Harvard researchers to study SAMe/antidepressant combination
Researchers at Harvard Medical School are conducting a study at Massachusetts General Hospital in Boston to determine if adding S-adenosyl-methionine (SAMe) to one of several popular antidepressants will improve symptoms in patients with limited response to the drugs. SAMe is a natural substance found in every cell of the body, low levels of which are associated with depression. It is available as a nutritional supplement in the United States and Europe. The trial will last eight weeks and will enroll thirty men and women between the ages of eighteen and seventy-five. Examples of popular antidepressant drugs are Paxil, Prozac, Effexor, Zoloft and Celexa. Because these drugs all have side effects, many patients fear combining them. The minimal side effects associated with SAMe may make it more acceptable to patients who require an additional therapy. Lead investigator Jonathan Alpert, MD, Ph.D., associate director of the Depression Clinical and Research Program at Massachusetts General and assistant professor of psychiatry at Harvard Medical School in Boston, explained, "Since there are more than 40 clinical trials that suggest SAMe's effectiveness for depression as a stand alone therapy, we are eager to study its effectiveness and safety as a possible alternative for use in combination with a prescription antidepressant." He added, "With so many treatment options today, we're certainly doing a better job of treating depression than we ever did before. However, we know that 50 percent of patients will have a less than ideal response or experience intolerable side effects the first time they try a traditional agent and many lose hope when prescribed one prescriptive treatment after another. This has really motivated our interests to develop guidelines for better use of existing treatments while pursuing promising leads that may result in novel treatments for depression."
Soy protein lowers LDL and homocysteine without increasing lipoprotein(a)
In an effort to determine the effect of two doses of soy protein on homocysteine, lipid and lipoprotein concentrations, researchers from Oslo, Norway and Copenhagen, Denmark randomly administered 30 or 50 grams isolated soy protein combined with fiber, or 30 or 50 grams of casein and fiber to 108 men and 22 women with serum low density lipoprotein (LDL) cholesterol levels of 4 micromoles per liter or greater. The soy or casein was administered as a beverage four to twenty-four weeks following the consumption of a cholesterol-lowering diet by the study participants. Subjects in the four groups consumed the beverages daily for a period of sixteen weeks.
At the conclusion of the study, the groups who received isolated soy protein experienced a decline of 3 to 4 percent greater than those receiving casein in total and LDL cholesterol concentrations, as well as a greater decrease in plasma homocysteine levels. There were no significant differences in response between the groups receiving the higher and lower dosages. Although an increase in lipoprotein(a) concentrations have been reported by individuals consuming soy protein diets, this study found no significant changes in concentrations.
The authors write that the 25 gram per day dose of soy protein that the US FDA allows to carry a health claim is supported by the data obtained for the soy dosages used in this study, and that larger amounts do not appear to confer an additional benefit on serum lipid and lipoprotein levels. The significant decrease in plasma LDL, as well as the lower plasma total homocysteine observed in the groups consuming soy suggest an antiatherosclerotic effect for soy protein.
The research was published in the July 2002 issue of The American Journal of Clinical Nutrition (http://www.ajcn.org/).
Inosine aids stroke recovery
In what is being referred to as a landmark study, researchers at Children's Hospital in Boston have found that the naturally occurring compound inosine stimulates nerve fiber growth in the brain and spinal cord, aiding in the recovery of function following a stroke. The report was published in the June 25 2002 issue of the Proceedings of the National Academy of Sciences.
In rats in whom a stroke was induced, one group was given inosine while the remaining rats served as controls. Animals treated with inosine showed a greater ability to place their paws on a table when their bodies were lowered toward it than the untreated group, and after nineteen days the treated animals demonstrated almost normal ability while the untreated rats experienced only half these gains. In a second experiment, rats who were trained to grasp food through the bars of their cages showed greater post-stroke recovery of their ability to use the stroke-effected paw. In addition, rats recovering from strokes given inosine regained their ability to swim normally after eight weeks, while untreated rats did not. When their brains were examined, treated rats showed three to four times the amount of compensatory growth of neurons into areas that had lost their normal connections than untreated animals.
Principle investigator and head of the laboratory at Children's Hospital, Dr Larry Benowitz, stated, "These findings are of both scientific and clinical interest. The study shows that inosine induces a great deal of rewiring in the brain after stroke. This rewiring is apparently sufficient to promote substantial functional recovery. In terms of clinical implications, inosine, which appears to have no apparent side effects in animals thus far, has potential as a novel nerve regeneration approach to treatment of stroke and other types of brain injuries."
Vitamin E boosts immune function in colon cancer patients
A study published in the June 2002 issue of Clinical Cancer Research (http://clincancerres.aacrjournals.org/) found an increase in T helper 1 cytokine production in patients with advanced colorectal cancer who were given vitamin E. Researchers at the Karolinska Institute in Sweden hypothesized that supplementation with the vitamin could boost immune function in patients with advanced cancer by diminishing the oxidative stress arising from the chronic inflammation seen in this population. Humans and animals with advanced cancer show signs of immune dysfunction including decreased T-cell proliferation, reduced CD4:CD8 ratios, and decreased production of T helper 1 cytokines, which have been correlated with lower survival.
