Nutrition studies' conclusions tied to funding source

Analysis of beverage studies shows pervasive bias

Recent analyses have documented bias in pharmaceutical studies funded by industry. Now, an analysis from Children's Hospital Boston finds a similar phenomenon in scientific articles about nutrition, particularly in studies of beverages. The analysis – the first systematic one performed on nutrition studies – found that beverage studies funded solely by industry were four to eight times more likely to have conclusions favorable to sponsors' financial interest than were studies with no industry funding. Findings are published online in the January 9 issue of the journal PLoS Medicine.

David Ludwig, MD, PhD, the study's senior author and director of the Optimal Weight for Life (OWL) program at Children's Hospital Boston, believes that bias in nutrition studies may have far greater effects than bias in pharmaceutical studies. Not only do the findings of nutrition studies receive frequent media attention, but they influence governmental and professional dietary guidelines, the design of intervention programs, and FDA regulation of health claims on foods and beverages.

"We don't all take drugs, but we eat every day," Ludwig says. "If the science base is compromised by conflict of interest, that's a top-order threat to public health."

Because the researchers focused their analysis on soft drinks, juice and milk, they aren't sure whether their findings extend to nutrition studies as a whole. "We chose beverages because they represent an area of nutrition that's very controversial, that's relevant to children, and involves a part of the food industry that is highly profitable and where research findings could have direct financial implications," Ludwig says.

The researchers began by conducting a Medline search of all existing scientific literature about soft drinks, juice and milk published during a five-year period (1999-2003). They retrieved 538 articles, of which 206 were eligible for analysis. Eligible articles had to look at health outcomes or disease markers, had to involve humans or human tissue, had to be classifiable as an interventional or observational study or a scientific review, and had to explicitly state the beverages' effects on health measures. Of the 206 eligible articles, 111 declared financial sponsorship.

To guard against bias, the studies were analyzed independently. One investigator selected the articles for inclusion according to pre-established criteria. Another two investigators, who had no knowledge of the financial sponsors, and who were not told the article's author, title or journal of publication, classified the articles' conclusions as "favorable," "neutral" or "unfavorable." A fourth investigator, who had no knowledge of the conclusions, determined the funding source (22 percent were funded entirely by industry, 47 percent had no industry funding, and 32 percent had mixed funding) and classified articles as to whether a favorable finding would be beneficial, negative or neutral to its funder's financial interests.

When analyzed statistically, article conclusions were significantly related to funding source. Interventional studies with all-industry funding were much less likely to have unfavorable conclusions than those with no industry funding (0 vs. 37 percent). Among all types of studies, comparing all-industry versus no-industry funding, the odds ratio for having a favorable versus unfavorable conclusion was 4.37, increasing to 7.61 when beverage type, publication year and examination of authors' personal conflicts of interest were taken into account.

The researchers note that during their five-year study, the overall proportion of papers declaring their funding sources increased, as journals tightened their disclosure requirements. However, taking publication year into consideration didn't weaken the study's findings. "This isn't an effect that's disappearing," Ludwig says.

The bias may take several forms, Ludwig adds. Although false data could be present in some studies, more likely the biases reflect subtle manipulations, such as framing the questions in a way that make the results more favorable to a sponsor. In other cases, papers with unfavorable results may simply go unpublished.

Gas giants jump into planet formation early

Gas-giant planets like Jupiter and Saturn form soon after their stars do, according to new research.

Observations from NASA's Spitzer Space Telescope show that gas giants either form within the first 10 million years of a sun-like star's life, or not at all. The study offers new evidence that gas-giant planets must form early in a star's history. The lifespan of sun-like stars is about 10 billion years.

Ilaria Pascucci of the University of Arizona Steward Observatory in Tucson led a team of astronomers who conducted the most comprehensive search for gas around 15 different sun-like stars, most with ages ranging from 3 million to 30 million years.

The scientists used Spitzer's heat-seeking infrared eyes to search for warm gas in the inner portions of star systems, an area comparable to the zone between Earth and Jupiter in our own solar system.

In addition, Pascucci, team member Michael Meyer of the UA Steward Observatory and their colleagues probed for cold gas in the outer regions of these star systems with the Arizona Radio Observatory's 10-meter Submillimeter Telescope (SMT) on Mount Graham, Ariz. The outer zones of these star systems are analogous to the region around Saturn's orbit and beyond in our own solar system.

All of the stars in the study – including those as young as a few million years – have less than 10 percent of Jupiter's mass in gas swirling around them, Pascucci said.

"This indicates that gas giant planets like Jupiter and Saturn have already formed in these young solar system analogs, or they never will," Meyer said.

