152 Health Research Report 05 APR 2013


Health Research Report

152nd Issue Date 5 Apr 2013

Compiled By Ralph Turchiano

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In this Issue:

Higher soy intake prior to lung cancer diagnosis linked to longer survival in women
Experts find link between low doses of vitamin D and adverse pregnancy outcomes
C. diff infection risk rises with antihistamine use to treat stomach acid, Mayo Clinic finds
Nothing fishy about it: Fish oil can boost the immune system
Eating fish associated with lower risk of dying among older adults
Verifying that sorghum is a new safe grain for people with celiac disease
Dental anesthesia may interrupt development of wisdom teeth in children
Vitamin D proven to boost energy — from within the cells
Higher soy intake prior to lung cancer diagnosis linked to longer survival in women

In this News Digest:

Summary of a study being published online March 25, 2013 in the Journal of Clinical Oncology, reports that Chinese women who consumed more soy before being diagnosed with lung cancer lived longer compared with those who consumed less soy.
Quote for attribution to Jyoti Patel, MD, American Society of Clinical Oncology Cancer Communications Committee member and lung cancer expert
Links to additional information on Cancer.Net, ASCO’s cancer information Website
New results from a large observational follow-up study conducted in Shanghai, China, indicate that women with lung cancer who consumed more soy food prior to their cancer diagnosis lived longer than those who consumed less soy. The study, published March 25 in the Journal of Clinical Oncology, provides the first scientific evidence that soy intake has a favorable effect on lung cancer survival.

“To our knowledge, this is the first study to suggest an association between high soy consumption before a lung cancer diagnosis and better overall survival,” said lead study author Gong Yang, MD, MPH, a research associate professor at Vanderbilt University Medical Center. “Although the findings are very promising, it’s too early to give any dietary recommendations for the general public on the basis of this single study.”

Lung cancer is the leading cause of cancer-related death among women worldwide, with only one in seven patients surviving for 5 years after diagnosis. Emerging evidence suggests that female hormones, particularly estrogens, may affect lung cancer outcomes. Soy contains isoflavones, estrogen-like substances that are also known to affect molecular pathways involved in tumor development and growth.

A recent study by the same research team showed that high intake of soy food was associated with a 40 percent decrease in lung cancer risk.

This new study assessed the impact of soy intake on lung cancer survival among participants of the Shanghai Women’s Health Study, which tracked cancer incidence in 74,941 Shanghai women. Information on usual dietary intake of soy food (soy milk, tofu, fresh and dry soybeans, soy sprouts, and other soy products) was collected in-person at study enrollment and again two years later. Soy food and isoflavone content of various food products was calculated based on the Chinese Food Composition tables. During the course of the study, 444 women were diagnosed with lung cancer. The median time between the first dietary assessment and cancer diagnosis was 5.8 years.

In this analysis, patients were divided into three groups according to soy food intake prior to lung cancer diagnosis. The highest and lowest intake levels were equivalent to approximately 4 oz or more and 2 oz or less tofu per day, respectively. Patients with the highest soy food intake had markedly better overall survival compared with those with the lowest intake ─ 60 percent of patients in the highest intake group and 50 percent in the lowest intake group were alive at twelve months after diagnosis.

The risk of death decreased with increasing soy intake until the intake reached a level equivalent to about 4 oz of tofu per day. Researchers found no additional survival benefit from consuming higher amounts of soy. Similar trends were observed when dietary isoflavone intake was evaluated.

The findings may not necessarily apply beyond this study’s population, which has a very low prevalence of cigarette smoking, a known risk factor for the development of lung cancer, and postmenopausal hormone replacement therapy use, –a factor that may negatively affect lung cancer prognosis. In addition, the overall soy food intake is higher in Chinese women than in Western women.

“But given the increasing popularity of soy food in the U.S. and elsewhere, and a sizable number of women who don’t smoke, the results of this study could have wider relevance,” said Yang.

Future research will explore whether consumption of soy food after diagnosis of lung cancer affects survival, particularly among patients with early-stage disease, who may benefit most from a nutritional intervention.

