Health for life

Research funded by the National Institutes of Health and the Howard Hughes Medical Institute, and appearing in this months online issue of Nature Medicine, has shed light on why women in one study who took Avandia (rosiglitazone) had decreased bone density. (See our post from earlier this year: Questions Surrounding Avandia and its Effect on Bone.)

Bone is not the static organ many people think. Its constantly being ormed. Cells called osteoclasts break down bone while cells called osteoblasts lay down new bone.

These researchers found that mice given the PPAR-gamma agonist Avandia (Avandia is a thiazolidinedione, a class of insulin-sensitizing drugs under which Actos also falls) had increased activity of their osteoclasts, leading researchers to speculate:

"These findings have potential clinical implications, as they suggest that long-term rosiglitazone usage in the treatment of type 2 diabetes and insulin resistance may cause osteoporosis, owing to a combination of decreased bone formation and increased bone resorption."

If more studies support this link, it may necessitate screening patients for osteoporosis before starting or continuing them on these drugs.
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Nature Medicine abstract:
PPAR-gamma Regulates osteoclastogenesis in Mice

News summaries:
Diabetes Drug Link To Weak Bones
Diabetes Drug May Increase Bone Thinning

A gender-bending chemical found in food packaging is linked to breathing problems in young babies, researchers have found.
A study showed pregnant mothers with the highest levels of bisphenol A in  their bodies were twice as likely to have babies who suffer from wheezing in their first six months.
Wheezing in babies can be a symptom of lung damage, asthma, bronchitis, allergies or an infection.
Bisphenol A, or BPA, which is used to harden plastics, is one of the world’s most widely manufactured chemicals and can be found in dozens of everyday items including baby bottles, CD cases and food and drink packaging.


If you use water bottles or plastic of any kind (#3, #7, etc), conventionally packed products of any kind or cans and insulated cartons of any kind, chances are you have been exposed to BPA.

Human studies have found BPA in many tissues and fluids, including urine, blood, breast milk, the amniotic fluid of pregnant women and the antral fluid of mature follicles. A national survey conducted by the federal Centers for Disease Control and Prevention in 2003-2004 found BPA in 93 percent of the 2,517 people (age 6 and up) who were tested.
Because the chemical mimics oestrogen, many scientists believe it interferes with the way hormones are processed by the body.

Previous research from North Carolina State University and the National Institute of Environmental Health Sciences (NIEHS) showed significant reproductive health effects in rats that have been exposed to bisphenol-A (BPA) at levels equivalent to or below the dose that has been thought not to produce any adverse effects.
Although several animal  studies have shown it to be safe, others have linked Bisphenol A to breast cancer, liver damage, obesity, diabetes and fertility problems.
The latest U.S. study looked  at the BPA levels of 367 pregnant women, with researchers at  Penn State College of Medicine measuring levels of the chemical in expectant mothers in the 16th and 26th week of pregnancy. 
They found 99 per cent of women had measurable levels of the chemical in their bodies – and those with the highest levels in their 16th week were twice as likely to have babies who wheezed at six months old than women with the lowest levels.
However, the study also found that high concentrations of BPA at 26 weeks and at birth were not connected to the condition.
Some experts suggest exposure to hormone-disrupting chemicals causes the most harm during a crucial window of development early on in pregnancy, and believe women of child-bearing age should avoid products containing BPA.
Elizabeth Salter-Green, director of the Chemicals, Health and Environment Monitoring Trust, said: ‘This new research adds further weight to the  need to reduce our exposure to this chemical, particularly  pregnant women.
It is the foetus developing in utero that is most vulnerable to BPA exposures.’
Last year Denmark became the first country in the EU to ban BPA in packaging for food and drink aimed at under-threes, while the EU itself voted to ban it from baby bottles  last year. Canada and three  U.S. states have also introduced restrictions.
Adam J. Spanier, lead author of the study, which was presented at a conference in the U.S. yesterday, called for more research into BPA

Researchers from New England found that men who slept either less than 6 hours, or greater than 8 hours, increased their risk for type 2 diabetes. That risk remained after adjustments were made for age, hypertension, smoking status, self-rated health status, education, and waist circumference.

These results suggest that even though you have a handle on your weight, blood pressure and smoking, you may still court a diagnosis of diabetes if your sleep is consistently short-changed, or over-indulged.

The study included 1564, primarily white men, aged 40 to 70, who were enrolled in the Massachusetts Male Aging Study (MMAS), and who did not have diabetes at baseline. The men were followed for up to 15 years. Similar, although less marked results were found in women who partook in the Nurses Health Study.

The study appears in the March 2006 issue of Diabetes Care.

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For the MMAS study:
Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes

For a summary of the MMAS study:
Diabetes Risk Raised By Too Much Or Too Little Sleep

For the Nurses Health Study:
A Prospective Study of Self-Reported Sleep Duration and Incident Diabetes in Women

Men who are overweight or obese when they are diagnosed with prostate cancer are more likely to die from the disease than men who are of healthy weight, according to a Kaiser Permanente study published today in the journal Obesity Research & Clinical Practice. In patients with more aggressive forms of prostate cancer, the researchers also found an even stronger correlation between obesity and mortality.