Twelve patients with colorectal cancer were given supplements containing 750 milligrams vitamin E, 60 micrograms selenium and 90 milligrams vitamin C, which was consumed in divided doses for fifteen days. Patients were given physical examinations at the beginning and conclusion of the study, and blood samples were collected. No side effects from the supplements were reported.
Plasma levels of vitamin E more than doubled as a result of the treatment, and the ratio of CD4 to CD8 ratios increased as well. Diminished CD4 counts have been correlated with late-stage colorectal cancer and may be indicative of immunosuppression. Treatment with vitamin E enabled T cells to more readily produce the T helper 1 cytokines interferon-gamma and interleukin 2. In ten of the twelve patients an average increase of 22% in the amount of T-cells that produced interleukin 2 was observed following vitamin treatment compared to pretreatment levels. Naive T helper cells exhibited a greater response than memory T cells. Because of the lack of an increase in interleukin-10 production observed, the authors speculate that the mechanism of action of vitamin E may be other than that of scavenging free radicals.
Cranberry fights antibiotic-resistant bacteria
In a letter published in the June 19 2002 issue of the Journal of the American Medical Association (http://jama.ama-assn.org/), scientists from Rutgers University, and the University of Michigan have discovered that cranberry juice provides protection to the urinary tract from antibiotic sensitive as well as antibiotic-resistant Escherichia coli bacteria. Antibiotic resistance occurs when bacteria develop immunity to common drugs used to combat them, and is a growing concern among public health officials.
The researchers isolated E. coli from the urine of women diagnosed with urinary tract infections (UTIs) and introduced them into urine samples collected from healthy participants before and after they were given eight ounces of cranberry juice cocktail. When the bacteria were introduced into the samples taken before cranberry juice was administered, bacteria stuck to urinary tract cells. In the samples taken after the cranberry juice was consumed, 79% of antibiotic resistant bacteria failed to adhere to the cells. The beneficial component of cranberries appears to be their proanthocyanidins which prevent certain E. coli bacteria from adhering to the urinary tract. Regular consumption of cranberry juice may help reduce the incidence of urinary tract infections and the need for antibiotics.
Study coauthor and Professor of Epidemiology at the University of Michigan School of Public Health, Betsy Foxman PhD, commented, "In light of the increasing antibiotic resistance of many bacteria, the public health significance of the role of foods, such as cranberry juice cocktail, in preventing infections warrants further consideration . . . Additional work that I co-authored, cited in the October 4, 2001 edition of The New England Journal of Medicine, suggests that an increasing number of new E. coli strains are resistant to the most common antibiotics used to treat UTIs, prompting physicians and researchers to look for alternatives."
Vitamins C and E block inflammatory response to high fat meal
At the American Diabetes Association annual meeting this month, researchers from the University of Buffalo reported the results of several experiments that showed an increase in inflammatory markers following consumption of a meal high in calories and fat or following a high intake of glucose, but the researchers also discovered that antioxidants vitamins C and E can halt this response.
In one experiment, participants were given a high fat, 900 calorie meal after fasting overnight. Blood samples were taken before and following the meal, and oxygen free radicals and inflammatory markers were measured. Free radicals injure the lining of the blood vessels, initiating the inflammatory process. The researchers found an increase in free radicals and proinflammatory indicators. In four additional experiments, the administration of glucose or fat caused a reduction in the blood vessels' ability to expand and contract in response to changes in blood flow as well as an increase in inflammation. However, when participants consumed vitamin C and vitamin E before receiving glucose, oxygen free radicals and inflammatory markers did not increase as they did in those receiving glucose alone.
Lead author and professor of medicine of the University of Buffalo School of Medicine and Biomedical Sciences' Division of Endocrinology, Paresh Dandona, MD, explained, "A meal high in calories and fat caused an increase in inflammatory markers that lasted three to four hours. We think the influx of macronutrients may alter cell behavior and that genes are activated to produce more powerful enzymes and mediators that are potentially more damaging to the lining of blood vessels . . . On the other hand, we found that one way to render an 'unsafe' meal 'safe' is to include antioxidant vitamins. The proinflammatory effect of glucose is stopped if right at the outset you give vitamins E and C."
Simple urine test detects free radical damage, Alzheimer's disease
The June 2002 issue of the journal Archives of Neurology (http://pubs.ama-assn.org/) published a study which confirmed the value of a urine test in diagnosing mild cognitive impairment which precedes Alzheimer's disease. Fifty percent of individuals diagnosed with mild cognitive impairment develop Alzheimer's disease in four years The test determines the level of a specific isoprostane, a marker of lipid peroxidation in the body. The amount of isoprostanes in urine, blood and cerebrospinal fluid was found to be correlated with the development of Alzheimer's.
University of Pennsylvania School of Medicine researchers collected urine and blood samples from fifty Alzheimer's disease patients, thirty-three patients with mild cognitive impairment and forty healthy controls. A second urine sample followed at two weeks as well as cerebrospinal fluid samples taken from approximately half of the members of each group. Higher levels of isoprostanes were found in all samples from patients with Alzheimer's disease and mild cognitive impairment than those taken from controls.
