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Antioxidants lower stroke risk

Eating a diet high in antioxidants may protect against ischemic stroke, an Italian cohort study showed.

People who had a diet high in total antioxidant capacity — an index that takes into account several different antioxidants and their interactions — had a 59% reduced relative risk of ischemic stroke (HR 0.41, 95% CI 0.23 to 0.74), according to Nicoletta Pellegrini, PhD, of the University of Parma in Italy, and colleagues. But there was no such relationship with hemorrhagic stroke, they reported in the January issue of the Journal of Nutrition. In fact, the highest intake of the antioxidant vitamin E was associated with a greater risk of hemorrhagic stroke (HR 2.94, 95% CI 1.13 to 7.62).
Considering evidence suggesting that oxidative stress and systemic inflammation are involved in the pathogenesis of ischemic stroke, the researchers noted that “a high-total antioxidant capacity diet could be protective as a consequence of its ability to deliver compounds with antioxidant activity and with a demonstrated anti-inflammatory effect.” But, they acknowledged that the mechanism for such activity was unclear may “go beyond the antioxidant activity of the numerous total antioxidant capacity contributors present in foods and beverages.”

Pellegrini and her colleagues set out to explore the relationship between dietary total antioxidant capacity and the risk of stroke among 41,620 people participating in EPICOR, the Italian segment of the European Prospective Investigation into Cancer and Nutrition (EPIC). None had a history of stroke or MI at baseline. Dietary intake was assessed with a food frequency questionnaire. In the study population, more than half of the total antioxidants consumed came from coffee, wine, and fruit. Through a mean follow-up of 7.9 years, there were 112 ischemic strokes, 48 hemorrhagic strokes, and 34 other types of strokes. After adjustment for energy intake, hypertension, smoking status, education, nonalcoholic energy intake at recruitment, alcohol intake, waist circumference, body mass index, and total physical activity, individuals eating a diet in the highest tertile of total antioxidant capacity had a reduced risk of ischemic — but not hemorrhagic — stroke.

Looking at individual antioxidants, the researchers found that participants consuming the highest amounts of vitamin C had a reduced risk of ischemic stroke (HR 0.58, 95% CI 0.34 to 0.99). Controlling for vitamin C intake did not negate the overall association between antioxidants and ischemic stroke, which ruled out the nutrient as the sole driver of the relationship. High intake of vitamin E, on the other hand, was associated with nearly triple the relative risk of hemorrhagic stroke. However, “it must be stressed that the small number of cases observed in this population strongly limits the validity of statistical observations on hemorrhagic stroke,” noted the researchers, who called for further studies.

Aside from anti-inflammatory effects, it is possible that the association between antioxidants and ischemic stroke risk can be explained by the interaction between polyphenols — the major contributors to total antioxidant capacity — and the generation of nitric oxide from the vascular endothelium. That interaction leads to the vasodilation and expression of genes that may be protective for the vascular system, according to the researchers. In addition, coffee — the main source of antioxidants in the study population — reduces blood pressure, which is a recognized risk factor for ischemic stroke, the researchers wrote.

They noted some limitations of the study, including the low numbers of cases when different types of stroke were analyzed, the measurement of total antioxidant capacity at baseline only, and the inability to rule out confounding effects of other dietary components, like sodium and potassium.

Source: Del Rio D, et al “Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort” J Nutr 2011; 141: 118-123.

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Red meat increases women stroke risk

Women consuming too much red meat may have a higher risk of stroke than women eating less, says a new study. Red meat is high in saturated fat and cholesterol; both are risk factors for cardiovascular disease, heart attack, and stroke. The United States Centers for Disease Control and Prevention suggests lowering saturated fat intake and eating more fresh fruits and vegetables to help reduce your risk of stroke. Writing in the journal Stroke, researchers examined nearly 35,000 Swedish women, ages 39 to 73. None of the women had heart disease prior to the start of the study in 1997.

After ten years, results showed 4% of the study participants, 1,680 women, had a stroke. Those consuming the most red meat had the highest risk of stroke. Women in the top tenth of red meat intake, consuming at least 3.6 ounces each day, were 42% more likely to have a stroke, compared to women who ate just under one ounce of red meat daily.

