In The News: April 2014

An article that appeared online in the British Journal of Cancer describes the findings of Harvard researchers of a lower risk of colorectal adenoma (polyps) in women who used multivitamin supplements.*

The current investigation included 43,641 women enrolled in the Nurses’ Health Study II who underwent initial colonoscopy or sigmoidoscopy examinations between 1991 and 2007. Questionnaires completed every two years by the participants beginning in 1991 provided information on the use of multivitamin supplements and whether colon or rectal polyps had been diagnosed. Over the course of follow-up, 2,277 women were diagnosed with colorectal adenomas, of which 1,090 were classified as low-risk and 696 were classified as at high risk of developing into cancer. Women who reported using multivitamins at any time over the course of follow-up had a 14% lower risk of colorectal adenoma than non-users.

Editor’s Note : When duration of use was examined, subjects who used vitamins for 20 to 26 years experienced the greatest protective effect, with a 20% lower risk in comparison with those who did not report using a multivitamin supplement.

A study described in Experimental Gerontology uncovered a protective effect for higher levels of the vitamin E subfractions gamma tocopherol, beta tocotrienol, and total tocotrienols against the risk of developing Alzheimer’s disease or mild cognitive impairment.*

Researchers evaluated the association between serum tocopherol and tocotrienol levels and cognitive impairment in 140 participants in the CAIDE study, which examined Finnish men and women at several time points during midlife and re-examined survivors in 1998 and 2005-2008. The current study compared 64 subjects diagnosed at the second re-examination with mild cognitive impairment or Alzheimer’s disease with 76 cognitively normal participants. Serum samples collected in 1998 were analyzed for tocopherols, tocotrienols, and cholesterol (which may influence serum vitamin E levels).

The researchers uncovered a 73% lower risk of cognitive impairment among those whose serum gamma tocopherol to cholesterol ratio was among the middle third of subjects in comparison with those whose ratio was among the lowest third.

Editor’s Note : Higher serum levels of gamma tocopherol, beta tocotrienol, and total tocotrienols were each associated with a significantly lower risk of being cognitively impaired.

Published in the journal European Urology, a team of researchers from Switzerland found that treatment with metformin in patients with castration-resistant prostate cancer increased progression-free survival and prolonged PSA doubling time.*

The one year study included 44 men diagnosed with progressive, metastatic castration-resistant prostate cancer at 10 different Swiss centers who were given1,000 mg of metformin twice daily. After 12 weeks of treatment, 36% of patients were progression free with over 25% of these men remaining progression free at 24 weeks. Over 52% of the patients experienced a prolongation of PSA doubling time (a reflection of slower tumor growth). Additionally, insulin sensitivity markers improved by 26% in the first 12 weeks of treatment.

Editor’s Note: The researchers concluded that “treatment with metformin is safe in non-diabetic patients, and it yields objective PSA responses and may induce disease stabilization. The activity of metformin in prostate cancer, along with its low cost, favorable toxicity profile, and positive effect on metabolic parameters” warrants further investigation of metformin as a treatment for prostate cancer.

A recent issue of the Journal of Clinical and Diagnostic Research published the findings of a study conducted at Mahatma Gandhi Medical College and Research Institute of reduced levels of vitamin D, calcium, and magnesium in diabetic individuals, as well as associations between decreased concentrations of serum vitamin D and magnesium with increased insulin resistance.*

The study compared 30 diabetic men and women with an equal number of non-diabetic control subjects matched for gender and age. Fasting blood samples were analyzed for serum glucose, insulin, 25-hydroxyvitamin D3, and insulin levels, and insulin resistance was determined.

Serum 25-hydroxyvitamin D3 levels averaged 12.29 ng/mL among those with type II diabetes in comparison with 19.55 ng/mL in the healthy controls. Serum calcium and magnesium levels were also significantly lower in the diabetic group and fasting glucose, insulin, and insulin resistance were greater among those with diabetes.

Greater insulin levels are seen in insulin resistant individuals who often secrete more insulin to keep glucose levels from acutely rising too high. This continues until pancreatic beta cells are no longer able to produce insulin, and the type II diabetic then requires insulin injections to keep glucose under control.

Editor’s Note : A significant correlation was determined between lower vitamin D levels and higher insulin levels as well as insulin resistance. Additionally, higher vitamin D levels were correlated with increased magnesium status, and low magnesium with insulin resistance.

The Journal of Clinical Endocrinology and Metabolism contained a report of the findings of researchers from England’s Medical Research Council Lifecourse Epidemiology Unit at the University of Southampton of a muscle strength benefit in the children of mothers who had higher vitamin D levels during pregnancy.*

The study included 678 pregnant participants in the Southampton Women’s Survey. The women’s serum 25-hydroxyvitamin D levels were measured at 34 weeks of gestation. When their children were four years old, hand grip strength, lean mass, percent lean mass, and physical activity were assessed.

A correlation was observed between higher serum 25-hydroxyvitamin D levels and an increase in hand grip strength. An additional association was found between total lean mass and increased vitamin D concentrations, which was reduced after adjustment for several factors.

Editor’s Note : Lead researcher Nicholas C. Harvey, who is a Senior Lecturer at the Medical Research Council Lifecourse Epidemiology Unit remarked that, “It is likely that the greater muscle strength observed at four years of age in children born to mothers with higher vitamin D levels will track into adulthood, and so potentially help to reduce the burden of illness associated with loss of muscle mass in old age.”

A recent article in the Journal of Clinical Nutrition reports on a study in which high homocysteine levels are associated with an increased risk of colorectal cancer independently of oxidative stress and antioxidant capacities.*

The study recruited 186 subjects with colorectal cancer and 188 healthy people as controls. The purpose of this study was to determine the associations of homocysteine, cysteine, vitamin B6 (as pyridoxal 5’-phosphate), and folate with oxidative stress indicators and antioxidant capacities, and to further analyze their relationships with respect to risk for colorectal cancer.

