In The News: March 2014

The Journal of Alzheimer’s Disease published the outcome of a recent trial conducted by researchers at Oregon Health & Science University in Portland, which revealed that supplementation with omega-3 fatty acids and alpha lipoic acid slowed functional and cognitive decline in Alzheimer’s disease patients.*

Lynne Shinto and colleagues randomized 39 participants with Alzheimer’s disease to receive a daily regimen consisting of fish oil concentrate, fish oil plus R-lipoic acid, or a placebo for one year. Blood tests and evaluations of cognitive and functional performance were administered before and after the treatment period.

In comparison with the placebo group, participants who received omega-3 fatty acids plus lipoic acid demonstrated a lesser decline in the Mini-Mental State Examination, which is an evaluation of global cognitive function, and in the Instrumental Activities of Daily Living (IADL) evaluation of functional ability.

Editor’s Note: Those who received omega-3 fatty acids alone also showed less functional decline as indicated by IADL performance.

An article published online in the American Medical Association journal, JAMA Surgery, reveals a greater risk of hospital-acquired infection among gastric bypass surgery patients with diminished
levels of vitamin D.*

Sadeq A. Quarishi, MD, MHA, of Massachusetts General Hospital and colleagues conducted a retrospective analysis of 770 obese adults who underwent gastric bypass surgery. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured within 30 days prior to the procedure. Hospital-acquired infection, including surgical site infection, catheter-related urinary tract infection, pneumonia or bacteremia, occurred in 41 men and women between two and 30 days after admission.

Among subjects whose 25-hydroxyvitamin D levels were less than 30 nanograms per milliliter (ng/mL) the risk of acquiring an infection while hospitalized was three times as great as the risk experienced by those whose levels were higher.

Editor’s Note: For surgical site infections, the risk among those with decreased vitamin D concentrations was four times as great in comparison with those who had higher levels.

Vitamin D’s benefits to the bone are well known, but what is perhaps more important is its recently recognized role in the brain. In the journal Free Radical Biology and Medicine researchers at the University of Kentucky report a damaging effect in the brains of rats that consumed vitamin D–deficient diets for three to four months.*

Allan Butterfield and his colleagues divided 27 one-year-old rats to receive diets that provided the same amount of calories but contained low, normal, or high amounts of vitamin D. After four to five months on the diets, the animals’ brains were examined for markers of oxidative and nitrosative stress.

Rats in the low vitamin D group showed increased nitrosative stress, which damages the cells. They also observed changes in the levels of several brain proteins, three of which are involved in glycolysis (the metabolic breakdown of glucose that releases energy).

Editor’s Note: Dr. Butterfield suggests that people get their blood tested to determine their vitamin D levels, and that they consume foods that are high in the vitamin and add vitamin D supplements if needed.

The journal Nutrition and Cancer published an article recently in which researchers from the University of Colorado report an anticancer effect in prostate cancer cells for a compound found in grape seed extract known as B2G2.*

The research is the result of years of investigating grape seed’s anticancer action. Alpna Tyagi, PhD, and colleagues found that the administration of B2G2 isolated from grape seed extract as well as synthesized B2G2 resulted in cell growth inhibition, cell cycle arrest, and apoptosis (programmed cell death) in several human prostate cancer cell lines.

“We’ve shown similar anticancer activity in the past with grape seed extract, but now we know B2G2 is its most biologically active ingredient which can be synthesized in quantities that will allow us to study the detailed death mechanism in cancer cells,” Dr. Tyagi remarked.

Editor’s Note: B2G2 was discovered to inhibit nuclear factor kappa-beta (NF-kB)
transcriptional activity and other factors.

The results of a review and meta-analysis published in the Annals of Internal Medicine suggest that so-called “healthy obesity,” characterized by an obese body mass index (BMI) in the absence of adverse metabolic features such as disordered lipids, elevated blood glucose, or hypertension, is not as healthy as some once believed.*

Researchers from Mount Sinai Hospital and the University of Toronto selected 12 observational studies that included a total of 67,127 subjects for their review. Studies included those that evaluated all-cause mortality and/or cardiovascular events, BMI, and metabolic status as defined by the presence of metabolic syndrome components. While normal weight, overweight, and obese subjects that were considered metabolically unhealthy had an elevated risk of mortality and/or cardiovascular events in comparison with metabolically healthy subjects over the course of the studies, those who were metabolically healthy but obese had a 24% greater risk of dying from all causes over 10 years or more of follow-up.

Editor’s Note: The authors of an editorial published in the same issue of the journal remark that physicians should focus on treating the obesity in the same manner as any other chronic disease that requires long-term treatment.

The results of a meta-analysis described in the Journal of the American Heart Association reveal a protective effect for high vitamin C levels and greater intake of the vitamin against the risk of stroke.*

Researchers selected 12 prospective studies involving vitamin C intake and six that examined serum or plasma vitamin C levels for their analysis. Studies of dietary vitamin C included a total of 217,454 men and women, and there were 29,648 participants in the studies involving circulating vitamin C.

For studies that examined vitamin C intake, subjects whose intake was classified as high had a 19% lower risk of stroke in comparison with those categorized as low. Pooled analysis of participants in studies of plasma or serum vitamin C revealed a 38% lower risk of stroke for subjects with high versus low levels.

