HHAL MEDICAL NEWS NOVEMBER 2012

CORVALLIS, Ore. – A new study has outlined for the first time a biological mechanism by which zinc deficiency can develop with age, leading to a decline of the immune system and increased inflammation associated with many health problems, including cancer, heart disease, autoimmune disease and diabetes.

The research was done by scientists in the Linus Pauling Institute at Oregon State University and the OSU College of Public Health and Human Sciences. It suggests that it’s especially important for elderly people to get adequate dietary intake of zinc, since they may need more of it at this life stage when their ability to absorb it is declining.

About 40 percent of elderly Americans and as many as two billion people around the world have diets that are deficient in this important, but often underappreciated micronutrient, experts say.

The study was published in the Journal of Nutritional Biochemistry, based on findings with laboratory animals. It found that zinc transporters were significantly dysregulated in old animals. They showed signs of zinc deficiency and had an enhanced inflammatory responseeven though their diet supposedly contained adequate amounts of zinc.

When the animals were given about 10 times their dietary requirement for zinc, the biomarkers of inflammation were restored to those of young animals.

“The elderly are the fastest growing population in the U.S. and are highly vulnerable to zinc deficiency,” said Emily Ho, an LPI principal investigator and associate professor in OSU School of Biological and Population Health Sciences. “They don’t consume enough of this nutrient and don’t absorb it very well.”

“We’ve previously shown in both animal and human studies that zinc deficiency can cause DNA damage, and this new work shows how it can help lead to systemic inflammation,” Ho said.

“Some inflammation is normal, a part of immune defense, wound healing and other functions,” she said. “But in excess, it’s been associated with almost every degenerative disease you can think of, including cancer and heart disease. It appears to be a significant factor in the diseases that most people die from.”

As a result of this and what is now know about zinc absorption in the elderly, Ho said that she would recommend all senior citizens take a dietary supplement that includes the full RDA for zinc, which is 11 milligrams a day for men and 8 milligrams for women. Zinc can be obtained in the diet from seafood and meats, but it’s more difficult to absorb from grains and vegetables – a particular concern for vegetarians.

“We found that the mechanisms to transport zinc are disrupted by age-related epigenetic changes,” said Carmen Wong, an OSU research associate and co-author of this study. “This can cause an increase in DNA methylation and histone modifications that are related to disease processes, especially cancer. Immune system cells are also particularly vulnerable to zinc deficiency.”

Research at OSU and elsewhere has shown that zinc is essential to protect against oxidative stress and help repair DNA damage. In zinc deficiency, the risk of which has been shown to increase with age, the body’s ability to repair genetic damage may be decreasing even as the amount of damage is going up.

Medical tests to determine zinc deficiency are rarely done, scientists say, and are not particularly accurate even if they are done. The best approach is to assure adequate intake of the nutrient through diet or supplements, they said, especially in the elderly.

Even though elderly people have less success in absorbing zinc, the official RDA for them is the same as in younger adults. That issue should be examined more closely, Ho said.

Levels of zinc intake above 40 milligrams per day should be avoided, researchers said, because at very high levels they can interfere with absorption of other necessary nutrients, including iron and copper.

These studies were supported by the National Institutes of Health and other agencies.

Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse.

Source

Institute of Biomedical Research of Barcelona (IIBB), CSIC, IDIBAPS, Barcelona, Spain.

Abstract

Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therapeutic value against AD. We assayed physical exercise and melatonin in 3xTg-AD male mice aged from 6 to 12 months, therefore from moderate to advanced phases of AD pathology. Analysis of behavior and brain tissue at termination showed differential patterns of neuroprotection for the 2 treatments. Both treatments decreased soluble amyloid β oligomers, whereas only melatonin decreased hyperphosphorylated tau. Melatonin was effective against the immunosenescence that 3xTg-AD mice present. Voluntary physical exercise protected against behavioral and psychological symptoms of dementia such as anxiety, a lack of exploration, and emotionality. Both treatments protected against cognitive impairment, brain oxidative stress, and a decrease in mitochondrial DNA (mtDNA). Interestingly, only the combined treatment of physical exercise plus melatonin was effective against the decrease of mitochondrial complexes. Therefore, melatonin plus physical exercise may exert complementary, additive, or even synergistic effects against a range of disturbances present in AD.

http://www.ncbi.nlm.nih.gov/pubmed/22177720

Vitamin C prevents hypogonadal bone loss.

Source

School of Stomatology, Wuhan University, Wuhan, Hubei, China ; The Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, New York, United States of America.

Abstract

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.

Effects of vitamin K2 on osteoporosis.

Source

Department of Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. jiwamoto@sc.itc.keio.ac.jp

Abstract

Vitamin K2 is a cofactor of gamma-carboxylase, which converts the glutamic acid (Glu) residue in osteocalcin molecules to gamma-carboxyglutamic acid (Gla), and is, therefore, essential for gamma-carboxylation of osteocalcin. Available evidence suggests that vitamin K2 also enhances osteocalcin accumulation in the extracellular matrix of osteoblasts in vitro. Osteocalcin-knockout mice develop hyperostosis, suggesting that the Gla-containing osteocalcin promotes normal bone mineralization. Although the precise role of osteocalcin in bone mineralization remains obscure, it probably regulates the growth of hydroxyapatite crystals. Furthermore, vitamin K2 also inhibits the expression of the osteoclast differentiation factor (ODF)/RANK ligand, tartrate-resistant acid phosphatase activity, and mononuclear cell formation, and induces osteoclast apoptosis in vitro. There is some evidence indicating that vitamin K2 prevents bone resorption in ovariectomized rats, retards the increase in bone turnover in orchidectomized rats, ameliorates the increase in bone resorption and decrease in bone formation in sciatic neurectomized rats, and prevents the decrease in bone formation in glucocorticoid-treated rats. These findings suggest that vitamin K2 may not only stimulate bone formation but also suppress bone resorption in vivo. Clinically, vitamin K2 sustains the lumbar bone mineral density (BMD) and prevents osteoporotic fractures in patients with age-related osteoporosis, prevents vertebral fractures in patients with glucocorticoid-induced osteoporosis, increases the metacarpal BMD in the paralytic upper extremities of patients with cerebrovascular disease, and sustains the lumbar BMD in patients with liver-dysfunction-induced osteoporosis. Vitamin K deficiency, as indicated by an increased circulating level of undercarboxylated osteocalcin, may contribute to osteoporotic fractures. Even though the effect of vitamin K2 on the BMD is quite modest, this vitamin may have the potential to regulate bone metabolism and play a role in reducing the risk of osteoporotic fractures. No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis.

Omega-3 Supplementation May Slow the Aging Process

Telomeres are the endcaps of chromosomes, the shortening of which has been associated with the aging process. Jan Kiecolt-Glaser, from Ohio State University (Ohio, USA), and colleagues enrolled overweight but healthy middle-aged and older adults in a study lasting four months. Subjects were given either 2.5 grams or 1.25 grams of omega-3 fatty acids, both of which were standardized to contain a 7:1 ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA); a placebo group served as controls. In both omega-3 supplented groups,white blood cell (leukocyte) telomeres actually lengthened; oxidative stress was reduced by about 15% (as compared to placebo). Observing that: “The data suggest that lower [omega-6:omega-3 polyunsaturated fatty acid] ratios can impact cell aging,” the study authors conclude that: “The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions.”

Omega-3 Intake Improves Memory In Young Adults

Healthy young adults can improve their working memory by increasing their Omega-3 fatty acids intake.
The finding came from a study, the first of its kind, from a team at the University of Pittsburgh and was published in PLOS One.
There have been several studies indicating that omega-3 essential fatty acids, found in foods such as grass-fed livestock and wild fish, are critical for the human body to function. One report indicated omega-3 fatty acids can lower a person's chance of developing colon cancer. Another study indicated that they can protect men against heart failure.
However, until now, there had been no research on their impact on the working memory of healthy young adults. Bita Moghaddam, project investigator and professor of neuroscience, said:

"Before seeing this data, I would have said it was impossible to move young healthy individuals above their cognitive best. We found that members of this population can enhance their working memory performance even further, despite their already being at the top of their cognitive game."

The experts examined healthy young males and females ages 18 to 25 from all ethnicities who heightened their Omega-3 intake with supplements for 6 months. Their progress was recorded through phone calls and outpatient procedures.

Before starting off on the supplements, all subjects had their blood samples analyzed and underwent positron emission tomography (PET) imaging, in order to observe how their tissues and organs were functioning.

A working memory test, known as "n-back test", was then given to the participants, in which they were provided a series of letters and numbers. They had to remember what number/letter had been revealed one, two, and three times prior.

