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.

Kegel exercises for men: Understand the technique and the benefits

Kegel exercises for men: Understand the technique and the benefits

---(Doctors will often recommend surgery when all you need to do is exercise your groin muscles. Plus, you may find 'its' harder and takes longer than it has in years. So you may be getting out of bed at night, but its for the right damn reasons!)
Kegel exercises for men can help improve bladder control and possibly improve sexual performance. Here's a guide to doing Kegel exercises correctly. By Mayo Clinic Staff

Think Kegel exercises are just for women? Think again.

Kegel exercises for men can strengthen the pelvic floor muscles, which support the bladder and bowel and affect sexual function. With practice, Kegel exercises for men can be done discreetly just about anytime — whether you're relaxing on the couch or driving your car.

Before you start doing Kegel exercises, find out how to locate the correct muscles and understand the proper technique.

Benefits of Kegel exercises for men

Many factors can weaken your pelvic floor muscles, including the surgical removal of the prostate (radical prostatectomy) and conditions such as diabetes and overactive bladder.

You might benefit from doing Kegel exercises if you:

Have urinary or fecal incontinenceDribble after urination — usually after you've left the bathroomSome studies suggest that Kegel exercises for men might also benefit some men who have erectile dysfunction. However, further research is needed.

How to do Kegel exercises for men

It takes diligence to identify your pelvic floor muscles and understand how to contract and relax them. Here are some pointers:

Find the right muscles. To identify your pelvic floor muscles, stop urination in midstream or tighten the muscles that keep you from passing gas. These are your pelvic floor muscles. If you contract your pelvic floor muscles while looking in the mirror, the base of your penis will move closer to your abdomen and your testicles will rise.Perfect your technique. Once you've identified your pelvic floor muscles, empty your bladder and lie on your back with your knees bent and apart. Tighten your pelvic floor muscles, hold the contraction for three seconds, and then relax for three seconds. Try it a few times in a row but don't overdo it. When your muscles get stronger, try doing Kegel exercises while sitting, standing or walking.Maintain your focus. For best results, focus on tightening only your pelvic floor muscles. Be careful not to flex the muscles in your abdomen, thighs or buttocks. Avoid holding your breath. Instead, breathe freely during the exercises.Repeat 3 times a day. Aim for at least three sets of 10 repetitions a day.

When to do your Kegels

Make Kegel exercises part of your daily routine. For example:

Fit in a set of Kegel exercises every time you do a routine task, such as brushing your teeth.Do another set after you urinate or have a bowel movement, to get rid of the last few drops of urine or to return any feces that haven't been voided to the rectum.Contract your pelvic floor muscles just before and during any activity that puts pressure on your abdomen, such as sneezing, coughing, laughing or heavy lifting.Tighten your pelvic floor muscles rhythmically during sexual activity to maintain an erection or delay ejaculation.

When you're having trouble

If you're having trouble doing Kegel exercises, don't be embarrassed to ask for help. Your doctor or other health care provider can give you important feedback so that you learn to isolate and strengthen the correct muscles.

In some cases, biofeedback training might help. In a biofeedback session, your doctor or other health care provider inserts a small probe into your rectum. As you relax and contract your pelvic floor muscles, a monitor will measure and display your pelvic floor activity.

When to expect results

If you do your Kegel exercises regularly, you can expect results — such as less frequent urine leakage — within three to six weeks. For continued benefits, make Kegel exercises a permanent part of your daily routine.

-----Keeping in shape is a great alternative to dropping the blue pill  

Vitamin D toxicity rare in people who take supplements, researchers report

Rochester, Minn. -- Over the last decade, numerous studies have shown that many Americans have low vitamin D levels and as a result, vitamin D supplement use has climbed in recent years. Vitamin D has been shown to boost bone health and it may play a role in preventing diabetes, cancer, cardiovascular disease and other illnesses. In light of the increased use of vitamin D supplements, Mayo Clinic researchers set out to learn more about the health of those with high vitamin D levels. They found that toxic levels are actually rare.

Their study appears in the May issue of Mayo Clinic Proceedings.

A vitamin D level greater than 50 nanograms per milliliter is considered high. Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. A normal level is 20-50 ng/mL, and deficiency is considered anything less than 20 ng/mL, according the Institute of Medicine (IOM).

