Watchful waiting associated with reduced survival
A study presented at the 2006 Prostate Cancer Symposium on February 25 in San Francisco found that older men with early stage prostate cancer who were treated for the disease lived longer than those for whom "watchful waiting" was advised.
Due to the development of the prostate-specific antigen blood test, prostate cancer is often diagnosed at early stages during which it can grow slowly. Older men with early stage disease are sometimes observed rather than treated. Yu-Ning Wong, MD, an oncologist at Fox Chase Cancer Center who presented the study explained, "Some prostate cancers grow so slowly that they never become life-threatening, especially in elderly men who may die of other causes before the cancer causes problems. But other men develop complications and die from their cancer making the decision to treat quite difficult."
The current study evaluated the survival of 48,606 men diagnosed with prostate cancer between the ages of 65 and 80 who survived at least one year. A total of 14,098 men underwent radical prostatectomy, 19,948 were treated with radiation therapy and 14,560 were observed without being treated.
At the study's conclusion, men who received radiation therapy or radical prostatectomies survived an average of 13 years, while untreated men survived ten years. "This large, population-based study demonstrates a survival advantage for men treated with either radical prostatectomy or radiation therapy compared to observation," Dr Wong concluded. "Eligible men should be considered for both treatment options."
This study supports the findings of researchers who reported in the May 12, 2005 issue of the New England Journal of Medicine that prostate cancer patients treated with surgery lived longer than those who were only observed. With the advent of longer life spans and better treatment for other diseases, more older men may opt for prostate cancer treatment.
N-acetylcysteine improves cognition in patients with elevated homocysteine
A case series presented online in Nutrition Journal revealed that adding the amino acid N-acetylcysteine to a regimen of B vitamins administered to cognitively impaired patients with high homocysteine levels resulted in improvement in all patients. High levels of plasma homocysteine have been linked with an elevated risk of vascular disease and dementia, and have been reported in patients with mild cognitive impairment and Alzheimer's disease.
Andrew McCaddon of Wales College of Medicine in Wrexham, North Wales presented seven cases of older individuals with memory loss and/or confusion who had high plasma levels of homocysteine. "Although plasma levels of homocysteine are largely determined by vitamin B12 and folate status," Dr McCaddon writes, "Antioxidant therapy might also be required for optimal reduction in neurovascular tissue."
The five women and two men were given 600 milligrams N-acetylcysteine per day, along with treatment with oral or injectable vitamin B12 and, for most of the patients, 5 milligrams folic acid.
All seven patients experienced subjective improvement in their cognitive function after a varying amount of weeks. Objective improvement, as assessed by cognitive function test scores, was noted in five patients. One patient who underwent magnetic resonance imaging prior to receiving supplementation showed cessation of the progression of small vessel disease upon re-examination after one year of supplementation.
Dr McCaddon observed that the mechanism underlying the association with elevated homocysteine could be its adverse effects on neurovascular tissue combined with neurotransmitter synthesis impairment caused by defects in methyl group metabolism. The responses to N-acetyl cysteine demonstrated in the case series suggests that homocysteine could be a marker for the effects of oxidative stress in brain tissue.
Risk factors at age 50 predict cardiovascular disease risk and life expectancy
A study published in the February 14, 2006 issue of Circulation reported the association between the presence of cardiovascular disease risk factors at age 50 and the risk of developing cardiovascular disease over the next 45 years. The study also calculated the association between cardiovascular disease risk factors and survival.
Donald M. Lloyd-Jones, MD, of Northwestern University in Chicago and colleagues followed 3,564 men and 4,362 women who participated in the Framingham Heart Study. Participants who were free of cardiovascular disease before their initial examination between 1971 and 2002 were included in the current analysis. Cardiovascular events occurred in 1,757 participants during the follow up period ending in 2002, and noncardiovascular deaths occurred in 1,641. Lifetime cardiovascular disease risk for men and women at age 50 were calculated as 51.7 and 39.2 percent.
Optimal risk factors were defined as a cholesterol level of 180 milligrams per deciliter or lower, blood pressure less than 120/80 mm Hg, being a nonsmoker, and being nondiabetic. Having a cholesterol level of 240 milligrams per deciliter or more, blood pressure 160/100 mm Hg or higher, being a smoker, and being diabetic were considered to be major risk factors. Men with optimal risk factors had a 5.2 percent risk of developing cardiovascular disease while those with two or more major risk factors experienced a 68.9 percent risk . For women with optimal risk factors, the risk was 8.2 percent, in contrast with a 50.2 percent risk incurred by those with at least two major risk factors. Survival among men and women with optimal risk factors at age 50 was 39 years, compared to 28 years for men and 31 years for women with two or more major risk factors.