Editor’s Note : The authors recommend greater vitamin C consumption for populations with low intake or who are at high risk of stroke and suggest that, since established risk factors appear to be responsible for just half of the cases of stroke that occur, vitamin C levels could serve as an additional predictor of risk.

In a supplement to the American Journal of Clinical Nutrition that covered the Fifth International Scientific Symposium on Tea and Human Health, researchers from the University of California, Los Angeles report their conclusion of a protective effect for tea drinking against stroke.*

Lenore Arab and her colleagues reviewed five meta-analyses of human studies of tea or flavonoid consumption and cardiovascular disease or stroke published between 2001 and 2011. A 21% lower risk of both stroke incidence and mortality from stroke was observed among those with high tea intake in comparison with low, and for those with a high intake of flavonoids, the risk was 20% lower. A similar reduction was associated with each three cups of tea consumed. A search for new studies published subsequent to the meta-analyses included in the current research revealed additional studies that supported the protective effect of tea-drinking against stroke.

Editor’s Note : The disease-preventive properties of tea have been attributed to its flavonoid content.

The Journal of the American Medical Association reports an association between the use of drugs that inhibit excess stomach acid and deficient levels of vitamin B12.*

The current study compared 25,956 men and women diagnosed with vitamin B12 deficiency over a four-and-a-half year period with 184,199 subjects who were not deficient. Pharmacy records provided information concerning patients who were dispensed two-year or greater supplies of proton-pump inhibitors (PPIs) or histamine 2 receptor-blocking drugs.

Subjects who received PPIs had a 65% greater risk of being diagnosed with a vitamin B12 deficiency and those who received histamine 2 receptor blockers had a 25% greater risk than those who received neither drug. For those who used the highest dose of proton pump inhibitors, the risk of deficiency was nearly double that of those who didn’t use the drugs. The strength of the association decreased after the drugs were discontinued.

Editor’s Note : By suppressing the production of the stomach’s acid, the drugs, which include proton pump inhibitors (PPIs) and histamine 2 receptor blockers used by patients with gastroesophageal reflux disease (GERD), reduce the amount of the vitamin that is absorbed. Those who need to take PPIs like Nexium ^®, Prolisec^® or Prevacid^® should consider taking vitamin B12 at a separate time or sublingually if a blood test reveals B12 deficit.

A recent study in the journal Breast Cancer Research may have found an association between diets that are high in fat in puberty and cases of breast cancer in adult women.* The study was conducted by researchers at Michigan State University and involved two groups of mice. One group was fed a low fat diet and another was fed a high fat diet (HFD), after which both groups were exposed to a carcinogen to induce tumors.

The high fat diet elevated mammary gland expression of inflammatory and growth factor genes as early as weeks 3 and 4 of the diet. At 10 weeks, the mice on the high fat diet, prior to the appearance of palpable tumors, showed increased numbers of abnormal mammary epithelial lesions and several other indications of potential tumor
proliferation.

The scientists concluded that, “Our results demonstrate that exposure to HFD in the peri-pubertal period, and the sensitivity of the pubertal gland to HFD, initiate a sequence of inflammatory, angiogenic, and growth-promoting effects starting as early as 3 weeks on diet, which can lead to the promotion of mammary cancer development in adulthood.”

An article published in Cell Reports describes the discovery of a significant extension of life span in worms known as C. elegans that were engineered to have two mutations linked to a longer life.¹ The genetically modified worms lived up to five times longer than worms without the mutations.

Pankaj Kapahi, PhD, of the Buck Institute for Research on Aging and colleagues combined a mutation in the nutrient signaling pathway known as Target of Rapamycin (TOR) with a mutation in the insulin signaling pathway Daf-2, which had been demonstrated to increase C. elegans’ life span by 30 and 100%, respectively. The combination elicited a far greater extension of life span than what would have resulted from an additive effect. “Instead, what we have here is a synergistic five-fold increase in life span,” Dr. Kapahi stated. “The two mutations set off a positive feedback loop in specific tissues that amplified life span. Basically these worms lived to the human equivalent of 400 to 500 years.”

Editor’s Note: Dr. Kapahi plans to conduct a similar study in mice. “The idea would be to use mice genetically engineered to have suppressed insulin signaling, and then treat them with the drug rapamycin, which is well-known to suppress the TOR pathway,” he said. The drug metformin down regulates the the TOR pathway, as does the nutrient curcumin.^2,3

A report published in the Proceedings of the National Academy
of Sciences explains how vitamin D, long suspected to play a role in the prevention of multiple sclerosis (MS), works to protect against the disease.*

Acting on the finding of a preventive benefit for vitamin D in a mouse model of MS, Anne R. Gocke, PhD, and her associates at Johns Hopkins University tested the effects of the form of vitamin D known as 1,25-dihyroxyvitamin D3 and found that administration of the vitamin prevented the animals from showing symptoms. Upon cessation of vitamin D treatment, the animals rapidly developed symptoms, showing that vitamin D temporarily halts the disease.

Editor’s Note: Johns Hopkins is currently conducting a trial of vitamin D in MS patients that will help determine whether supplementing with the vitamin is beneficial to humans.