JNCI.OxfordJournals.org - Women who have a high blood level of insulin have a higher risk of developing breast cancer than women who have a lower level of the hormone. A higher insulin level appears to be an independent risk factor for breast cancer.

Obesity is a known risk factor for postmenopausal breast cancer. This relationship usually has been attributed to the high estrogen levels in many obese postmenopausal women. Obesity, however, is also associated with high insulin levels. Until recently it has not been known whether high levels of insulin, which stimulates the growth of breast cells in tissue culture, are also associated with breast cancer. The current investigation was the first study to prospectively examine the role of insulin in breast cancer while controlling for estrogen levels.

In the current study, Marc Gunter, Ph.D., and Howard Strickler, M.D., of the Albert Einstein College of Medicine in New York, and colleagues, examined the association between incident breast cancer and baseline fasting insulin, insulin-like growth factor-1 (a related hormone), and estradiol levels in 835 women enrolled in the Women’s Health Initiative Observational Study who developed breast cancer and a randomly-selected sample of 816 women in the study who did not develop breast cancer.

When the researchers divided the women into four groups based on their fasting insulin levels, they found that women with the highest insulin levels had nearly a 1.5-fold higher risk of developing breast cancer than the women with the lowest insulin levels. Further, the investigators separately analyzed women who were not using hormone therapy and found that, in these women, those individuals with the highest insulin levels had a 2.4-fold increased risk of developing breast cancer compared to those with the lowest levels, even after accounting for multiple other breast cancer risk factors, including estrogen levels.

“These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship,” the authors conclude (Courtesy of EurekAlert!, a service of AAAS).

Lots of experts disagree over the seemingly obvious notion of keeping weight off by trying to eat less ? a debate that centers on whether the practice backfires, leading to binging and weight gain.

Now a new study shows that practicing restraint becomes more important with age.

Women who participated in the study had more than twice the risk of substantial weight gain if they did not become more restrained in their eating.

?Some suggest that restrained eating is not a good practice,? said Brigham Young University professor Larry Tucker, the study?s lead author. ?Given the environmental forces in America?s food industry, not practicing restraint is essentially a guarantee of failure.?

The study followed 192 middle-aged women for three years and tracked information on lifestyle, health and eating habits. Their analysis revealed that women who did not become more restrained with eating were 138 percent more likely to put on 6.6 pounds or more.

Columbia University researcher Lance Davidson, who was not involved with the analysis, said the findings highlight an important principle of weight management.

?Because the body’s energy requirements progressively decline with age, energy intake must mirror that decrease or weight gain occurs,? said Davidson, a research fellow at Columbia?s Obesity Research Center. ?Dr. Tucker’s observation that women who practice eating restraint avoid the significant weight gain commonly observed in middle age is an important health message.?

Tucker says watching what you eat is not about physical appearance ? it?s a direct investment in your health.

?Weight gain and obesity bring a greater risk of diabetes and a number of other chronic diseases,? Tucker said. ?Eating properly is a skill that needs to be practiced.?

The study will be published January 2, 2009 in the American Journal of Health Promotion.

Professor Tucker?s Tips for Better Eating:
- Record what you eat and how much
- Put less food on your plate
- Eat more fruits and vegetables; the food pyramid recommends at least five servings per day (Newswise).

Researchers at the University Of Southern California, School Of Dentistry release results of clinical data that links oral bisphosphonates to increased jaw necrosis. The study is among the first to acknowledge that even short-term use of common oral osteoporosis drugs may leave the jaw vulnerable to devastating necrosis, according to the report appearing in the January 1, 2009 Journal of the American Dental Association (JADA).

Osteoporosis currently affects 10 million Americans. Fosamax is the most widely prescribed oral bisphosphonate, ranking as the 21st most prescribed drug on the market since 2006, according to a 2007 report released by IMS Health.

?Oral Bisphosphonate Use and the Prevalence of Osteonecrosis of the Jaw: An Institutional Inquiry? is the first large institutional study in the U.S. to investigate the relationship between oral bisphosphonate use and jaw bone death, said principal investigator Parish Sedghizadeh, assistant professor of clinical dentistry with the USC School of Dentistry.

After controlling for referral bias, nine of 208 healthy School of Dentistry patients who take or have taken Fosamax for any length of time were diagnosed with osteonecrosis of the jaw (ONJ). The study?s results are in contrast to drug makers? prior assertions that bisphosphonate-related ONJ risk is only noticeable with intravenous use of the drugs, not oral usage, Sedghizadeh said. ?We?ve been told that the risk with oral bisphosphonates is negligible, but four percent is not negligible,? he said.