Prior to this study, lifetime risk for cardiovascular disease had not been estimated. The additional years of life associated with having optimal risk factors at age 50 should encourage younger people to achieve them.
Extended lifespans could be a reality in just a few years
The annual meeting of the American Association for the Advancement of Science in St. Louis was the site of a talk on February 17, 2006 by biologist Shripad Tuljapurkar on the possible effects of longer lifespans. Dr Tuljapurkar predicts that antiaging technologies could extend human lifespan by 20 years between 2010 and 2030. Dr Tuljapurkar, who is the Dean and Virginia Morrison Professor of Population Studies at Stanford University, stated "Some people believe we are on the brink of being able to extend human lifespan significantly, because we've got most of the technologies we need to do it."
By examining relationships between trends in aging, population growth, and economic activity in various countries, and combining the data with forecasts from researchers in the field of aging, Dr Tuljapurkar concluded that "Starting around 2010, we could see lifespan increase dramatically."
The extension of average lifespan in industrialized countries from 80 to 100 years reflects a growth rate in human lifespan that is five times the current rate. Although this will boost global population, creating a number of challenges, a longer lived population could be the solution to the population decline forecasted for countries with low fertility rates. Dr Tuljapukar predicts that the extension in lifespan will occur in wealthier countries in which people can afford antiaging technologies, leaving poorer countries behind. "Big pharmaceutical companies have a well-established track record of being very difficult when it comes to making things available to those who can't pay for them," he observed.
"What we've tended to do historically with medical advances is to take the reasonable position that we should implement everything that comes along," Dr Tuljapurkar concluded. "However, we are now approaching a stage where it's necessary to look the implications before we rush in--at least so we can prepare ourselves."
Vitamin C supplements help maintain vitamin E in smokers
Research published in the February 15, 2006 issue of the journal Free Radical Biology and Medicine found that supplementing smokers with vitamin C can halt the depletion of vitamin E that occurs in this population. Vitamin E offers protection to the lungs from free radicals created by smoking, but can itself be transformed into a destructive free radical without adequate vitamin C.
Prior to the double-blind trial, researchers at the Linus Pauling Institute at Oregon State University asked 11 smokers and 13 nonsmokers to consume a diet containing low amounts of fruits and vegetables for three months to create a vitamin C depleted state. Participants were then given 500 milligrams vitamin C or a placebo twice daily for two weeks. The team found that smokers who received vitamin C had a plasma vitamin E disappearance rate similar to that of nonsmokers, but those who received a placebo and were therefore deficient in vitamin C lost the form of vitamin E known as alpha-tocopherol 25 percent more rapidly than nonsmokers and gamma-tocopherol about 45 percent faster.
The research is the first to demonstrate this interaction between the vitamins in humans, and could help explain how smoking causes cancer. Lead researcher and OSU professor of nutrition Maret Traber stated, "A lot of nutrition research in the past has been done by studying one nutrient or another in isolation, sometimes with conflicting results. What this and other studies like it are showing is that the protection we get from proper diet or supplements often comes from combinations of nutrients working together. This has implications not only for smokers but also for many other people."
Dr Traber also noted that many studies showing "no benefit" from vitamin supplements have been done in people with existing disease, but for antioxidants to be successful, they usually have to be present in advance.
Twelve questions predict death within four years in over-50s
The February 15, 2006 issue of the Journal of the American Medical Association published a report announcing the development of a prognostic index that can be used to predict death within the next four years among men and women aged fifty and up.
Researchers at the San Francisco Veterans Administration Medical Center developed the index from data obtained from 11,701 adults participating in the Health and Retirement Study (HRS) from 1998 to 2002. Participants were asked in telephone interviews about the presence of specific diseases, demographic characteristics and whether they experienced difficulty with several functions. A point scoring system was developed on twelve predictors: increased age, male gender, diabetes, cancer, lung disease, heart failure, tobacco use, body mass index of less than 25, difficulty bathing, difficulty walking several blocks, difficulty managing money, and difficulty pushing large objects.
During the follow-up period there were 1,361 deaths. Index scores divided into quarters of increasing ranges corresponded with a rising risk of mortality over the four year period. The index was subsequently validated in 8,009 other HRS participants among whom there were 1,072 deaths, and was found to be 82 percent accurate.
