Health for life

In an analysis of 446 compounds for their the ability to boost the innate immune system in humans, researchers in the Linus Pauling Institute at Oregon State University discovered just two that stood out from the crowd – the resveratrol found in red grapes and a compound called pterostilbene from blueberries.

Both of these compounds, which are called stilbenoids, worked in synergy with vitamin D and had a significant impact in raising the expression of the human cathelicidin antimicrobial peptide, or CAMP gene, that is involved in immune function.

The findings were made in laboratory cell cultures and do not prove that similar results would occur as a result of dietary intake, the scientists said, but do add more interest to the potential of some foods to improve the immune response.

The research was published in Molecular Nutrition and Food Research, in studies supported by the National Institutes of Health.

"Out of a study of hundreds of compounds, just these two popped right out," said Adrian Gombart, an LPI principal investigator and associate professor in the OSU College of Science. "Their synergy with vitamin D to increase CAMP gene expression was significant and intriguing. Its a pretty interesting interaction."

Resveratrol has been the subject of dozens of studies for a range of possible benefits, from improving cardiovascular health to fighting cancer and reducing inflammation. This research is the first to show a clear synergy with vitamin D that increased CAMP expression by several times, scientists said.

The CAMP gene itself is also the subject of much study, as it has been shown to play a key role in the "innate" immune system, or the bodys first line of defense and ability to combat bacterial infection. The innate immune response is especially important as many antibiotics increasingly lose their effectiveness.

A strong link has been established between adequate vitamin D levels and the function of the CAMP gene, and the new research suggests that certain other compounds may play a role as well.

Stilbenoids are compounds produced by plants to fight infections, and in human biology appear to affect some of the signaling pathways that allow vitamin D to do its job, researchers said. It appears that combining these compounds with vitamin D has considerably more biological impact than any of them would separately.

Continued research could lead to a better understanding of how diet and nutrition affect immune function, and possibly lead to the development of therapeutically useful natural compounds that could boost the innate immune response, the researchers said in their report.

Despite the interest in compounds such as resveratrol and pterostilbene, their bioavailability remains a question, the researchers said. Some applications that may evolve could be with topical use to improve barrier defense in wounds or infections, they said.

The regulation of the CAMP gene by vitamin D was discovered by Gombart, and researchers are still learning more about how it and other compounds affect immune function. The unique biological pathways involved are found in only two groups of animals – humans and non-human primates. Their importance in the immune response could be one reason those pathways have survived through millions of years of separate evolution of these species.

A continual supply of quality nutrients are required every day to fuel our metabolic machinery. Natural diet and whole food based multi-vitamins are the best source of the vitamins and minerals we need to thrive. Millions of people continue to subside on a diet dominated by processed junk food and fail to eat the minimum servings of fresh vegetables and fruits needed to prevent chronic illness.

Based on the largest comprehensive systematic review to date, researchers at the Perelman School of Medicine at the University of Pennsylvania concluded that available evidence does not support an association between statins and memory loss or dementia. The new study, a collaborative effort between faculty in Penn Medicines Preventive Cardiovascular Program, the Penn Memory Center, and the Penn Center for Evidence-Based Practice, will be published in Annals of Internal Medicine.

"Statins are prescribed to approximately 30 million people in the United States," said senior study author Emil deGoma, MD, assistant professor of Medicine and medical director of the Preventive Cardiovascular Program at Penn. "A wealth of data supports a benefit of these cholesterol-lowering medications among individuals at risk for cardiovascular disease in terms of a reduction in the risk of heart attack and stroke; however, potential side effects of statins are less well understood. In February 2012, largely based on anecdotal reports, the U.S. Food and Drug Administration (FDA) issued a safety statement warning patients of possible adverse cognitive effects associated with statin use. Many concerned patients have asked if there is a relationship between statins and memory problems. Their concerns, along with the FDA statement, prompted us to pursue a rigorous analysis of all available evidence to better answer the question -- are statins associated with changes in cognition?"

The research team conducted a systematic review of the published literature and identified 57 statin studies reporting measures of cognitive function. Dr. deGoma and colleagues found no evidence of an increased risk of dementia with statin therapy. In fact, in cohort studies, statin users had a 13 percent lower risk of dementia, a 21 percent lower risk of Alzheimers disease, and a 34 percent lower risk of mild cognitive impairment compared to people who did not take statins.

Most importantly, cognitive test scores were not adversely affected by statin treatment in randomized controlled trials. In these trials, roughly half of the study participants received statins and the other half received placebo. All study participants underwent formal testing of memory and other cognitive domains through tests such as the ability to recall a set of numbers. The analysis of 155 cognitive tests spanning eight categories of cognitive function, including 26 tests of memory, revealed no differences between study participants treated with statins and those provided placebo.

The research team additionally performed an analysis of the FDA post-marketing surveillance databases and found no difference in the frequency of cognitive adverse event reports between statins and two commonly prescribed cardiovascular medications that have not been associated with cognitive impairment, namely, clopidogrel and losartan.

"Overall, these findings are quite reassuring. I wouldnt let concerns about adverse effects on cognition influence the decision to start a statin in patients suffering from atherosclerotic disease or at risk for cardiovascular disease. I also wouldnt jump to the conclusion that statins are the culprit when an individual who is taking a statin describes forgetfulness. We may be doing more harm than good if we withhold or stop statins -- medications proven to reduce the risk of heart attack and stroke -- due to fears that statins might possibly cause memory loss," said Dr. deGoma.

The team acknowledges that while their analysis is reassuring, large, high-quality randomized controlled trials are needed to confirm their findings.

"For many of the cognitive outcomes that we examined, the identified studies were small, were at risk for bias, used varying diagnostic tests to assess cognitive domains, and did not include patients on high-dose statins, which is important given the increasing use of high-dose statins for secondary prevention," noted study co-author Craig Umscheid, MD, MSCE, assistant professor of Medicine and Epidemiology and director of the Penn Center for Evidence-based Practice. "Thus, additional trials addressing these limitations would strengthen our conclusions. Despite this, the totality of the evidence does reassure us that theres unlikely to be a significant link between statins and cognitive impairment."