New Study Shows Women's Metabolism Slowed By A Combination Of Stress And High-Fat Meals

Dr. Enrique Jacome

A new study in women suggests that experiencing one or more stressful events the day before eating a single high-fat meal can slow the body's metabolism, potentially contributing to weight gain.

Researchers questioned study participants about the previous day's stressors before giving them a meal consisting of 930 calories and 60 grams of fat. The scientists then measured their metabolic rate - how long it took the women to burn calories and fat - and took measures of blood sugar, triglycerides, insulin and the stress hormone cortisol.

On average, the women in the study who reported one or more stressors during the previous 24 hours burned 104 fewer calories than non-stressed women in the seven hours after eating the high-fat meal - a difference that could result in weight gain of almost 11 pounds in one year.

The stressed women also had higher levels of insulin, which contributes to the storage of fat, and less fat oxidation - the conversion of large fat molecules into smaller molecules that can be used as fuel. Fat that is not burned is stored.

"This means that, over time, stressors could lead to weight gain," said Jan Kiecolt-Glaser, professor of psychiatry and psychology at The Ohio State University and lead author of the study. "We know from other data that we're more likely to eat the wrong foods when we're stressed, and our data say that when we eat the wrong foods, weight gain becomes more likely because we are burning fewer calories."

Previous research also has shown that people who experience stress and other mood disruptions are at higher risk of becoming overweight or obese. This study, the researchers say, appears to illustrate at least one mechanism behind that connection.

The research is published in the journal Biological Psychiatry.

The study was conducted in 58 women, average age 53, and included two admissions to Ohio State's Clinical Research Center for daylong analyses. To regulate their food intake for 24 hours before eating the high-fat meal, researchers supplied the participants with three standardized meals on the previous day and instructed them to fast for 12 hours before reporting for their study visit.

On the day of admission, the participants completed several questionnaires to assess their depressive symptoms and physical activity and were interviewed about stressful events on the prior day. Thirty-one women reported at least one prior day stressor on one visit and 21 reported stressors at both visits. Six women reported no stressors.

Most of the reported stressors were interpersonal in nature: arguments with co-workers or spouses, disagreements with friends, trouble with children or work-related pressures.

The research meal consisted of eggs, turkey sausage, biscuits and gravy - roughly equivalent in calories and fat to a loaded two-patty hamburger and French fries at a fast-food restaurant. Participants were required to eat the entire meal within 20 minutes.

"This is not an extraordinary meal compared to what many of us would grab when we're in a hurry and out getting some food," said Kiecolt-Glaser, also director of the Institute for Behavioral Medicine at Ohio State.

The control for comparison in this randomized trial was that one meal contained saturated fat and another was high in a different kind of fat: sunflower oil containing monounsaturated fat, which is associated with a variety of health benefits.

"We suspected that the saturated fat would have a worse impact on metabolism in women, but in our findings, both high-fat meals consistently showed the same results in terms of how stressors could affect their energy expenditure," said Martha Belury, professor of human nutrition at Ohio State and a co-author of the study.

Before the meal, participants rested for 30 minutes and their energy expenditure - or calories burned by converting food to energy - was tested during that time. After they ate their meal, their metabolic rate was tested for 20 minutes of every hour for the next seven hours. Researchers obtained this data by using equipment that measured inhaled and exhaled airflow of oxygen and carbon dioxide.

"By measuring the gas exchange, we can determine their metabolic rate: how much energy their body needs during the time being measured," Belury said. "The participants burned fewer calories over the seven hours after the meal when they had a stressor in their life the day before the meal."

Researchers also took multiple blood samples "so we could follow throughout the day what was happening metabolically after eating the high-fat meal," Kiecolt-Glaser said.

The stressors' effects of increasing insulin had a time element: Insulin spiked soon after the high-fat meal was consumed and then decreased to roughly match insulin levels in nonstressed women after another 90 minutes.

A history of depression alone did not affect metabolic rate, but depression combined with previous stressors led to a steeper immediate rise in triglycerides after the meal. Triglycerides are a form of fat in the blood, and high levels are considered a risk for cardiovascular disease.