Eating processed meat also increased stroke risk. Women eating 1.5 ounces of processed meat each day were 24% more likely to suffer a cerebral infarction, compared to woman consuming less than half an ounce of processed meat each day. Processed meat was not linked to any other form of stroke. Cerebral infarction is a type of stroke caused by a disturbance in the blood vessels supplying blood to the brain. Other types of stroke involve a rupturing of a blood vessel, called hemorrhagic strokes.

The scientists blame red meat and processed meat’s effect on raising blood pressure for the increased stroke risk. According to the World Health Organization (WHO), every year an estimated 17 million people die due to cardiovascular diseases, most notably stroke and heart attack. The WHO lists physical inactivity and unhealthy diet as the main risk factors for heart disease and major cardiac events.

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Simple steps to prevent cancer

About a third of some of the most common forms of cancer could be prevented through healthy diet, physical fitness, and limiting alcohol intake, the American Institute for Cancer Research and the World Cancer Research Fund say in a new report. About 7.6 million people die from cancer every year worldwide, and 12.7 million new cases are diagnosed. According to the Union for International Cancer Control, a third of cancer cases could be cured through early diagnosis and treatment and 30% to 40% could be prevented. About 340,000 cases of cancer could be prevented annually in the U.S. if more people started eating a varied and healthy diet, started a regimen of physical activity, limited alcohol intake, and maintained a healthy weight, the new report says.

“Physical activity is recommended for people of all ages as a means to reduce risks for certain types of cancers and other non-communicable diseases,” says Tim Armstrong, MD, of the World Health Organization, says in a news release. “In order to improve their health and prevent several diseases, adults should do at least 150 minutes moderate physical activity throughout the week. This can be achieved by simply walking 30 minutes five times per week or by cycling to work daily.”

To reduce cancer risk, people also should quit smoking, avoid excessive sun exposure, and protect themselves against cancer-causing infections.

Tim Byers, MD, MPH, of the Colorado School of Public Health, says scientists urge Americans “to make the simple lifestyle changes of eating healthy food, getting regular physical activity, and maintaining a healthy weight to reduce cancer risk.” The World Cancer Declaration outlines 11 targets it says could be achieved by 2020 to fight cancer. These goals include: significant drops in global tobacco use, obesity, and alcohol intake; universal vaccination programs for hepatitis B and human papilloma virus (HPV); universal availability of effective pain medication; and efforts to dispel misconceptions about cancer. The health organizations say in a detailed report that the most common cancers in the U.S. and Britain are of the breast, colon/rectum, lung, and prostate.

The American Institute for Cancer Research recommends the following cancer-prevention steps.

  • Limit consumption of calorie-dense foods, particularly processed foods high in added sugar, low in fiber, or high in fat.
  • Avoid sugary drinks.
  • Eat more of a variety of vegetables, fruits, whole grains, and beans.
  • Limit consumption of red meats such as beef, pork, and lamb, and avoid processed meats.
  • Limit consumption of salty foods and foods processed with sodium.
  • Dietary supplements for lowering cancer risk are not recommended.
  • Be as lean as possible without becoming underweight.
  • Be physically active for 30 minutes or more every day.
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‘No evidence’ for Vitamin B allergy

Consumption of Vitamin B during pregnancy does not increase the risk of allergy in the infants, says a new study from Japan that challenges previous findings. Maternal consumption of folate and vitamins B2, B6, and B12 during pregnancy was not associated with the risk of the infant developing asthma or eczema, according to findings from 763 infants published in Pediatric Allergy and Immunology.

Contradictory science

The link between folate and folic acid, the synthetic form of the vitamin, and respiratory health is not clear cut, with contradictory results reported in the literature. A study from Johns Hopkins Children’s Center found that higher levels of folate were associated with a 16 per cent reduction of asthma in (Journal of Allergy & Clinical Immunology, June 2009, Vol. 123, pp. 1253-1259.e2). However, a Norwegian study reported that folic acid supplements during the first trimester were associated with a 6 per cent increase in wheezing, a 9 per cent increase in infections of the lower respiratory tract, and a 24 per cent increase in hospitalisations for such infections, (Archives of Diseases in Childhood, doi:10.1136/adc.2008.142448). In addition, researchers from the University of Adelaide in Australia reported that folic acid supplements in late pregnancy may increase the risk of asthma by about 25 per cent in children aged between 3 and 5 years (American Journal of Epidemiology, 2010, doi:10.1093/aje/kwp315).