Most doctors who have prescribed bisphosphonates have not told patients about any oral health risks associated with the use of the drugs, despite even short-term usage posing a risk due to the drug?s tenacious 10-year half life in bone tissue. Lydia Macwilliams of Los Angeles said no one told her about the risk posed by her three years of Fosamax usage until she became a patient of Sedghizadeh at the School of Dentistry. ?I was surprised,? she said. ?My doctor who prescribed the Fosamax didn?t tell me about any possible problems with my teeth.?

Macwilliams was especially at risk for complications because she was to have three teeth extracted. The infection is a biofilm bacterial process, meaning that the bacteria infecting the mouth and jaw tissues reside within a slimy matrix that protects the bacteria from many conventional antibiotic treatments, and bisphosphonate use may make the infection more aggressive in adhering to the jaw, Sedghizadeh said. The danger is especially pronounced with procedures that directly expose the jaw bone, such as tooth extractions and other oral surgery. After her extractions, two of the three extraction sites had difficulty healing due to infection, Macwilliams said. Luckily, with treatment as well as the rigorous oral hygiene regimen USC dentists developed especially for patients with a history of bisphosphonate usage, the remaining sites slowly but fully healed. ?It took about a year to heal,? she said, ?but it?s doing just fine now.?

Sedghizadeh hopes to have other researchers confirm his findings and thus encourage more doctors and dentists to talk with patients about the oral health risks associated with the widely used drugs. The results confirm the suspicions of many in the oral health field, he said. ?Here at the School of Dentistry we?re getting two or three new patients a week that have bisphosphonate-related ONJ,? he said, ?and I know we?re not the only ones seeing it? (Newswise).

Antioxidant supplementation was found to be effective in relieving pain and reducing levels of oxidative stress in patients with chronic pancreatitis (CP), reports a new study in Gastroenterology. CP is a progressive inflammatory disease of the pancreas in which patients experience abdominal pain (in early stage) and diabetes and maldigestion (in late stage). Pain is the major problem in 90 percent of patients with chronic pancreatitis and currently, there is no effective medical therapy for pain relief. Gastroenterology is the official journal of the American Gastroenterological Association (AGA) Institute.

In this placebo-controlled, double blind trial, 127 patients, ages 30.5+/-10.5, were assigned to placebo or antioxidant groups. After six months, the reduction in the number of painful days per month was significantly higher in the antioxidant group, compared with the placebo group (7.4?6.8 versus 3.2?4, respectively). The reduction in the number of analgesic tablets used per month was also higher in the antioxidant group (10.5?11.8 versus 4.4?5.8, respectively). Furthermore, 32 percent and 13 percent of patients became pain free in the antioxidant and placebo groups, respectively; the beneficial effect of antioxidants on pain relief was noted early at three months.

“Abdominal pain, the predominant symptom in patients with CP, is difficult to treat. The main reason for a largely ineffective medical treatment is that the mechanism of pain in CP is not well understood,” said Pramod Kumar Garg, MD, DM, of the All India Institute of Medical Sciences, New Delhi and lead author of the study. “We are encouraged by our findings, as significant improvement was noted with antioxidants in respect to all the parameters of pain in this study. In addition, reduction in pain resulted in fewer man-days lost, thus providing functional employment gain to the patients. The findings should spur further research in this exciting area.”

There are two important implications of this study - the fact that measures of oxidative stress were increased initially and decreased subsequently after supplementation with antioxidants suggests that there is a state of heightened free radical mediated injury in chronic pancreatitis, and that injury is reversible. Second, with regard to pain management, this trial showed that antioxidant therapy is effective for pain relief in patients with CP. This assumes significance since no effective medical therapy exists for pain relief for such patients.

Pancreatitis is inflammation of the pancreas that usually begins as a sudden attack and is often caused by gallstones, alcohol abuse or genetic mutations. Symptoms of pancreatitis start with a gradual or sudden severe pain in the center part of the upper abdomen going through to the back. Treatment often focuses on the nutritional and metabolic needs of the patient and on relieving pain. Most people with chronic pancreatitis have a good prognosis if they follow their treatment regimen. “Aside from medication, abstaining from alcohol and smoking are most important and key to halt the progression of CP,” added Dr. Garg (Courtesy of EurekAlert!, a service of AAAS).

AACR.org - An natural extract from grape seeds forces laboratory leukemia cells to commit cell suicide, according to researchers from the University of Kentucky. They found that within 24 hours, 76 percent of leukemia cells had died after being exposed to the commercially available extract. Grape seed extract - high in proanthocyanidins - has long been available over-the-counter in the US as a dietary supplement.