The researchers analyzed data collected between 2002 and 2011 from patients in the Rochester Epidemiology Project, a National Institutes of Health-funded medical records pool that makes Olmsted County, Minn., the home of Mayo Clinic, one of the few places worldwide where scientists can study virtually an entire geographic population to identify health trends.

Of 20,308 measurements, 8 percent of the people who had their vitamin D measured had levels greater than 50 ng/mL, and less than 1 percent had levels over 100 ng/mL.

"We found that even in those with high levels of vitamin D over 50 ng/mL, there was not an increased risk of hypercalcemia, or elevated serum calcium, with increasing levels of vitamin D," says study co-author Thomas D. Thacher, M.D., a family medicine expert at Mayo Clinic.

Hypercalcemia, or high blood calcium, can occur when there are very high levels of vitamin D in the blood. Too much calcium in the blood can cause weakness, lead to kidney stones, and interfere with the heart and brain, and even be life threatening.

The Mayo researchers also found that women over age 65 were at the highest risk of having vitamin D levels above 50 ng/mL. The result was not surprising because that's a group that often takes vitamin D supplements, Dr. Thacher says.

Another notable outcome: The occurrence of high vitamin D levels over 50 ng/mL increased during the 10-year period of the study, from nine per 100,000 people at the start of the study up to 233 per 100,000 by the end.

"We were surprised by that degree of dramatic increase in vitamin D levels," Dr. Thacher says.

Only one case over the 10-year study period was identified as true acute vitamin D toxicity; the person's vitamin D level was 364 ng/mL. The individual had been taking 50,000 international units (IU) of vitamin D supplements every day for more than three months, as well as calcium supplements. The IOM-recommended upper limit of vitamin D supplementation for people with low or deficient levels is 4,000 IU a day.

It's important for doctors to ask their patients about the doses of vitamin D supplements that they are using, Dr. Thacher says, because even capsules containing as much as 50,000 IU of vitamin D are available without prescription. If taken on a daily basis, that amount could lead to toxicity.

Some natural sources of vitamin D include oily fish such as mackerel and salmon, fortified milk, and sunlight.

"Our bodies will naturally produce vitamin D when our skin is exposed to sunlight, however, we don't recommend excessive exposure to sun due to the risk of skin cancer," Dr. Thacher added.

In an accompanying editorial in Mayo Clinic Proceedings, Dr. Michael F. Hollick, Ph.D., M.D., describes vitamin D's dramatic medical history, the need for judicious dosing, but the importance of vitamin D supplementation in those with low or deficient levels.

"The evidence is clear that vitamin D toxicity is one of the rarest medical conditions and is typically due to intentional or inadvertent intake of extremely high doses," writes Hollick, a professor of medicine, physiology and biophysics at Boston University School of Medicine.


Story Source:

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

Scientists discover protein that boosts immunity to viruses and cance

Scientists have discovered a protein that plays a central role in promoting immunity to viruses and cancer, opening the door to new therapies.

Experiments in mice and human cells have shown that the protein promotes the proliferation of cytotoxic T cells, which kill cancer cells and cells infected with viruses. The discovery was unexpected because the new protein had no known function and doesn’t resemble any other protein.

Researchers from Imperial College London who led the study are now developing a gene therapy designed to boost the infection-fighting cells, and hope to begin human trials in three years.

The study also involved researchers at Queen Mary University of London, ETH Zurich and Harvard Medical School. Their discovery, which has been six years in the making, is reported today in the journal Science.

Cytotoxic T cells are an important component of the immune system, but when faced with serious infections or advanced cancer, they are often unable to proliferate in large enough quantities to fight the disease.

By screening mice with genetic mutations, the Imperial team discovered a strain of mice that produced 10 times as many cytotoxic T cells when infected with a virus compared with normal mice. These mice suppressed the infection more effectively, and were more resistant to cancer. They also produced more of a second type of T cells, memory cells, enabling them to recognise infections they have encountered previously and launch a rapid response.

The mice with enhanced immunity produced high levels of a hitherto unknown protein, which the researchers named lymphocyte expansion molecule, or LEM. They went on to show that LEM modulates the proliferation of human T cells as well as in mice.