Illumination from the Land of the Rising Sun?

The new study, performed by researchers from Fukuoka University, the University of Tokyo, and Osaka City University, goes beyond folate and folic acid, and reports no link between Vitamin B intake and the risk of asthma or eczema in children. “To the best of our knowledge, there has been no birth cohort study on the relationship between maternal consumption of Vitamin B during pregnancy and the risk of allergic disorders in the offspring,” wrote the researchers. The findings were based on data from 763 pairs of Japanese mother and child. A diet history questionnaire was used to assess maternal intakes of the various B vitamins during pregnancy, and the infants were followed until the age of 16 to 24 months. Japan has no mandatory fortification of flour with folic acid.

Results showed that, according to criteria from the International Study of Asthma and Allergies in Childhood, 22 and 19 percent of the children had symptoms of wheeze and eczema, respectively, but there was no association between these children and the dietary intakes of the various B vitamins by their mothers. “Our results suggest that maternal intake of folate, vitamin B12, vitamin B6, and vitamin B2 during pregnancy was not measurably associated with the risk of wheeze or eczema in the offspring,” said the researchers. “Further investigation is warranted to draw conclusions as to the question of whether maternal Vitamin B intake during pregnancy is related to the risk of childhood allergic,” they concluded.

According to the European Federation of Allergy and Airway Diseases Patients Association (EFA), over 30m Europeans suffer from asthma, costing Europe €17.7bn every year. The cost due to lost productivity is estimated to be around €9.8bn. The condition is on the rise in the Western world and the most common long-term condition in the UK today. According to the American Lung Association, almost 20m Americans suffer from asthma. The condition is reported to be responsible for over 14m lost school days in children, while the annual economic cost of asthma is said to be over $16.1bn.

Source: Pediatric Allergy and Immunology. Volume 22, Issue 1-Part-I, February 2011, Pages: 69–74 DOI: 10.1111/j.1399-3038.2010.01081.x
“Maternal B vitamin intake during pregnancy and wheeze and eczema in Japanese infants aged 16–24 months: The Osaka Maternal and Child Health Study”. Authors: Y. Miyake, S. Sasaki, K. Tanaka, Y. Hirota

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Sugary Drinks, Foods Might Put Teens at Risk for Heart Disease

Teens whose diets include lots of sugary drinks and foods show physical signs that they are at increased risk for heart disease as adults, researchers from Emory University report. Among 2,157 teens who took part in the National Health and Nutrition Examination Survey, the average amount of added sugar eaten in a day was 119 grams (476 calories), which was 21.4 percent of all the calories these teens consumed daily, the researchers noted. “We need to be aware of sugar consumption,” said lead researcher and postdoctoral fellow Jean Welsh. “It's a significant contributor of calories to our diet and there are these associations that may prove to be very negative,” she said. “Sugar-sweetened soft drinks and sodas are the major contributor of added sugar and are a major source of calories without other important nutrients.” Awareness of the negative effects of added sugar may help people, particularly teens, cut down on the amount of sugar they consume, Welsh added. “Parents and adolescents need to become aware of the amount of added sugar they are consuming and be aware that there may be some negative health implications if not now, then down the line,” she said.

The report is published in the Jan. 10 online edition of Circulation.

Welsh's team found that teens who consumed the most added sugar had 9 percent higher LDL (“bad”) cholesterol levels, and 10 percent higher triglyceride levels (another type of blood fat), compared with those who consumed the least added sugar. Teens who took in the highest amount of added sugar also had lower levels of HDL (“good”) cholesterol than those who consumed the least amount of added sugar. In addition, teens who consumed the highest amount of added sugar showed signs of insulin resistance, which can lead to diabetes and its associated risk of heart disease, the researchers found.

The American Heart Association has recommended an upper limit for added sugars intake, based on the number of calories you need. “Most American women [teens included] should consume no more than 100 calories of added sugars per day; most men, no more than 150 calories,” the association states.

One caveat to these findings is that because of the way the study was done it is not clear if added sugars caused the differing cholesterol levels, only that they are linked. In addition, the data are only for one day and may not reflect the teen's usual diet, the researchers noted. Commenting on the study, Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, said that “this study does not prove that dietary sugar is a cardiac risk factor in this population, but it strongly suggests it.”