Moghaddam explained: "What was particularly interesting about the presupplementation n-back test was that it correlated positively with plasma Omega-3. This means that the Omega-3s they were getting from their diet already positively correlated with their working memory."

The subjects completed the same series of outpatient prodecures after they finished taking Lovaza, an Omega-3 supplement approved by the Food and Drug Administatiom, for six months. Results of this last stage, from the working memory test and blood samples, showed an improvement in working memory.

"So many of the previous studies have been done with the elderly or people with medical conditions, leaving this unique population of young adults unaddressed," revealed Matthew Muldoon, associate professor of medicine at Pitt. "But what about our highest-functioning periods? Can we help the brain achieve its full potential by adapting our healthy behaviors in our young adult life? We found that we absolutely can."

Although the main goal of the research was to recognize the effects of Omega-3s on young adults, the scientists also wanted to observe the brain mechanism linked to regulating Omega-3.

Prior research on rodents suggested that eliminating Omega-3 from the diet can lower dopamine storage - the neurotransmitter linked to mood and working memory - and reduce density in the striatal vesicular monoamine transporter type 2 (VMAT2) - a protein linked to decision making.

This made the team believe that cognitive performance was raised by the increase of VMAT2 protein. However, PET imaging showed that this was not true.

Rajesh Narendarn, research leader and associate professor of radiology, concluded:

"It is really interesting that diets enriched with Omega-3 fatty acid can enhance cognition in highly functional young individuals. Nevertheless, it was a bit disappointing that our imaging studies were unable to clarify the mechanisms by which it enhances working memory."

Ongoing trials in the Moghaddam lab on animals demonstrate that brain mechanisms that are impacted by Omega-3s may be affected differently in young adults and adolescents than in older adults.

Keeping this in mind, the experts are further analyzing the influence of Omega-3 fatty acids in younger people to determine the mechanism that affects cognition

Diabetics with low levels of vitamin D commonly develop clogged arteries, which can result in heart disease, says a new study published in the Journal of Biological Chemistry, by researchers from Washington University School of Medicine in St. Louis.

According to the researchers, blood vessels are not as likely to clog in diabetics who have sufficient levels of vitamin D. However, in those with low levels, immune cells trap cholesterol in the blood vessels close to the heart, resulting in blockage.

A study published in 2011 said that vitamin D can improve cholesterol levels and heart disease biomarkers in diabetics.

Carlos Bernal-Mizrachi, MD, lead investigator of the trial, said:

“About 26 million Americans now have type 2 diabetes. And as obesity rates rise, we expect even more people will develop diabetes. Those patients are more likely to experience heart problems due to an increase in vascular inflammation, so we have been investigating why this occurs."

During prior research, Bernal-Mizrachi, who is an assistant professor of medicine and of cell biology and physiology, and his team discovered that vitamin D seems to play an important part in heart disease. The recent trial goes one step further, stating that when levels are low, a certain kind ofwhite blood cell is more likely to stick to cells in the blood vessel walls.

Vitamin D works together with microphages (a type of immune cell) to clear arteries or block them. These immune cells are born as white blood cells called monocytes, which move and spread through the blood. However, when monocytes meet inflammation they turn into macrophages, which do not move around.

During the recent trial, the experts examined 43 type 2 diabetics' vitamin D levels, and the vitamin D levels of 25 non-diabetics of the same sex, body type, and age.

The researchers discovered that in diabetics who had insufficient vitamin D levels, or less than 30 nanograms per milliliter of blood, the macrophages were more apt to stick to the blood vessel walls, which can lead to cholesterol buildup in the cells. In time, this will result in hardening of the arteries and obstructed movement of blood.

"We took everything into account. We looked at blood pressure, cholesterol, diabetes control, body weight and race. But only vitamin D levels correlated to whether these cells stuck to the blood vessel wall," said Amy E. Riek, MD, a teacher in medicine.

The authors said that it is uncertain whether giving vitamin D to diabetics can alter their chances of getting clogged arteries, a condition called atherosclerosis. Currently, the experts are giving vitamin D to mice to determine whether it can stop monocytes from clinging to blood vessel walls close to the heart, and they are carrying out two studies on human patients.

One of the studies involves the researchers giving diabetics with hypertension vitamin D to find out whether their blood pressure is lowered by the treatment. For the other study, the experts are giving African Americans with type 2 diabetes vitamin D, in addition to their normal every day drugs, in order to determine if the supplements can delay or reverse the development of heart disease.

In the near future, the experts hope to reveal the effects of vitamin D on risk factors linked to cardiovascular disease.

Bernal-Mizrachi concluded:

"In the future, we hope to generate medications, potentially even vitamin D itself, that help prevent the deposit of cholesterol in the blood vessels. Previous studies have linked vitamin D deficiency in these patients to increases in cardiovascular disease and in mortality. Other work has suggested that vitamin D may improve insulin release from the pancreas and insulin sensitivity. Our ultimate goal is to intervene in people with diabetes and to see whether vitamin D might decrease inflammation, reduce blood pressure and lessen the likelihood that they will develop atherosclerosis or other vascular complications."

New study sheds light on cancer-protective properties of milk

Findings reported in the Journal of Dairy Science

Rich in magnesium, milk helps to reduce a person’s odds of developing metabolic syndrome, diabetes, and certain cancers. Previously, Stina Oredsson, from University of Lund (Sweden), and colleagues studied a milk protein, lactoferricin4-14 (Lfcin4-14), significantly reduces the growth rate of colon cancer cells over time by prolonging the period of the cell cycle before chromosomes are replicated. The team has now published findings from an investigation in which they exposed colon cancer cells to ultraviolet (UV) light that caused DNA damage and then grew the cells in the absence or presence of Lfcin4-14. The researchers found that UV light exposure resulted in an increase in assay expression – denoting increase in DNA damage, whereas treatment with Lfcin4-14 reduced that expression – correlating to reduced DNA damage. The mechanism for this effect was identified as an increase in flap endonuclease-1, a protein associated with DNA synthesis; a decrease in b-cell lymphoma 2-associated X protein, which is involved with cell death; and a decrease in the level of gamma-H2AX, indicating more efficient DNA repair. Observing that cancer cells, in general, have defects in the DNA repair mechanisms, the study authors conclude that: “lactoferricin4-14 treatment has beneficial effects.”

Amsterdam, The Netherlands, October 3, 2012 – Milk consumption has been linked to improved health, with decreased risks of diabetes, metabolic syndrome, and colon cancer. A group of scientists in Sweden found that lactoferricin4-14 (Lfcin4-14), a milk protein with known health effects, significantly reduces the growth rate of colon cancer cells over time by prolonging the period of the cell cycle before chromosomes are replicated. In a new study, investigators report that treatment with Lfcin4-14 reduced DNA damage in colon cancer cells exposed to ultraviolet (UV) light. Their results are published in the October issue of the Journal of Dairy Science®.

"We previously hypothesized that the prolongation of the cell cycle in colon cancer cells as a result of Lfcin4-14 treatment may give the cells extra time for DNA repair," says one of the lead investigators, Professor Stina Oredsson, of the Department of Biology at the University of Lund, Sweden. "Indeed, UV light-induced damage was decreased in colon cancer cells treated with Lfcin4-14 compared with controls. The differences were small but significant."

Investigators exposed colon cancer cells to UV light that caused DNA damage and then grew the cells in the absence or presence of Lfcin4-14. They evaluated DNA damage using a sensitive technique known as comet assay. After the cells are processed, the cells with DNA damage resemble a comet with a tail, and the intensity of the tail compared to the comet head indicates the number of DNA breaks. UV light exposure resulted in an increase in the number of comets while treatment with Lfcin4-14 reduced the number of comets in UV light-exposed cells.

To understand the mechanism by which Lfcin4-14 reduced DNA damage, investigators evaluated the levels of several proteins involved in cell cycle progression, DNA repair, and cell death. They found an increase in flap endonuclease-1, a protein associated with DNA synthesis-H2AX, indicating more efficient DNA repair.; a decrease in b-cell lymphoma 2-associated X protein, which is involved with cell death; and a decrease in the level of "These changes in expression support our hypothesis that Lfcin4-14 treatment resulted in increased DNA repair," says Dr. Oredsson.

Dr. Oredsson notes that cancer cells, in general, have defects in the DNA repair mechanisms. Thus, Lfcin4-14 may have a greater effect on normal cells than on cancer cells. "Our data suggest that the effects of Lfcin4-14 in prolonging the cell cycle may contribute to the cancer preventive effect of milk. This must be further investigated in different systems," she concludes.

