All Posts tagged proteins

Fruit & Veg may not help allergy

Eating more fruits and vegetables may not protect children from developing allergies, according to a large Swedish study that questions earlier hints of benefit. Fruits and vegetables are rich in antioxidants, which are thought to reduce airway inflammation. So recent studies reporting less asthma, wheezing and hay fever among children who consumed more produce appeared to make sense.

But not all research has found that link, and the studies that did may have had a surprising flaw, said Helen Rosenlund of Karolinska Institutet in Stockholm, who led the new study. She said some proteins in fruits like apples and pears resemble the pollen parts that trigger hay fever, meaning that kids might react to both. In other words, existing allergies may have caused them to eat around the produce, rather than the other way around. “This could confuse research findings,” explained Rosenlund, “falsely suggesting that diets with fewer fruits and vegetables result in more allergic disease.”

To find out if this was the case, Rosenlund and her colleagues looked at data on nearly 2,500 eight-year-olds who had participated since birth in a larger Swedish study. Based on blood tests and questionnaires filled out by parents, the researchers found that seven percent of the children had asthma. The rates of hay fever and skin rashes were more than twice as high. The average child ate between one and two servings of fruit, and between two and three servings of vegetables each day.

At first glance, some produce did seem helpful: Kids with the biggest appetite for fruit had less than two-thirds the odds of developing hay fever than those who ate the least amount. Apples, pears and carrots appeared to be particularly helpful, the researchers report in the Journal of Allergy and Clinical Immunology, but there was no such link for vegetables overall. However, it turned out that half the children with hay fever were sensitive to birch tree pollen, one of the pollens known to resemble the proteins in apples and carrots. And sure enough, after the team repeated their analysis excluding the 122 kids with food-related allergy symptoms, the hay fever link disappeared as well. “Fruits do not seem to offer protection against allergic if diet modifications are considered,” say Rosenlund.

The researchers say more studies are needed, particularly in other parts of the world that may have a different variety of allergy triggers, or allergens. And they advise those studies should not forget to look at how allergies might influence what participants eat. “Studying diet it is not so easy when it comes to the relation with allergic disease,” Rosenlund said, “because it is such a complex disease pattern.”

SOURCE: bit.ly/g3DpI7 The Journal of Allergy and Clinical Immunology, online January 10, 2011.

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Age related protein linked to cancer

Age related protein linked to cancer

The most common type of breast cancer in older women — estrogen and progesterone receptor (ER/PR) positive breast cancer — has been linked to a protein that fends off aging-related cellular damage. A new study led by Vanderbilt-Ingram Cancer Center researcher David Gius, M.D., Ph.D., now shows how a deficiency in this aging-associated protein may set the stage for these tumors to develop.

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The findings, published in Molecular Cell, provide information that could assist in the screening, prevention and treatment of these common age-related cancers. While the young are certainly not spared cancer’s wrath, cancer is primarily a disease of aging, with the majority of cases occurring in people over 50. However, the biological processes that underlie this association are not clear.

“The connection between aging and cancer is one of the most established phenomena in cancer research,” said Gius, associate professor of Cancer Biology, Pediatrics and Radiation Oncology. “The problem to address this clinically significant question is that this field lacks in vivo models to study this.”

In the late-1990s, proteins called “sirtuins” were linked to extended lifespan observed in several species maintained on a calorically restricted diet. These nutrient-sensing sirtuin proteins seemed to defend against aging-related cellular damage. Sirtuins are present in all living organisms, with humans having seven different sirtuin proteins. “When (the sirtuins) were discovered, it seemed obvious to conclude that there might be a mechanistic connection between the genes that determine length of survival and cancer,” Gius said. Previously, while at the National Cancer Institute, Gius and colleagues created mice lacking some of these sirtuins.

They reported last January in Cancer Cell that when they knocked out Sirt3 — a sirtuin localized in the mitochondria, the cellular “power plants” — the mice developed ER/PR positive breast tumors, the most common type of breast cancer in postmenopausal women. These tumors also exhibited increased levels of damaging free radicals and “reactive oxygen species” (ROS) — including superoxide, the primary metabolite of oxygen in the mitochondria — which provided an important clue as to how Sirt3 deficiency might permit these tumors to develop. “The mechanism, at least in part, for why these mice develop receptor positive breast cancer is altered mitochondrial ROS, including superoxide,” Gius said. But how deficiency in a longevity gene led to increased ROS was not clear. Since superoxide is generally removed from the cell with the help of a detoxifying enzyme called manganese superoxide dismutase (MnSOD), Gius hypothesized that the Sirt3 deficiency may abnormally regulate MnSOD.

