Fatty acids found in fish linked to lower risk of breast cancer

A high intake of fatty acids found in fish is associated with a 14% reduction in the risk of breast cancer in later life, finds a study published on bmj.com.

The results show that each 0.1 g per day or 0.1% energy per day increment of intake of n-3 polyunsaturated fatty acid (n-3 PUFA) derived from fish was associated with a 5% reduction in risk. To achieve this risk reduction, intake of oily fish such as salmon, tuna or sardines should be 1-2 portions per person per week.

Breast cancer is one of the most common cancers, accounting for 23% of total cancer cases and 14% of cancer deaths in 2008. Studies suggest that a healthy diet and lifestyle is crucial for the prevention of breast cancer, and dietary fat is one of the most intensively studied dietary factors closely related with risk.

The n-3 PUFAs include ALA, EPA, DPA and DHA. They are involved in chemical messaging in the brain, helping to regulate blood vessel activity and areas of the immune system. The main dietary sources of EPA, DPA and DHA come from oily fish, while ALA is found mainly in nuts, seeds, and leafy green vegetables.

Although n-3 PUFAs are the most promising types of fat to reduce cancer risk, results from human studies are inconsistent.

So a team of researchers based in China set out to investigate the association between fish and n-3 PUFA intake and the risk of breast cancer. Levels were measured from both dietary sources and blood tests.

They reviewed and analysed the results of 26 studies from the United States, Europe and Asia involving over 800,000 participants and over 20,000 cases of breast cancer.

Marine n-3 PUFA was associated with a 14% reduction of breast cancer between the highest and lowest category of marine n-3 PUFA intake. The risk was lowest in Asian populations, probably because fish intake is much higher in Asia than in western countries, say the authors.

Further analysis indicated a dose response: each 0.1 g per day or 0.1% energy per day increment of intake was associated with a 5% reduction in risk. However, no significant protective association was found for ALA - the plant based n-3 PUFA.

The authors say their analysis, together with previous publications, “supports a protective role of marine n-3 PUFA on the incidence of breast cancer.”

They conclude: “Our present study provides solid and robust evidence that marine n-3 PUFA are inversely associated with risk of breast cancer.”

Higher omega-3 fatty acids in blood = reduced risk of hip fractures

Higher levels of omega-3 fatty acids in the blood may reduce the risk for hip fractures in postmenopausal women, recent research suggests.

Scientists analyzed red blood cell samples from women with and without a history of having a broken hip. The study showed that higher levels of omega-3 fatty acids from both plant and fish sources in those blood cells were associated with a lower likelihood of having fractured a hip.

In addition to omega-3s, the researchers looked at omega-6 fatty acids, which are generally plentiful in a Western diet. The study also showed that as the ratio of omega-6 fatty acids to omega-3s increased, so did the risk for hip fracture.

Though the study did not define the mechanisms for these relationships, the researchers hypothesized that inflammation may contribute to bone resorption, the breaking down of bone caused by the release of cells called osteoclasts.

“Inflammation is associated with an increased risk of bone loss and fractures, and omega-3 fatty acids are believed to reduce inflammation. So we asked if we would see fractures decrease in response to omega-3 intake,” said Rebecca Jackson, the study’s senior author and a professor of endocrinology, diabetes and metabolism at The Ohio State University.

“One thing that was critically important was that we didn’t use self-report of food intake, because there can be errors with that. We looked directly at the exposure of the bone cell to the fatty acids, which is at the red blood cell level,” said Jackson, also associate dean for clinical research in Ohio State’s College of Medicine. “Red blood cell levels also give an indication of long-term exposure to these fatty acids, which we took into account in looking for a preventive effect.”

Broken hips are the most common osteoporosis-related fractures, with an estimated 350,000 occurring annually in the United States. About 20 percent of people die in the year following a hip fracture.

The research is published in a recent issue of the Journal of Bone and Mineral Research.

The observational study did not measure cause and effect, so the researchers say the findings are not definitive enough to suggest that taking omega-3 supplements would prevent hip fractures in postmenopausal women.

“We don’t yet know whether omega-3 supplementation would affect results for bone health or other outcomes,” said Tonya Orchard, assistant professor of human nutrition at Ohio State and first author of the study. “Though it’s premature to make a nutrition recommendation based on this work, I do think this study adds a little more strength to current recommendations to include more omega-3s in the diet in the form of fish, and suggests that plant sources of omega-3 may be just as important for preventing hip fractures in women.”

Omega-3 and omega-6 fatty acids are both polyunsaturated fatty acids and essential fatty acids, meaning they contribute to biological processes but must be consumed because the body does not produce them on its own. Previous research has suggested that while both types of fatty acids are linked to health benefits, omega-3 fatty acids have anti-inflammatory properties and omega-6 fatty acids seem to have both anti- and pro-inflammatory effects.

