and sirtuin activation, which I’ve discussed in this letter, are part of that research. Similarly, scientists studying rapamycin believe that the naturally occurring compound’s demonstrated life-extension effects in animals are related to calorie restriction pathways.

Longo was concerned, however, that fasting might be impractical or even dangerous for cancer patients and others who already suffered from extremely low body weight. This seems to have led him to wonder if absolute fasting was actually necessary to tip cells into protective mode. Instead, he put animals on very low-calorie restriction diets and found the same benefits.

This is described in an excellent paper in Cell Metabolism. The title of the study is, “A Periodic Diet That Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.”

Longo found that animals enjoyed significant benefits from periodic “fasting-mimicking diet” (FMD). Animals eating a calorie-restricted diet four or five days per month experienced improvements in organ function and intelligence, as well as health spans.

In a pilot study of 19 people who ate the same kind of diet, subjects showed the same improvements in markers, such as weight loss and reductions in IGF-I. Moreover, the fat people lost using FMD was the dangerous abdominal organ fat, which is usually very hard to shed.

This is pretty big news, for several reasons.

First, it implies that we may not need to endure permanent calorie-restricted hunger to gain many of the benefits of calorie restriction (CR). Longo speculates that for many people, a five-day fasting-mimicking diet every two to three months could reboot their bodies’ system and deliver profound health benefits, including weight loss.

It’s possible, in fact, that periodic CR might be better than permanent CR because many of the benefits he describes come after the low-calorie diet. There seems to be a pruning of older, less effective cells during the FMD. For example, Longo’s research indicates that a cycle of FMD results in the death of about one-third of some types of immune cells, which are then replaced by younger, stronger versions when a normal diet is restarted. These younger, stronger replacements improve immune system function.

Obviously, I’m not your doctor and I’m not going to encourage you to try this at home. On the other hand, I think this study represents a really important breakthrough for those of us who want to optimize health and BMI. For more information, the Cell Metabolism article is here. Science Daily has a good article about the study here and NIH Research Matters describes the results here.

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Sincerely,

Patrick Cox
Editor, Transformational Technology Alert

Make no bones about it: Female athlete triad can lead to problems with bone health

Participation in sports by women and girls has increased from 310,000 individuals in 1971 to 3.37 million in 2010. At the same time, sports-related injuries among female athletes have skyrocketed. According to a new study in the Journal of the American Academy of Orthopaedic Surgeons(JAAOS), women with symptoms known as the "female athlete triad" are at greater risk of bone stress injuries and fractures.

"The female athlete triad is a spectrum of symptoms that include low energy availability, menstrual cycle abnormalities, and low bone mineral density. Low energy availability can mean taking in inadequate calories or expending more energy than the body is designed to do. It can result from poor nutrition or eating habits or any type of eating disorder. Any combination of these conditions can lead to premature bone loss in females," explains lead study author and orthopaedic surgeon Elizabeth Matzkin, MD.

Both athletes and nonathletes participating in any sports and exercise can develop symptoms of the female athlete triad. But the likelihood of female athletes sustaining a bone stress injury significantly increases as the number of symptoms they have increases. 

The increase is substantial--
15 percent to 21 percent with one symptom;
21 percent to 30 percent with two symptoms; and,
29 percent to 50 percent with all three symptoms.

The study authors also found that female athletes diagnosed with poor nutrition or low energy availability are two to four times more likely to sustain a sports-related injury. Female athletes who self-reported menstrual cycle abnormalities had a nearly three times greater risk of a bone and joint injury.

"Proper nutrition and energy balance are key to staying healthy in athletes of all ages. But maximizing bone health when you are young is paramount to your bone health later in life," says Dr. Matzkin. "It is important for young females to maximize their bone density until about the age of 25--anything lost before then cannot be regained. After age 25 we can only hope to maintain what we have."

As participation in sports by women and girls continues to increase and become more competitive, it is important to prevent, diagnose, and manage the components of the female athlete triad. Although the female athlete triad poses a great health risk, the benefits of participation in sports significantly outweigh the risks.

"Any athlete who falls under the 'umbrella' of the triad should be questioned by their physicians and educated regarding all of the components and potential health risks of this condition. By preventing premature bone loss in young female athletes, we can potentially prevent future fragility fractures," says Dr. Matzkin.