Lead author and San Francisco VA Medical Center geriatric specialist Sei J. Lee, MD, commented, "There's a real need for this kind of prognostic index, for several reasons. For example, is it worth it to order a Pap smear or colonoscopy for a particular patient? Those sorts of screening interventions generally don't help patients until five to eight years after they are given. Doctors need to get a sense of who will survive long enough to benefit"
"This index has the advantage of being applicable to everyone who is seen in a clinic who is older than 50," he added"There aren't many indexes that are as widely applicable"
People who drink more green tea have a lower incidence of cognitive impairment
The February 2006 issue of the American Journal of Clinical Nutrition published the finding of researchers at Tohoku University Graduate School of Medicine in Sendai, Japan, that consuming more green tea is associated with a lower prevalence of cognitive impairment. To the researchers' knowledge, the study is the first to examine the association between green tea drinking and cognitive function in humans.
Shinichi Kuriyama, of the school's departments of public health and forensic medicine, and colleagues evaluated data from 1002 men and women aged 70 and older who participated in the Japanese Comprehensive Geriatric Assessment in 2002. Subjects completed questionnaires concerning the frequency of green tea, black tea, and coffee consumption among other questions. Cognitive function test scores were used to classify the participants as having no impairment, slight cognitive impairment, cognitive impairment, or severe cognitive impairment.
High consumption of green tea at two or more cups per day by the top one-third of participants was associated with less than half the incidence of cognitive impairment, including severe cognitive impairment, than that found among participants whose intake was in lowest third at three or fewer cups per week. Participants whose tea consumption was in the middle third experienced a 38 percent reduction. No significant relationship between black tea or coffee consumption and cognitive impairment was observed.
The authors suggest that the lower prevalence of dementia and Alzheimer's disease in Japan could be explained by the green tea consumed by this population. "Given the high prevalence, worldwide rapid increase, and clinical significance of dementia," they write, "any association between the intake of green tea, a drink with little toxicity and no calorific value, and cognitive function could have considerable clinical and public health relevance."
Soy and cruciferous vegetables enhance DNA repair
The February 13, 2006 issue of the British Journal of Cancer reported the findings of researchers at Georgetown University's Lombardi Comprehensive Cancer Center that genistein and indole-3-carbinol, found in soy and cruciferous vegetables such as broccoli, enhance DNA repair. The finding could explain, in part, the protective effect these compounds have shown to provide against some cancers.
After administering increasing doses of I3C and genistein to two prostate cancer and two breast cancer cell lines, the researchers found a rise in levels of BRCA1 and BRCA2 proteins, which repair damaged DNA. Mutations in the genes for these proteins hinders DNA repair, which leads to the proliferation of abnormal cells and the initiation of cancer. Individuals with these mutations are at an increased risk of breast, ovarian, or prostate cancer. Because low amounts of the BRCA proteins are found in cancer cells, high levels may be protective.
The increased expression of BRCA1 and BRCA2 occurred with relatively low doses of either compound, and became greater with more time exposure and with higher doses. When I3C and genistein were administered together in low doses to two of the cell lines, a synergistic effect resulted in a greater expression of BRCA2 than that elicited by either compound alone.
The study is among the first to discover a molecular explanation behind the ability of increased vegetable consumption to reduce cancer risk. Senior author and professor of oncology, cell biology, and radiation medicine at Georgetown University, Eliot M. Rosen, MD, PhD, commented, "It is now clear that the function of crucial cancer genes can be influenced by compounds in the things we eat. Our findings suggest a clear molecular process that would explain the connection between diet and cancer prevention."
Lower colon cancer risk for women with high magnesium intake
Aaron R Folson and Ching-Ping Hong at the University of Minnesota in Minneapolis have found an association between diets that contain higher amounts of magnesium and a reduced risk of colon cancer among women. Their report was published in the February 1, 2006 issue of the American Journal of Epidemiology.
Acting on the findings of a recent study that discovered a link between higher amounts of the mineral and a lower incidence of colorectal cancer among Swedish women, Drs Folson and Hong analyzed data from 35,196 women aged 55 to 69 who had taken part in the Iowa Women's Health Study. Food frequency questionnaires completed upon enrollment were used to determine the amount of magnesium and other nutrients obtained from food and supplements. The participants were followed from 1986 though 2002, during which 1,112 women were diagnosed with colorectal cancer.
The average magnesium intake of the women was found to be 302 milligrams per day. Although no association was found between low magnesium intake and rectal cancer, colon cancer risk decreased as magnesium intake rose. Women whose magnesium was in the top fifth had a 23 percent lower risk of developing colon cancer than those whose intake was in the lowest fifth, while those whose intake was in the second and third fifths experienced a 15 and 12 percent reduction.
The authors suggested decreased insulin resistance, oxidative stress and cell proliferation as possible preventive mechanisms for magnesium, and remarked that foods high in magnesium such as vegetables and grains have already been shown to be protective against colorectal cancer because of their fiber content and beneficial micronutrients. Therefore, it is not clear whether magnesium or other aspects of high-magnesium foods are responsible for the effects revealed in this study.
