In The News: June 2015

An article by Dr. Sanjai Sinha, MD, FACP, of Weill Cornell Medical College in New York City, asked the question: Do age-related decreases in testosterone contribute to a shortened life span in men in relation to cardiovascular disease (CVD)?*

Along with age, blood pressure, antihypertensive treatment, diabetes, and total and HDL cholesterol, gender has long been considered a risk factor for cardiovascular disease. Males experience their first cardiovascular event up to 10 years earlier than women and overall life expectancy in men is approximately five to eight years shorter than that of females. The Framingham Heart Study found that “hard” CVD death rates for males was 18.3% and 7.6% in women.

Hypoandrogenemia (an abnormally low amount of androgens, such as testosterone, in the blood) has been associated with other known CVD risk factors including visceral obesity, high LDL levels, and type II diabetes. A population-based study evaluated the risk of cardiovascular morbidity, all-cause and cardiovascular disease between men and women, and the added risk of low testosterone in men. In the study, 4,152 people between 20 and 70 were tracked for an average of five years.

Compared with women, men were at higher risk of cardiovascular morbidity, including hypertension, dyslipidemia, metabolic syndrome, and type II diabetes. Men 20 to 49 had a much higher relative risk compared to women in their age group for these risk factors versus older men to older women. Compared to men with higher testosterone concentrations, men with low testosterone concentrations had a significantly higher 10-year CVD risk, all-cause mortality ( 82%), and CVD mortality risk (125%).

Eating a handful of nuts—including peanuts, a legume—is associated with a 20% reduced rate of all-cause mortality and specifically, death from cardiovascular disease, say researchers at Vanderbilt University and the Shanghai Cancer Institute in an article published in JAMA Internal Medicine.*

The research, which came from three large prospective cohort studies involving 71,764 low-income Americans and 134,254 Chinese, examined the correlation of nut consumption with lower death rates among low-income and racially diverse populations and found that eating nuts was associated with fewer deaths, especially from heart disease.

The American participants were between 40 and 79 years, while the Chinese were between 40 and 74. For the Americans, peanuts made up about half of total nut consumption.

“Nuts are rich in nutrients, such as unsaturated fatty acids, fiber, vitamins, phenolic [compounds,] arginine, and other phytochemicals. All of them are known to be beneficial to cardiovascular health, probably through their anti-oxidative, anti-inflammatory and endothelial function maintenance properties,” said senior author Xiao-Ou Shu, MD, PhD.

Editor’s Note: This is not the first study to associate nut consumption with lower mortality, but previous studies focused primarily on upper income, white populations who eat more expensive nuts. This is the first study to determine that all races may potentially boost heart health by eating nuts and peanuts.

Many US citizens believe that new drug approval should occur more rapidly and that the 114^th Congress should take action on pharmaceutical development and delivery, according to the results of polls conducted by the nonprofit organization Research!America.*

In 2015, 38% of Americans believed the FDA should act faster to secure approval of new therapies for patients in need of them, despite potential risks—a figure that is up from 30% in 2013. Nearly half of poll respondents believe that increased health care research is part of the solution to high medical costs.

James L. Madara, MD, of the American Medical Association said: “Like Research!America, the American Medical Association is committed to improving the health of the nation and ardently supports funding for medical research that not only generates lifesaving discoveries, but also fuels economic growth by increasing jobs and productivity, and helps control health care costs.”

Editor’s Note: “Our polls show that Americans view research as an economic driver as well as being the answer to health threats that continue to outrun us,” stated Research!America President and CEO Mary Woolley. “Americans expect our elected officials to provide sufficient resources and 21^st century policies to speed development of the therapies, devices, prevention, and cures necessary to save lives and maintain our global competitiveness.”

A recent study published in Thrombosis and Haemostasis found that supplementation with vitamin K2 in the form of MK-7 (menaquinone-7) can help reduce the risk of age-related arterial wall stiffness in middle-aged women.*

The randomized, double-blind trial included 244 healthy postmenopausal women between the ages of 55 and 65 who were given either a daily dose of 180 micrograms of vitamin K2 for three years or a placebo. Researchers evaluated cardiovascular effects with ultrasound and pulse wave velocity. Data from the 227 women who completed the study reveals that vitamin K2 supplements led to significant reductions in vascular stiffness and improved the flexibility of the vascular wall. The effects were most noticeable in women who had a higher degree of vascular stiffness at the beginning of the study.