Caffeine's Effect On The Brain's Adenosine Receptors Visualized For The First Time

Molecular imaging with positron emission tomography (PET) has enabled scientists for the first time to visualize binding sites of caffeine in the living human brain to explore possible positive and negative effects of caffeine consumption. According to research published in the November issue of The Journal of Nuclear Medicine, PET imaging with F-18-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (F-18-CPFPX) shows that repeated intake of caffeinated beverages throughout a day results in up to 50 percent occupancy of the brain's A1 adenosine receptors.

"The effects of caffeine to the human body are generally attributed to the cerebral adenosine receptors. In the human brain the A1 adenosine receptor is the most abundant," said David Elmenhorst, MD, lead author of "Caffeine Occupancy of Human Cerebral A1 Adenosine Receptors: In Vivo Quantification with F-18-CPFPX and PET." "In vitro studies have shown that commonly consumed quantities of caffeine have led to a high A1 adenosine occupancy. Our study aimed to measure the A1 adenosine receptor occupancy with in vivo imaging."

Fifteen male volunteers participated in the study. They abstained from caffeine intake for 36 hours and then underwent a PET scan with F-18-CPFPX. Caffeine was then introduced in short intravenous infusions, increasing in amount. To estimate the occupancy of A1 adenosine receptors by caffeine, the distribution volume at the baseline period of the PET scan was compared with the distribution volume after caffeine administration. Researchers determined that the concentration of the caffeine that displaces 50 percent of the binding of F-18-CPFPX to the A1 adenosine receptor was 13 mg/L, or approximately four to five cups of coffee.

Structural Damage To The Brain From High Blood Pressure Demonstrated Among People As Young As 40

Uncontrolled high blood pressure damages the brain's structure and function as early as young middle-age, and even the brains of middle-aged people who clinically would not be considered to have hypertension have evidence of silent structural brain damage, a study led by researchers at UC Davis has found.

The investigation found accelerated brain aging among hypertensive and prehypertensive individuals in their 40s, including damage to the structural integrity of the brain's white matter and the volume of its gray matter, suggesting that vascular brain injury "develops insidiously over the lifetime with discernible effects."

The study is the first to demonstrate that there is structural damage to the brains of adults in young middle age as a result of high blood pressure, the authors said. Structural damage to the brain's white matter caused by high blood pressure previously has been associated with cognitive decline in older individuals.

Published online in the medical journal The Lancet Neurology, the study will appear in print in the December 2012 issue. It emphasizes the need for lifelong attention to vascular risk factors for brain aging, said study senior author Charles DeCarli, professor of neurology and director of the UC Davis Alzheimer's Disease Center.

"The message here is really clear: People can influence their late-life brain health by knowing and treating their blood pressure at a young age, when you wouldn't necessarily be thinking about it," DeCarli said. "The people in our study were cognitively normal, so a lack of symptoms doesn't mean anything."

Normal blood pressure is considered a systolic blood pressure -- the top number -- below 120 and a diastolic pressure -- the bottom number -- below 80. Prehypertensive blood pressure range is a top number between 120 and 139 and a bottom number between 80 and 89. Blood pressures above 140 over 90 are considered high.

New patients taking dabigatran (Pradaxa) don't have higher rates of bleeding than those on warfarin, according to the results of an FDA investigation. Despite that reassurance, patients may ask about a story in the New York Times about the bleeding risks associated with the drug.

The findings of the agency's safety evaluation are consistent with those from the clinical trial used to approve the drug, says the FDA. However, this may do little to reassure critics who point out that, unlike warfarin, there is no way to reverse dabigatran's anticoagulant effects. The Timesreports that the drug has been linked to over 500 deaths in the U.S.

The FDA says it will continue evaluating "multiple sources of data" as part of an ongoing safety review. In the meantime, dosing recommendations should be carefully followed to reduce the risk for bleeding, especially in patients with renal impairment.

The FDA-approved indications for rivaroxaban (Xarelto) have been expanded to include treating deep-vein thrombosis and pulmonary embolism and preventing their recurrence, the agency announced on Friday.

Rivaroxaban, a factor Xa inhibitor, was previously approved for preventing venous thromboembolism after knee and hip replacement, as well as for preventing stroke in patients with nonvalvular atrial fibrillation.

Once-Yearly Zoledronic Acid for Men with Osteoporosis

This drug lowered the incidence of radiographic, but not clinical, vertebral fractures.

In a 2007 study, once-yearly infusions of the bisphosphonate drug zoledronic acid (Reclast, Aclasta) lowered the incidence of fractures in postmenopausal women (JW Gen Med May 2 2007). Now, in another industry-sponsored randomized trial, 1199 men (age range, 50–85) at high risk for fractures received zoledronic acid (5-mg dose, given intravenously at baseline and at 12 months) or placebo. The study was open to men with osteoporosis defined by bone-density testing and to men with osteopenia plus one to three mild-to-moderate vertebral fractures identified by lateral spine radiographs.

At 2 years, the proportion of men with new radiographic vertebral fractures was significantly lower in the zoledronic acid group than in the placebo group (1.6% vs. 4.9%). A small difference in incidence of symptomatic vertebral or nonvertebral fractures (1.0% vs. 1.8%) did not reach significance. About 20% to 25% of zoledronic acid recipients developed fever, myalgia, or arthralgia (compared with about 5%–10% of placebo recipients), but the duration of these adverse effects was not reported. No cases of jaw osteonecrosis or atypical femoral fractures were noted, but myocardial infarction

Boonen S et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med 2012 Nov 1; 367:1714. (http://dx.doi.org/10.1056/NEJMoa1204061)

Fat May Fuel Cancer

Study suggests how expanding waistlines may contribute to cancer

HOUSTON - (Oct. 15, 2012) – Fat progenitor cells may contribute to cancer growth by fortifying the vessels that provide needed blood to tumors, according to preclinical research findings by investigators at The University of Texas Health Science Center at Houston (UTHealth).

Studies of groups of people have demonstrated a link between obesity and certain cancers; however, the physiological causes have not been identified. The World Health Organization reports that in 2008 there were more than 1.4 billion obese adults in the world and that cancer claimed the lives of 7.6 million that year.

The UTHealth scientists found a new link between tumor growth and obesity. They report that tumors emit a signal that attracts progenitor cells from white adipose tissue in mouse models of cancer. These cells in turn support the network of blood vessels that nourish tumors - a process called tumor angiogenesis.

“For the first time, we have demonstrated that excess fat is a key factor in cancer progression regardless of the diet contributing to the extra weight,” Kolonin said.

“In an attempt to understand how fat tissue fuels tumor growth, our laboratory has focused on a possible role of adipose stromal progenitor cells. These cells serve as stem cells in fat tissue. We have discovered that they expand in obesity and are mobilized into the systemic circulation,” Kolonin said.

“Our experiments show that fat progenitors are recruited by tumors, where they incorporate into blood vessels and become fat cells,” said Yan Zhang, M.D., Ph.D., the study’s lead author and research scientist at the UTHealth Medical School. “We found that obese animal fat progenitor cells recruited by tumors improved vascular function and, therefore, increased survival and proliferation of cancer cells.”

Chieh Tseng, study author and graduate research assistant at the The University of Texas Graduate School of Biomedical Sciences at Houston, said, “Our work has the potential to help a lot of people. Currently, we are investigating the molecular mechanisms of fat progenitor cell homing to tumor. We are also screening for new molecules targeting the pathways through which cells traffic from fat tissue to promote tumor growth.”

“The next step in this research would be to inactivate fat progenitor cells in an effort to slow cancer progression,” said Kolonin, who is on the faculty of the graduate school and is the holder of the Jerold B. Katz Distinguished Professorship in Stem Cell Research at UTHealth.

Other UTHealth study authors include Alexes Daquinag, Ph.D., Felipe Amaya-Manzanares and Olga Sirin, Ph.D.

Multivitamins in the Prevention of Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial

Conclusion In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer.

Veggies Boost Longevity

With lower saturated fats and completely cholesterol-free, abundant dietary fiber, and phytochemicals (including polyphenol antioxidants), a diet rich in vegetables has been shown by a variety of studies to beneficially impact type-2 diabetes and cardiovascular disease, as well as potentially reduce the risks of cancer. Gary E. Fraser, from Loma Linda University (California), and colleagues lead the Adventist Health Study-2, involving 96,000 US and Canadian citizens – including thousands of Seventh-day Adventists (who follow a vegetarian diet). The researchers report that vegans are, on average, 13 kg lighter than meat eaters and five units lighter on the Body Mass Index (BMI) scale, as compared to meat-eaters. As well, the team reveals that vegetarian men live an average of 9.5 years longer, and women an average of 6.1 years longer, than meat-eating counterparts. A potential factor in this longevity is the beneficial effect that the vegetarian diet exerts on blood pressure. Studying a subgroup of 500 subjects of the Adventist Health Study-2 population, the researchers observed that: “vegetarians, especially vegans, do have lower systolic and diastolic BP and less hypertension.”