In the current study, the researchers show that Sirt3 knockout mice have decreased MnSOD activity despite having normal levels of the protein. Gius and colleagues determined that the MnSOD in Sirt3 knockout mice was abnormally modified (with a chemical “acetyl” group) at a specific amino acid (lysine 122). This aberrant modification of MnSOD reduced the enzyme’s ability to detoxify superoxide and appeared to explain the increase in ROS in Sirt3 knockout mouse tumors. “These results suggest that aberrant regulation of MnSOD plays a role in receptor positive breast cancer,” said Gius.

Gius and colleagues also developed an antibody that can assess the acetylation status of MnSOD, which he says can potentially be used “to screen breast tissue samples to determine what women are at risk for (receptor positive) cancer or for recurrence because of this dysregulation of MnSOD.” Additionally, agents that target the acetylation of this amino acid on MnSOD may be useful as chemopreventive therapies in women at risk of these cancers and of recurrence, he noted. The research was supported by grants from the National Cancer Institute and the Department of Defense.

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Not All Infant Formulas Are Alike

New findings from the Monell Center reveal that weight gain of formula-fed infants is influenced by the type of formula the infant is consuming. The findings have implications related to the infant’s risk for the development of obesity, diabetes and other diseases later in life. “Events early in life have long-term consequences on health and one of the most significant influences is early growth rate,” said study lead author Julie Mennella, Ph.D., a developmental psychobiologist at Monell. “We already know that formula-fed babies gain more weight than breast-fed babies. But we didn’t know whether this was true for all types of formula.”

While most infant formulas are cow’s milk-based, other choices include soy-based and protein hydrolysate-based formulas. Protein hydrolysate formulas contain pre-digested proteins and typically are fed to infants who cannot tolerate the intact proteins in other formulas. In adults, pre-digested proteins are believed to act in the intestine to initiate the end of a meal, thus leading to smaller meals and intake of fewer calories. Based on this, the authors hypothesized that infants who were feeding protein hydrolysate formulas would eat less and have an altered growth pattern relative to infants feeding cow’s milk-based formula.

In the study, published online in the journal Pediatrics, infants whose parents had already decided to bottle-feed were randomly assigned at two weeks of age to feed either a cow’s milk-based formula (35 infants) or a protein hydrolysate formula (24 infants) for seven months. Both formulas contained the same amount of calories, but the hydrolysate formula had more protein, including greater amounts of small peptides and free amino acids. Infants were weighed once each month in the laboratory, where they also were videotaped consuming a meal of the assigned formula. The meal continued until the infant signaled that s/he was full.

Over the seven months of the study, the protein hydrolysate infants gained weight at a slower rate than infants fed cow milk formula. Linear growth, or length, did not differ between the two groups, demonstrating that the differences in growth were specifically attributable to weight. “All formulas are not alike,” said Mennella. “These two formulas have the same amount of calories, but differ considerably in terms of how they influence infant growth.”

When the data were compared to national norms for breast-fed infants, the rate of weight gain of protein hydrolysate infants was comparable to the breast milk standards; in contrast, infants fed cow’s milk formula gained weight at a greater rate than the same breast milk standards. Analysis of the laboratory meal revealed the infants fed the protein hydrolysate formula consumed less formula during the meal. “One of the reasons the protein hydrolysate infants had similar growth patterns to breast-fed infants, who are the gold standard, is that they consumed less formula during a feed as compared to infants fed cow’s milk formula” said Mennella. “The next question to ask is: Why do infants on cow’s milk formula overfeed?”

The findings highlight the need to understand the long-term influences of infant formula composition on feeding behavior, growth, and metabolic health. Future studies will utilize measures of energy metabolism and expenditure to examine how the individual formulas influence growth, and how each differs from breastfeeding. Also contributing to the study, which was funded by the National Institute of Child Health and Human Development, were Monell scientists Gary Beauchamp and Alison Ventura.

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Low Level of “Good” Cholesterol Associated with Alzheimer’s

A low level of “good” cholesterol is a well-known risk factor for heart disease. A new study by investigators at Columbia University College of Physicians & Surgeons now suggests that a low level of good cholesterol may also raise the risk of developing Alzheimer's disease.

“Low levels of 'good' cholesterol (a.k.a. high-density lipoproteins or HDL) are very common in the United States,” says the study's lead author, Christiane Reitz, MD, PhD, assistant professor of neurology (in the Sergievsky Center and Taub Institute). “If raising HDL can lower a person's risk of developing Alzheimer's disease, that means we may be able to significantly reduce the rate of Alzheimer's disease in the population,” Reitz says, though she cautions that the finding still must be confirmed in other studies.