Astronomers suspect that gas around a star may also be important for sending terrestrial, or rocky, planets like Earth into relatively circular orbits as they form. If Earth had a highly elliptical orbit rather than relatively circular one, its temperature swings would be so extreme that humans and other complex organisms might not have evolved.

Many of the sun-like star systems in the study don't currently contain enough gas to send developing rocky planets into circular orbit, Pascucci said. One possibility is that terrestrial planets around these stars have highly elliptical orbits that hinder the development of complex life. Another possibility is that some mechanism other than gas moves the terrestrial planets into circular orbits once they are fully formed. "Our observations tested only the effect of gas," Pascucci said.

Pascucci's paper was published in the Astrophysical Journal in November 2006. The astronomers are presenting a poster of their findings today at the 209th meeting of the American Astronomical Society in Seattle, Wash. The observations were part of the Spitzer Legacy Science Program "Formation and Evolution of Planetary Systems" (FEPS). Meyer, a co-author of the paper, is the principal investigator of the FEPS program.

Higher folate levels linked to reduced risk for Alzheimer's disease

Individuals who take in higher levels of the nutrient folate through both diet and supplements may have a reduced risk of developing Alzheimer's disease, according to a report in the January issue of Archives of Neurology, one of the JAMA/Archives journals.

By the year 2047, the prevalence of Alzheimer's disease is expected to quadruple, according to background information in the article. Delaying the onset of this neurodegenerative disease would significantly reduce the burden it causes. Researchers suspect that elevated levels of the amino acid homocysteine in the blood, which is linked to a higher risk for cardiovascular disease and stroke, may also increase the risk for Alzheimer's disease. Folate, vitamin B12 and vitamin B6, are important in the body's processing of homocysteine-therefore, deficiencies in these nutrients increase homocysteine levels and may contribute to cardiovascular disease, stroke and dementia.

José A. Luchsinger, M.D., Columbia University Medical Center, New York, and colleagues examined, interviewed and assessed the diets of 965 individuals without dementia between 1992 and 1994 and then followed them for an average of 6.1 years to see if they developed Alzheimer's disease. The participants had an average age of 75.8 and 70.2 percent were women, 32.6 percent African-American, 45.3 percent Hispanic and 22.1 percent white.

During the follow-up period, 192 of the participants developed Alzheimer's disease. When the individuals were divided into four groups based on the total level of folate they took in through food and supplements and the analysis was adjusted for patient characteristics, comorbid diseases and B12 and B6 intake, the risk of Alzheimer's disease was lower in the groups with higher intake. Neither dietary folate nor supplements alone were significantly linked to Alzheimer's disease risk; only the two in combination appeared to produce an effect. Levels of the vitamins B12 and B6 were not associated with Alzheimer's disease risk.

Higher folate intake was modestly correlated with lower homocysteine levels, "indirectly suggesting that a lower homocysteine level is a potential mechanism for the association between higher folate intake and a lower Alzheimer's disease risk," the authors write.

Definitive conclusions about the role of folate in the development of Alzheimer's disease cannot yet be made, they continue. The findings of this study are in contrast to those of some other research, and other compounds (such as hormones) perceived to reduce the risk for dementia in observational studies did not do so in randomized trials. "Thus, the decision to increase folate intake to prevent Alzheimer's disease should await clinical trials," they conclude.

Annual plants may cope with global warming better than long-living species

Irvine, Calif. - Countering Charles Darwin's view that evolution occurs gradually, UC Irvine scientists have discovered that plants with short life cycles can evolutionally adapt in just a few years to climate change.

This finding suggests that quick-growing plants such as weeds may cope better with global warming than slower-growing plants such as Redwood trees - a phenomenon that could lead to future changes in the Earth's plant life.

"Some species evolve fast enough to keep up with environmental change," said Arthur Weis, professor of ecology and evolutionary biology. "Global warming may increase the pace of this change so that certain species may have difficulty keeping up. Plants with longer life cycles will have fewer generations over which to evolve."

The study appears the week of Jan. 8 in the Proceedings of the National Academy of Sciences.

Weis and researchers Steven Franks and Sheina Sim studied field mustard, a weedy plant found throughout the Northern Hemisphere. In a greenhouse, they grew mustard plants at the same time from seeds collected near the UCI campus in the spring of 1997 - two years before a five-year drought - and seeds collected after the drought in the winter of 2004. Seeds can remain dormant but alive for years and be revived with a little water and light. The plants were divided into three groups, each receiving different amounts of water mimicking precipitation patterns ranging from drought to very wet conditions. In all cases, the post-drought generation flowered earlier, regardless of the watering scheme.