Sitting for protracted periods increases risk of diabetes, heart disease and death – study

Sitting around compromises health of people- even if they meet typical physical activity guidelines

A new study led by the University of Leicester, in association with colleagues at Loughborough University, has discovered that sitting for long periods increases your risk of diabetes, heart disease and death.

The study, which combined the results of 18 studies and included a total of 794,577 participants, was led by Dr. Emma Wilmot, a research fellow in the Diabetes Research Group at the University of Leicester. It was done in collaboration with colleagues from the newly established National Institute for Health Research (NIHR) Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit and was published in Diabetologia, the journal of the European Association of the Study of Diabetes.

According to the study, those who sit for long periods have a two fold increase in their risk of diabetes, heart disease and death. Importantly, associations were independent of the amount of moderate-to-vigorous physical activity undertaken, suggesting that even if an individual meets typical physical activity guidelines, their health may still be compromised if they sit for long periods of time throughout the day.

Dr Wilmot, a Clinical Research Fellow in Diabetes and Endocrinology based at the Leicester Diabetes Centre, Leicester General Hospital, said: "The average adult spends 50-70% of their time sitting so the findings of this study have far reaching implications. By simply limiting the time that we spend sitting, we may be able to reduce our risk of diabetes, heart disease and death".

"Our study also showed that the most consistent associations were between sitting and diabetes. This is an important message because people with risk factors for diabetes, such as the obese, those of South Asian ethnic origin, or those with a family history of diabetes, may be able to help reduce their future risk of diabetes by limiting the time spent sitting. "

Professor Stuart Biddle, of Loughborough University, and a co-investigator on the study, said: "There are many ways we can reduce our sitting time, such as breaking up long periods at the computer at work by placing our laptop on a filing cabinet. We can have standing meetings, we can walk during the lunch break, and we can look to reduce TV viewing in the evenings by seeking out less sedentary behaviours."

Professor Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and honorary consultant at University Hospitals of Leicester is a co-investigator and Director of the NIHR Leicester-Loughborough Diet, Lifestyle and Physical Activity Biomedical Research Unit. She said:

"This paper has a very important message for the public but also for health care professionals - namely that being sedentary is common and dangerous for our long term health, particularly for diabetes and cardiovascular disease, and that this link appears to be over and above other lifestyle factors such as our diet and physical activity."

One of the most prevalent malignancies in the Western world, prostate cancer is often only diagnosed only after metastatic tumors have formed in other organs; in 3% of cases, these metastases are lethal. Curcumin, a spice compound extracted from the rootstalks of the turmeric plant and gives curry its yellow color and pungent flavor, has been used for centuries in folk medicine and is becoming recognized for its ability to curb the inflammatory response. In previous work, Beatrice Bachmeier, from Ludwig-Maximillians University Munchen (Germany), and colleagues established that curcumin reduces statistically significantly the formation of lung metastases in an animal model of advanced breast cancer. In the present study, the researchers aimed to investigate the efficacy of curcumin in the prevention of prostate cancer metastases, and to determine the compound’s mechanism of action. The researchers first examined the molecular processes that are abnormally regulated in prostate carcinoma cells, finding that tumor cells produce pro-inflammatory immunomodulators including the cytokines CXCL1 and CXCL2. The researchers demonstrated hat curcumin specifically decreases the expression of these two proteins, and in a mouse model, this effect correlated with a decline in the incidence of metastases. Observing that: “Chronic inflammation can induce a metastasis prone phenotype in prostate cancer cells by maintaining a positive pro-inflammatory and pro-metastatic feed-back loop between [inflammatory markers implicated in cancer],” the study authors conclude that: “Curcumin disrupts this feed-back loop by the inhibition of NFκB signalling leading to reduced metastasis formation in vivo.”

In Acute VTE, Novel Oral Anticoagulants and Conventional Therapy Show Similar Efficacy

Novel oral anticoagulants and vitamin K antagonists offer similar protection against venous thromboembolism recurrence, according to a BMJ meta-analysis. However, one of the newer agents, rivaroxaban, seems to offer better protection against bleeding.

The analysis included nine randomized controlled trials comparing apixaban, dabigatran, rivaroxaban, or ximelagatran (no longer on the market) with traditional vitamin K antagonists (e.g, warfarin) in nearly 17,000 patients with acute VTE. Follow-up ranged from 2 weeks to 12 months.

There were no significant differences between any of the novel anticoagulants and vitamin K antagonists with respect to recurrent VTE or all-cause mortality. The newer agents tended to lower the risk for major bleeding, but only the effect of rivaroxaban was statistically significant. An indirect comparison between rivaroxaban and dabigatran did not favor either drug for any outcome.

Asked to comment, David Green of Journal Watch Oncology and Hematology said: "The benefits of the new oral anticoagulants are that monitoring is not required and there are fewer interactions with other drugs; the downside is that there are no readily available reversing agents and experience is still accumulating about effectiveness and safety in various populations."

Vitamin D Insufficiency Contributes To Pain In Black Americans With Knee Osteoarthritis

08 Nov 2012

A new study reveals that black Americans display lower levels of vitamin D and greater pain sensitivity compared to white Americans. Findings published in Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR), indicate that vitamin D deficiency may be one of many factors that account for increased pain in older black Americans with knee osteoarthritis (OA).

Those with OA experience painful swelling and stiffness of the joints such as knees, hips and fingers. The National Arthritis Data Workgroup estimates that 27 million Americans over 25 years of age have OA (based on 2005 U.S. census data). A long-term study by researchers from the University of North Carolina - the Johnston County OA Project - suggests that lifetime risk of developing knee OA is roughly 46%.

A cross-sectional study in the Archives of Internal Medicine calls into question the need for fasting before lipid measurements, as current guidelines recommend.

Researchers in Canada used laboratory data to measure variations in lipid measurements according to the time since a patient's last meal (range, 1-16 hours). Nearly 210,000 individuals were included.

Overall, mean total and HDL cholesterol levels varied little, by less than 2%, with differing fasting times. LDL and triglyceride levels varied more, by less than 10% and 20%, respectively.

An editorialist concludes: "The incremental gain in information of a fasting profile is exceedingly small for total and HDL cholesterol values and likely does not offset the logistic impositions placed on our patients, the laboratories, and our ability to provide timely counseling to our patients. This, in my opinion, tips the balance toward relying on nonfasting lipid profiles as the preferred practice."

Meta-Analysis: Probiotics Safely Reduce Risk for C. difficile–Associated Diarrhea

Probiotic therapy helps prevent Clostridium difficile–associated diarrhea (CDAD) in patients on antibiotics, according to a meta-analysis in the Annals of Internal Medicine.

Researchers analyzed 20 randomized trials that compared probiotics with placebo or no treatment in some 3800 children and adults who were taking antibiotics. The following probiotic species were included: Bifidobacterium, Lactobacilli, Saccharomyces, and Streptococcus. (Roughly half the studies excluded patients who were immunocompromised.)

Probiotics cut the risk for CDAD by 66%, with similar effects seen in both children and adults and with different probiotic species. Adverse events (e.g., nausea, fever) occurred in 13% of the control group and just 9% of the treated group.

The researchers conclude: "Moderate quality evidence supports a large protective effect of probiotics in preventing CDAD. Given the low cost of probiotics and the moderate quality evidence suggesting the absence of important adverse effects, there seems little reason not to encourage the use of probiotics in patients receiving antibiotics who are at appreciable risk of CDAD."

The addition of testosterone to sildenafil does not appear to improve erectile function in men with low testosterone, according to an Annals of Internal Medicine study.

During a 3- to 7-week run-in phase, 140 men with erectile dysfunction (ED) and low testosterone levels were given dose-optimized sildenafil. They were then randomized to either transdermal testosterone or placebo gel for 14 weeks.

After sildenafil treatment, both groups experienced an improvement in erectile function. But after the addition of testosterone, there were no significant differences between the groups in any measure of sexual function. The authors speculate that sildenafil may have raised men's testosterone levels enough so that additional testosterone would not have an effect. The authors note that they did not test the effect of testosterone alone.