The study, which appears in the December issue of Archives of Neurology, is co-authored with Jose Luchsinger, MD, MPH, associate professor of medicine and epidemiology, and Richard Mayeux, MD, director of the Gertrude Sergievsky Center and Sergievsky Professor of Neurology, Psychiatry, and Epidemiology.

Previously, the relationship between HDL and Alzheimer's disease had been unclear. Some studies found an association, but others, including one of Reitz's own, found no connection. The new study, Reitz says, follows subjects for a longer period of time than previous studies, resulting in a more accurate account of the number of subjects who ultimately develop Alzheimer's.

After monitoring 1130 elderly residents of northern Manhattan for an average of four years, the researchers found a 40 percent higher incidence of Alzheimer's in residents with low HDL (less than 55 mg/dl). The reason that low HDL is associated with a higher rate of Alzheimer's isn't understood. One possibility is that it works through stroke. “We know low HDL raises the risk of stroke and that stroke is associated with Alzheimer's, so stroke may be the mediator,” Reitz says. “But there's also evidence that HDL works by itself to clear amyloid proteins [the proteins believed to cause Alzheimer's] from the brain.”

Because the study included a large number of African Americans and Hispanics, unlike previous studies that focused on whites, the finding may indicate that low HDL is linked to a high risk of Alzheimer's in many different ethnicities.

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Diogenes: Has The Secret To Preventing Obesity Been Discovered?

Diogenes: Has The Secret To Preventing Obesity Been Discovered?

Throughout the project, the families received expert guidance from dietitians and were asked to provide blood and urine samples.

Diogenes: The five diet types

The design comprised the following five diet types:

  • A low-protein diet (13% of energy consumed) with a high glycemic index (GI)*
  • A low-protein, low-GI diet
  • A high-protein (25% of energy consumed), low-GI diet
  • A high-protein, high-GI diet
  • A control group which followed the current dietary recommendations without special instructions regarding glycemic index levels

A high-protein, low-GI diet works best

A total of 938 overweight adults with a mean body mass index (BMI) of 34 kg/sq m were initially placed on an 800-kcal-per-day diet for eight weeks before the actual diet intervention was initiated. A total of 773 adult participants completed this initial weight-loss phase and were then randomly assigned to one of five different diet types, where 548 participants completed the six-month diet intervention (completion rate of 71%).

Fewer participants in the high-protein, low-GI groups dropped out of the project than in the low-protein, high-GI group (26.4% and 25.6%, respectively, vs. 37.4%; P = 0.02 and P = 0.01 for the two comparisons, respectively). The initial weight loss on the 800-kcal diet was an average of 11.0 kg.

The average weight regain among all participants was 0.5 kg, but among the participants who completed the study, those in the low-protein/high-GI group showed the poorest results with a significant weight gain of 1.67 kg. The weight regain was 0.93 kg less for participants on a high-protein diet than for those on a low-protein diet and 0.95 kg less in the groups on a low-GI diet compared to those on a high-GI diet.

The children's study

The results of the children's study have been published in a separate article in Pediatrics. In the families, there were 827 children who only participated in the diet intervention. Thus, they were never required to go on a diet or count calories – they simply followed the same diet as their parents. Approx. 45% of the children in these families were overweight. The results of the children's study were remarkable: In the group of children who maintained a high-protein, low-GI diet the prevalence of overweight dropped spontaneously from approx. 46% to 39% – a decrease of approx. 15%.

Proteins and low-GI foods ad libitum – the way ahead

The Diogenes study shows that the current dietary recommendations are not optimal for preventing weight gain among overweight people. A diet consisting of a slightly higher protein content and low-GI foods ad libitum appears to be easier to observe and has been documented to ensure that overweight people who have lost weight maintain their weight loss. Furthermore, the diet results in a spontaneous drop in the prevalence of overweight among their children.

Citation: Thomas Meinert Larsen, Ph.D., Stine-Mathilde Dalskov, M.Sc., Marleen van Baak, Ph.D., Susan A. Jebb, Ph.D., Angeliki Papadaki, Ph.D., Andreas F.H. Pfeiffer, M.D., J. Alfredo Martinez, Ph.D., Teodora Handjieva-Darlenska, M.D., Ph.D., Marie Kunešová, M.D., Ph.D., Mats Pihlsgård, Ph.D., Steen Stender, M.D., Ph.D., Claus Holst, Ph.D., Wim H.M. Saris, M.D., Ph.D., and Arne Astrup, M.D., Dr.Med.Sc. for the Diet, Obesity, and Genes (Diogenes) Project, 'Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance', N Engl J Med 2010; 363:2102-2113 November 25, 2010

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