This shift in genetic timing was further confirmed with an experiment that crossed the ancestors and descendents. As predicted, the intergenerational hybrids had an intermediate flowering time.

"Early winter rainfall did not change much during the drought, but the late winters and springs were unusually dry. This precipitation pattern put a selective pressure on plants to flower earlier, especially annual plants like field mustard," Franks said. "During drought, early bloomers complete seed production before the soil dries out, whereas late bloomers wither before they can seed."

The technique of growing ancestors and descendents at the same time allowed the scientists to determine that the change in flower timing was in fact an evolutionary shift - not a simple reaction to changing weather conditions. This method, pioneered by Albert Bennett, professor of ecology and evolutionary biology and acting dean of the School of Biological Sciences at UCI, has been used with bacteria, but this is the first study to make full use of it with a plant species. Bennett and his colleagues froze ancestral strains of E. coli so they could evaluate the bacterium's adaptive evolution after culturing it at elevated temperatures for thousands of generations.

Today, Weis is the organizing chairman of Project Baseline, a national effort to collect and preserve seeds from contemporary plant populations. Decades from now, plant biologists will be able to "resurrect" these ancestral generations and compare them to their descendents. By that time, advanced DNA technology may make it possible to sequence the entire genome of individual plants and at low cost. If so, biologists will be able to measure how much plants have evolved with climate change and pinpoint the evolution's underlying genetic basis.

Scientists expect global warming to alter air circulation patterns over the Pacific Ocean, and climate models predict frequent and extreme fluctuations in precipitation along the coast, which likely will affect plant life.

"If we go out today and collect a large number of seeds and freeze them, they will be a resource available to the next generation of scientists," Weis said. "Because of global warming, the evolution explosion is already under way. If we act now, we'll have the tools necessary to determine in the future how species respond to climate change."

Researchers warn milk eliminates cardiovascular health benefits of tea

Research published on-line (Tuesday 9 January) in European Heart Journal[1] has found that the protective effect that tea has on the cardiovascular system is totally wiped out by adding milk.

Tests on volunteers showed that black tea significantly improves the ability of the arteries to relax and expand, but adding milk completely blunts the effect. Supporting tests on rat aortas (aortic rings) and endothelial (lining) cells showed that tea relaxed the aortic rings by producing nitric oxide, which promotes dilation of blood vessels. But, again, adding milk blocked the effect.

The findings, by cardiologists and scientists from the Charité Hospital, Universitätsmedizin-Berlin, Campus Mitte, Germany, are bad news for tea-drinking nations like the British, who normally add milk to their beverage. The results have led the researchers to suggest that tea drinkers who customarily add milk should consider omitting it some of the time.

Their study showed that the culprit in milk is a group of proteins called caseins, which they found interacted with the tea to decrease the concentration of catechins in the beverage. Catechins are the flavonoids in tea that mainly contribute to its protection against cardiovascular disease.

Senior researcher Dr Verena Stangl, Professor of Cardiology (Molecular Atherosclerosis) at the hospital, said: "There is a broad body of evidence from experimental and clinical studies indicating that tea exerts antioxidative, anti-inflammatory and vasodilating effects, thereby protecting against cardiovascular diseases. As worldwide tea consumption is second only to that of water, its beneficial effects represent an important public health issue. But, up to now, it's not been known whether adding milk to tea, as widely practised in the UK and some other countries, influences these protective properties. So, we decided to investigate the effects of tea, with and without milk, on endothelial function, because that is a sensitive indicator of what is happening to blood vessels."

Sixteen healthy postmenopausal women drank either half a litre of freshly brewed black tea, black tea with 10% skimmed milk, or boiled water (as a control) on three separate occasions under the same conditions. The endothelial function of the brachial artery in the forearm was measured by high resolution ultrasound before and two hours after drinking, with measurements being taken every 15 seconds for up to two minutes a time.

Said first author Dr Mario Lorenz, a molecular biologist: "We found that, whereas drinking tea significantly increased the ability of the artery to relax and expand to accommodate increased blood flow compared with drinking water, the addition of milk completely prevents the biological effect. To extend our findings to a functional model, we determined vasodilation in rat aortic rings by exposing them to tea on its own and tea with individual milk proteins added, and got the same result."

Milk contains a number of different proteins: by testing each one separately, the researchers found that it was the three caseins that accounted for the inhibiting effect, probably by forming complexes with tea catechins.

Said Dr Stangl: "The well-established benefits of tea have been described in many studies. Our results thus provide a possible explanation for the lack of beneficial effects of tea on the risk of heart disease in the UK, a country where milk is usually added."