They conclude that the findings "do not support the routine addition of testosterone therapy for improving erectile response to selective PDE5 inhibitors in men with ED who have low testosterone levels, which has become commonplace in clinical practice."

General wellness checks to identify disease risk factors and symptoms in healthy people appear to have no effect on mortality, according to a Cochrane meta-analysis in BMJ.

Researchers analyzed the results of 14 randomized trials comprising some 180,000 adults (geriatric trials were excluded). Patients were randomized either to health checks conducted in a primary care or community setting or to no health checks. The exams were not associated with a reduction in all-cause, cardiovascular, or cancer-related mortality.

An editorialist concludes: "The history of health promotion through routine health checks has been one of glorious failure, but generations of well meaning clinicians and public health physicians struggle to allow themselves to believe it. We need to reinforce the message lest some enthusiast reinvent the health check in another guise."

Dariush Mozaffarian, MD, DrPH; Roberto Marchioli, MD; Alejandro Macchia, MD; Maria G. Silletta, MS; Paolo Ferrazzi, MD; Timothy J. Gardner, MD; Roberto Latini, MD; Peter Libby, MD; Federico Lombardi, MD; Patrick T. O’Gara, MD; Richard L. Page, MD; Luigi Tavazzi, MD; Gianni Tognoni, MD; for the OPERA Investigators

Conclusion In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF

Comparing Diabetes Medications, Metformin Offers Cardio Benefits Over Sulfonylureas

A Vanderbilt study examining the impact of the two most commonly prescribed oral diabetes medications on the risk for heart attack, stroke and death has found the drug metformin has benefits over sulfonylurea drugs.

It was important to examine the cardiovascular impact of the more commonly used diabetes drugs after recent controversy surrounded another diabetes medication, rosiglitazone, because it was associated with an increased cardiac risk, said lead author, Christianne L. Roumie, M.D., MPH, assistant professor of Internal Medicine and Pediatrics. Smaller studies pointed to a potential advantage of taking the drug metformin but this study confirms this in a large population.

"We demonstrated that for every 1,000 patients who are using metformin for a year there are two fewer heart attacks, strokes or deaths compared with patients who use sulfonylureas. I think this reinforces the recommendation that metformin should be used as the first medication to treatdiabetes," Roumie said.

The researchers looked at the charts of more than 250,000 veterans receiving care in Veterans Health Administration hospitals throughout the United States. The patients were started on oral therapy for their diabetes with either metformin or a sulfonylurea and followed for about a year. Results are in Annals of Internal Medicine.

"Both drugs do a good job helping control diabetes and preventing nerve damage and eye disease associated with high sugar levels. We did this study because there was an important knowledge gap about whether metformin was superior to sulfonylureas for prevention of heart disease, stroke and death," said senior author Marie R. Griffin M.D., MPH, professor of Preventive Medicine.

The limitations of the study include that neither patient group was compared with diabetic patients who take no oral medications, and that the veteran patients were mostly men.

Metformin is already the recommended first-line therapy for those needing oral medication to control type 2 diabetes. The most common side effect is stomach upset, which can often be overcome by titrating the dosage up slowly. It has not been recommended that patients with kidney impairment take metformin, so sulfonylureas might be a better choice for those patients.

Roumie said this study suggests it might be prudent to take a second look at those patients who have been taking sulfonylureas to see if a switch to metformin might be recommended.

Aspirin Associated with Lower Risks for Chronic Liver Disease, Hepatocellular Carcinoma

Use of NSAIDs, particularly aspirin, is associated with reduced risks for hepatocellular carcinoma and death from chronic liver disease, according to a study in the Journal of the National Cancer Institute.

As part of the NIH-AARP Diet and Health study, some 300,000 people aged 50 to 71 completed questionnaires about NSAID use. Outcomes — incidence of hepatocellular carcinoma and death from chronic liver disease — were confirmed through registries.

After roughly 10 years' follow-up, aspirin use was associated with a lower relative risk for hepatocellular carcinoma (hazard rate ratio, 0.59) and death from chronic liver disease (0.55). Users of nonaspirin NSAIDS had a reduced risk for chronic liver disease deaths (0.74), but not for incident hepatocellular carcinoma.

The authors speculate that the effect may come from NSAIDs' role in reducing chronic inflammation. Editorialists remind readers that bleeding risks come with NSAID use; they also remind us that alcohol abuse and obesity have emerged as major — and controllable — risk factors for liver disease in high-income countries.

Newly Discovered Effects Of Vitamin D On Cancer

Vitamin D slows the progression of cells from premalignant to malignant states, keeping their proliferation in check

A team of researchers at McGill University have discovered a molecular basis for the potential cancer preventive effects of vitamin D. The team, led by McGill professors John White and David Goltzman, of the Faculty of Medicine's Department of Physiology, discovered that the active form of vitamin D acts by several mechanisms to inhibit both the production and function of the protein cMYC. cMYC drives cell division and is active at elevated levels in more than half of all cancers. Their results are published in the latest edition of Proceedings of the National Academy of Sciences.

Although vitamin D can be obtained from limited dietary sources and directly from exposure to the sun during the spring and summer months, the combination of poor dietary intake and sun avoidance has created vitamin D deficiency or insufficiency in large proportions of many populations worldwide. It is known that vitamin D has a wide range of physiological effects and that correlations exist between insufficient amounts of vitamin D and an increased incidence of a number of cancers. These correlations are particularly strong for cancers of the digestive tract, including colon cancer, and certain forms of leukemia.

"For years, my lab has been dedicated to studying the molecular mechanisms of vitamin D in human cancer cells, particularly its role in stopping their proliferation," said Prof. White. "We discovered that vitamin D controls both the rate of production and the degradation of cMYC. More importantly, we found that vitamin D strongly stimulates the production of a natural antagonist of cMYC called MXD1, essentially shutting down cMYC function".

The team also applied vitamin D to the skin of mice and observed a drop in the level of cMYC and found evidence of a decrease in its function. Moreover, other mice, which lacked the specific receptor for vitamin D, were found to have strongly elevated levels of cMYC in a number of tissues including skin and the lining of the colon.

"Taken together, our results show that vitamin D puts the brakes on cMYC function, suggesting that it may slow the progression of cells from premalignant to malignant states and keep their proliferation in check. We hope that our research will encourage people to maintain adequate vitamin D supplementation and will stimulate the development of large, well-controlled cancer chemoprevention trials to test the effects of adequate supplementation," said Dr. White.

This work was funded by the Canadian Institutes of Health Research and the National Cancer Institute/Canadian Cancer Society Research Institute

A systematic review and meta-analysis suggests an association between Alzheimer disease and Vitamin D levels.

Characterized by central obesity, hypertension, and adverse glucose and insulin metabolism, Metabolic Syndrome is a condition associated with increased risk of type-2 diabetes and cardiovascular disease. Eva Prescott, from Bispebjerg University (Denmark), and colleagues conducted a study that included both cross-sectional and longitudinal analyses, using data from the Copenhagen City Heart Study. For the cross-sectional analysis, the researchers included 10,135 subjects evaluated between 1991 and 1994, while the longitudinal analysis included 3,992 subjects seen between 2001 and 2003. The team observed that brisk walking halved the risk that metabolic syndrome would develop over a 10-year period. Leisurely walking, even for more than an hour each day, had no preventive effects. In the longitudinal analysis, the team found that both brisk walking and jogging were associated with an adjusted lower risk for developing metabolic syndrome, as was an overall high level of physical activity. Citing the factor that higher intensity exercise boosts cardiorespiratory fitness, the study authors conclude that: “Our results confirm the role of physical activity in reducing [metabolic syndrome] risk and suggest that intensity more than volume of physical activity is important.”

Folate & B12 Deficiency Linked To Some Depression Subtypes

A low intake of folate and vitamin B12 is linked to a greater risk of melancholic depressive symptoms.

Folate is a water soluble vitamin that helps produce chemicals that control brain functions, such as sleep, mood, and appetite, and can be found in foods like green vegetables. Vitamin B12 is also a water soluble vitamin and it plays a crucial role in the function of the brain, nervous system, and formation of red blood cells.

The finding came from a study that analyzed nearly 3,000 middle-aged and elderly people from Finland. The research also showed that non-melancholic depressive symptoms are associated with an elevated risk the metabolic syndrome.

These observations suggest that melancholic and non-melancholic depression are possibly different depressive subtypes which do not have the same causes regarding diet and proinflammation. This report was the first to examine these sub-types separately.

The research was conducted as part of the Finnish Type 2 Diabetes Prevention Program and was published in the Journal of Affective Disorders.