This study included 751 Kaiser Permanente patients with prostate cancer who underwent radical prostatectomy, an operation that includes removal of the prostate and surrounding tissue. The researchers explored the association between the patients body mass index and prostate cancer mortality, adjusted for tumor aggressiveness and other characteristics.

The researchers found men who died from prostate cancer were 50 percent more likely to be overweight or obese at diagnosis compared to men who did not die from the disease. Men with high Gleason scores, a rating of the aggressiveness of prostate cancer cells, had the highest association between BMI and death, specifically men with Gleason scores of 8 or higher. The Gleason score ranges from 2 to 10, with the highest number representing the greatest likelihood of tumor cells spreading.

"We found among patients undergoing surgical treatment for prostate cancer, weight at time of diagnosis is more strongly correlated with prostate cancer survival than many other factors researchers have studied in the past, including some prostate cancer treatments," said lead author Reina Haque, PhD, a researcher at Kaiser Permanente Southern Californias Department of Research & Evaluation in Pasadena, Calif. "Moving forward, we are hoping future studies will examine the effect of weight loss and other lifestyle modifications on prostate cancer mortality."

Additional studies are needed to determine which lifestyle modifications, such as diet or exercise, could prolong a prostate cancer patients life. Further investigation also is needed to determine if the findings of this study, which looked at men who had prostate cancer surgery, apply to men who received other treatments such as radiation or hormone therapy.

Although the connection between mens weight at prostate cancer diagnosis and likelihood of survival has been examined, many previous studies were limited by self-reported body weight data or it was unclear when the BMI data were obtained. So the link between obesity and prostate cancer mortality remains controversial. However, the methodology of this study was different because the researchers used BMI collected from medical records, instead of self-reported data. The researchers identified men who died of prostate cancer and compared their BMI at time of diagnosis to controls to determine if body weight is related prostate cancer death. The biological relationship between obesity and prostate cancer prognosis is still not understood, and is an active area of research.

A new study has outlined for the first time a biological mechanism by which zinc deficiency can develop with age, leading to a decline of the immune system and increased inflammation associated with many health problems, including cancer, heart disease, autoimmune disease and diabetes.

The research was done by scientists in the Linus Pauling Institute at Oregon State University and the OSU College of Public Health and Human Sciences. It suggests that it’s especially important for elderly people to get adequate dietary intake of zinc, since they may need more of it at this life stage when their ability to absorb it is declining.

About 40 percent of elderly Americans and as many as two billion people around the world have diets that are deficient in this important, but often underappreciated micronutrient, experts say.

The study was published in the Journal of Nutritional Biochemistry, based on findings with laboratory animals. It found that zinc transporters were significantly dysregulated in old animals. They showed signs of zinc deficiency and had an enhanced inflammatory response even though their diet supposedly contained adequate amounts of zinc.

When the animals were given about 10 times their dietary requirement for zinc, the biomarkers of inflammation were restored to those of young animals.

“The elderly are the fastest growing population in the U.S. and are highly vulnerable to zinc deficiency,” said Emily Ho, an LPI principal investigator and associate professor in OSU School of Biological and Population Health Sciences. “They don’t consume enough of this nutrient and don’t absorb it very well.”

“We’ve previously shown in both animal and human studies that zinc deficiency can cause DNA damage, and this new work shows how it can help lead to systemic inflammation,” Ho said.

“Some inflammation is normal, a part of immune defense, wound healing and other functions,” she said. “But in excess, it’s been associated with almost every degenerative disease you can think of, including cancer and heart disease. It appears to be a significant factor in the diseases that most people die from.”

As a result of this and what is now know about zinc absorption in the elderly, Ho said that she would recommend all senior citizens take a dietary supplement that includes the full RDA for zinc, which is 11 milligrams a day for men and 8 milligrams for women. Zinc can be obtained in the diet from seafood and meats, but it’s more difficult to absorb from grains and vegetables – a particular concern for vegetarians.

“We found that the mechanisms to transport zinc are disrupted by age-related epigenetic changes,” said Carmen Wong, an OSU research associate and co-author of this study. “This can cause an increase in DNA methylation and histone modifications that are related to disease processes, especially cancer. Immune system cells are also particularly vulnerable to zinc deficiency.”

Research at OSU and elsewhere has shown that zinc is essential to protect against oxidative stress and help repair DNA damage. In zinc deficiency, the risk of which has been shown to increase with age, the body’s ability to repair genetic damage may be decreasing even as the amount of damage is going up.

Medical tests to determine zinc deficiency are rarely done, scientists say, and are not particularly accurate even if they are done. The best approach is to assure adequate intake of the nutrient through diet or supplements, they said, especially in the elderly.

Even though elderly people have less success in absorbing zinc, the official RDA for them is the same as in younger adults. That issue should be examined more closely, Ho said.

Levels of zinc intake above 40 milligrams per day should be avoided, researchers said, because at very high levels they can interfere with absorption of other necessary nutrients, including iron and copper.