The paper has three important messages, he said. First, dietary sugar intake in a representative population of teenagers is nearly double the recommended level. Second, the higher the intake of sugar, the greater the signs of cardiac risk, including elevated LDL (“bad”) cholesterol and low HDL (“good”) cholesterol. Third, the apparent harms of excess sugar are greater in overweight than in lean adolescents.

“Sugar is by no means the sole dietary threat to the health of adolescents, or adults,” Katz said. “But we now have evidence it certainly counts among the important threats to both. Reducing sugar intake by adolescents, to prevent them becoming adults with diabetes or heart disease, is a legitimate priority in public health nutrition,” he said.

SOURCES: HealthDay; Jean Welsh, M.P.H., Ph.D., R.N., postdoctoral fellow, Emory University, Atlanta; David L. Katz, M.D., M.P.H., director, Prevention Research Center, Yale University School of Medicine, New Haven, Conn.; Jan. 10, 2011, Circulation, online

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The deadliest diets : 10 year study

Two specific eating patterns increase the risk of death for older adults, a 10-year study finds.Compared to people who ate healthy foods, men and women in their 70s had a 40% higher risk of death if they got most of their calories from high-fat dairy foods or from sweets and desserts. University of Maryland researcher Amy L. Anderson, PhD, and colleagues monitored the eating patterns of 2,582 adults aged 70 to 79. They found that these diets fell into six patterns or clusters.

After adjusting for risk factors such as sex, age, race, education, physical activity, smoking, and total calories, “the High-Fat Dairy Products cluster and the Sweets and Desserts cluster still showed significantly higher risk of mortality than the Healthy Foods cluster,” Anderson and colleagues found.

The six dietary patterns were:

  • Healthy Foods: Higher intake of low-fat dairy products, fruit, whole grains, poultry, fish, and vegetables. Lower intake of meat, fried foods, sweets, high-energy drinks, and added fat.
  • High-Fat Dairy Products: Higher intake of ice cream, cheese, and 2% and whole milk and yogurt. Lower intake of poultry, low-fat dairy products, rice, and pasta.
  • Sweets and Desserts: Higher intake of doughnuts, cake, cookies, pudding, chocolate, and candy. Lower intake of fruit, fish and other seafood, and dark green vegetables.
  • Meat, Fried Foods, and Alcohol: Higher intake of beer, liquor, fried chicken, mayonnaise/salad dressings, high-energy density drinks, nuts, snacks, rice/pasta dishes, and added fat. Lower intake of low-fat dairy products, fiber/bran breakfast cereal, and other breakfast cereal.
  • Breakfast Cereal: Higher intake of fiber/bran and other breakfast cereals (especially the latter). Low intake of nuts, refined grains, dark yellow vegetables, and dark green vegetables.
  • Refined Grains: Higher intake of refined grains (such as pancakes, waffles, breads, muffins, and cooked cereals such as oatmeal) and processed meat (such as bacon, sausage, ham, and other lunchmeats). Lower intake of liquor, breakfast cereals, and whole grains.

Several of the groups got an unusually large amount of their total calories from just one food group:

The sweets and desserts cluster got 25.8% of its total energy from sweets.The refined grains cluster got 24.6% of its total energy from refined grains.The breakfast cereal group got 19.3% of its total energy from cold cereals other than those full of fiber and bran.The high-fat dairy products group got 17.1% of its total energy from higher-fat dairy foods.

Overall, people in the healthy foods cluster had more years of healthy life and a lower death rate than all other groups. Moreover, their blood tests came back with significantly more indicators of health than the other groups.

But not all of the study findings were so predictable. “Unexpectedly, in this and in several other studies, a [dietary] pattern higher in red meat was not significantly associated with increased risk of mortality,” Anderson and colleagues note. It's also not entirely clear why the Meat, Fried Food, and Alcohol cluster didn't have a significantly higher death risk, as most diets warn people to limit or avoid such foods.

“In our study, the Meat, Fried Food, and Alcohol cluster did have a slightly higher percentage of total energy from vegetables, fruit, and whole grains than both the High-Fat Dairy Products and Sweets and Desserts clusters, which showed higher risk of mortality,” Anderson and colleagues suggest.