Mr. Jussi Seppälä, MD, Chief of the Department of Psychiatry of the Hospital District of Southern Savo, explained:

"The findings have practical implications in the care of patients with depressive symptoms. For example, it may be wise to avoid medication causing weight gain among patients with non-melancholic depression, whereas melancholic depressive symptoms may call for a closer look at the quality of the patient's diet."

Typical depressive symptoms are associated with melancholic depression, such as a depressed mood, while non-melancholic depression occurs with other types of symptoms, including anxiety, feelings of worry, and low self-esteem.

The results from the study showed:

The subjects with the highest folate intake had a 50% lower risk for melancholic depressive symptoms, compared to those with the lowest intake.

The people who had the highest vitamin B12 levels had a 3 times lower risk for melancholic depressive symptoms than those with the lowest levels.

The researchers did not find a comparable association with non-melancholic depressive symptoms.

The report also found that patients with non-melancholic depressive symptoms have a two times higher risk for the metabolic syndrome than those with non-melancholic depressive symptoms or those with no depressive symptoms.

Association Between Attentional State And Length Of Telomeres

Scientific studies have suggested that a wandering mind indicates unhappiness, whereas a mind that is present in the moment indicates well-being. Now, a preliminary UCSF study suggests a possible link between mind wandering and aging, by looking at a biological measure of longevity.

In the study, telomere length, an emerging biomarker for cellular and general bodily aging, was assessed in association with the tendency to be present in the moment versus the tendency to mind wander, in research on 239 healthy, midlife women ranging in age from 50 to 65 years.

Being present in the moment was defined as an inclination to be focused on current tasks, while mind wandering was defined as the inclination to have thoughts about things other than the present or being elsewhere.

According to the findings, published online in the new Association for Psychological Science journal Clinical Psychological Science, those who reported more mind wandering had shorter telomeres, while those who reported more presence in the moment, or having a greater focus and engagement with their current activities, had longer telomeres, even after adjusting for current stress.

Telomeres are the DNA-caps that protect the ends of chromosomes, preventing them from deteriorating or fusing with neighboring chromosomes. Telomeres typically shorten with age and in response to psychological and physiological stressors. In research pioneered at UCSF, scientists have discovered that telomere shortness predicts early disease and mortality.

As the study assessed mind wandering and telomeres at the same time, the researchers don't yet know whether mind wandering leads to shorter telomeres, whether the reverse occurs, or some common third factor is contributing to both.

Mindful meditation interventions, which promote attention on the present with a compassionate attitude of acceptance, lead to increases in some aspects of health. Previous studies have found that they are associated with increased activity of an enzyme known as telomerase, which is responsible for protecting and in some cases, replenishing telomeres.

Along with the new UCSF study, these findings support the possibility that a focus on the present may be part of what promotes health measurable at the cellular level, the researchers said.

"Our attentional state - where our thoughts rest at any moment - turns out to be a fascinating window into our well-being. It may be affected by our emotional state as well as shape our emotional state," said Elissa Epel, PhD, associate professor of psychiatry and lead author on the study. "In our healthy sample, people who report being more engaged in their current activities tend to have longer telomeres. We don't yet know how generalizable or important this relationship is."

Moving forward, Epel, along with Eli Puterman, PhD, a psychologist in the UCSF Department of Psychiatry, and colleagues are developing a series of classes to promote more mindful presence, to see if this intervention protects telomere maintenance or even lengthens telomeres.

In the current study, participants self-reported a tendency to mind wander, and were measured for aspects of psychological distress and well-being. The sample was highly educated and had a narrow range of both chronological age and psychological stress (most were low stress), all of which might have contributed to the ability to detect this relationship, Epel said.

The study is the first to link attentional state to telomere length and to control for stress and depression, Epel said. Previous studies have shown links between telomere length and particular types of stress and depression. Since this study relied on self-reported attentional state, she said, further studies directly measuring presence and mind wandering will be needed.

"This study was a first step and suggests it's worth delving into understanding the link between mind wandering and cell health to get a better understanding of whether there is causality and reversibility," said Epel. "For example, does reducing mind wandering promote better cell health? Or are these relationships just reflective of some underlying long-standing characteristics of a person?"

"Results suggest the possibility that the attitude of acceptance of negative experiences might be one of the factors that promotes greater ability to be more present - to be okay with one's current experience and not avoid the unpleasant aspects of everyday experiences," she said.

"A number of emotion theories suggest that greater attentional control leads to less suppression of negative emotions, and thus less of the rebound effect of unsuccessful suppression," said Wendy Berry Mendes, PhD, associate professor and Sarlo/Ekman Endowed Chair of Emotion at UCSF and co-author on this study. "Alternatively, attentional control may help us interpret emotions in a more constructive way, what we call 'positive reappraisals.' Such styles of thinking have been associated with healthy physiological states."

In addition to Epel, Mendes and Puterman, co-authors on this study include Jue Lin, UCSF research biochemist in the Department of Biochemistry and Biophysics; Elizabeth Blackburn, PhD, UCSF molecular biologist and Alanie Lazaro, UCSF laboratory manager in the Department of Psychiatry.

Research on telomeres, and the enzyme that makes them, was pioneered by three Americans, including Blackburn, who co-discovered the telomerase enzyme in 1985. The scientists received the Nobel Prize in Physiology or Medicine in 2009 for this work.

The FDA publicly released the adverse event reports for four energy drinks — 5-Hour Energy, Monster Energy, Rockstar Energy, and Red Bull. Thus far, 18 fatalities have been linked to the highly caffeinated energy drinks (5 to Monster Energy, 13 to 5-Hour).

Some of the symptoms mentioned in the reports include increased heart rate, fatigue, vomiting, loss of consciousness, and cardiac and respiratory arrest. A federal report also found that an energy drink was listed as a possible cause for over 13,000 emergency room visits in 2009, the New York Times reports.

The FDA says that important information may be missing from the adverse event reports, making it "difficult ... to fully evaluate" whether the energy drinks caused the injuries reported. Nevertheless, the agency advises consumers to consult a healthcare provider before using the products.

Physical activity and statin use, both independently and combined, are associated with reduced mortality risk among patients with elevated cholesterol, according to a Lancet study.

Researchers prospectively collected data on roughly 10,000 veterans (mostly male) with dyslipidemia who underwent exercise tolerance tests. Over a median follow-up of 10 years, statin users had a mortality risk of 18.5%, while nonusers had a mortality risk of 27.7%. The mortality risk was reduced among the fittest participants, both among nonusers and users of statins.

The authors conclude: "Improved fitness is an attractive adjunct treatment to statins or an alternative when statins cannot be prescribed. The low exercise capacity (roughly 7 MET) associated with the aforementioned health benefits is clinically significant and reinforces the importance of physical activity for individuals with dyslipidemia."

Should Anyone Not Take a Statin?

In a meta-analysis, benefits of statins outweighed risks, even in the healthiest patients.

Meta-analyses have shown that statins safely lower the incidence of major vascular events (MVEs, including nonfatal myocardial infarction or coronary death, any stroke, or coronary revascularization) by about 20% for every 40 mg/dL reduction in LDL cholesterol level. But the net benefit of statin therapy in patients at low vascular risk has been unclear.

In a new meta-analysis of patient-level data from 27 randomized trials of statins versus control treatments or high- versus low-dose statins, researchers stratified 170,000 participants by their pretrial 5-year risk for MVEs (from <5% to 30%). Overall, statins lowered 5-year relative risk for MVEs by 21% per 40 mg/dL reduction in LDL cholesterol level, and risk reductions were more pronounced in the lowest risk categories (as much as 38% per 40 mg/dL reduction in LDL cholesterol level for participants with 5-year vascular risk <5%). Similar relative risk reductions occurred when patients with prior vascular disease, diabetes, or chronic kidney disease were excluded. Statins lowered 5-year relative risk for vascular death by at least 12% and did not raise risk for nonvascular death in patients with or without histories of vascular disease.

Genetically elevated HDL cholesterol level was not associated with lower risk for myocardial infarction.

Indoor tanning appears to double the likelihood of developing a basal cell carcinoma during early adulthood. The risk is more pronounced in young women.

New Benzodiazepine Use Is Associated with Risk for Dementia

Risk rose by about 60% among elders in whom treatment with these drugs was initiated.

Benzodiazepines are prescribed often for insomnia and anxiety; however, such symptoms can be early manifestations of dementia when reported in older adults. Although the short-term adverse effects of benzodiazepine use on cognition are recognized, whether benzodiazepine use is associated with excess risk for dementia is unclear. In this prospective, population-based study, investigators assessed the association between benzodiazepine use and incident dementia.