Editor’s Note: “This is the first study showing that long-term use of vitamin K2 in the form of MK-7 beneficially affects cardiovascular health,” said lead researcher Dr. Cees Vermeer of Maastricht University Holding (The Netherlands). “Our data demonstrated that a nutritional dose of vitamin K2 in fact improves cardiovascular outcomes.”

Researchers at Children’s Hospital of Philadelphia published the results of a trial in which treatment with 7,000 IU vitamin D3 benefited HIV-positive children and young adults.* The supplements used in the trial were provided by the Life Extension^® Foundation.

Over a 12-month period, 50 HIV-positive individuals aged 5 to 24.9 years were given 7,000 IU of vitamin D3 or placebo daily. Vitamin D3 supplementation increased average serum 25-hydroxyvitamin D3 levels from 18 ng/mL at baseline to 32 ng/mL at three months. After 12 months, vitamin D3 subjects maintained a 12 ng/mL increase in vitamin D blood levels compared to placebo.

Several measures of immune function improved with vitamin D3 supplementation compared with placebo. There was an increase in the percentage of naïve T helper cells, CD4+ cells, and a reduction in RNA viral load at several time points during the study.

Editor’s Note : “It’s encouraging to see that high-dose vitamin D3 improved important aspects of immune function in these HIV-positive study participants without causing any major side effects,” stated Dr. Steven Hirsh, director of clinical research for Life Extension^®. “This study certainly supports further research into the use of high-dose vitamin D3 supplementation for individuals with HIV.”

An article published in Molecular Nutrition and Food Research reports that a compound found in green tea may kill oral cancer cells by triggering a process in the mitochondria, which leads to cell death while leaving healthy cells alone.*

“EGCG (epigallocatechin-3-gallate) is doing something to damage the mitochondria and that mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death,” said lead study author Dr. Joshua Lambert of Pennsylvania State. “It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.”

The study compared the effects of EGCG in human oral squamous carcinoma cells, premalignant cells, and normal human gingival fibroblasts. The researchers found that the compound induced reactive oxygen species formation in the mitochondria of the cancerous and premalignant cells but not in normal cells.

Editor’s Note: Dr. Lambert ensured that the study was applicable by using levels of EGCG that would be found when consuming green tea. “We designed the study to use concentrations of EGCG that are achievable in the oral cavity, and we looked at normal, oral leukoplakia (a precancerous lesion), and oral cancer cells to get an idea of what the effect of EGCG would be on different stages in the oral cancer development process.”

Yale University researchers have discovered a compound produced by the body during calorie restriction that can block a part of the immune system involved in inflammatory disorders, including type II diabetes, atherosclerosis, Alzheimer’s disease, and autoinflammatory disorders. The results were published in Nature Medicine in February 2015.*

The scientists described how a compound called BHB (b-hydroxybutyrate) can inhibit NLRP3, which is part of a complex set of proteins called inflammasomes, which drive inflammatory responses in many disorders. BHB are elevated in the liver during calorie restriction, consumption of a low carbohydrate ketogenic diet, and high-intensity exercise.

Working with mice and human immune cells, lead author Vishwa D. Dixit and colleagues focused on how macrophages, the specialized immune cells that produce inflammation, react when exposed to ketone bodies and whether that impacts the inflammasome complex.

After introducing BHB to mouse models of inflammatory diseases caused by NLRP3, they reported reduced inflammation.

Editor’s Note: Professor Dixit noted: “These findings are important because endogenous metabolites like BHB that block the NLRP3 inflammasome could be relevant against many inflammatory diseases, including those where there are mutations in the NLRP3 gene.”