Researchers from the American Academy of Neurology publishing in the journal Neurology have released the result of a study showing that being overweight or obese in midlife significantly increases the risk of developing certain forms of dementia, including Alzheimer`s disease as we age. Worldwide this places 1.6 billion people at risk, including more than half of the US adult population.

Patients who consume high-fat dairy products following breast cancer diagnosis increase their chances of dying from the disease years later, according to a study by Kaiser Permanente researchers.

The study, published in the Journal of the National Cancer Institute, is the first to examine the relationship between high-fat and low-fat dairy consumption following a diagnosis of breast cancer and long-term breast cancer survival.

Previous studies have shown that higher lifetime exposure to estrogen is a causal pathway to breast cancer. Estrogen levels are believed to be elevated in dairy products consumed in the Western world, because most of its milk comes from pregnant cows. Estrogenic hormones reside primarily in fat, so levels are higher in high-fat than in low-fat dairy products.

The researchers studied a cohort of women who were diagnosed with early-stage, invasive breast cancer between 1997 and 2000, primarily from Kaiser Permanentes Northern California region (83 percent) and the Utah Cancer Registry (12 percent).

Those consuming larger amounts of high-fat dairy (one serving or more per day) had "higher breast cancer mortality as well as higher all-cause mortality and higher non-breast cancer mortality," wrote lead author Candyce H. Kroenke, ScD, MPH, staff scientist with the Kaiser Permanente Division of Research, and co-authors.

"Specifically, women consuming one or more servings per day of high-fat dairy had a 64 percent higher risk of dying from any cause and a 49 percent increased risk of dying from their breast cancer during the follow-up period," said Kroenke. The category of high-fat dairy products researchers tracked included cream, whole milk, condensed or evaporated milk, pudding, ice cream, custard, flan, and also cheeses and yogurts that were not low-fat or non-fat.

In general, the women studied reported that they consumed low-fat milk and butter most often, and they consumed relatively limited amounts of low-fat dairy desserts, low-fat cheese and high-fat yogurt. Overall, low-fat dairy intake was greater (median 0.8 servings per day) than high-fat dairy (median 0.5 servings per day).

The study found an association between high-fat dairy and breast cancer mortality, but no association with low-fat dairy products and breast cancer outcomes.

"High-fat dairy is generally not recommended as part of a healthy diet," said senior author Bette J. Caan, DrPH, research scientist with the Kaiser Permanente Division of Research. "Switching to low-fat dairy is an easy thing to modify."

Women entered into the cohort approximately two years after their breast cancer diagnosis. At the beginning of the study, 1,893 women completed a self-administered food-frequency questionnaire, and 1,513 of these women completed a follow-up questionnaire six years later. They were followed for 12 years on average following study entry.

The women were asked how often they consumed dairy foods during the previous year; what portion sizes they generally consumed; which products they ate, including milk, cheese, dairy desserts, yogurt, and beverages made with milk (such as hot chocolate or lattes); and whether the dairy products were full fat, low fat or nonfat.

Of the total sample, 349 women had a recurrence of breast cancer and 372 died of any cause, 189 (50.8 percent) of them from breast cancer.

This research was part of the Life After Cancer Epidemiology (LACE) study, one of several efforts by investigators with the Kaiser Permanente Division of Research to consider the role of lifestyle factors such as nutrition, exercise and social support on long-term breast cancer survival and recurrence. While hundreds of studies have examined the role of lifestyle factors in cancer risk and prevention, this study is one of a small but growing number that focus on the role of lifestyle factors after a breast cancer diagnosis.

For example, the Pathways study of breast cancer survivorship, based at the Division of Research, is collecting and analyzing data about womens genetic background, tumor characteristics and lifestyle choices immediately after diagnosis. Findings from this study, along with the LACE study, are providing objective information to help guide women as they make decisions following a breast cancer diagnosis; among these findings are that soy decreases the risk of breast cancer recurrence, quality of life after diagnosis influences outcomes, and physical activity is beneficial.

Susan E. Kutner, MD, chair of the Kaiser Permanente Northern California Regional Breast Care Task Force, said that the new study bolsters the counseling that Kaiser Permanente gives breast cancer survivors about the importance of a low-fat diet, as well as exercise and weight management, in preventing recurrence of the disease. "Women have been clamoring for this type of information," Kutner said. "Theyre asking us, Tell me what I should eat? With this information, we can be more specific about recommending low-fat dairy products."

Maternal nutrition is important to a developing embryo and to the health of the child later in life. Supplementing the diet with specific vitamins is known to increase health of the fetus for example folic acid (vitamin B9) reduces the risk of spina bifida. However not everything an adult might consume is beneficial to a developing baby. New research published in BioMed Centrals open access journal BMC Medicine shows that caffeine is linked to low birth weight babies and that caffeine from coffee in linked to increasing length of pregnancy.

Along with nutrients and oxygen, caffeine freely passes the placental barrier, but the developing embryo does not express the enzymes required to inactivate it efficiently. The WHO currently suggests a limit of 300mg per day during pregnancy but some countries recommend a limit of 200mg, which can be less than a single cup of coffee from some high street cafes.