Participants were 1000 older adults (mean age, 78) who were free of dementia at baseline and at 5-year follow-up. Ninety-five participants wereclassified as new benzodiazepine users (no declared benzodiazepine use at baseline or at 3 years of follow-up but declared use at 5 years of follow-up), and 968 participants were classified as nonusers (no declared benzodiazepine use at baseline or at 3 or 5 years of follow-up). During 15 years of follow-up, incident dementia was diagnosed in 32% of new benzodiazepine users and in 23% of nonusers. In two statistical analyses, risk for dementia was 50% to 60% higher among new benzodiazepine users after adjustment for confounding variables. Similar results were obtained when recent and past users were compared with nonusers. The researchers provided no information on dosage of benzodiazepine or duration of use.

Inpatients who were given zolpidem were six times more likely to fall than patients who were prescribed the drug but didn't take it, according to a cohort study in the Journal of Hospital Medicine.

Researchers assessed zolpidem prescriptions among all non-ICU, non-pregnant inpatients at the Mayo Clinic in 2010. After adjusting for factors such as delirium and insomnia, patients who were administered zolpidem had a higher rate of falls than those who did not take zolpidem (3.04 vs. 0.71 falls per 100 patients). The authors estimate for every 55 patients treated with zolpidem, one additional fall could be expected to occur.

They note that at their institution, order sets have been changed to discourage use of zolpidem, and they recommend that other hospitals follow suit.

Intensive blood pressure control lowered stroke risk but not risk for myocardial infarctions.

In the U.S. and Sweden, men diagnosed with prostate cancer were less likely to die from the disease than from other causes.

Another study links diabetes to increased breast cancer risk
Postmenopausal women with type 2 diabetes were 35% more likely than those without diabetes to develop breast cancer, a study in the journal Cancer Causes and Control found. Nonwhite women with diabetes had a 289% increased risk for developing breast cancer, compared with those without diabetes. FoodConsumer.org

Resistance training in the elderly
Protein supplementation in addition to resistance-type exercise in a 24-week training program can increase lean body mass and improve strength and physical performance in the elderly. In a companion article these authors looked at protein supplementation alone vs. placebo and its impact on physical performance, reporting improvement only in the protein supplement group. (Free abstract only.) Journal of the American Medical Directors Association

to a meta-analysis published in the journal BMJ. However, U.K. researchers found that omega-3 supplementation did not affect the risk of cerebrovascular events. MedPage Today

Efficacy of statins in the elderly
Many patients ≥80 years of age receive statin therapy for primary prevention and are treated to aggressive low-density lipoprotein levels. Since efficacy is uncertain and potential adverse effects are many, we urgently need to define the cost, benefit and risk of statin use in the very elderly. The American Journal of Cardiology

Risks of self-weighing
Frequent self-weighing among young adults is associated with greater engagement in both healthy and unhealthy weight-control practices. Health care professionals should monitor young adults who engage in self-weighing behaviors and screen for unhealthy weight-control practices and poor psychological well-being. (Full-text access is time-limited.) Journal of Adolescent Health

Survey finds higher ideal body weight over time
A Gallup survey found 59% of men and 69% of women were heavier than their average ideal weight by at least one pound. Researchers also found 60% of adults said their weight was just about right, despite the worsening obesity epidemic, suggesting that Americans are moving to higher ideal weights to change their expectations as their actual weights increase. Gallup.com

Statin use after pneumonia
Although statin use is associated with decreased mortality after pneumonia, this effect weakens in important subgroups. Only a randomized controlled study can fully explore the link between statins and pneumonia mortality. The American Journal of Medicine

Predictors for bradycardia requiring a pacemaker
This study concluded that among atrial fibrillation patients, heart failure and permanent atrial fibrillation each nearly triple the odds of developing bradycardia requiring a permanent pacemaker; while not statistically significant, our results suggest that women are more likely and African-Americans less likely to develop bradycardia requiring pacemaker implantation. The American Journal of Cardiology

Type 2 diabetes control might not lower stroke risk
Patients with well-controlled type 2 diabetes showed lower blood pressure and cholesterol levels but had higher pulse wave velocity than patients in a control group, according to a study in Diabetes Care. Researchers said pulse wave velocity was associated with white matter lesions in diabetes patients and "may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes."PhysiciansBriefing.com/HealthDay News

Men don't see heart benefits from daily multivitamins
An analysis of data from the Physicians' Health Study II involving almost 15,000 men found that taking multivitamins regularly for about 11 years did not significantly reduce the odds of heart attack, stroke or death from heart conditions. The findings were published in the Journal of the American Medical Association and presented at the American Heart Association meeting.WebMD (11/5), InternalMedicineNews.com

Atrial fibrillation in hospitalized patients
Despite a reduction in the rates of, and mortality from, atrial fibrillation, this arrhythmia exerts a significant adverse effect on survival among patients hospitalized with an acute coronary syndrome. Opportunities exist to improve the identification and treatment of patients with acute coronary syndrome with, or at risk for, atrial fibrillation to reduce the incidence and resultant complications of this dysrhythmia. The American Journal of Medicine

The fast pace of today’s 24/7 lifestyle leaves many people neglecting to follow the “Five a Day” recommendation by most developed nations that aim at improving cardiovascular health and reducing cancer risk. David G. Blanchflower, from the University of Warwick (United Kingdom), and colleagues completed a review of cross-sectional data involving 80,000 Britons who were measured by standardized assessments to ascertain life satisfaction, happiness, nervousness, etc., and surveyed for the daily portions of fruits and vegetables consumed. The researchers found that happiness and mental health rise in an approximately dose-response way with the number of daily portions of fruit and vegetables. The researchers find that “well-being peaks at approximately 7 portions per day,” thus leading them to submit that: “Our findings are consistent with the need for high levels of fruit-and-vegetable consumption for mental health and not merely for physical health.”

But rising serum creatinine levels and decreasing glomerular filtration rate also were noted in a meta-analysis.

Among 85- to 90-year-olds, high blood pressure was associated with less cognitive and physical decline.

A systematic review shows modest benefit that is explained partly by the placebo effect.

The incidence of early-stage breast cancer has doubled, but the incidence of late-stage disease hasn't changed much.

The premise of screening mammography is that early detection and treatment prevent late and incurable presentations of breast cancer. If this premise is true, then a rise in incidence of early-stage cancers attributed to mammography should be followed by fewer advanced cancers. Conversely, if early detection is not followed by correspondingly fewer late-presenting cancers, overdiagnosis has occurred: That is, mammography is detecting cancers that are not destined to become clinically important during a patient's lifetime.

To estimate the extent of overdiagnosis, researchers used various U.S. databases to examine breast cancer trends between 1976 (just before screening mammography became widespread) and 2008. During that interval, the annual incidence of early-stage cancers (ductal carcinoma in situ and localized disease) doubled, from 112 to 234 per 100,000 women — an increase of 122 cases per 100,000 women. However, the annual incidence of late-stage cancers during that interval decreased minimally, from 102 to 94 per 100,000 women — a decrease of only 8 per 100,000 women. The excess of early-stage cases identified annually over late-stage cases avoided annually (112 vs. 8 per 100,000 women) suggests substantial overdiagnosis occurred.

Statins as Anticancer Drugs?

In an observational study with limitations, statin use by cancer patients was associated with lower 3-year mortality.

In some basic science studies, statins inhibit cancer growth through various pathways. These observations raise the following question: Could statins lower cancer- mortality? Danish researchers used national databases to address this question.

Among nearly 300,000 people who received cancer diagnoses between 1995 and 2007, 6% had used statins regularly before and after their diagnoses. During average follow-up of 3 years (but as long as 15 years in some cases), two thirds of the patients died. In analyses adjusted for several confounding variables, statin use was associated with a significant 15% drop in all-cause and cancer- deaths. Mortality reductions were noted for most cancer types (although differences did not reach statistical significance for every type).

Comment: This observational study suggests that statins might influence tumor growth favorably in patients with cancer. In contrast, a recent meta-analysis of randomized trials showed that statins did not increase or decrease the incidence of cancer (PLoS One 2012; 7:e29849). An editorialist notes that the current analysis could not be controlled for several potentially important confounding factors and recommends caution in interpreting the findings. Until these results are confirmed or refuted by additional research, clinicians will have to decide whether to apply them to cancer patients; at the least, one might argue that patients who already are taking statins (and tolerating them) at the time of cancer diagnosis should continue.