This research was supported by the U.S. National Cancer Institute and conducted by investigators at Vanderbilt University in collaboration with those from the Shanghai Cancer Institute and NCI.

ASCO Perspective Jyoti Patel, MD, ASCO Cancer Communications Committee member and lung cancer expert

“This study provides some early evidence that consuming large amounts of soy food may help women, particularly never smokers, live longer if they should develop lung cancer.”

Experts find link between low doses of vitamin D and adverse pregnancy outcomes

Supplements may reduce these risks

Research: Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies

Editorial: Vitamin D sufficiency in pregnancy

There is a link between vitamin D insufficiency and adverse health outcomes such as gestational diabetes and preeclampsia in mothers-to-be and low birth weight in newborns, suggests a paper published on bmj.com today.

Vitamin D insufficiency has been associated with a number of adverse health outcomes and has been recognised as a public health concern. Plus, observational data has suggested a link between low vitamin D and increased risk of adverse pregnancy outcomes (such as gestational diabetes, preeclampsia, risk of infections, caesarean section and foetal growth restriction). Knowledge of these associations is however limited.

Literature on this topic is growing rapidly. As such, researchers from the University of Calgary in Canada carried out a systematic review and meta-analysis of all existing evidence on the effect of vitamin D concentration on pregnancy and birth outcomes.

Data from 31 studies were included in the analysis – all published between 1980 and 2012 with between 95 and 1,100 participants. Differences in study design and quality were taken into account to minimise bias.

Results showed that pregnant women with low levels of 5-OH vitamin D were more likely to develop gestational diabetes (odds ratio of 0.49), had an increased chance of developing preeclampsia (odds ratio of 0. 79) and an increased chance of giving birth to a baby small for gestational age (odds ratio of 0.85). No significant differences were found in birth length and head circumference.

The researchers say these results are “concerning” given recent evidence that vitamin D insufficiency is common during pregnancy, especially among high risk women, particularly vegetarians, women with limited sun exposure and ethnic minorities with darker skin.

The researchers conclude that the findings identify a significant association, but there remains a need for large, well-designed randomized controlled trials to determine whether “strategies to optimize vitamin D concentration are effective in improving pregnancy and neonatal outcomes”. They also suggest that future studies should look at the dose-response relationship between vitamin D supplements and adverse health outcomes.

In an accompanying editorial, Dr Lucas from the National Centre for Epidemiology and Population Health at the Australian National University says that the findings of this study support a goal of vitamin D sufficiency for all pregnant women. She says that “supplements, diet and sunlight exposure” are all influences which “should be used together, with care”. Dr Lucas adds that a previous editorial called for large well designed controlled trials “to clarify the causal association” which she believes is needed to find the magnitude of importance between vitamin D and pregnancy.

C. diff infection risk rises with antihistamine use to treat stomach acid, Mayo Clinic finds

ROCHESTER, Minn. — Patients receiving antihistamines to suppress stomach acid are at greater risk of infection from Clostridium difficile, or C. diff, a common cause of diarrhea, particularly in health care settings, Mayo Clinic researchers have found. The study focused on histamine 2 receptor antagonists. The researchers found no significant risk for people taking over-the-counter antihistamine drugs, however. The findings appear in the online journal PLOS ONE.

Researchers reviewed 35 observations based on 33 separate studies involving C. diff and antihistamines used for stomach acid suppressive therapy. The researchers found a clear association between histamine 2 receptor antagonists use and C. diff infection. They say it was especially pronounced and caused the greatest risk for hospitalized patients receiving antibiotics. “It’s not clear why these antihistamines increase the risk of C. diff infection, because gastric acid does not affect C. diff spores,” says senior author Larry Baddour, M.D., a Mayo infectious diseases expert. “However, it may be that vegetative forms of C.diff, which are normally killed by stomach acid, survive due to use of stomach acid suppressors and cause infection.”

Researchers say the study highlights the need for judicious use of histamine 2 receptor antagonists in hospitalized patients, and that reducing the use of these drugs could significantly reduce the risk of C. diff infections.