"With depression, we found there was an additional layer. In women who had stress the day before and a history of depression, triglycerides after the meal peaked the highest," Kiecolt-Glaser said. "The double whammy of past depression as well as daily stressors was a really bad combination."

The researchers are reluctant to extend these findings to men because men tend to have more muscle than women, which would affect their metabolic rate, Belury said.

But the findings do offer one more motivation to keep healthful foods nearby.

"We know we can't always avoid stressors in our life, but one thing we can do to prepare for that is to have healthy food choices in our refrigerators and cabinets so that when those stressors come up, we can reach for something healthy rather than going to a very convenient but high-fat choice," Belury said.

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Study Shows Puberty In Girls Is Timed By Genes From One Parent

Dr. Enrique Jacome

A large international study finds that the age at which girls reach puberty - marked by the timing of their first menstrual period - is decided by a small subset of genes they inherit from one parent. For the study, published in the journal Nature, scientists from 166 research centers worldwide analyzed data on over 180,000 women.

One of the investigating centers was the University of Cambridge in the UK.Senior author and pediatrician Dr. Ken Ong, of Cambridge's Medical Research Council (MRC) Epidemiology Unit, says:

"There is a remarkably wide diversity in puberty timing - some girls start at age 8 and others at 13. While lifestyle factors such as nutrition and physical activity do play a role, our findings reveal a wide and complex network of genetic factors."

Previous studies show that the timing of puberty in girls is a trait that is inherited, varies widely among individuals, and is linked to risks for obesity, type 2 diabetes, heart disease, breast cancer, and early death.

However, the underlying mechanisms that determine the timing of puberty, and how they link to disease, are not clear.

This study examines data from 57 studies that had analyzed the DNA of 182,416 women of European descent, and identifies 123 gene variants linked to timing of first menstrual cycle.

When a child is conceived, he or she has a new genome made of pairs of genes. Each pair of genes has one version from the biological mother and the other from the biological father.

The "usual" rule is that the two copies of a gene are expressed equally in the new individual. For example, if a child inherits a gene for blood group A from one parent, and the gene for blood group B from the other, the child's blood group will be AB.

But there are subsets of genes, called "imprinted" genes, that do not follow these equal expression rules. In imprinted genes, only one version, either the one inherited from the mother, or the one inherited from the father, is expressed. The other gene is effectively silenced with a chemical tag.

Six of the variants linked to puberty in girls are 'imprinted' genes

The researchers in this new study discovered that six of the 123 gene variants linked to timing of first menstrual cycle in girls are clustered within imprinted regions of the genome.

Lead author Dr. John Perry, Senior Investigator Scientist in the Cambridge MRC Epidemiology Unit says:

"Our findings imply that in a family, one parent may more profoundly affect puberty timing in their daughters than the other parent."

The parent the gene comes from appears to determine the activity of imprinted genes. Some genes are only active if the mother's copy is expressed, while others are only active if the father's copy is expressed.

The study finds both types influence puberty timing in girls, suggesting a potential conflict between the parents' genes over their child's rate of development.

The researchers found more evidence to support the idea of imbalance between the father's and the mother's genes from analyzing data on another 35,000 women in Iceland.

This is the first study to show imprinted genes can influence development after birth:

"We knew that some imprinted genes control antenatal growth and development," Dr. Perry explains, "but there is increasing interest in the possibility that imprinted genes may also control childhood maturation and later life outcomes, including disease risks."

Dr. Ong says they will continue to study these factors "to understand how early puberty in girls is linked to higher risks of developing diabetes, heart disease and breast cancer in later life - and to hopefully one day break this link."

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Study Shows New, Successful IVF Technique Could Make Treatment Safer

Dr. Enrique Jacome

Approximately 3% of infertile women in the US undergo IVF in an attempt to get pregnant. But for some, such treatment can result in severe side effects. Now, a new study published in the Journal of Clinical Investigation details a new, safer technique that has been found to successfully boost ovulation in women undergoing IVF, resulting in 12 newborn babies.