The U.S. Preventive Services Task Force is about to update its 2004 recommendations on screening for hepatitis C. Evidence reviews on screening adults, reducing mother-to-infant transmission, and antiviral treatments are available in the Annals of Internal Medicine.

The 2004 statement recommended against routine screening in adults not at increased risk and found no evidence for or against screening those at high risk.

The USPSTF's evidence review on adult screening points out that the CDC's recent recommendation to screen all baby-boomers was based on cost-effectiveness analyses and that information on the clinical outcomes of such strategies is needed. Targeting screening of high-risk patients will miss some patients with infection, they observe.

The review on preventing mother-child transmission finds that no intervention has been shown to reduce risk — including the avoidance of breast-feeding.

Oral steroids are recommended for new-onset Bell palsy to improve recovery of facial function, according to updated guidelines from the American Academy of Neurology.

The guidelines, published in Neurology, conclude that six to eight people need to be treated with steroids for one to achieve a complete recovery of facial function.

Antiviral drugs, however, did not show the same level of effectiveness. The academy says that antivirals may be offered in addition to steroids, but patients should be counseled that the benefit is unknown and likely modest at best.

In Journal Watch Neurology, Robert T. Naismith comments: "The side-effect profile for oral glucocorticoids is relatively favorable, and a 10-day course can be recommended within 3 days after facial-weakness onset. If the patient is evaluated for treatment after 3 days, the benefit may be smaller, and treatment would be up to the judgment of the physician and patient."

Patients who use statins regularly before receiving a cancer diagnosis have a decreased risk for dying from cancer, according to an observational study in the New England Journal of Medicine.

Using Danish national registries, researchers identified nearly 300,000 adults aged 40 and older who were diagnosed with cancer between 1995 and 2007. Of these, 6% were regular statin users before diagnosis.

During a median 2.6 years' follow-up, cancer-related mortality was reduced by 15% among statin users versus nonusers, with reductions observed for 13 types of cancer. All-cause mortality was similarly reduced among statin users.

An editorialist points out numerous study limitations that "mandate caution in interpreting the findings" — for example, patients' smoking status was not available. Meanwhile, Allan S. Brett of Journal Watch General Medicine commented: "At the least, one might argue that patients who are already taking statins (and tolerating them) at the time of cancer diagnosis should continue taking them."

Rates of major hemorrhage during warfarin therapy for atrial fibrillation are about 4% per person-year, which is higher than those observed in randomized trials, according to an observational study published in the Canadian Medical Association Journal.

Researchers studied the medical records of 125,000 people in Canada who started warfarin therapy after a diagnosis of atrial fibrillation. Over a 13-year period, they found that an overall hemorrhage rate of 3.8% per person-year. The risk was highest in the first 30 days of treatment, at 11.8%. In patients with a CHADS₂ score of 4 or greater, the 30-day rate was even higher, at 16.7%.

The authors attribute the higher "real-world" rates to the strict inclusion criteria and close monitoring that are characteristic of clinical trials.

At 6 months, type 2 diabetic patients who received liraglutide attained slightly lower glycosylated hemoglobin levels.

Conclusions Initiation of aldosterone antagonist therapy at hospital discharge was not independently associated with improved mortality or cardiovascular readmission but was associated with improved heart failure readmission among eligible older patients with heart failure and reduced ejection fraction. There was a significant increase in the risk of readmission with hyperkalemia, predominantly within 30 days after discharge.

Adrian F. Hernandez, MD, MHS; Xiaojuan Mi, PhD; Bradley G. Hammill, MS; Stephen C. Hammill, MD; Paul A. Heidenreich, MD; Frederick A. Masoudi, MD, MSPH; Laura G. Qualls, MS; Eric D. Peterson, MD, MPH; Gregg C. Fonarow, MD; Lesley H. Curtis, PhD

Conclusion Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

Lars H. Lund, MD, PhD; Lina Benson, MSc; Ulf Dahlström, MD, PhD; Magnus Edner, MD, PhD

Conclusion Discontinuation of warfarin treatment within 6 months after bioprosthetic AVR surgery was associated with increased cardiovascular death.

Charlotte Mérie, MD; Lars Køber, MD, DMSc; Peter Skov Olsen, MD, DMSc; Charlotte Andersson, MD, PhD; Gunnar Gislason, MD, PhD; Jan Skov Jensen, MD, PhD, DMSc; Christian Torp-Pedersen, MD, DMSc

A Patient's History Of Falls Is Useful In Predicting Future Fractures
http://mnt.to/l/49tF

Scientists Identify Potential Drug Target For Inflammatory Diseases Including Cancers
http://mnt.to/l/49rR

Vitamin D Insufficiency Contributes To Pain In Black Americans With Knee Osteoarthritis
http://mnt.to/l/499Q

Vitamin D Levels Decrease During Winter Months In Women With Health Conditions
http://mnt.to/l/497V

Caffeine's Effect On The Brain's Adenosine Receptors Visualized For The First Time
http://mnt.to/l/496J

Structural Damage To The Brain From High Blood Pressure Demonstrated Among People As Young As 40
http://mnt.to/l/495n

Allergy Risk May Be Increased By Triclosan In Cosmetics And Personal Care Products
http://mnt.to/l/49k3

In Mouse Model, Dietary Glucose Affects The Levels Of A Powerful Oncogene
http://mnt.to/l/49kq

Possible Link Between Glutamate Neurotransmission System And Depression Risk
http://mnt.to/l/49jc

Diet Enriched With Arginine And Proline May Speed Wound Healing In Diabetes
http://mnt.to/l/49mD

Ingredients For A Successful Cell Death: A Sip Of Resveratrol And A Full P53
http://mnt.to/l/49hX

Five Fall Foods That Protect Against Cancer
http://mnt.to/l/49nd

Research Finds Kids Who Drank More Milk Have Faster Walking Times And Better Balance As Older Adults
http://mnt.to/l/49kV

Safety Of Calcium Supplements Confirmed In Relation To Cardiovascular Disease
http://mnt.to/l/49kT

Inflammation Marker Linked To Increased Risk For Death From Cancer In Korean Men
http://mnt.to/l/49bb

Plaque Build-Up In Mice Decreased By Consumption Of Genetically Engineered Tomatoes
http://mnt.to/l/498p

Comparing Diabetes Medications, Metformin Offers Cardio Benefits Over Sulfonylureas
http://mnt.to/l/49cd

Drinking Green Tea With Starchy Food May Help Lower Blood Sugar Spikes
http://mnt.to/l/49dK

Measures Developed To Prevent Health Problems Associated With Biogenic Amines In Wine
http://mnt.to/l/49bX

2-3 Cups Of Coffee Improve Brain Processing Of Positive, But Not Negative Or Neutral Words
http://mnt.to/l/49bN

"Salty Six" - Which Foods Should We Avoid?
http://mnt.to/l/49cr

Lower Vitamin D Levels, Genetic Variants And Familial Longevity
http://mnt.to/l/498g

Blueberry Compound Helps to Lower Blood Pressure

The Zinc Link

ZINC DEFICIENCY MECHANISM LINKED TO AGING, MULTIPLE DISEASES

Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse.

Source

Abstract

http://www.ncbi.nlm.nih.gov/pubmed/22177720

Vitamin C prevents hypogonadal bone loss.

Source

Abstract

Effects of vitamin K2 on osteoporosis.

Source

Abstract

Omega-3 Supplementation May Slow the Aging Process

Omega-3 Intake Improves Memory In Young Adults

New study sheds light on cancer-protective properties of milk

Findings reported in the Journal of Dairy Science

Structural Damage To The Brain From High Blood Pressure Demonstrated Among People As Young As 40

Once-Yearly Zoledronic Acid for Men with Osteoporosis

Fat May Fuel Cancer

Study suggests how expanding waistlines may contribute to cancer

Multivitamins in the Prevention of Cancer in Men: The Physicians' Health Study II Randomized Controlled Trial

Veggies Boost Longevity

Sitting for protracted periods increases risk of diabetes, heart disease and death – study

Sitting around compromises health of people- even if they meet typical physical activity guidelines

Vitamin D Insufficiency Contributes To Pain In Black Americans With Knee Osteoarthritis

Comparing Diabetes Medications, Metformin Offers Cardio Benefits Over Sulfonylureas

Newly Discovered Effects Of Vitamin D On Cancer

Folate & B12 Deficiency Linked To Some Depression Subtypes

Association Between Attentional State And Length Of Telomeres

Should Anyone Not Take a Statin?

New Benzodiazepine Use Is Associated with Risk for Dementia

Statins as Anticancer Drugs?