ScienceDaily, 1 July 2015. <www.sciencedaily.com/releases/2015/07/150701152329.htm>.

If you are concerned about your bone density read up on Vit D3 and K supplementation and natural ways of increasing these nutrients in your diet.   Calcium supplementation is not necessarily a direct path to increased bone density.  

Stopping Candida in its tracks

Scientists are one step closer to understanding how a normally harmless fungus changes to become a deadly infectious agent.

The opportunistic fungus Candida albicans is normally a harmless member of the microbial community that occupies the human gut. However, it is also the causative agent of oral thrush and, more severely, it is responsible for approximately 400,000 life-threatening blood infections each year. Understanding what triggers this switch from benign resident to dangerous enemy could help to protect those who are most at risk -- including the elderly, HIV patients and those receiving organ transplants.

Most of the time, the human immune system is able to suppress C. albicansso that it lives in a harmless, round "yeast" form. When the immune system is compromised however -- such as during organ transplants to prevent tissue rejection -- the fungus switches to a new and deadly mode of growth. The round cells start to produce long filaments (called hyphae) which burrow into the underlying tissue layers. This allows the fungus to invade and form infectious colonies.

Researchers at the University of Aberdeen have recently found that a small signalling molecule, called Rsr1, controls the steering mechanisms that hyphae use to probe host surfaces. "Rsr1 helps the hyphae to penetrate tissues and to steer through barriers" says Tina Bedekovic, who studies this protein as part of her research. 

"Without Rsr1, the ability of the fungus to cause disease is significantly reduced." Brewer's Yeast (Saccharomyces cerevisiae) does not form filaments but Rsr1 still functions to control polarised growth. In this case, it is known to be activated by another molecule called Bud5. When the researchers deleted Bud5 in C. albicans, however, its hyphae were still able to penetrate tissues and steer around obstacles. This suggests that Rsr1 in C. albicans is regulated by a different activator specific for this function.

According to Tina Bedekovic, identifying this activator may help to develop clinical treatments. "Humans also have a version of Rsr1 and Bud5 so it is unlikely that we could develop a drug to inhibit these in C. albicans without also affecting human cells" she says. "But if they are part of a fungus-specific signalling pathway that controls directional growth, this could be targeted with therapeutic drugs without harming the patient."

The researchers now plan to investigate which molecules can bind to Rsr1 in C. albicans and, from these, to identify the activator required for invasive filamentous growth.

ScienceDaily. ScienceDaily, 3 July 2015. <www.sciencedaily.com/releases/2015/07/150703072618.htm>.

Common antibiotic may be the answer to many multidrug-resistant bacterial infections