To investigate the impact of maternal caffeine during pregnancy on babies, a research team from the Norwegian Institute for Public Health used information about mothers diet and birth details collected over ten years. After excluding women with medical and pregnancy-related conditions almost 60,000 pregnancies were included in the study. All sources of caffeine were monitored in the study: coffee, tea, fizzy drinks, as well as food including cocoa-containing cakes and deserts and chocolate.

Explaining their results, Dr Verena Sengpiel, from Sahlgrenska University Hospital, Sweden, who led the project said, "Although caffeine consumption is strongly correlated with smoking which is known to increase the risk for both preterm delivery and the baby being small for gestational age at birth (SGA). In this study we found no association between either total caffeine or coffee caffeine and preterm delivery but we did find an association between caffeine and SGA. This association remained even when we looked only at non-smoking mothers which implies that the caffeine itself is also having an effect on birth weight."

In fact they found that caffeine from all sources reduced birth weight. For a child of expected average weight (3.6kg) this equates to 21-28g lost per 100mg caffeine per day. But it was not just caffeine, but the source of caffeine, which affected pregnancy outcomes. Caffeine from all sources increased the length of the pregnancy by 5hr per 100mg caffeine per day, but caffeine intake from coffee was associated with an even longer gestational length -- 8hr extra for every 100mg caffeine per day.

This association means that it is not just the caffeine in coffee which increases gestational length but either there must be a substance in coffee which is responsible for the extra time or there is a behaviour associated with coffee drinking not present in women who drink only tea (for example). SGA babies are at higher risk of both short term and lifelong health problems and it seems from these results that since even 200-300mg caffeine per day can increase the risk of SGA by almost a third these recommendations need to be re-evaluated.

Irons link to diabetes has been in the news over the last few years.

In February, 2004, a study that appeared in the Journal of the American Medical Association found that high levels of iron in the body almost tripled womens risk for developing diabetes. Researchers had examined iron stores in over 32,000 women who took part in the Nurses Health Study and followed them for 10 years.

Recently, a study which appears in this months issue of Diabetes Care found that women with high intakes of heme iron - the kind found primarily in meat - had a 28% greater risk of developing diabetes than women whose meat intake was lower. Researchers examined dietary intake of over 85,000 women who took part in the Nurses Health Study and followed them for 20 years.

One item to note - This recent study found no association between diabetes and iron intake from supplements, iron intake from non-heme sources (such as spinach and other greens, beans, and fortified cereals), or total iron intake from all sources. It could only document a link between diabetes and the intake of heme iron. (Heme iron is a constituent of hemoglobin and myoglobin molecules in animals. Only about 40% of the total iron supplied by meat is in the heme form.)

Although this study investigated irons association with the risk for developing diabetes, it did not reveal a mechanism, nor did it discuss what effect intake of heme iron would have in those already dealing with the disease. However, in an interview with Reuters Health, one of its authors theorized:

"In excess, these molecules create a state of "oxidative stress" that damages body cells over time. Oxidative stress could theoretically set the stage for diabetes by reducing body cells sensitivity to the hormone insulin, Rajpathak explained."
- More evidence ties iron intake to diabetes risk

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For the 2004 JAMA study:
Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women

For a news summary of the JAMA study:
Diabetes risk may be associated with elevated iron levels

For the June, 2006 Diabetes Care study:
Iron Intake and the Risk of Type 2 Diabetes in Women

College education and alcohol consumption may be linked to risk for chronic obstructive pulmonary disease (COPD). Researchers from Kaiser Permanente Medical Group in Oakland, California, followed 126,019 people who supplied baseline data from 1978 – 1985 through 2008 with analyses of hospitalizations attributed to COPD (emphysema, chronic bronchitis, or chronic airway obstruction).

Although cigarette smoking, increasing age, and history of respiratory disease/symptoms were powerful predictors of COPD, results also showed that Asian Americans (vs whites) and college graduates (vs no college) were at a moderately lower risk for COPD, as were persons reporting 1 to 2 drinks per day (vs lifelong abstainers).

You probably know some of the leading risk factors for osteoporosis -- being female and past menopause, smoking, or having a small frame. But did you know that some fairly common medical conditions are also among the causes of osteoporosis bone loss?

If you have one of these conditions, either because of the disease itself or because of the medications you have to take to manage it, you face an increased risk of developing osteoporosis:
1. Diabetes Mellitus and Osteoporosis

For reasons scientists still dont fully understand, people with type 1 diabetes tend to have lower bone density.

Studies show that people with type 1 diabetes may have low bone turnover and lower than normal bone formation.

"It seems that high blood sugar may shut down bone formation, just as with steroids," says Beatrice Edwards, MD, MPH, associate professor of medicine and director of the Bone Health and Osteoporosis Center at Northwestern University Feinberg School of Medicine. Since type 1 diabetes usually develops in childhood, when the body is still building bone, someone with type 1 diabetes may never have the opportunity to reach their peak bone density.