The investigators, who report their findings in the January 1, 2009 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, also teased apart the cell signaling pathway associated with use of grape seed extract that led to cell death, or apoptosis. They found that the extract activates JNK, a protein that regulates the apoptotic pathway.

While grape seed extract has shown activity in a number of laboratory cancer cell lines, including skin, breast, colon, lung, stomach and prostate cancers, no one had tested the extract in hematological cancers nor had the precise mechanism for activity been revealed.

?These results could have implications for the incorporation of agents such as grape seed extract into prevention or treatment of hematological malignancies and possibly other cancers,? said the study?s lead author, Xianglin Shi, Ph.D., professor in the Graduate Center for Toxicology at the University of Kentucky.

?What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grape seed extract fits into this category,? he said.

Shi adds, however, that the research is not far enough along to suggest that people should eat grapes, grape seeds, or grape skin in excess to stave off cancer. ?This is very promising research, but it is too early to say this is chemo-protective.?

Hematological cancers ? leukemia, lymphoma and myeloma ? accounted for an estimated 118,310 new cancer cases and almost 54,000 deaths in 2006, ranking these cancers as the fourth leading cause of cancer incidence and death in the U.S.

Given that epidemiological evidence shows that eating vegetables and fruits helps prevent cancer development, Shi and his colleagues have been studying chemicals known as proanthocyanidins in fruits that contribute to this effect. Proanthocyanidins are related to natural plant chemicals sometimes referred to as polyphenols or flavonoids. Shi has found that apple peel extract contains these flavonoids, which have antioxidant activity, and which cause apoptosis in several cancer cell lines but not in normal cells. Based on those studies, and findings from other researchers that grape seed extract reduces breast tumors in rats and skin tumors in mice, they looked at the effect of the compound in leukemia cells.

Using a commercially available grape seed extract, Shi exposed leukemia cells to the extract in different doses and found the marked effect in causing apoptosis in these cells at one of the higher doses.

They also discovered that the extract does not affect normal cells, although they don?t know why.

The researchers then used pharmacologic and genetic approaches to determine how the extract induced apoptosis. They found that the extract strongly activated the JNK pathway, which then led to up-regulation of Cip/p21, which controls the cell cycle.

They checked this finding by using an agent that inhibited JNK, and found that the extract was ineffective. Using a genetic approach ? silencing the JNK gene ? also disarmed grape seed extract?s lethal attack in leukemia cells.

?This is a natural compound that appears to have relatively important properties,? Shi said.

Indulgence in a high-fat diet can not only lead to overweight because of excessive calorie intake, but also can affect the balance of circadian rhythms ? everyone’s 24-hour biological clock, Hebrew University of Jerusalem researchers have shown.

The biological clock regulates the expression and/or activity of enzymes and hormones involved in metabolism, and disturbance of the clock can lead to such phenomena as hormone imbalance, obesity, psychological and sleep disorders and cancer.

While light is the strongest factor affecting the circadian clock, Dr. Oren Froy and his colleagues of the Institute of Biochemistry, Food Science and Nutrition at the Hebrew University’s Robert H. Smith Faculty of Agriculture, Food and Environment in Rehovot, have demonstrated in their experiments with laboratory mice that there is a cause-and-effect relation between diet and biological clock imbalance.

To examine this thesis, Froy and his colleagues, Ph.D. student Maayan Barnea and Zecharia Madar, the Karl Bach Professor of Agricultural Biochemistry, tested whether the clock controls the adiponectin signaling pathway in the liver and, if so, how fasting and a high-fat diet affect this control. Adiponectin is secreted from differentiated adipocytes (fat tissue) and is involved in glucose and lipid metabolism. It increases fatty acid oxidation and promotes insulin sensitivity, two highly important factors in maintaining proper metabolism.

The researchers fed mice either a low-fat or a high-fat diet, followed by a fasting day, then measured components of the adiponectin metabolic pathway at various levels of activity. In mice on the low-fat diet, the adiponectin signaling pathway components exhibited normal circadian rhythmicity. Fasting resulted in a phase advance. The high-fat diet resulted in a phase delay. Fasting raised and the high-fat diet reduced adenosine monophosphate-activated protein kinase (AMPK) levels. This protein is involved in fatty acid metabolism, which could be disrupted by the lower levels.

In an article soon to be published by the journal Endocrinology, the researchers suggest that this high-fat diet could contribute to obesity, not only through its high caloric content, but also by disrupting the phases and daily rhythm of clock genes. They contend also that high fat-induced changes in the clock and the adiponectin signaling pathway may help explain the disruption of other clock-controlled systems associated with metabolic disorders, such as blood pressure levels and the sleep/wake cycle (Courtesy of EurekAlert!, a service of AAAS).