New Research Developments in the News

New Study Shows Iron Supplements Help Only Certain Women

This story has been adapted from a news release issued by Cornell University News Service web site and may be viewed at  http://www.news.cornell.edu/releases/May04/lowiron.endurance.ssl.html

About 10 to 12 percent of U.S. women and 40 to 80 percent of women in developing countries are iron deficient but not anemic, yet most are unaware of their condition. The new study provides mounting evidence that mild to moderate iron depletion should be of greater concern.

It has long been known that iron-deficiency anemia compromises physical work capacity because of decreased oxygen delivery to the working muscles and decreased ability to produce energy at the tissue level.

A new study by Cornell University nutritionists published in the American Journal of Clinical Nutrition (2004; 79:437-43), is the first to show differences between the physical abilities of nonanemic women with low-liver vs. low-tissue iron. The researchers are also the first to show that low iron without anemia does have functional consequences in humans.

In previous work, the Cornell researchers had shown that mild iron deficiency reduces endurance, the capacity for physical work and exercise performance, and that iron supplementation improves exercise training.

"Millions of women who are mildly iron deficient must work harder than necessary when exercising or working physically, and they can't reap the benefits of endurance training very easily," says Jere Haas, the Meinig Professor of Maternal and Child Nutrition at Cornell and a co-author of the study. "As a result, exercise is more difficult so these women are more apt to lose their motivation to exercise." The new study shows among women who are not anemic, only those with tissue-iron deficiencies can benefit from taking iron supplements.

"Supplementation makes no difference in exercise-training improvements in women with low iron storage who are not yet tissue-iron deficient or anemic," says Thomas Brownlie, the first author of the study and a Cornell doctoral candidate in nutritional sciences.

Women with low body iron, but who are not anemic, may not experience any improvements following training if their tissues are low in iron. Whereas women who have low iron storage in their liver only, and who are not anemic, appear to have no functional impairments.

Forty-two iron-depleted (but not anemic) women, ages 18 to 33, participated in the six-week study. They first cycled 15 kilometers (about nine miles) on a stationary bike to determine how quickly they could complete the bout before supplementation. Then, half took iron supplements (100 milligrams of ferrous sulfate per day) while the other half took placebos. After participating in an exercise program during the final four weeks of the study, the women then cycled nine miles again.

Only the tissue-iron-deficient women who did not take iron supplements failed to significantly improve on the endurance test.

A woman's tissue iron status can be assessed with a technique called serum transferrin receptor concentration, which can be given by health professionals. "It would be useful for women who test low for iron but who are not yet anemic to have this test," says Brownlie. "Women found to be tissue-iron deficient will find exercise exceedingly difficult without improving their iron status -- which could be achieved by increasing consumption of iron-rich foods or iron supplementation."

Women who are physically active, dieting or are vegetarians are particularly at high risk for iron depletion, the researchers point out. "In developing countries, iron depletion can have dramatic consequences on a woman's ability to do physical work and make a living," says Haas. Iron is an essential component of hemoglobin in the blood and plays an important role in oxygen transport and utilization. When people consume iron-deficient diets, they first deplete stores of iron in the liver; at the final stage, they become anemic due to insufficient iron to produce new red blood cells.

To prevent iron depletion, the researchers recommend red meat; for vegetarians, they recommend consuming citrus fruit and juice (vitamin C) with meals to improve absorption from iron-rich foods, such as legumes, whole grains and green vegetables.

For a copy of the article: http://www.ajcn.org/ and in the search box, type "Brownlie"

Novel Vitamin Discovery Offers Clues for Cancer Chemotherapy and Lipid Disorders

This story has been adapted from a news release issued by Dartmouth Medical School and published on their website at http://www.dartmouth.edu/dms/news

Dartmouth Medical School cancer researchers, in a fusion of biochemistry and genetics, have discovered a new vitamin in a molecular pathway central to such vital processes as gene regulation, metabolism and aging. And, they found that milk contains this nutrient.

The work, published in the May 14 issue of Cell, defines another metabolic route to a compound called NAD and suggests that therapeutic approaches for cancer or heart disease may depend on the enzymes discovered.

NAD (nicotinamide adenine dinucleotide) is one of the most well known small molecules in the cell.  It is essential for life in all organisms, from bacteria to humans, and very versatile, working both as a partner that helps enzymes and as an ingredient that other enzymes consume, according to Dr. Charles Brenner, associate professor of genetics and of biochemistry and author of the study with Dr. Pawel Bieganowski, a postdoctoral fellow.

NAD is a co-enzyme for hundreds of cellular enzymes. Niacin, or vitamin B3, a mixture of the NAD precursors nicotinic acid and nicotinamide, which were discovered in 1938, prevents pellagra and can help control cholesterol. A class of anti-cancer drugs including tiazofurin and benzamide riboside is converted to toxic NAD analogs. And, more recently, proteins dependent on NAD have been shown to prolong life in experimental systems.

Brenner's laboratory at the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center was studying an enzyme involved in NAD synthesis that was similar to an enzyme implicated in cancer development. Their explorations revealed a novel twist. In yeast without the enzyme, every known NAD biosynthetic pathway was shut down, so in theory, the cells should die; no vitamins or supplements were known to keep the cells alive. However, the researchers discovered that another NAD precursor, nicotinamide riboside, thought to be a vitamin form of NAD only in certain bacteria, served as a vitamin in yeast and could prevent death. The researchers discovered the genes and enzymes in yeast and humans responsible for this vitamin conversion pathway and then they found the vitamin in milk.

Their findings upend some assumptions underlying biosynthetic schemes for NAD that have been in textbooks for decades and refocus the cancer pharmacology of tiazofurin and benzamide riboside. "Cancer drugs that look like nicotinamide riboside are converted to toxic NAD analogs through a pathway that is likely to be the same as our vitamin activation pathway," Brenner said.

The researchers considered nicotinamide riboside as a nutrient through its role in a bizarre bacterium, Haemophilus influenza that lives in blood. When they determined that the compound also supported the growth of yeast cells, they began a search for the yeast equivalent of the bacterial kinase enzyme that is required to begin turning it into NAD.

They used what Brenner termed a "biochemical genomics approach," taking advantage of shortcuts developed since the entire the yeast genome was sequenced. The team analyzed large yeast gene pools for the enzyme activity and quickly zeroed in on the gene for their novel kinase. Yeast has similarities to mammalian cells, and a gene or enzyme in yeast is likely to have an equivalent in humans.

"We cloned the yeast nicotinamide riboside kinase, and validated it genetically by knocking it out and seeing that the vitamin no longer supported growth," said Brenner. "We then identified two human nicotinamide riboside kinases and showed that all three have the biochemical specificity for nutrient and prodrug [precursor] activation and that all three work in vivo."

To reinforce the vitamin premise, the scientists sought the compound in a food. Testing for it nonfat milk, they separated out the curds from the whey and found it in the whey.

Brenner thinks that nicotinamide riboside may be a useful nutrient for certain metabolic disorders and that kinase screening may benefit certain cancer patients. Niacin, for example, can help lower cholesterol, but it has uncomfortable flushing effects in patients, so nicotinamide riboside supplementation may offer an alternative.

For more information, read the complete press release at http://www.dartmouth.edu/dms/news/2004_h1/13may2004_clues.shtmal