The researchers used blood samples and hip fracture records from the Women’s Health Initiative (WHI), a large national prospective study of postmenopausal women that enrolled participants between 1993 and 1998 and followed them for 15 years. For this new work, the sample consisted of red blood cell samples and records from 324 pairs of WHI participants, half of whom had broken their hips before Aug. 15, 2008, and the other half composed of age-matched controls who had never broken a hip.

The analysis showed that higher levels of total omega-3 fatty acids and two other specific kinds of omega-3s alone were associated with a lower risk of hip breaks in the study sample.

On the other hand, women who had the highest ratio of omega-6 to omega-3 fatty acids had nearly twice the risk of hip fractures compared to women with the lowest ratios. The current typical American diet contains between 15 and 17 times more omega-6 than omega-3, a ratio that previous research has suggested should be lowered to 4-to-1, or even 2-to-1, by increasing omega-3s, to improve overall health. The primary omega-6 fatty acid in the diet is linoleic acid, which composes about 99 percent of Americans’ omega-6 intake and is found in corn, soybean, safflower and sunflower oils.

The specific omega-3 sources associated with lower risk for broken hips were ALA (alpha-linolenic acid), which comes from plant sources such as flaxseed oil and some nuts, and EPA (eicosapentaenoic acid), which is found in fatty types of fish. The other marine-sourced omega-3, DHA (docosahexaenoic acid), on its own did not have a significant link to lower hip-fracture risk, “but all three omega-3s were in the protective direction,” Orchard said.

Jackson, who was a vice chair of the WHI for more than a decade, said continuing analyses of data from the WHI will dig down to the genetic influences on metabolism and absorption of nutrients, and whether such genetic differences could affect health risk factors in postmenopausal women.

Total amount of exercise important, not frequency, research shows

A new study by Queen’s University researchers has determined that adults who accumulated 150 minutes of exercise on a few days of the week were not any less healthy than adults who exercised more frequently throughout the week.

Ian Janssen and his graduate student Janine Clarke studied 2,324 adults from across Canada to determine whether the frequency of physical activity throughout the week is associated with risk factors for diabetes, heart disease and stroke.

“The findings indicate that it does not matter how adults choose to accumulate their 150 weekly minutes of physical activity,” says Dr. Janssen. “For instance, someone who did not perform any physical activity on Monday to Friday but was active for 150 minutes over the weekend would obtain the same health benefits from their activity as someone who accumulated 150 minutes of activity over the week by doing 20-25 minutes of activity on a daily basis.”

Physical activity was measured continuously throughout the week by having research participants wear accelerometers on their waists. Accelerometers are tiny electrical devices (about the size of a small package of matches) that record how much a person moves every minute.

Dr. Janssen divided the adults who met the physical activity guidelines (more than 150 minutes per week of aerobic activity) into those who were frequently active (active five to seven days of the week) and infrequently active (active one to four days of the week).

“The important message is that adults should aim to accumulate at least 150 minutes of weekly physical activity in whatever pattern that works for their schedule.”

The paper was published today in Applied Physiology, Nutrition and Metabolism

Eating more red meat associated with increased risk of Type 2 diabetes

Eating more red meat over time is associated with an increased risk of type-2 diabetes mellitus (T2DM) in a follow-up of three studies of about 149,000 U.S. men and women, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication.

Red meat consumption has been consistently related to an increased risk of T2DM, but previous studies measured red meat consumption at a baseline with limited follow-up information. However, a person's eating behavior changes over time and measurement of consumption at a single point in time does not capture the variability of intake during follow-up, the authors note in the study background.

An Pan, Ph.D., of the National University of Singapore, and colleagues analyzed data from three Harvard group studies and followed up 26,357 men in the Health Professionals Follow-up Study; 48,709 women in the Nurses' Health Study; and 74,077 women in the Nurses' Health Study II. Diets were assessed using food frequency questionnaires.

During more than 1.9 million person-years of follow-up, researchers documented 7,540 incident cases of T2DM.

"Increasing red meat intake during a four-year interval was associated with an elevated risk of T2DM during the subsequent four years in each cohort," according to the study.

The results indicate that compared with a group with no change in red meat intake, increasing red meat intake of more than 0.50 servings per day was associated with a 48 percent elevated risk in the subsequent four-year period. Reducing red meat consumption by more than 0.50 servings per day from baseline to the first four years of follow-up was associated with a 14 percent lower risk during the subsequent entire follow-up.

The authors note the study is observational so causality cannot be inferred.

"Our results confirm the robustness of the association between red meat and T2DM and add further evidence that limiting red meat consumption over time confers benefits for T2DM prevention," the authors conclude.

(JAMA Intern Med. Published online June 17, 2013. doi:10.1001/jamainternmed.2013.6633. Available pre-embargo to the media at http://media.jamanetwork.com.)