Around 1 in 8 couples in the US have problems getting pregnant or sustaining a pregnancy, and around a third of these cases are attributable to the female partner. Most infertility cases are treated with medication or surgery, but when these fail, assisted reproductive therapies - such as IVF (in vitro fertilization) - become an option.

IVF involves manually inserting sperm into an egg in a laboratory dish. If fertilization is successful, the embryo is then physically placed in the uterus. Prior to this procedure, patients may be required to take injectable fertility drugs - such as a hormone called hCG - to trigger egg production.

But the research team, led by Prof. Waljit Dhillo of the Department of Medicine at Imperial College London in the UK, notes that as a result of such drugs, some IVF patients experience ovarian hyperstimulation syndrome (OHSS).

OHSS is a condition that triggers overstimulation of ovaries, causing them to become swollen and painful. In some cases, women may experience rapid weight gain, shortness of breath, abdominal pain and vomiting.

"OHSS is a major medical problem," says Prof. Dhillo. "It can be fatal in severe cases and it occurs in women undergoing IVF treatment who are otherwise very healthy."

Kisspeptin results in 'good outcome' compared with standard IVF treatment

For their study, Prof. Dhillo and colleagues tested a naturally occurring hormone called kisspeptin on 53 women undergoing IVF to see whether it could trigger ovulation induction in a safe and effective manner.

After each woman received one injection of kisspeptin, 51 out of 53 developed mature eggs, and 49 had either one or two fertilized embryos that could be transferred to the uterus. Of these women, 12 became pregnant, which the researchers say is a "good outcome" when compared with standard IVF therapy using hCG.

One of the participants, Alison Harper, gave birth to a baby boy, Owen, in October last year. She says that after several cycles of IVF, the one used in this study was the least uncomfortable, causing less pain and swelling.

The research team explains that kisspeptin does not stay in the blood for long periods like hCG. This means the hormone is broken down faster, reducing the occurrence of ovary overstimulation.

Commenting on the team's findings, Prof. Dhillo says:

"Our study has shown that kisspeptin can be used as a physiological trigger for egg maturation in IVF therapy. It's been a joy to see 12 healthy babies born using this approach. We will now be doing more studies to test whether kisspeptin reduces the risk of OHSS in women who are most prone to developing it, with a view to improving the safety of IVF therapy."

The researchers now plan to conduct a second study among women with polycystic ovary syndrome, who have the highest risk of OHSS as a result of treatment with fertility medication.

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For Women Taking Certain Kinds Of Pain Relievers, A Heart Attack Could Be Waiting In Their Medicine Cabinets

Dr. Enrique Jacome

A University of Florida study has found that the regular use of some non-steroidal anti-inflammatory drugs, or NSAIDs, increases the risk of stroke, heart attack and death in postmenopausal women. The study was published this week in the journal Circulation: Cardiovascular Quality and Outcomes.

The researchers found that regular use of the NSAID naproxen, the active ingredient in medications such as Aleve, is associated with a 10 percent increased risk of heart attack, stroke and death in postmenopausal women, said UF cardiologist Anthony Bavry, M.D., the study's lead author. Regular use was defined as at least twice per week for the previous two weeks.

"That is counter to the medical community's perception of NSAIDs, in which most people believe naproxen to be safer," Bavry said. "Our study showed naproxen was not safer - it was actually harmful."

Bavry, in collaboration with researchers from Harvard and other universities, combed through data from more than 160,000 postmenopausal women who were surveyed as part of the Women's Health Initiative - a 15-year research study funded by the National Institutes of Health. Of these women, 53,142 regularly used NSAIDs. Even after controlling for obesity, hypertension, diabetes, use of aspirin and other health factors, the researchers found the increased risk for heart attack, stroke or death among the women who used certain types of NSAIDs.

One of the study's co-authors, Marian Limacher, M.D., has been the UF principal investigator for the Women's Health Initiative since 1994. She emphasized that the study was observational in nature, which helped the researchers find associations between use of NSAIDs and cardiovascular impacts. Limacher also noted that this was the first study of its size to examine the effects of regular NSAID use on women.