This was by far the most common eating pattern seen in the study: 27% of participants were in the meat, fried food, and alcohol cluster. But Anderson and colleagues do not recommend such a diet. Instead, they point to the fact that 14.5% of study participants were in the healthy foods cluster. “Adherence to such a diet appears a feasible and realistic recommendation for potentially improved survival and quality of life in the growing older adult population,” Anderson and colleagues conclude.

The study appears in the January 2011 issue of the Journal of the American Dietetic Association.
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White rice increases diabetes risk

Japanese women who eat three or more bowls of rice a day face a 50 percent greater risk of developing diabetes than those who eat one bowl, according to research by the National Cancer Center and other institutions. Although it has long been known that consuming large amounts of carbohydrates can increase the risk of developing the disease, the study was the first of its kind to explore the connection between eating rice and developing diabetes.

Conducted over five years from the early 1990s, the study covered about 60,000 people aged 45 to 74 in Iwate, Nagano, Ibaraki, Okinawa and four other prefectures. Of the subjects, 1,103–625 men and 478 women–developed diabetes during the study period.

Women who ate three bowls of rice a day were 1.48 times more likely to develop diabetes than those who ate one serving daily, the study found. Eating four or more bowls of rice a day raised the risk of women developing diabetes to 1.65 times that of women who ate only one bowl of rice a day. However, among women who performed physical labor or exercised vigorously for at least one hour a day, there was no significant difference in their risk of developing diabetes regardless of whether they habitually gorged on the grain.

For men, there was less evidence of a connection between rice intake and diabetes risk.

But regardless of gender, the less physical exercise a person did, the higher their risk of developing the disease.

While it is possible that eating a lot of rice can contribute to the onset of diabetes in some women, the study produced no conclusive evidence that overindulging is a direct cause of diabetes. Researchers at the National Center for Global Health and Medicine who analyzed the study’s results said it was important to monitor rice intake as part of maintaining a balanced diet.

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Studies support 3 glasses of milk daily

Individuals who drink three glasses of milk a day decrease their risk of cardiovascular disease by 18 percent, according to new research published in the American Journal of Clinical Nutrition.Researchers at Wageningen University and Harvard University examined 17 studies from the United States, Europe and Japan and found no link between the consumption of regular or low fat dairy and any increased risk of heart disease, stroke or total mortality. “Milk and dairy are the most nutritious and healthy foods available and loaded with naturally occurring nutrients, such as calcium, potassium and protein, to name a few,” said Cindy Schweitzer, technical director of the Global Dairy Platform. “It's about going back to the basics; maintaining a healthy lifestyle doesn't have to be a scientific equation.”

Schweitzer said during the past three decades as research sought to understand influencers of cardiovascular disease, simplified dietary advice including consuming only low fat dairy products emerged. However, in 2010 alone, a significant amount of new research was published from all over the world, supporting the health benefits of dairy. From dispelling the myth that dairy causes heart disease, to revealing dairy's weight loss-benefits, the following is a roundup of select dairy research conducted in 2010:

  • U.S. researchers examined 21 studies that included data from nearly 350,000 and concluded that dietary intakes of saturated fats are not associated with increases in the risk of either coronary heart disease or cardiovascular disease. The study was published in the American Journal of Clinical Nutrition.
  • A study published in the American Journal of Epidemiology examined 23,366 Swedish men and revealed that intakes of calcium above the recommended daily levels may reduce the risk of mortality from heart disease and cancer by 25 percent.
  • An Australian study published in the European Journal of Clinical Nutrition concluded that overall intake of dairy products was not associated with mortality. The 16-year prospective study of 1,529 Australian adults found that people who ate the most full-fat dairy had a 69-percent lower risk of cardiovascular death than those who ate the least.
  • A Danish study published in Physiology & Behavior concluded that an inadequate calcium intake during an energy restricted weight-loss program may trigger hunger and impair compliance to the diet.
  • An Israeli study published in the American Journal of Clinical Nutrition showed that a higher dairy calcium intake is related to greater diet-induced weight loss. The study sampled more than 300 overweight men and women during two years and found those with the highest dairy calcium intake lost 38-percent more weight than those with the lowest dairy calcium intake.

The amount of dairy recommended per day varies by country and is generally based on nutrition needs and food availability. “In the US and some European countries, three servings of dairy foods are recommended daily, said Dr. Schweitzer.”