The researchers now aim to develop a gene therapy designed to improve immunity by boosting the production of LEM. With the support of Imperial Innovations, the technology commercialisation company for the College, the researchers have filed two patents. A company called ImmunarT has been formed with the aim of commercialising the technology.

Professor Philip Ashton-Rickardt from the Section of Immunobiology in the Department of Medicine at Imperial, who led the study, said: “Cancer cells have ways to suppress T cell activity, helping them to escape the immune system. Genetically engineering T cells to augment their ability to fight cancer has been a goal for some time and techniques for modifying them already exist. By introducing an active version of the LEM gene into the T cells of cancer patients, we hope we can provide a robust treatment for patients.

“Next we will test the therapy in mice, make sure it is safe and see if it can be combined with other therapies. If all goes well, we hope to be ready to carry out human trials in about three years.”

Dr Claudio Mauro, who led the research from the Centre for Biochemical Pharmacology, based within Queen Mary University of London’s William Harvey Research Institute, said: “This study has identified the novel protein LEM and unlocked an unexpected way of enhancing the ability of our immune system to fight viruses or cancers. This is based on the ability of the protein LEM to regulate specific energy circuits, and particularly mitochondrial respiration, in a subset of white blood cells known as cytotoxic T cells. This discovery has immediate consequences for the delivery of innovative therapeutic approaches to cancer. Its ramifications, however, are far greater as they can help explaining the biological mechanisms of widespread human diseases involving altered immune and inflammatory responses. These include chronic inflammatory and autoimmune disorders, such as atherosclerosis and rheumatoid arthritis.”

The research was funded by the Medical Research Council, the Wellcome Trust and the British Heart Foundation.

Dr Mike Turner, Head of Infection and Immunobiology at The Wellcome Trust, said: “The discovery of a protein that could boost the immune response to not only cancer, but also to viruses, is a fascinating one. Further investigation in animal models is needed before human trials can commence, but there is potential for a new type of treatment that capitalises on the immune system’s innate ability to detect and kill abnormal cells.”

Story Source:

The above story is based on materials provided by Imperial College London. The original article was written by Sam Wong. Note: Materials may be edited for content and length.

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Virus

Important connection between the mouth and heart

A new study from the Forsyth Institute is helping to shed more light on the important connection between the mouth and heart. According to research recently published online by the American Heart Association, scientists at Forsyth and Boston University have demonstrated that using an oral topical remedy to reduce inflammation associated with periodontitis, more commonly known as gum disease, also results in the prevention of vascular inflammation and can lower the risk of heart attack.

This study is the first time researchers anywhere have demonstrated the ability of an oral treatment for gum disease to also reduce inflammation in the artery wall. The active ingredient is an inflammation resolving molecule, known as Resolvin E1. This discovery further underscores the increasing body of evidence showcasing how problems in the mouth -- and how they are treated -- can have life changing influences on other key systems in the body, such as the heart in this case.

"Our research is helping to underscore the very real link between oral health and heart disease," said Lead Investigator Hatice Hasturk, DDS, PhD, an associate member of Forsyth's Department of Applied Oral Sciences and director of Forsyth's Center for Clinical and Translational Research. "The general public understands the connection between heart health and overall wellness, and often takes appropriate steps to prevent heart disease. More education is needed to elevate oral wellness into the same category in light of proven connections to major health conditions."

According to the CDC, heart disease accounts for one in four deaths in the United States, and the rate continues to rise. Forsyth's findings suggest a need to expand the public's understanding of risk factors beyond cholesterol, smoking, hypertension and diabetes to include a focus on oral health. With support from the scientific community, Forsyth aims to generate greater awareness of gum disease (affecting 64.7 million American adults according to the CDC) as a critical risk factor for heart disease, independent from diet and lifestyle.

The study, titled, "Resolvin E1 Prevents Atheromatous Plaque Formation," will be published in print in the May issue of Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a journal of the American Heart Association. It is the first paper to show a rabbit model of accelerated heart disease, demonstrating a range of atherosclerotic plaque stages that more closely resemble those in humans without genetic modification of the animal. This research is authored by Hatice Hasturk, Rima Abdallah, Alpdogan Kantarci, Daniel Nguyen, Nicholas Giordano, James Hamilton and Thomas E. Van Dyke.