The results showed that there were no significant associations of homocysteine, cysteine, and folate with oxidative stress indicators and antioxidant capacities, but subjects with higher plasma homocysteine concentration exhibited significantly increased risk of colorectal cancer independently of oxidative stress indicators and antioxidant capacities. However, cysteine, B6, and folate were not found to be related to oxidative stress, antioxidant capacities, and the risk of colorectal cancer.

The European Journal of Preventive Cardiology reports the finding of a lower risk of death from cardiovascular disease among men and women with a higher intake of the omega-3 fatty acids EPA and DHA, which are derived from marine sources, and alpha-linolenic acid (ALA), which occurs in plant foods.*

The current study evaluated data obtained from the Singapore Chinese Health Study, which recruited 63,257 Chinese men and women between the ages of 45 and 74 years from 1993 to 1998. Responses to questionnaires completed upon enrollment provided information on the intake of omega-3 fatty acids. Over the follow-up period through 2011, 4,780 deaths from cardiovascular disease occurred, which included 2,697 attributable to coronary heart disease and 1,298 from stroke.

When subjects in the top quartile of omega-3 fatty acid intake were compared with the lowest quartile, a 17% lower risk of dying from cardiovascular disease was observed.

Editor’s Note : When EPA combined with DHA intake was separately examined, a 14% lower risk for those in the top 25% compared to the lowest was found, and for ALA, the risk of dying from cardiovascular disease was 19% lower for those among the highest fourth.

An article published in PLOS One reports the finding of a chemosensitizing benefit for curcumin, a compound occurring in turmeric, in colon cancer cells resistant to treatment with the chemotherapy drug 5-fluorouracil (5-FU).*

The current study utilized cultures of two high density colorectal cell lines that were sensitive to 5-fluorouracil and cultures of their 5-FU resistant clones. One of the two non-resistant lines and its resistant clone were deficient in their DNA mismatch repair systems, which results in genetic instability, increased susceptibility to neoplastic transformation, and greater development of chemoresistant cells. Cells were treated with varying concentrations of 5-FU or BCM-95 curcumin, or received pretreatment with curcumin followed by exposure to one of four concentrations of 5-FU.

While 5-FU dose-dependently reduced the proliferation of the non-resistant cell lines, curcumin alone decreased proliferation in all cell lines, showing the most significant effects in the lines that were not deficient in their DNA mismatch repair systems.

Editor’s Note : Pretreatment with curcumin prior to 5-FU administration revealed a benefit in 5-FU sensitive as well as resistant cells. Either treatment or their combination also decreased markers of cancer stem cells in all lines, with the greatest benefit observed in association with combination therapy.

A report published in the journal Pain describes the outcome of a trial involving vitamin D supplementation by adults with fibromyalgia, which found a benefit for the vitamin in relieving the chronic pain that characterizes the syndrome.*

The trial included 30 subjects diagnosed with fibromyalgia syndrome who had low serum 25-hydroxyvitamin D levels. Half of the participants received vitamin D3, and the remaining half received a placebo for 24 weeks. The goal for the treatment group was to achieve serum calcifediol levels between 32 and 48 ng/mL for 20 weeks. Serum vitamin D levels were measured before treatment and at 5, 13, and 25 weeks. Pain, health-related quality of life, anxiety and depression, disease-related impairment, and physical sensations were evaluated at the beginning of the study and at various points over the course of the investigation. A significant reduction in pain occurred over time in those who received the vitamin, while remaining essentially unchanged in the placebo group.

Editor’s Note : Physical role functioning also improved among those given vitamin D, while remaining constant in the control subjects.

An article published in the American Journal of Clinical Nutrition reports a protective effect for a Mediterranean diet against the risk of undergoing sudden cardiac death among postmenopausal women.*

The investigation evaluated the effects of adherence to a Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet among 93,122 participants who enrolled in the Women’s Health Initiative study between 1993 and 1998. Dietary questionnaires completed twice during the 10.5-year average follow-up period were scored on adherence to both diets.

Over the follow-up period, 237 sudden cardiac deaths occurred. Among those whose Mediterranean diet scores were among the top 20% of participants, there was an adjusted 33% lower risk of undergoing sudden cardiac death in comparison with women whose scores were among the lowest 20%. Higher DASH diet scores were not correlated with a lower risk of sudden cardiac death after adjustment for numerous factors.

Editor’s Note : As a possible explanation for the lack of benefit associated with the DASH diet observed in the current study, authors Monica L. Bertoia and her colleagues remark that the intake of salt, an important factor in the DASH diet, was not well characterized by the questionnaires.

An article published in Nature Neuroscience reveals a memory-enhancing effect for caffeine, found in coffee, tea, and other beverages.*

In a double-blinded trial, participants who were not regular caffeine consumers received 200 milligrams of caffeine or a placebo five minutes after studying a series of images. Saliva samples collected prior to treatment and one, three, and 24 hours afterward tracked caffeine levels. The subjects were tested the following day on how well they remembered the images.

Participants who received caffeine were better able to identify images viewed the day before, and to recognize those that were similar but different. “If we used a standard recognition memory task without these tricky similar items, we would have found no effect of caffeine,” senior author Michael Yassa explained. “However, using these items requires the brain to make a more difficult discrimination—what we call pattern separation, which seems to be the process that is enhanced by caffeine in our case.”

Editor’s Note : “We also know that caffeine is associated with healthy longevity and may have some protective effects from cognitive decline like Alzheimer’s disease,” Dr. Yassa added.