Common antibiotic may be the answer to many multidrug-resistant bacterial infections (Neat, because the assumptions of the medical mob, proved not so correct for a long period of time, and until somebody bothered to say 'Really, let's test that!' Sounds a lot like D3 fears of overdose, or apylori?? the gut bacteria that causes ulcers....until somebody asked if it was a bacteriologic infection not do to acid indigestion) Contrary to current medical dogma, researchers at University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences report that the common antibiotic azithromycin kills many multidrug-resistant bacteria very effectively -- when tested under conditions that closely resemble the human body and its natural antimicrobial factors. The researchers believe the finding, published June 10 by EBioMedicine, could prompt an immediate review of the current standard of care for patients with certain so-called "superbug" infections. Azithromycin is the most often prescribed antibiotic in the United States, where short courses can cure common bacterial infections such as strep throat and sinusitis. But azithromycin, also sold commercially as Zithromax Z-Pak, is never given to patients with some of the most nefarious multidrug-resistant bacterial infections. That's because years of testing in standard laboratory media -- the nutrient broth that helps bacteria grow -- concluded that azithromycin doesn't kill these types of bacteria. "Unquestioning adherence to a single standardized lab practice may be keeping doctors from considering potentially life-saving antibiotics -- therapies that are proven safe and readily available in any hospital or pharmacy," said senior author Victor Nizet, MD, professor of pediatrics and pharmacy. "While bacterial agars and testing media are useful in providing consistency for hospital laboratories around the world, the actual infection is taking place in the blood and tissues of the patient, and we know the action and potency of drugs can change quite dramatically in different surroundings." The bacteria at the center of this study are Gram-negative rods, so-called due to their cell wall structure (they appear "negative" in a classic typing test known as the Gram stain) and their shape. Nizet's team studied extremely antibiotic-resistant strains of three medically important Gram-negative rods:Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. These opportunistic pathogens rarely infect healthy people but instead strike debilitated patients in hospitals, such as those with weakened immune systems, or following trauma or surgery, sometimes with deadly consequences. The Centers for Disease Control and World Health Organization have warned that resistance is rapidly spreading in these species, and no new antibiotic candidates are on the horizon. In this study, Nizet's team found that simply growing these Gram-negative rod bacteria in mammalian tissue culture media -- the same stuff used to sustain human cells in the lab -- instead of standard bacteriologic media made a huge difference in their sensitivity to azithromycin. Even more striking, the drug-resistant superbugs were completely wiped out when azithromycin was paired with the antibiotic colistin or with antimicrobial peptides produced naturally by the human body during infection. To test these promising laboratory results in a live infection system, Nizet and team moved the experiment into a mouse model of multidrug-resistantA. baumannii pneumonia. They treated the mice with a single injected dose of azithromycin at a concentration that mimics the amount typically given by IV to human patients. Twenty-four hours after infection, azithromycin-treated mice had 99 percent fewer bacteria in their lungs than untreated mice. Similarly, in mouse models of multidrug-resistant P. aeruginosa and K. pneumoniae infections, a single dose of azithromycin reduced bacterial counts by more than 10-fold. According to the authors, the study suggests that the general effectiveness of antibiotics in the decades since the discovery of penicillin has led to complacency in our approach to antibiotic evaluation. In the current era of ever-increasing antibiotic resistance, they recommend a more holistic approach that considers both the bug and the patient's immune system. "If something this simple could be overlooked for so many years, what else might we be missing?" Nizet said. Story Source: The above story is based on materials provided by University of California, San Diego Health Sciences. The original article was written by Heather Buschman. Note: Materials may be edited for content and length.

Get Your solid Eight. (Even if you have to exercise to relax enough!)

A new study suggests that one night of partial sleep deprivation promotes biological aging in older adults. Results show that one night of partial sleep deprivation activates gene expression patterns in peripheral blood mononuclear cells (PBMCs) consistent with increasing accumulation of damage that initiates cell cycle arrest and increases susceptibility to senescence. These findings causally link sleep deprivation to the etiology of biological aging, and further supports the hypothesis that sleep deprivation may be associated with elevated disease risk because it promotes molecular processes involved in biological aging. "Our data support the hypothesis that one night of not getting enough sleep in older adults activates important biological pathways that promote biological aging," said lead author Judith Carroll, PhD, assistant professor of psychiatry and biobehavioral science at the UCLA Cousins Center for Psychoneuroimmunology in Los Angeles, Calif. The research abstract was published recently in an online supplement of the journal Sleep and will be presented June 10, in Seattle, Washington, at SLEEP 2015, the 29th annual meeting of the Associated Professional Sleep Societies LLC. The study group comprised 29 community-dwelling older adults. They were age 61-86 years and 48 percent were male. Participants underwent an experimental partial sleep deprivation protocol over four nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (restricted 3 a.m. -- 7 a.m.) and another uninterrupted night of sleep (recovery). Blood samples were obtained each morning to assess PBMC gene expression using Illumina HT-12 arrays. Story Source: The above story is based on materials provided by American Academy of Sleep Medicine. Note: Materials may be edited for content and length.

Heart attack risk increases 16-21% with use of common antacid

Heart attack risk increases 16-21% with use of common antacid

[[Personal Experience: The Doctors screwed-up my mother's stomach with all kinds of pills, gave her a proton pump inhibitor to cure the reflux, and, then shook their heads sadly when she died of a heart attack. Think about what it is they feed you to cure you!]]

Adults who use proton pump inhibitors are between 16 and 21 percent more likely to experience a heart attack than people who don't use the commonly prescribed antacid drugs, according to a massive new study by Houston Methodist and Stanford University scientists.