Story Source:

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


Journal Reference:
Hatice Hasturk, Rima Abdallah, Alpdogan Kantarci, Daniel Nguyen, Nicholas Giordano, James Hamilton and Thomas E. Van Dyke. Resolvin E1 Prevents Atheromatous Plaque Formation. Arteriosclerosis, Thrombosis, and Vascular Biology, May 2015

Vitamin D research history, and toxicity examples.

I include this entire article, to make a point that massive is about 1,000 time what I believe is beneficial  (a planned and monitored 50,000 iu per day dose of D3.) Here is the history of Vitamin D3 use and research. 

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The article:

  

Warning: If you intend to take massive doses of vitamin D based on this newsletter, which I highly recommend you do not, read the entire newsletter. In addition, accurate determination of side effects of massive doses of vitamin D was not available in the early 1930s, nor was accurate determination of the true amount in each pill possible.

Is 2,000,000 IU/day of vitamin D toxic?

Ask Gary Null, alternative medicine guru and entrepreneur. He took his own supplement, Ultimate Power Meal, for a month and became extremely ill; one batch of Power Meal apparently contained 1,000 times more vitamin D than it should. That is, it contained 2,000,000 IU of vitamin D3 per serving instead of 2,000 IU per serving. Mr. Null became sicker and sicker as he gulped it down.

1. LA Times: Supplements guru sues over his own product
2. New York Post: Putting the ‘die’ in diet

After suing his own supplier for permanent physical damage, Mr. Null then reported it took 3 months to get the extra vitamin D out of his system and that he is now alive and well.

New York Post: ‘Death’ is now Null and void

If Mr. Null took it for the full month that he claims, and if his Power Meal contained 2,000,000 IU per dose, Mr. Null consumed 60,000,000 IU in one month. Could he really be fine now with no lasting injuries?

In an attempt to answer that question, I went back to the 1930s and 40s.

Massive doses in the 1930s

The earliest references I could find to enormous doses of vitamin D were in the 1930s. In 1935, Drs. Dreyer and Reed, of the University of Illinois School of Medicine, published their observations on 700 patients treated with “massive” doses of vitamin D for up to two years.1

First, the authors report that vitamin D had remarkable treatment effects on all kinds of arthritis, especially rheumatoid arthritis. They report on 67 arthritic patients so treated, with 75% of the patients responding most dramatically.

The dose used? Drs. Dreyer and Reed started all patients on 200,000 IU per day! They started some patients on 200,000 IU/day of D2 and others on 200,000 IU/day of D3, noticing no difference in efficacy. They used vitamin D preparations made by Mead Johnson, Glaxo, and Abbott.

“If there was no improvement and no evidence of sensitivity, the daily dose was increased by 50,000 units each week until there was some improvement or evidence of overdosage. In some stubborn cases, it was found necessary to increase to 600,000 or even 1,000,000 units for a few days and then reduce to 200,000 to 500,000 units. Most of our results have been obtained with daily doses of 300,000 to 500,000 units.”

The authors report that 63 of the 700 patients on this dosage became clinically toxic. That is, about 10% of the patients on these doses became sick (toxic) from the vitamin D. Today, we usually think of vitamin D toxicity as asymptomatic high blood calcium but these were old time doctors; toxic meant sick.

How did they treat the 63 patients who became sick from massive doses of vitamin D? Hospitalize them in the ICU? No, they simply stopped the vitamin D, told them to drink plenty of fluids, waited for the symptoms of toxicity to dissipate, and then restarted them on a lower dose, such as 150,000 IU per day.

The authors do mention that many of the patients had high blood calcium, one in the 20s, but if the patients were not sick, the doctors didn’t care about the calcium. As the authors did not draw serum calcium on all of the 700 patients, we don’t know what percentage of patients on these doses became hypercalcemic.

Symptoms of Toxicity

The authors report that the symptoms of vitamin D toxicity began with persistent nausea, which the doctors instructed their patients to be on the lookout for, as well as increased frequency of urination without increased volume of urine. Weakness and increased thirst were common, and “if the treatment is continued, diarrhea, gripping pain in the gastrointestinal tract, and vomiting.” The authors bragged that they could not report on pathological findings in toxicity, because none of their 700 patients had died and “come to autopsy.”