Even if their bone mass isnt that much lower than normal, people with both type 1 and type 2 diabetes have a much higher risk of fractures than other people, adds Edwards. 
2. Lupus and Rheumatoid Arthritis

Nearly 3 million adults in the U.S. have either lupus or rheumatoid arthritis. Both of these diseases are autoimmune conditions, in which the body attacks its own healthy cells and tissues, causing inflammation.

Any chronic inflammatory disease can put you at greater risk of osteoporosis, says Edwards, because it appears to increase the rate of bone turnover, in which old bone is replaced with healthy new bone. People with both lupus and RA usually take corticosteroids for an extended period of time to manage their symptoms. Long-term use of steroids such as prednisone is also a leading cause of osteoporosis, possibly because they slow the activity of bone-building cells.

Lupus is a particular problem because it is common in women between the ages of 15 and 45 -- often during the peak bone-building years up to age 30. "Anything that impedes the growth of bone during these years puts you at greater risk for osteoporosis," says Edwards.
3. Hyperthyroidism

Hyperthyroidism occurs when the thyroid gland -- a small, butterfly-shaped gland at the base of the neck -- becomes overactive and produces too much thyroid hormone.

"Hyperthyroidism increases the number of bone-remodeling cycles you go through," explains Edwards. "And after age 30, every bone-remodeling cycle is inefficient. You lose bone mass rather than building it. So the more cycles you go through, the more bone mass you lose."

Hyperparathyroidism, a similar condition involving related, but different glands, also ups the risk of osteoporosis.

4. Celiac Disease

A number of digestive disorders, such as Crohns disease, can be causes of osteoporosis. Perhaps the most common such cause, says Edwards, is celiac disease, an allergy to a protein called gluten that is often found in wheat products.

Left untreated, celiac disease can damage the lining of the digestive system and interfere with the digestion of nutrients -- including the calcium and vitamin D that are so important to bone health. So even if youre getting the recommended daily amounts of calcium and vitamin D in your diet, if you have celiac disease, you probably dont have enough of those nutrients in your system, and you likely have low bone density.
5. Asthma

Asthma itself does not increase your risk of developing osteoporosis, but the medications used to treat it do. Approximately 20 million people in the U.S. have asthma, including some 9 million children under the age of 18.

Many people with asthma use corticosteroids -- such as asthma "inhalers" -- to help control their disease. During asthma attacks it is not uncommon to start drugs like prednisone for small periods of time. These are very effective in relieving the shortness of breath and wheezing that are common with asthma or emphysema, but they may also contribute to bone loss and osteoporosis.

"In addition to this, many young people with asthma may have more difficulty participating in some activities, which means they might not get as much weight-bearing exercise as they need to help build bone," says Andrew Bunta, MD, associate professor and vice chair of orthopaedics at Northwestern University Feinberg School of Medicine.
6. Multiple Sclerosis

Asthma and multiple sclerosis are two very different conditions, but there are very similar reasons why they both increase the risk of osteoporosis. Like people with asthma, people with multiple sclerosis take steroid-based medications to help manage their symptoms, and steroids are associated with bone loss. Since multiple sclerosis also affects balance and movement for many people, someone with MS may find it more difficult to get as much weight-bearing exercise as they need to in order to build and maintain bone.

"Anything that impedes your ability to walk accelerates bone loss," says Edwards.

If you have one of these conditions, how can you help protect yourself from osteoporosis? First, dont assume that your doctor will take care of it for you.

"When you are troubleshooting a primary condition like MS, asthma, or lupus, youre not thinking about the side effects. Osteoporosis can take a back seat," says Felicia Cosman, MD, medical director of the Clinical Research Center at Helen Hayes Hospital in Haverstraw, N.Y., and an editor of Osteoporosis: An Evidence-Based Guide to Prevention and Management. "Thats understandable -- but you dont want osteoporosis to add more disability to an already disabling condition."

So if the doctor treating your celiac disease or rheumatoid arthritis hasnt already brought up osteoporosis with you, ask to discuss it. Depending on your age and your specific condition, you may have several options to help prevent osteoporosis symptoms:

    * Get an early bone density test. Doctors dont usually recommend bone density tests for postmenopausal women, but if you have one of these conditions, you may need to be monitored more closely, and treated for bone loss more aggressively.
    * Push for more vitamin D and calcium in your diet, and supplement. Edwards recommends that people with conditions that accelerate bone loss get at least 1,000 to 1,500 milligrams of calcium and 400 to 600 international units (IU) of vitamin D from food and supplements. Look for low-fat dairy and fortified foods.
    * Consider getting the vitamin D levels in your blood measured. "Thats not a specific recommendation from the National Osteoporosis Foundation, but it makes so much clinical sense," says Cos man. "Because vitamin D levels vary so much between individuals, its hard to know how much supplementation is needed to reach sufficient levels."

Nutrition researchers from Northwestern Medicine in Chicago report that a diet naturally high in fiber provides critical protection from heart disease in a study of adults aged 20 to 59 years. Results presented to the American Heart Association`s Nutrition, Physical Activity and Metabolism/Cardiovascular Disease Epidemiology and Prevention Scientific Sessions draws the direct correlation between fiber consumption and heart disease risk.