"When we study agents such as aspirin, we have found differential effects in men and women," Limacher said. "Men had reduction in heart attack, and older women had a reduction in stroke but not heart attack, which is part of the reason those of us studying women feel we really need to have adequate information on commonly used drugs for both men and women."

NSAIDs include over-the-counter medications such as naproxen and ibuprofen as well as prescription drugs such as rofecoxib, commercially branded as Vioxx, and celecoxib, branded as Celebrex. Because of its association with increased risk of heart attack or stroke, Vioxx was taken off the market in 2004.

The study's main finding confirmed that the regular use of any NSAID was associated with harm such as digestive bleeding. Although it found for the first time that the risk of heart attack, stroke or death was associated with the use of naproxen, the study found no cardiovascular or stroke harm associated with ibuprofen.

NSAIDs work by inhibiting two enzymes responsible for inflammation, called cox-1 and cox-2. They also can cause bleeding in the stomach and digestive tract. NSAIDs that target just the cox-2 enzyme, which is present mainly at the site of inflammation, are designed to prevent bleeding in the digestive tract, Bavry said.

However, previous studies showed that NSAIDs that solely target the cox-2 enzyme, which include Vioxx and Celebrex, have been associated with adverse cardiovascular events such as heart attack or stroke. Bavry thinks the culprit in naproxen is also cox-2 inhibition.

"People will have to think about what they have in their own medicine cabinet," Bavry said. "Do they have naproxen, ibuprofen or something else?"

The study looked only at the association between cardiovascular events and use of NSAIDs - not the effects of NSAIDs on the kidneys, for example.

"We would encourage patients to use medications for as short a time as they need, and to be sure they follow up with their physicians regularly to monitor for effects on the kidneys, and potentially for risk for heart disease," Limacher said.

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The Contraceptive Microchip: Could It Revolutionize Global Birth Control?

Dr. Enrique Jacome

MicroCHIPS, an IT start-up company with links to Massachusetts Institute of Technology, is developing a radical new contraceptive - a tiny microchip implanted under the skin that can be operated wirelessly by remote control.

In the 1990s, Robert S. Langer - the David H. Koch Institute Professor at Massachusetts Institute of Technology (MIT) and reportedly "the most cited engineer in history" - and his colleagues Michael Cima and John Santini, developed a microchip technology that could release controlled amounts of chemicals.

Fast-forward to 2012, and Langer's MIT lab received a visit from Bill Gates, who inquires with Langer whether it would be feasible to create a new method of birth control that a woman could turn on and off as she likes and which she can use for many years.

Langer proposed that his controlled release microchip might offer a solution. Leasing the technology to MicroCHIPS, the company have developed a device measuring just 20 x 20 x 7 mm designed to be implanted under the skin of the buttocks, abdomen or upper arm.

The chip contains tiny reservoirs of the hormone levonorgestrel, which is already used in some contraceptives. The chip dispenses 30 mcg of levonorgestrel every day, and can hold enough of the hormone to do this for up to 16 years.

When a woman wishes to conceive, she simply turns off the device with a remote. The chip would not need to be removed from the woman until 16 years of use have elapsed. By contrast, current hormonal birth control implants last a maximum of 5 years.

The levonorgestrel is contained on the chip using a hermetic titanium and platinum seal developed by MicroCHIPS. The hormone is released by passing an electric current from an internal battery through the seal, which melts it temporarily, allowing a small dose of levonorgestrel to be released each day.

According to MicroCHIPS president Robert Farra, "the idea of using a thin membrane like an electric fuse was the most challenging and the most creative problem we had to solve."

Speaking to BBC News, Farra suggested "the ability to turn the device on and off provides a certain convenience factor for those who are planning their family."

Although some critics of the device are worried about the potential for the microchip to be "hacked," Farra claims that the communication between the remote and implant "has to occur at skin contact level distance," so "someone across the room cannot reprogramme your implant."

"Then we have secure encryption," he says. "That prevents someone from trying to interpret or intervene between the communications."