Editor's Note: This work was supported by grants from the National Institutes of Health. An author also made a funding disclosure. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Commentary: Oxygen-Carrying Proteins in Meat and Risk of Diabetes Mellitus

In an invited commentary, William J. Evans, Ph.D., of GlaxoSmithKline and Duke University, Durham, N.C., writes: "The article by Pan et al confirms previous observations that the consumption of so-called red meat is associated with an increased risk of type 2 diabetes mellitus (T2DM)."

"Perhaps a better description of the characteristics of the meat consumed with the greatest effect on risk is the saturated fatty acid (SFA) content rather than the amount of oxygen-carrying proteins," Evans continues.

"A recommendation to consume less red meat may help to reduce the epidemic of T2DM. However, the overwhelming preponderance of molecular, cellular, clinical and epidemiological evidence suggests that public health messages should be directed toward the consumption of high-quality protein that is low in total and saturated fat. … These public health recommendations should include cuts of red meat that are also low in fat, along with fish, poultry and low-fat dairy products. It is not the type of protein (or meat) that is the problem: it is the type of fat," Evans concludes.

Aspirin may fight cancer by slowing DNA damage

Aspirin is known to lower risk for some cancers, and a new study led by a UC San Francisco scientist points to a possible explanation, with the discovery that aspirin slows the accumulation of DNA mutations in abnormal cells in at least one pre-cancerous condition.

"Aspirin and other non-steroidal anti-inflammatory drugs, which are commonly available and cost-effective medications, may exert cancer-preventing effects by lowering mutation rates," said Carlo Maley, PhD, a member of the UCSF Helen Diller Family Comprehensive Cancer Center, and an expert on how cancers evolve in the body over time.

In the study, published June 13 in the online journal PLOS Genetics, Maley, working with gastroenterologist and geneticist Brian Reid, MD, PhD, of the Fred Hutchinson Cancer Research Center, analyzed biopsy samples from 13 patients with a pre-cancerous condition called Barrett's esophagus who were tracked for six to 19 years. In an "observational crossover" study design, some patients started out taking daily aspirin for several years, and then stopped, while others started taking aspirin for the first time during observation. The goal was to track the rate of mutations in tissues sampled at different times.

The researchers found that biopsies taken while patients were on an aspirin had on average accumulated new mutations about 10 times more slowly than biopsies obtained during years when patients were not taking aspirin.

"This is the first study to measure genome-wide mutation rates of a pre-malignant tissue within patients for more than a decade, and the first to evaluate how aspirin affects those rates," Maley said.

Gender and ethnic distribution of study patients reflected the known demographics of esophageal cancer, which predominantly affects, white, middle-aged and elderly men, he said. Barrett's esophagus only occasionally progresses to esophageal cancer.

Cancers are known to accumulate mutations over time much more rapidly than normal tissue, and different mutations arise in different groups of cells within the same tumor. The acquisition of key mutations ultimately allows tumor cells to grow out of control, and diversity within a tumor may foster drug resistance, a phenomenon that is a major focus of Maley's research.

Maley plans to test a hypothesis that may explain the results — that aspirin's lowering of mutation rates is due to the drug's effect of reducing inflammation. Inflammation, a response of the immune system, in recent years has been recognized as a hallmark of cancer. Maley said that less inflammation may result in less production within pre-cancerous tissue of oxidants known to damage DNA, and may dampen growth-stimulating signaling.

For the duration of the study, the rate of accumulation of mutations measured in the biopsied tissue between time points was slow, even when patients were not taking aspirin, with the exception of one patient. While mutations accumulated at a steady rate, the vast majority of mutations arose before the abnormal tissue was first detected in the clinic, the researchers concluded.

These findings are consistent with the fact that although Barrett's esophagus is a significant risk factor for esophageal cancer, the vast majority of cases do not progress to cancer, Maley said.

In the one patient who later went on to develop cancer, a population of cellular "clones" with a great number of mutations emerged shortly before he started taking aspirin.

More studies are needed to further explore the link between non-steroidal anti-inflammatory drugs, mutation rates and the development of invasive cancer, Maley said. He plans to continue studying Barrett's esophagus and esophageal cancer, and to expand his research to investigate lung cancer.

Rather than aiming to kill the most tumor cells, it may be better to try to halt or slow growth and mutation. Current drug treatments for cancer may in many cases hasten the emergence of cancer that is more difficult to eradicate, according to Maley. The capability to mutate frequently allows tumors to become resistant to drug treatment, he said. A better-adapted mutant can begin to spin off a population of genetic clones that survives and grows, while poorly adapted tumor cells die off.