Based on the largest comprehensive systematic review to date, researchers at the Perelman School of Medicine at the University of Pennsylvania concluded that available evidence does not support an association between statins and memory loss or dementia. The new study, a collaborative effort between faculty in Penn Medicines Preventive Cardiovascular Program, the Penn Memory Center, and the Penn Center for Evidence-Based Practice, will be published in Annals of Internal Medicine.

"Statins are prescribed to approximately 30 million people in the United States," said senior study author Emil deGoma, MD, assistant professor of Medicine and medical director of the Preventive Cardiovascular Program at Penn. "A wealth of data supports a benefit of these cholesterol-lowering medications among individuals at risk for cardiovascular disease in terms of a reduction in the risk of heart attack and stroke; however, potential side effects of statins are less well understood. In February 2012, largely based on anecdotal reports, the U.S. Food and Drug Administration (FDA) issued a safety statement warning patients of possible adverse cognitive effects associated with statin use. Many concerned patients have asked if there is a relationship between statins and memory problems. Their concerns, along with the FDA statement, prompted us to pursue a rigorous analysis of all available evidence to better answer the question -- are statins associated with changes in cognition?"

The research team conducted a systematic review of the published literature and identified 57 statin studies reporting measures of cognitive function. Dr. deGoma and colleagues found no evidence of an increased risk of dementia with statin therapy. In fact, in cohort studies, statin users had a 13 percent lower risk of dementia, a 21 percent lower risk of Alzheimers disease, and a 34 percent lower risk of mild cognitive impairment compared to people who did not take statins.

Most importantly, cognitive test scores were not adversely affected by statin treatment in randomized controlled trials. In these trials, roughly half of the study participants received statins and the other half received placebo. All study participants underwent formal testing of memory and other cognitive domains through tests such as the ability to recall a set of numbers. The analysis of 155 cognitive tests spanning eight categories of cognitive function, including 26 tests of memory, revealed no differences between study participants treated with statins and those provided placebo.

The research team additionally performed an analysis of the FDA post-marketing surveillance databases and found no difference in the frequency of cognitive adverse event reports between statins and two commonly prescribed cardiovascular medications that have not been associated with cognitive impairment, namely, clopidogrel and losartan.

"Overall, these findings are quite reassuring. I wouldnt let concerns about adverse effects on cognition influence the decision to start a statin in patients suffering from atherosclerotic disease or at risk for cardiovascular disease. I also wouldnt jump to the conclusion that statins are the culprit when an individual who is taking a statin describes forgetfulness. We may be doing more harm than good if we withhold or stop statins -- medications proven to reduce the risk of heart attack and stroke -- due to fears that statins might possibly cause memory loss," said Dr. deGoma.

The team acknowledges that while their analysis is reassuring, large, high-quality randomized controlled trials are needed to confirm their findings.

"For many of the cognitive outcomes that we examined, the identified studies were small, were at risk for bias, used varying diagnostic tests to assess cognitive domains, and did not include patients on high-dose statins, which is important given the increasing use of high-dose statins for secondary prevention," noted study co-author Craig Umscheid, MD, MSCE, assistant professor of Medicine and Epidemiology and director of the Penn Center for Evidence-based Practice. "Thus, additional trials addressing these limitations would strengthen our conclusions. Despite this, the totality of the evidence does reassure us that theres unlikely to be a significant link between statins and cognitive impairment."

Results of two studies presented at the American Diabetes Associations 71st Scientific Sessions last week described risks of consuming diet soft drinks.

The first study found that users of diet soda, on average, experienced a 70% greater increase in waist size compared with non-users. Those with the greatest consumption - two or more diet sodas a day - experienced waist size increases that were 500% greater (5 times greater) than those of non-users:

Diet Soft Drink Consumption Is Associated With Increased Waist Circumference In The San Antonio Longitudinal Study Of Aging

There were 474 participants, aged 65 to 74, who were followed for approximately 9.5 years. To lessen the effect of confounders, results were adjusted for gender, age, beginning waist circumference, diabetes and smoking status, education, ethnicity, leisure-time activity, neighborhood, and length of follow-up.



The authors concluded:

“The promotion of diet sodas as healthy alternatives [to sugar-sweetened drinks] may be ill-advised: they may be free of calories, but not of consequences.”

The second study found a link between artificial sweetener consumption and blood glucose in mice:

Aspartame Consumption Is Associated With Elevated Fasting Glucose In Diabetes-Prone Mice

After three months of eating aspartame-spiked chow, mice had higher fasting glucose levels (144 vs. 105 mg/dl) and lower insulin levels than control mice.

As to mechanism, Sharon Fowler, coauthor of both studies, said in an interview with the Daily Mail:

"Artificial sweeteners could have the effect of triggering appetite but unlike regular sugars they don’t deliver something that will squelch the appetite."