Nothing fishy about it: Fish oil can boost the immune system

New research published in the Journal of Leukocyte Biology suggests that instead of suppressing the body’s immune response, fish oil actually enhances the function of B cells

Fish oil rich in DHA and EPA is widely believed to help prevent disease by reducing inflammation, but until now, scientists were not entirely sure about its immune enhancing effects. A new report appearing in the April 2013 issue of the Journal of Leukocyte Biology, helps provide clarity on this by showing that DHA-rich fish oil enhances B cell activity, a white blood cell, challenging the notion that fish oil is only immunosuppressive. This discovery is important as it shows that fish oil does not necessarily reduce the overall immune response to lower inflammation, possibly opening the doors for the use of fish oil among those with compromised immune systems.

“Fish oil may have immune enhancing properties that could benefit immunocompromised individuals,” said Jenifer Fenton, Ph.D., M.P.H., a researcher involved in the work from the Department of Food Science and Human Nutrition at Michigan State University in East Lansing, Michigan.

To make this discovery, researchers used two groups of mice. One group was fed a control diet, and the other was fed a diet supplemented with DHA-rich fish oil for five weeks. B cells were harvested from several tissues and then stimulated in culture. Researchers then looked for markers of B cell activation on the cell surface, B cell membrane changes, and B cell cytokine production. They found that DHA-enriched fish oil enhanced B cell activation and select antibody production, which may actually aid immune responses associated with pathogen clearance, while possibly dampening the totality of the inflammatory response.

“This work confirms similar findings on fish oil and B cells from our lab, and moves us one step closer to understanding the immune enhancing properties of EPA and DHA,” said S. Raza Shaikh, Ph.D., a researcher also involved in the work from the Department of Biochemistry and Molecular Biology at East Carolina University.

Eating fish associated with lower risk of dying among older adults

Risk of dying from heart disease significantly lowered

Boston, MA – Older adults who have higher levels of blood omega-3 levels—fatty acids found almost exclusively in fatty fish and seafood—may be able to lower their overall mortality risk by as much as 27% and their mortality risk from heart disease by about 35%, according to a new study from Harvard School of Public Health (HSPH) and the University of Washington. Researchers found that older adults who had the highest blood levels of the fatty acids found in fish lived, on average, 2.2 years longer than those with lower levels.

“Although eating fish has long been considered part of a healthy diet, few studies have assessed blood omega-3 levels and total deaths in older adults,” said lead author Dariush Mozaffarian, associate professor in the Department of Epidemiology at HSPH. “Our findings support the importance of adequate blood omega-3 levels for cardiovascular health, and suggest that later in life these benefits could actually extend the years of remaining life.”

The study—the first to look at how objectively measured blood biomarkers of fish consumption relate to total mortality and specific causes of mortality in a general population—appears online April 1, 2013 in Annals of Internal Medicine.

Previous studies have found that fish, which is rich in protein and heart-healthy fatty acids, reduces the risk of dying from heart disease. But the effect on other causes of death or on total mortality has been unclear. With this new study, the researchers sought to paint a clearer picture by examining biomarkers in the blood of adults not taking fish oil supplements, in order to provide the best assessments of the potential effects of dietary consumption of fish on multiple causes of death.

The researchers examined 16 years of data from about 2,700 U.S. adults aged 65 or older who participated in the Cardiovascular Health Study (CHS), a long-term study supported by the National Heart, Lung, and Blood Institute. Participants came from four U.S. communities in North Carolina, California, Maryland, and Pennsylvania; and all were generally healthy at baseline. At baseline and regularly during follow-up, participants had blood drawn, underwent physical examinations and diagnostic testing, and were questioned about their health status, medical history, and lifestyle.

The researchers analyzed the total proportion of blood omega-3 fatty acids, including three specific ones, in participants’ blood samples at baseline. After adjusting for demographic, cardiovascular, lifestyle, and dietary factors, they found that the three fatty acids—both individually and combined—were associated with a significantly lower risk of mortality. One type in particular—docosahexaenoic acid, or DHA—was most strongly related to lower risk of coronary heart disease (CHD) death (40% lower risk), especially CHD death due to arrhythmias (electrical disturbances of the heart rhythm) (45% lower risk). Of the other blood fatty acids measured—eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA)—DPA was most strongly associated with lower risk of stroke death, and EPA most strongly linked with lower risk of nonfatal heart attack. None of these fatty acids were strongly related to other, noncardiovascular causes of death.