MIT Technology Review points out that recently an international coalition of governments, companies, philanthropies and nonprofit organizations committed to providing family planning to 120 million more women in the world by 2020.

As new birth control options are rarely produced by private companies, MIT believe that the MicroCHIPS implant could play an important role in this mission.

MicroCHIPS, with the backing of Bill Gates, plan to submit the implant for preclinical testing in the US next year, and believe that the device could go on sale by 2018.

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Researchers Discover Potential New Treatment For Aggressive Breast Cancer

Dr. Enrique Jacome

Researchers have discovered a "viable" new target for the treatment of a particularly aggressive form of breast cancer. The molecule, known as alpha-v-beta-6, could also be used to identify those women with HER2-positive breast cancer who have a higher risk of developing secondary tumors.

The researchers found they could stop cancer cells invading, which these could do only with the help of alpha-v-beta-6 (αvβ6). Using the experimental antibody 264RAD, the team publishing in the Journal of the National Cancer Institute, found they could block the assistance given by the αvβ6 molecule.

Over 2,000 breast cancer patients gave samples for analysis, which revealed that there was no trace of αvβ6 in normal breast tissue but high levels of it in 40% of tumors from HER2-positive patients. The researchers found that the molecule was also a marker of poor chances of survival due to cancer spread.

UK breast cancer research charity the Breast Cancer Campaign, which funded the work, says the results offer hope that an effective treatment could be developed for the group of women with HER2-positive breast cancer who fail to respond to the first-line drug trastuzumab (Herceptin).

Trastuzumab blocks the signals sent from HER2 that promote tumor growth, but "up to 70% of patients either do not respond to Herceptin, or develop a resistance to the therapy," says the research advocate.

The authors of the research paper add:

"The results of this pre-clinical study suggest that targeting the αvβ6 molecule may enhance the effectiveness of Herceptin - and that a combination treatment could be effective for patients where Herceptin alone has not worked."

Early-stage experiments

The research was pre-clinical - that is, it was early-stage research that did not test any treatments in humans. Both laboratory cell analyses and tests in mice were undertaken.

The laboratory work analysed the αvβ6 molecule in tissue from breast cancer patients, and the role of αvβ6 in relation to HER2 effects on tumor expression, proliferation, invasion and growth was assessed in the mice.

The mice were randomized to receive 264RAD (the antibody that blocked αvβ6), trastuzumab, or both 264RAD and trastuzumab. This last group with combined blockade of αvβ6 and HER2 showed eradication of the tumors in all the mice treated.

The authors conclude that "simultaneous antibody targeting of αvβ6 (with 264RAD) and HER2 (with trastuzumab) statistically significantly improves the therapeutic effect of trastuzumab alone and statistically significantly increases survival."

The results on the tissue sample investigations, says Dr. John Marshall, reader in tumor biology at Queen Mary University of London's Barts Cancer Institute, UK, mean that:

"High αvβ6 levels could be tested for in routine biopsies to identify which women are at a high risk of metastasis, ensuring these women can receive personalised treatment, improving their chances of survival."

The Medical Research Council also provided grants for the research alongside the Breast Cancer Campaign, whose chief executive Baroness Delyth Morgan says:

"There is a desperate need for drugs which work in new ways to give the thousands of women diagnosed with HER2-positive breast cancer the best possible chances of surviving the disease.

"This study could pave the way for new treatments and bring us closer to our goal of preventing half of the deaths from breast cancer by 2025, through improved and personalised treatments."

Dr. Marshall and his team are building on their findings by investigating the most effective time to use 264RAD against tumors and potentially stop the spread of HER2-positive breast cancer.

In other recent news about potential new targets for the fight against breast cancer, researchers announcing their results in June 2014 found that a cholesterol-busting compound may halt breast cancer.

Early menopause and infertility can be side effects for younger women undergoing chemotherapy for breast cancer but May 2014 findings indicate that new drug regimen 'reduces early menopause risk'.

Finally, you may be interested in our recent analysis, What is science doing to improve the health and lives of cancer survivors?

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