Timing of calcium and vitamin D supplementation may affect how bone adapts to exercise

Taking calcium and vitamin D before exercise may influence how bones adapt to exercise, according to a new study. The results will be presented on Tuesday at The Endocrine Society's 95th Annual Meeting in San Francisco.

"The timing of calcium supplementation, and not just the amount of supplementation, may be an important factor in how the skeleton adapts to exercise training," said study lead author Vanessa D. Sherk, PhD, postdoctoral research fellow at the University of Colorado Anschutz Medical Campus. "Further research, however, is needed to determine whether the timing of calcium supplementation affects the skeletal adaptations to exercise training."

Previous research has shown that a year of intense training is associated with substantial decreases in bone mineral density among competitive road cyclists. Experts believe that this kind of exercise-induced bone loss could be related to the loss of calcium during exercise. As blood calcium levels drop, the parathyroid gland produces excess parathyroid hormone, which can mobilize calcium from the skeleton.

In this study, investigators found that an exercise-induced decrease in blood calcium occurred whether calcium supplements were taken before or after exercising. Pre-exercise supplementation, however, resulted in less of a decrease. Although not statistically significant, parathyroid hormone levels increased slightly less among cyclists who took calcium before exercising.

"These findings are relevant to individuals who engage in vigorous exercise and may lose a substantial amount of calcium through sweating," Sherk said. "Taking calcium before exercise may help keep blood levels more stable during exercise, compared to taking the supplement afterwards, but we do not yet know the long-term effects of this on bone density."

The timing of calcium supplementation did not cause a difference in blood levels of a compound that is a biological indicator of bone loss. Both the before- and after-exercise groups exhibited 50-percent increases in the level of this compound, called CTX, for collagen type-1 C-telopeptide.

Study participants included 52 men aged 18 to 45 years. Investigators randomly assigned participants to take 1,000 milligrams of calcium and 1,000 international units of vitamin D either 30 minutes before or one hour after exercise. The exercise comprised a simulated 35-kilometer time trial, and participants wore skin patches to absorb sweat.

Investigators measured blood levels of calcium and parathyroid hormone before and immediately after exercise. They also measured CTX before and 30 minutes after exercise. They used pre- and post-body weight, adjusted for fluid intake, combined with the calcium measured in the sweat from the skin patches, to estimate the amount of calcium lost through the skin during exercise.

Vitamin D Can Help Prevent Hypertension

The world's largest study to examine the link between vitamin D levels and hypertension has found that low levels of Vitamin D can be a major cause of hypertension.

Researchers presented their findings at the annual conference of the European Society of Human Genetics (ESHG).

Data were gathered from 35 studies, which included more than 155,000 participants from different parts of Europe and North America.

Dr. Vimal Karani S, from the Institute of Child Health, University College London, London, UK, led the study.

Participants with high levels of 25-hydroxyvitamin D (25(OH)D) had reduced blood pressure and were at a lower risk of developing hypertension.

Dr. Vimal Karani S, said:

"We knew from earlier observational studies that low 25(OH)D concentrations were likely to be associated with increases in blood pressure and hypertension, but correlation is not causality.

Additionally, randomized controlled trials of vitamin D supplementation in humans have produced inconsistent effects on cardiovascular outcomes. The whole picture was somewhat confused, and we decided to try to figure it out once and for all."


To measure the individuals' vitamin D status and test for an association with blood pressure, the researchers used genetic variations called single nucleotide polymorphisms, or SNPs as proxy markers.

For every 10% increase in 25(OH)D concentrations the researchers noted the risk of developing hypertension decreased by 8.1%.

Dr. Karani S., said that the approach they followed, called Mendelian randomization, allowed them to make accurate conclusions, "by using this approach we can determine the cause and effect and be pretty sure that we've come to the right conclusion on the subject."

The researchers said that Vitamin D deficiency is a very common problem in the Western world, particularly because obesity can cause Vitamin D deficiency and obesity levels are highest in Western countries, according to a study published in a recent issue of PLoS Medicine

People with high levels of vitamin D in their blood enjoy several benefits, apart from improved bone health. Researchers from Boston University School of Medicine reported in PLOS ONE that people with high levels of vitamin D have significantly better immunity and a reduced risk of several diseases.

Vitamin D insufficiency (between 21-29 ng/mL) and vitamin D deficiency (<20 ng/mL) lead to a heightened risk of:

Dr. Karani said that the study provides further data to support the importance of vitamin D. It suggests that vitamin D supplements or food fortification can significantly reduce the risk of cardiovascular disease.

He concluded:

"We now intend to continue this work by examining the causal relationship between vitamin D status and other cardiovascular disease-related outcomes such as lipid-related phenotypes, for example,cholesterol, inflammatory markers such as C-reactive protein, and type 2 diabetes and markers of glucose metabolism.

We believe that we still have a lot to find out about the effect of Vitamin D deficiency on health, and we now know that we have the tools to do so."