In 1934, the Journal of the American Medical Association published a study on vitamin D overdose:Reed CI. Symptoms of Viosterol overdosage in human subjects. JAMA. 1934;102:1745–1748.

They reported on 300 patients given high doses of vitamin D2 for asthma and hay fever. The author reported that each cc contained 900,000 IU of vitamin D2. The good doctor gave one patient 3 cc per day for five days (that would be a total dose of 13.5 million units) “without the slightest evidence of injury.”

However, in his conclusion, Dr. Reed was much more conservative:

“There need be little apprehension about the administration of amounts ranging up to 150,000 international units daily for indefinite periods. Larger amounts had better be limited to periods of a few months at most, depending on the therapeutic effects desired.”

Dr. Rappaport and colleagues at the University of Illinois studied the effects of Viosterol (vitamin D2) on asthma and hay fever in 212 patients, giving placebo to a control group. The authors reported that 82% of the hay fever patients and 96% of the asthma patients “experienced definitive significant relief.” The authors concluded that the “optimum dose” of vitamin D was 60,000 to 300,000 IU per day.

Rappaprt BZ, et al. The treatment of hay fever and asthma with Viosterol of high potency. J. of Allergy. 1934;5:541–553.

Why these doctors did not try 5,000 or 10,000 IU/day, instead of 200,000 IU/day, I could not ascertain.

Death in the 1940s

Things began to change in the 1940s. In 1946, two case reports of fatal vitamin D toxicity in adults (the authors report five previous fatal cases in children) appeared in the medical literature.1

Another case report of a fatal dose of vitamin D in adults appeared in 1947. This death was from Ertron, vitamin D2, at a dose of 150,000 IU daily for 18 months, and it included a description of foot lesions similar to what Gary Null reported. This paper is free to download and I suggest everyone who is flirting with the idea of using massive doses of vitamin D obtain it and read it. It is chilling to read the detailed autopsy report.2

By 1948, the medical community began condemning the use of such massive doses of vitamin D as evidenced by a paper from Johns Hopkins University:

Howard JE and Meyer RJ. Intoxication with vitamin D. J. Clin. Endocrinology. 1948;8(11);895–910.

The authors reference 12 earlier papers on vitamin D intoxication with calcification of everything from the kidneys to the sclera of the eyes. The first symptoms of vitamin D toxicity in their series of 11 patients were weight loss and fatigue, which occurred before the anorexia (poor appetite) and vomiting. All of their patients suffered from kidney damage and anemia. Virtually all of the patients had a characteristic eye lesion, which are calcium deposits in the sclera and cornea, just beneath the conjunctival basement membrane.

All patients had high blood calcium, ranging from 12.4 to 15.1 mg per 100 cc. Dosages of vitamin D ranged from the lowest at 150,000 IU/day for 4 months (serum calcium 13.9) to the highest at 500,000 IU/day for 18 months (serum calcium 14.3). They reported on another patient who developed hypercalcemia after she reported taking 300,000 IU of vitamin D2 for only 2 weeks; she also had eye lesions evident on slit lamp exam. Although accurate follow up was not possible due to the fact the patients came from around the country, no patients died but some suffered permanent renal damage from the excessive doses of vitamin D.

The treatment the authors used for vitamin D toxicity was discontinuing the vitamin D, drinking 4,000 cc of fluid per day, and a low calcium diet. Improvement occurred within 2–8 weeks when nausea, vomiting, and lassitude disappeared. Blood calcium fell in all patients by one month but continued to be elevated for as long as a year in one patient.

These reports of toxicity were all the medical profession needed to condemn vitamin D as dangerous, as I learned in medical school in the early 1970s. The dark ages of vitamin D meant that for several generations of doctors, vitamin D was toxic at all but the most meaningless doses. Its use to treat asthma and arthritis became verboten. For fifty years, doctors forgot about vitamin D — other than vitamin D deficient rickets — because of fear of toxicity. During these dark ages, the Food and Nutrition Board periodically reviewed vitamin D and repeatedly distributed toxicity alarms, along with their recommendations that we only take insignificant doses.