Overall, study participants with the highest levels of all three types of fatty acids had a 27% lower risk of total mortality due to all causes.

When the researchers looked at how dietary intake of omega-3 fatty acids related to blood levels, the steepest rise in blood levels occurred when going from very low intake to about 400 mg per day; blood levels rose much more gradually thereafter. “The findings suggest that the biggest bang-for-your-buck is for going from no intake to modest intake, or about two servings of fatty fish per week,” said Mozaffarian.

Verifying that sorghum is a new safe grain for people with celiac disease

Strong new biochemical evidence exists showing that the cereal grain sorghum is a safe food for people with celiac disease, who must avoid wheat and certain other grains, scientists are reporting. Their study, which includes molecular evidence that sorghum lacks the proteins toxic to people with celiac disease, appears in ACS’ Journal of Agricultural and Food Chemistry.

Paola Pontieri and colleagues explain that those gluten proteins, present in wheat and barley, trigger an immune reaction in people with celiac disease that can cause abdominal pain and discomfort, constipation, diarrhea and other symptoms. The only treatment is lifelong avoidance of gluten. Sorghum, they note, has emerged as an alternative grain for people with celiac disease. In Western countries, sorghum traditionally has been an animal feed. But in Africa and India, it long has been a food for people. Recently, U.S. farmers have begun producing sorghum hybrids that are a white grain, known as “food-grade” sorghum. The researchers set out to make a detailed molecular determination of whether sorghum contains those toxic gluten proteins.

They describe evidence from an analysis of the recently published sorghum genome, the complete set of genes in the plant, and other sources, that verify the absence of gluten proteins. The authors also report that sorghum has high nutritional value. “Food-grade sorghums should be considered as an important option for all people, especially celiac patients,” the report concluded

Dental anesthesia may interrupt development of wisdom teeth in children

BOSTON (April 3, 2013) — Researchers from Tufts University School of Dental Medicine have discovered a statistical association between the injection of local dental anesthesia given to children ages two to six and evidence of missing lower wisdom teeth. The results of this epidemiological study, published in the April issue of The Journal of the American Dental Association, suggest that injecting anesthesia into the gums of young children may interrupt the development of the lower wisdom tooth.

“It is intriguing to think that something as routine as local anesthesia could stop wisdom teeth from developing. This is the first study in humans showing an association between a routinely- administered, minimally-invasive clinical procedure and arrested third molar growth,” said corresponding author, Anthony R. Silvestri, D.M.D., clinical professor in the department of prosthodontics and operative dentistry at Tufts University School of Dental Medicine.

Wisdom teeth are potentially vulnerable to injury because their development – unlike all other teeth – does not begin until well after birth. Between two and six years of age, wisdom tooth (third molar) buds begin to develop in the back four corners of the mouth, and typically emerge in the late teens or early adulthood. Not everyone develops wisdom teeth, but for those who do, the teeth often become impacted or problematic.

The American Association of Oral and Maxillofacial Surgeons reports that nine out of 10 people will have at least one impacted wisdom tooth, which can cause bad breath, pain, and/or infection. For this reason, many dentists recommend surgery to remove wisdom teeth to prevent disease or infection.

A developing wisdom tooth, called a bud, is vulnerable to injury for a relatively long time because it is tiny, not covered by bone, and only covered by a thin layer of soft tissue. When a tooth bud first forms, it is no bigger than the diameter of the dental needle itself. The soft tissue surrounding the budding tooth is close to where a needle penetrates when routine dental anesthesia is injected in the lower jaw, for example when treating cavities.

Using the Tufts digital dental record system, the researchers identified records of patients who had received treatment in the Tufts pediatric dental clinic between the ages of two and six and who also had a dental x-ray taken three or more years after initial treatment in the clinic. They eliminated records with confounding factors, such as delayed dental development, and analyzed a total of 439 sites where wisdom teeth could develop in the lower jaw, from 220 patient records.