It was noted that artificial sweeteners may also damage or inhibit brain cells that are involved in feelings of satiety.
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A new study suggests caffeinated coffee drinkers should limit their intake to reduce their chances of developing vision loss or blindness. According to a scientific paper in Investigative Ophthalmology & Visual Science, heavy caffeinated coffee consumption is associated with an increased risk of developing exfoliation glaucoma, the leading cause of secondary glaucoma worldwide.

The study, The Relation between Caffeine and Coffee Consumption and Exfoliation Glaucoma or Glaucoma Suspect: A Prospective Study in Two Cohorts, is the first to examine the link between caffeinated coffee and exfoliation glaucoma in a U.S. -based population.

"Scandinavian populations have the highest frequencies of exfoliation syndrome and glaucoma," said author, Jae Hee Kang, ScD, of Channing Division of Network Medicine at Brigham and Womens Hospital in Boston, Mass. "Because Scandinavian populations also have the highest consumption of caffeinated coffee in the world, and our research group has previously found that greater caffeinated coffee intake was associated with increased risk of primary open-angle glaucoma, we conducted this study to evaluate whether the risk of exfoliation glaucoma or glaucoma suspect may be different by coffee consumption."

The study was composed of two cohorts: 78,977 women from the Nurses Health Study (NHS) and 41,202 men from the Health Professionals Follow-up Study (HPFS) who were at least 40 years of age, did not have glaucoma and reported undergoing eye examinations from 1980 (for NHS participants) and 1986 (for HPFS participants) to 2008. The research team used questionnaires to obtain and validate the consumption of beverages containing caffeine and reviewed medical records to determine incident cases of exfoliation glaucoma, which contributes to elevated pressure sufficient enough to damage the optic nerve, or exfoliation glaucoma suspect that have milder or only suspect optic nerve damage.

A meta-analysis of the two cohorts showed that, compared to abstainers, participants who drank three cups or more of caffeinated coffee daily were at an increased risk of developing exfoliation glaucoma or glaucoma suspect. The researchers did not find associations with consumption of other caffeinated products, such as soda, tea, chocolate or decaffeinated coffee. The results also showed that women with a family history of glaucoma were at an increased risk.

Kang, along with his colleagues, report that this study represents a much needed effort to better understand the causes of exfoliation glaucoma, which are largely unknown.

"Because this is the first study to evaluate the association between caffeinated coffee and exfoliation glaucoma in a U.S. population, confirmation of these results in other populations would be needed to lend more credence to the possibility that caffeinated coffee might be a modifiable risk factor for glaucoma," said Kang. "It may also lead to research into other dietary or lifestyle factors as risk factors.

A prospective study led by researchers from the University of California, San Diego School of Medicine has found that low serum vitamin D levels in the months preceding diagnosis may predict a high risk of premenopausal breast cancer.

The study of blood levels of 1,200 healthy women found that women whose serum vitamin D level was low during the three-month period just before diagnosis had approximately three times the risk of breast cancer as women in the highest vitamin D group. The study is currently published online in advance of the print edition of the journal Cancer Causes and Control.

Several previous studies have shown that low serum levels of vitamin D are associated with a higher risk of premenopausal breast cancer. "While the mechanisms by which vitamin D could prevent breast cancer are not fully understood, this study suggests that the association with low vitamin D in the blood is strongest late in the development of the cancer, "said principal investigator Cedric Garland, DrPH, FACE, professor in the Department of Family and Preventive Medicine at UC San Diego.

Analyses of vitamin D levels measured more than 90 days before diagnosis have not conclusively established a relationship between serum levels and risk of premenopausal breast cancer in the present cohort. However, this new study points to the possibility of a relevant window of time for cancer prevention in the last three months preceding tumor diagnosis –a time physiologically critical to the growth of the tumor.

According to Garland, this is likely to be the point at which the tumor may be most actively recruiting blood vessels required for tumor growth. "Based on these data, further investigation of the role of vitamin D in reducing incidence of premenopausal breast cancer, particularly during the late phases of its development, is warranted," he said.

The new study drew upon 9 million blood serum specimens frozen by the Department of Defense Serum Repository for routine disease surveillance. The researchers thawed and analyzed pre-diagnostic samples of serum from 1,200 women whose blood was drawn in the same time frame – samples from 600 women who later developed breast cancer, and from 600 women who remained healthy.

A 2011 meta-analysis by Garland and colleagues estimated that a serum level of 50 ng/ml is associated with 50 percent lower risk of breast cancer. While there are some variations in absorption, those who consume 4000 IU per day of vitamin D from food or a supplement normally would reach a serum level of 50 ng/ml.

Garland added that a consensus of all available data has shown no known risk associated with this concentration of vitamin D, which is measured as serum 25-hydroxyvitamin D. But he urges patients to ask their health care provider to measure their serum 25(OH)D before substantially increasing vitamin D intake.

"Reliance should not be placed on different forms of vitamin D, such as vitamin D2, and megadoses should be avoided except those ordered by a doctor for short-term use," Garland added.

Recent studies have linked caffeine consumption to a reduced risk of Alzheimers disease, and a new University of Illinois study may be able to explain how this happens.