Carnitine reduces fatigue and improves quality of life in patients undergoing cancer treatment
A study published in the February 2006 issue of the journal Nutrition reported that supplementing cancer patients with the amino acid L-carnitine reduced fatigue and high oxidative stress levels which are commonly seen in advanced cancer patients.
Carnitine is an amino acid involved in the production of energy in the body. Cancer patients may be at risk of carnitine deficiency due to their decreased calorie intake and increased metabolic requirements, in addition to the interference of carnitine absorption and synthesis, and increased excretion caused by chemotherapy drugs.
For the current study, researchers from the University of Cagliari, in Monserrato, Italy, enrolled twelve men and women being treated for advanced tumors who reported fatigue and/or had high blood levels of reactive oxygen species. Two grams L-carnitine three times daily was administered for four weeks, during which the patients continued to undergo cancer therapy. Fatigue, quality of life as related to oxidative stress levels, body composition, and inflammatory cytokines were evaluated before the treatment period, and at two and four weeks.
While proinflammatory cytokine levels remained basically the same, reactive oxygen species levels decreased over the course of the study. Fatigue significantly decreased, while lean body mass and appetite increased following L-carnitine supplementation.
The authors believe that the fatigue experienced by people with cancer is primarily a consequence of cachexia. They conclude that the "improvement of symptoms with respect to fatigue and quality of life in relation to oxidative stress may be explained mainly by an increase in lean body mass, which may be considered the most important nutritional or functional parameter in assessing the cachectic state of patients. In this view, fatigue with related symptoms can well be considered an important constituent of cancer-related anorexia cachexia syndrome."
Our bodies, our cells
In an advance online publication on February 2, 2006 in the journal Science, biologists from Brown University reported a connection between the age of baboons and the number of aging cells in their skin, boosting the theory that cellular senescence is associated with an aged body. Replicative senescence occurs when cells lose their ability to divide after a number of replications. Senescent cells are associated with skin wrinkles, weakened immune response and other age related conditions and diseases.
Professor of medical science John Sedivy and colleagues examined skin samples from the forearms of 30 baboons aged 5 to 30 for biomarkers of cellular aging. They found an exponential increase in DNA double-strand breakage with the animals' increasing age, reaching 30-35 percent in the oldest animals. The most important biomarker, telomere dysfunction-induced foci (TIF) which show that telomeres have shrunk to the extent that cell division is halted, were found in 4 percent of the tissue cells of 5 year old baboons and in up to 20 percent of the cells of the 30 year olds.
The authors observed that telomeric DNA damage may not be entirely due to replicative exhaustion, and note that oxidative stress increases the rate of telomere shrinkage.
Dr Sedivy commented, "For 40 years, we've known about replicative senescence. Whether it promotes the aging of our bodies, however, is highly controversial. While it may make intuitive sense, skeptics say 'Show us the evidence.' The first solid evidence is in this study. These initial findings won't settle the debate, but they make a strong case."
"There is good evidence that senescent cells are not benign," he added. "But until now, no one has been able to confirm that they exist in appreciable numbers in old animals."
Omega-6 fatty acids fuel prostate cancer growth
A study published in the February 1 2006 issue of the journal Cancer Research reported that the addition of an omega-6 fatty acid to cultured prostate cancer cells doubled their growth rate compared to untreated prostate cancer cells. Omega-6 fatty acids are found in corn and other oils, and while they are essential, some researchers believe that the high level of omega 6 relative to omega-3 fatty acids (which are found in fish and other foods) in the modern American diet may be harmful.
Researchers at the San Francisco Veterans Administration Medical Center led by Millie Hughes-Fulford, PhD, based the current investigation on findings from previous research that omega-6 fatty acid arachidonic acid stimulates the production of an enzyme known as cPLA-2, which produces a chain reaction ending in tumor growth. In the current study, arachidonic acid was found to fuel prostate tumor cell growth by turning on a gene signaling pathway.
"After we added omega-6 fatty acids to the growth medium in the dish, and only omega-6, we observed that tumors grew twice as fast as those without omega-6," Dr Fulford-Hughes explained. "Investigating the reasons for this rapid growth, we discovered that the omega-6 was turning on a dozen inflammatory genes that are known to be important in cancer. We then asked what was turning on those genes, and found that omega-6 fatty acids actually turn on a signal pathway called PI3-kinase that is known to be a key player in cancer."
Dr Hughes-Fulford observed that the rate of prostate cancer in the U.S. has increased along with omega-6 intake. She added, "I'm not a physician, and do not tell people how to eat, but I can tell you what I do in my own home. I use only canola oil and olive oil. We do not eat deep-fried foods."