Group one, the control group (376 sites), contained x-rays of patients who had not received anesthesia on the lower jaw where wisdom teeth could develop. Group two, the comparison group (63 sites), contained x-rays from patients who had received anesthesia.

In the control group, 1.9% of the sites did not have x-ray evidence of wisdom tooth buds. In contrast, 7.9% of the sites in the comparison group – those who had received anesthesia – did not have tooth buds. The comparison group was 4.35 times more likely to have missing wisdom tooth buds than the control group.

“The incidence of missing wisdom teeth was significantly higher in the group that had received dental anesthesia; statistical evidence suggests that this did not happen by chance alone. We hope our findings stimulate research using larger sample sizes and longer periods of observation to confirm our findings and help better understand how wisdom teeth can be stopped from developing,” Silvestri continued. “Dentists have been giving local anesthesia to children for nearly 100 years and may have been preventing wisdom teeth from forming without even knowing it. Our findings give hope that a procedure preventing third molar growth can be developed.”

Silvestri has previously published preliminary research on third molar tooth development, showing that third molars can be stopped from developing when non- or minimally-invasive techniques are applied to tooth buds.

Vitamin D proven to boost energy — from within the cells

Vitamin D is vital for making our muscles work efficiently and boosting energy levels, new research from Newcastle University has shown.

A study led by Dr Akash Sinha has shown that muscle function improves with Vitamin D supplements which are thought to enhance the activity of the mitochondria, the batteries of the cell.

A hormone normally produced in the skin using energy from sunlight, Vitamin D can also be found in a few foods – including fish, fish liver oils, egg yolks and fortified cereals but it can also be effectively boosted with Vitamin D supplements.

It is thought around 60% of people in the UK are vitamin D deficient, with children under five, people with dark skin and the elderly being particularly vulnerable. While it has a well-established association with helping in bone formation and a deficiency can lead to rickets, its role in other health issues is just emerging.

The researchers used non-invasive magnetic resonance scans to measure the response to exercise in 12 patients with severe deficiency before and after treatment with vitamin D.

Lead author Dr Akash Sinha who also works within the Newcastle upon Tyne Hospitals NHS Foundation Trust said: “The scans provided a unique window into what is really going on in the muscle as it works.

“Examining this small group of patients with vitamin D deficiency who experienced symptoms of muscle fatigue, we found that those with very low vitamin D levels improved their muscle efficiency significantly when their vitamin D levels were improved.”

Alongside poor bone health, muscle fatigue is a common symptom in vitamin D deficient patients. This fatigue could be due to reduced efficiency of the mitochondria: the ‘power stations’ within each cell of the body.

Mitochondria use glucose and oxygen to make energy in a form that can be used to run the cell – an energy-rich molecule called ATP. Muscle cells need large amounts of ATP for movement and they use phosphocreatine as a ready and available energy source to make ATP. The mitochondria also replenish this phosphocreatine store after muscle contraction and measuring the time taken to replenish these stores is a measure of mitochondrial efficiency: better mitochondrial function is associated with shorter phosphocreatine recovery times.

The team found that these recovery rates significantly improved after the patients took a fixed dose of oral vitamin D for 10-12 weeks. The average phosphocreatine recovery half time decreased from 34.4 sec to 27.8 sec. All patients reported an improvement in symptoms of fatigue after having taken the supplements. In a parallel study, the group demonstrated that low Vitamin D levels were associated with reduced mitochondrial function.

Dr Sinha added: “We have proved for the first time a link between vitamin D and mitochondria function.

“Of the patients I see, around 60% are vitamin D deficient and most people living north of Manchester will struggle to process enough vitamin D from sunlight alone, particularly during winter and spring. So a simple vitamin D tablet could help boost your energy levels – from within the cells.”

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These reports are done with the appreciation of all the Doctors, Scientist, and other Medical Researchers who sacrificed their time and effort. In order to give people the ability to empower themselves. Without base aspirations of fame, or fortune. Just honorable people, doing honorable things.

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