"We have discovered a novel signal that activates the brain-based inflammation associated with neurodegenerative diseases, and caffeine appears to block its activity. This discovery may eventually lead to drugs that could reverse or inhibit mild cognitive impairment," said Gregory Freund, a professor in the U of Is College of Medicine and a member of the U of Is Division of Nutritional Sciences.

Freunds team examined the effects of caffeine on memory formation in two groups of mice—one group given caffeine, the other receiving none. The two groups were then exposed to hypoxia, simulating what happens in the brain during an interruption of breathing or blood flow, and then allowed to recover.

The caffeine-treated mice recovered their ability to form a new memory 33 percent faster than the non-caffeine-treated mice. In fact, caffeine had the same anti-inflammatory effect as blocking IL-1 signaling. IL-1 is a critical player in the inflammation associated with many neurodegenerative diseases, he said.

"Its not surprising that the insult to the brain that the mice experienced would cause learning memory to be impaired. But how does that occur?" he wondered.

The scientists noted that the hypoxic episode triggered the release of adenosine by brain cells.

"Your cells are little powerhouses, and they run on a fuel called ATP thats made up of molecules of adenosine. When theres damage to a cell, adenosine is released," he said.

Just as gasoline leaking out of a tank poses a danger to everything around it, adenosine leaking out of a cell poses a danger to its environment, he noted.

The extracellular adenosine activates the enzyme caspase-1, which triggers production of the cytokine IL-1β, a critical player in inflammation, he said.

"But caffeine blocks all the activity of adenosine and inhibits caspase-1 and the inflammation that comes with it, limiting damage to the brain and protecting it from further injury," he added.

Caffeines ability to block adenosine receptors has been linked to cognitive improvement in certain neurodegenerative diseases and as a protectant against Alzheimers disease, he said.

"We feel that our foot is in the door now, and this research may lead to a way to reverse early cognitive impairment in the brain. We already have drugs that target certain adenosine receptors. Our work now is to determine which receptor is the most important and use a specific antagonist to that receptor," he said.

Study highlights importance of social ties during midlife


Could marriage, and associated companionship, be one key to a longer life? According to new research, not having a permanent partner, or spouse, during midlife is linked to a higher risk of premature death during those midlife years. The work, by Dr. Ilene Siegler and colleagues from Duke University Medical Center in the US, is published online in Springers journal Annals of Behavioral Medicine.

Survival through middle age to become elderly is expected; theore understanding who does not survive to become elderly and why is important. Siegler and colleagues looked at the effect of marriage history and timing of marriage on premature death during midlife. They were also interested in testing the role of pre-marital personality and quantifying the role of health behaviors.

The researchers analyzed data for 4,802 individuals who took part in the University of North Carolina Alumni Heart Study (UNCAHS) - an ongoing study of individuals born in the 1940s. The authors were particularly interested in stability and change in patterns of marital and non-marital status during midlife, controlling for personality at college entry (average age 18), socioeconomic status and health risk behaviors.

They found that having a partner during middle age is protective against premature death: those who never married were more than twice as likely to die early than those who had been in a stable marriage throughout their adult life. Being single, or losing a partner without replacement, increased the risk of early death during middle age and reduced the likelihood that one would survive to be elderly. Even when personality and risky behaviors were taken into account, marital status continued to have a major impact on survival.

The authors conclude: "Our results suggest that attention to non-marital patterns of partnership is likely to become more important for these Baby Boomers. These patterns appear to provide different levels of emotional and functional social support, which has been shown to be related to mortality. Social ties during midlife are important to help us understand premature mortality."
Reference:
Siegler IC et al (2012). Consistency and timing of marital transitions and survival during midlife: the role of personality and health risk behaviors. Annals of Behavioral Medicine; DOI 10.1007/s12160-012-9457-3

A recent study in the Archives of Internal Medicine investigated the effect of combined lifestyle factors on the development of type 2 diabetes in older adults.¹

Researchers analyzed data from participants of the Cardiovascular Health Study:

• 4883 men and women 65 years or older
  
• Followed for a 10-year period (1989-1998)

Five lifestyle factors were studied:

• Physical activity level.
  
• Dietary score. A low-risk score lected:
  • Higher fiber intake
    
  • Higher polyunsaturated-to-saturated fat ratio
    
  • Lower trans-fat intake
    
  • Lower glycemic index
• Smoking. Never smoked or former smoker greater than 20 years lected low-risk.
  
• Alcohol use. Light or moderate intake lected low-risk.
  
• Body fat. Low-risk lected:
  • BMI less than 25 (Calculate your BMI here.)
    
  • Waist circumference 88 cm or less for women (34.6 in), 92 cm for men (36.2 in)

The study found:

"The rate of incident diabetes was 35% lower for each 1 additional lifestyle factor in the low-risk group.

Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes.

When absence of adiposity (either body mass index < 25 or waist circumference ≤ 88/92 cm for women/men) was added to the other 4 low-risk lifestyle factors, incidence of diabetes was 89% lower.

Overall, 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors."

The authors concluded:

"Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus."

________
¹ Lifestyle Risk Factors And New-Onset Diabetes Mellitus In Older Adults, Archives of Internal Medicine, April 27, 2009