An examination of 16 million clinical documents representing 2.9 million patients also showed that patients who use a different type of antacid drug called an H2 blocker have no increased heart attack risk. The findings, reported in PLOS ONE, follow aCirculation report in 2013 in which scientists showed how -- at a molecular level -- PPIs might cause long-term cardiovascular disease and increase a patient's heart attack risk.

"Our earlier work identified that the PPIs can adversely affect the endothelium, the Teflon-like lining of the blood vessels," said John Cooke, M.D., Ph.D., a senior author of the PLOS ONE report. "That observation led us to hypothesize that anyone taking PPIs may be at greater risk for heart attack. Accordingly, in two large populations of patients, we asked what happened to people that were on PPIs versus other medications for the stomach."

The PLOS ONE study's principal investigator was Stanford vascular medicine specialist Nicholas J. Leeper, M.D.

In the present study, the researchers found a clear and significant association between exposure to PPIs and the occurrences of heart attack.

"By looking at data from people who were given PPI drugs primarily for acid reflux and had no prior history of heart disease, our data-mining pipeline signals an association with a higher rate of heart attacks," said the PLOS ONE report's lead author, Nigam H. Shah, M.B.B.S., Ph.D., an assistant professor of biomedical informatics at Stanford, where the work was done. "Our results demonstrate that PPIs appear to be associated with elevated risk of heart attack in the general population, and H2 blockers show no such association."

The estimated increase of heart attack risk ranges from 16 to 21 percent, because of uncertainty in the estimation process, Shah said.

The FDA estimates about 1 in 14 Americans has used proton pump inhibitors. In 2009, PPIs were the third-most taken type of drug in the U.S., and are believed to account for $13 billion in annual global sales. Doctors prescribe PPIs to treat a wide range of disorders, including gastro-esophageal reflux disease, or GERD, infection by the ulcer-causing bacteriumHelicobacter pylori, Zollinger-Ellison syndrome, and Barrett's esophagus. The drugs can also be purchased over the counter. PPIs come in a variety of slightly different chemical forms, always ending with the suffix "-prazole," for example, omeprazole or lansoprazole. Brand examples of PPIs are Nexium, Prilosec, and PrevAcid.

H2 blockers are another type of antacid drug. They are not believed to be associated with increased risk of heart attack or cardiovascular disease. Examples of the drug are cimetidine and ranitidine. Brand examples of H2 blockers are Zantac and Tagamet.

The researchers collected data from two repositories -- STRIDE (Stanford Translational Research Integrated Database Environment), which contains information about 1.8 million Stanford hospital and clinic patients, and a subset of information for 1.1 million patients from the Web-based electronic medical records company Practice Fusion, Inc. Both sources of patient information were anonymized before the researchers accessed the data.

The group scanned the databases for patients who were prescribed proton pump inhibitors or other drugs, such as H2 blockers, and also looked to see if a given patient had a mention of having experienced a major cardiovascular event, such as myocardial infarction (heart attack), in their medical record.

Patients who had used PPIs were found to be at 1.16-1.21-fold-increased risk of heart attack.

Scrutiny of PPIs has only increased with time. Initially it was believed PPIs only posed a risk to a very narrow subset of patients -- those with coronary artery disease who were using the anti-platelet drug clopidogrel to prevent future heart attacks.

"Investigators originally assumed this was due to a drug-drug interaction between these compounds, and the FDA went so far as to release a warning about their concomitant use," said Nicholas Leeper.

A 2013 report to Circulation by several of the present report's coauthors, including Cooke, raised the possibility that PPIs could lead to cardiovascular disease in the general population.

"This led us to use powerful 'big-data' approaches to try to determine whether PPIs might in fact be associated with risk in 'all comers,' Leeper said. "Our report raises concerns that these drugs -- which are available over the counter and are among the most commonly prescribed drugs in the world -- may not be as safe as we previously assumed."

In the future, the researchers say they hope to conduct a large, prospective, randomized trial to determine whether PPIs are harmful to a broader population of patients.


Story Source:

The above story is based on materials provided by Houston Methodist.Note: Materials may be edited for content and length.