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Caffeine consumption common in kids

Even young children appear to be consuming more caffeine, so much so that caffeine could be contributing to sleep problems in primary school children, researchers found. Three-quarters of children ages 5 to 12 consumed caffeine on an average day in a survey of parents at routine clinic visits by William J. Warzak, PhD, of the University of Nebraska Medical Center in Omaha, and colleagues. The more caffeine children consumed, the fewer hours they slept on average (P=0.02), the researchers reported online in the Journal of Pediatrics, although not drawing a causal link. The average intake was two or three times higher than the 22- to 23-mg daily average reported nearly a decade ago, they noted.

Eight- to 12-year-olds in Warzak's study averaged 109 mg of caffeine — the equivalent of nearly three 12-oz cans of soda each day. But even the 52 mg of caffeine consumed by 5- to 7-year-olds on an typical day was well above the level known to have a physiologic effect on adults, the researchers noted. “There's really no role for caffeine in kids,” Marcie Schneider, MD, of the Albert Einstein College of Medicine in New York City, emphasized in commenting on the study. “We know that caffeine raises your blood pressure, raises your heart rate, and can be addictive.” Unlike older teens who are likely drinking coffee to wake up in the mornings for school, the assumption is that younger kids are getting most of their caffeine from soda, noted Schneider, who serves as a member of the American Academy of Pediatrics Committee on Nutrition.

She urged pediatricians to raise parents' awareness of the issue, perhaps as part of the yearly checkup. “We routinely ask kids what they're eating and drinking,” “It may be something that is worth pediatricians pointing out to parents that this kid does not need caffeine in their life partially because it does some things that are negative.”

Warzak's group surveyed parents of 228 children seen at an urban outpatient pediatric clinic during routine visits about the children's average daily consumption of drinks and snacks with an emphasis on caffeine-containing items. None of the children had a known sleep disorder or medical condition that might cause bedwetting. Illustrated depictions were provided to help parents accurately estimate serving sizes.

Nearly all of the caffeine intake was consumed through beverages. Few children got a meaningful amount of caffeine from food. “Caffeine's diuretic properties have encouraged behavioral health practitioners to eliminate caffeine from the diet of children with enuresis,” the researchers noted. However, they found that intake didn't correlate with the number of nights a child wet the bed (P=0.49). Overall, enuresis was actually less likely in children who consumed caffeine.

The researchers cautioned that interpretation of these results may be complicated by cultural differences in reporting children's behavioral health concerns and that their study could not draw any causal conclusions. Schneider also noted the use of parental reports and the relatively small sample as limitations. Although the findings offered no support for removing caffeine from children's diets on the basis of bedwetting, Warzak's group concluded in the paper that “given the potential effects of caffeine on childhood behavior, a screen of caffeine consumption might be beneficial when evaluating childhood behavioral health concerns.”

Source: Warzak WJ, et al “Caffeine consumption in young children” J Pediatr 2011; DOI: 10.1016/j.jpeds.2010.11.022.

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Children’s sugar and fat easier to reduce than salt

Study details

Bouhlal and co workers reported that salt had an impact on intake but fat did not. They found that in general food intake increased with salt level, noting that compared with the 'normal' salt levels, a suppression of salt induced a 25 per cent decrease in green bean intake, whereas an addition of salt induced a 15 per cent increase in pasta intake. Contrarily to initial beliefs, the researchers observed no increase in food intake with increasing added sugar level. They said the findings indicate that two to three year old children's food intake may not be affected by its added sugar content.

The study data also showed that preschool children with a higher BMI score consumed more pasta when fat level was higher. The authors said this finding may confirm previous results which highlight fatter children prefer high-fat foods. The researcher said their results imply that fat and sugar addition could be avoided in foods for children without having an impact on palatability, allowing the energy density of children's diet to be limited.

“Furthermore, these findings suggest that there is no need to add salt to pasta which is consumed anyway. On the contrary, salt suppression in vegetables, whose intake is to be promoted, should be considered cautiously,” they said.

Source: British Journal of Nutrition
Published online ahead of print, doi: 10.1017/S0007114510003752
“The impact of salt, fat and sugar levels on toddler food intake”
Authors: S. Bouhlal, S. Issanchou, S. Nicklaus

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