The Journal of Biological Chemistry published the finding of a potential benefit for a combination of metformin and the gene inhibitor B12536 in late-stage prostate cancer.*

Late-stage prostate cancer is commonly treated with androgen deprivation therapy (ADT); however, the disease eventually becomes resistant to treatment. Androgen deprivation can disturb the body’s metabolism, leading to insulin resistance that can stimulate androgen production. Metformin, a drug commonly used to treat diabetes, helps reduce insulin resistance and has been associated with protection against specific cancers.

Acting on the knowledge that the gene polo-like kinase 1 (Plk1) can become overexpressed during ADT and that its overexpression can also stimulate androgen synthesis, Xiaoqui Liu and colleagues tested the effects of administering the Plk1-inhibitor B12536 with low-dose metformin in prostate cancer cells. The team found that the drugs worked synergistically to inhibit prostate cancer cell proliferation.

Editor’s Note : The findings were confirmed in mice that received human prostate cancer cell grafts.

Findings reported in the American Journal of Clinical Nutrition indicate less reason to worry about mercury in fish than ever before, particularly among pregnant women.*

Researchers at the University of Rochester and the University of Ulster, in collaboration with the Republic of Seychelles Ministry of Health, analyzed data from 1,265 mother-child pairs enrolled in the Seychelles Child Development Study Nutrition Cohort 2. (Seychelles Islanders have an average intake of fish that is higher than that of the US.)

Maternal blood samples collected at 28 weeks of gestation were analyzed for serum polyunsaturated fatty acids, and hair samples were evaluated for total mercury to assess prenatal mercury exposure. Tests administered to the children at 20 months of age evaluated motor skills, behavior, and communication.

“These findings show no overall association between prenatal exposure to mercury through fish consumption and neurodevelopmental outcomes,” reported study co-author Edwin van Wijngaarden, PhD.

Editor’s Note : “It is also becoming increasingly clear that the benefits of fish consumption may outweigh, or even mask, any potentially adverse effects of mercury,” Dr. van Wijngaarden noted.

In an article in Scientific Reports, researchers at Texas A&M University describe a benefit for resveratrol in the maintenance of cognitive function in older rats.*

Ashok K. Shetty, PhD, and associates divided 23-month-old rats to receive resveratrol or a placebo for four weeks. Learning ability and memory were evaluated prior to treatment and at approximately 25 months of age.

While spatial learning and spatial memory formation did not differ prior to treatment, animals that received resveratrol showed improvement in these abilities at 25 months. Examination of the rats’ brains revealed significantly increased neurogenesis and improved microvasculature in those that received resveratrol in comparison with the control group. There was also less inflammation in the hippocampus, an area that is vital for learning, memory, and mood.

“The study provides novel evidence that resveratrol treatment in late middle age can help improve memory and mood function in old age,” Dr. Shetty concluded.

Editor’s Note : The authors list increased expression of the longevity gene SIRT1, altered expression of nuclear factor kappa-beta (NF-kB), activation of adenosine monophosphate activated protein kinase (AMPK), improved glucose metabolism, and other factors as possible mechanisms for improvements in cognitive function observed in association with resveratrol.

The Journal of Neuroscience reveals a significant difference between the brains of “normal” 80-year-olds and those of so-called “SuperAgers” of the same chronologic age.* “SuperAgers” is a term applied to men and women who retain good episodic memory function well into their advanced years.

Subsequent to finding a region of the brain’s anterior cingulate cortex that was thicker in SuperAgers in comparison with healthy 50- to 65-year-olds, the researchers utilized magnetic resonance imaging of the cingulate cortex to compare postmortem brains of SuperAgers, cognitively average older men and women, and those who had mild cognitive impairment. The researchers found that, in addition to a thicker and larger cingulate cortex, SuperAgers had 90% fewer neurofibrillary tangles of the type observed in Alzheimer’s disease and increased density of von Economo neurons related to social intelligence.

Editor’s Note: “It’s thought that these von Economo neurons play a critical role in the rapid transmission of behaviorally relevant information related to social interactions, which is how they may relate to better memory capacity,” senior author Changiz Geula explained. “These cells are present in such species as whales, elephants, dolphins, and higher apes.”