Out of the dark ages

Then, at the turn of the century, Professor Reinhold Vieth of the University of Toronto showed us the way out of the dark ages with an objective review of the toxicity literature.

What Vieth’s paper showed was that there is a difference between 5,000 IU per day and 50,000 IU per day, the first being a physiological dose and the second being a pharmacological dose, a drug. However, in 1999 the world was using neither dose properly, in that no doctors were prescribing 5,000 IU per day and no scientists were studying 50,000 IU per day.

After Vieth’s paper, in the first few years of this century, a steady stream of vitamin D papers began flowing out of research labs, with the number of publications increasing every year. For example, scientists published 1,582 new papers on vitamin D in the first six months of 2010. Very few are about toxicity, instead they cover a breathtaking variety of diseases. These papers raise the possibility that many of the diseases that we take as being part of the human condition are not part of the human condition, instead they are simply the result of the toxicity scare: vitamin D deficiency. That is, these diseases are simply different presentations of the same deficiency. In that way, vitamin D deficiency is similar to syphilis.

Sir William Osler said, “Know syphilis in all its manifestations and relations and all other things clinical will be added unto you. Know syphilis and the whole of medicine is opened to you.” He called it the “Great Imitator,” because late stages of syphilis simulate almost every disease known to man. Smoking is similar, some smokers get emphysema, some lung cancer, some heart disease, some bladder cancer, some pancreatic cancer, and some live to be 100. Increasingly, vitamin D deficiency looks as if it may do the same thing. Some vitamin D deficient people will get asthma, others cancer, others heart disease, others autoimmune illness, and some will live to be 100.

Let’s look at one rare disease, childhood multiple sclerosis, a nightmare for any parent to face. The child will have problems with vision, co-ordination, or balance, with relapses and remissions, that is the disease seems to come and go. Recently, Dr. Ellen Mowry and her colleagues discovered that these relapses, these periods of active autoimmune illness, are associated with low levels of vitamin D. The disease comes and goes as vitamin D levels come and go. Dr. Mowrey speculated that a 15 ng/mL increase in vitamin D levels would cut the relapse rate in half.3

Dr. Mowry did not raise the fundamental question: would these children have become ill in the first place if they had adequate amounts of vitamin D during their growth and development? The average vitamin D level of these 110 children was 22 ng/mL, so Dr. Morey could not say what an increase to 50 ng/mL would do, nor could she say if low vitamin D levels were what allowed the disease to appear in the first place.

That is, is juvenile multiple sclerosis simply one of many possible presentations of childhood vitamin D deficiency? Some vitamin D deficient children will get multiple sclerosis, some asthma, some diabetes, some rickets, and others autism. That is, is vitamin D deficiency the modern day syphilis?

Unlike syphilis, vitamin D deficiency is largely an iatrogenic disease, caused by the medical profession’s near hysterical fear of vitamin D toxicity. Physicians simply forgot what Paracelsus said many years ago, “All things are poison and nothing is without poison, the dose alone permits something to be poisonous.” We went from intemperance in the 1930s to hysteria in the 1950s and we are only now coming to our senses.

We look around at the diseases debilitating our children, the triple A epidemics of autoimmune disorders, asthma, and autism. All are truly epidemic, all are debilitating or worse, and vitamin D is involved in all three. We failed to make sure our children had enough vitamin D throughout their growth and development and now our children suffer, in large part because of the hysteria over vitamin D toxicity.

What dose is toxic? I don’t know but I’d guess for some adults it is around 50,000 IU/day. However, it will vary widely and some people may get asymptomatic side effects on lower doses, such as kidney damage, without getting clinical signs of toxicity. Just because you feel fine, that does not mean your kidneys are fine.

Getting back to Mr. Gary Null and his ingestion of 60,000,000 IU over one month, could he have survived that dose? Apparently, the answer is yes, although I doubt he took it every day, especially as he got sicker and sicker. Could he have survived that dose without permanent kidney damage? I doubt it.

1

About John Cannell, MD

Dr. John Cannell is founder of the Vitamin D Council. He has written many peer-reviewed papers on vitamin D and speaks frequently across the United States on the subject. Dr. Cannell holds an M.D. and has served the medical field as a general practitioner, emergency physician, and psychiatrist.

View all posts by John Cannell, MD →

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