Assistant professor of the University of Pennsylvania Department of Pharmacology, Domenico Praticò, MD, announced, "This is the first noninvasive test that can predict a clinical diagnosis of Alzheimer's disease. Since there is no cure for Alzheimer's disease, physicians could slow the course of the disease if it is caught early enough." He explained, "One hypothesis is that, in AD, healthy brain tissue is damaged by the local formation of large amounts of free radicals. Isoprostanes are the byproducts of fats in the human body that were warped by free radical attack. They then accumulate in CSF, blood, and urine as the body works to get rid of them... With an easier test, doctors can diagnose the disease sooner and respond better to the patient's needs."
Centenarian siblings also long-lived
In the latest of a series of National Institute on Aging-supported studies, research published in the June 11 2002 issue of the journal Proceedings of the National Academy of Sciences (http://www.pnas.org/) found that sisters of individuals who survived 100 years or more were eight times more likely and brothers were seventeen times more likely to also live to the age of one hundred in comparison with U.S. citizens born in 1900. Data was gathered from 444 families of centenarians, which included 2,092 siblings. The information was analyzed by researchers participating in the New England Centenarian Study in Boston, led by Thomas Perls MD. Earlier research led by Dr Perls located a region on chromosome 4 that is likely to predispose its inheritors to long lives.
The study also found that sisters of centenarians had half the risk of dying at any age compared to the national average and that brothers had similar rates except during the teen and young adult years.
Although survival to advanced ages may be partly the result of socioeconomic or environmental factors, the differences in mortality between social groups tend to disappear in old age, lending support to genetic factors involved in exceptional longevity.
Further studies are being conducted in this important area of longevity research.
Short-term study shows vitamin A supplements okay for bones
The results of a study published in the June 2002 issue of the Journal of Nutrition (http://www.nutrition.org/) challenges previous findings that vitamin A supplementation is associated with bone loss, or at least not in the long-run. Studies have shown that individuals who consume the highest levels of vitamin A have an increased fracture risk, although this does not establish a cause and effect relationship. In a prospective, randomized study, forty health men between the ages of eighteen and fifty-eight received 25,000 international units retinol palmitate daily with dinner, while another forty received a placebo. Participants had blood drawn at the start of the study, and at two, four and six weeks to measure serum bone specific alkaline phosphatase and N-telopeptide of type 1 collagen, markers of bone turnover. Another bone turnover marker, serum osteocalcin, was measured at the beginning of the study and at six weeks.
Although serum osteocalcin was lower in the group receiving vitamin A at the beginning of the study, serum bone specific alkaline phosphatase and N-telopeptide of type 1 collagen were the same in both groups. Levels of all three markers did not change in either group throughout the study's course.
Despite the fact that limited data suggests that vitamin A toxicity increase bone resorption and diminishes bone formation, the relatively high dose used in this study did not affect serum markers of bone turnover in this group of healthy men. Short-term supplementation with vitamin A is considered to be unlikely to have adverse effects on the skeleton according to the authors. Future studies of greater duration will be needed to confirm the vitamin's longterm effect on bone mass.
More on preeclampsia
Women with preeclampsia, a life-threatening condition of high blood pressure and proteinuria that occurs late in pregnancy, have been found to have deficient levels of vitamin C, but it was not known how this affected the disorder. The 13th World Congress of the International Society for the Study of Hypertension in Pregnancy was the site of a presentation by scientists from the Magee-Women's Research Institute and the University of Pittsburgh School of Medicine that a mild vitamin C deficiency may impact preeclampsia by negatively affecting vascular function and elasticity, which is a symptom of the condition.
The research was conducted by Carl A. Hubel, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and his colleagues, who examined arterial pressure and elasticity in rats - animals who, like humans, are unable to synthesize their own vitamin C. They discovered that blood vessel stiffness increased in pregnant rats who were administered insufficient amounts of the vitamin, yet this was not observed in nonpregnant rats. Although pregnancy initiates a change that increases blood vessel elasticity and consequently influences blood pressure, this did not compensate for the results of a vitamin C deficiency.
President of the International Society for the Study of Hypertension in Pregnancy, James M. Roberts, MD, who is a professor and chairman of research in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine and director of the Magee-Women's Research Institute, spoke optimistically: "Preeclampsia is one of the leading causes of maternal, fetal and neonatal disability and death . . . Research is closing in on this menace. But there is still much to do."
Vitamin C reduces kidney reperfusion injury
Researchers in Spain discovered that rabbits undergoing renal ischemia, or lack of blood flow to the kidney, experienced a release of platelet activating factor (PAF) and PAF-like lipids leading to an increase in oxidation during reperfusion, or restoration of circulation, and that vitamin C helps prevent these changes. The study, published in the June issue of the Federation of American Societies for Experimental Biology Journal, (http://www.fasebj.org/) was the first in vivo study of its kind.
Rabbits in whom blood flow to the kidney was blocked for sixty minutes had blood drawn from the renal vein after circulation was restored. All rabbits showed a peak in the release of PAF and PAF-like lipid release in the first fifteen minutes of reperfusion. However, when rabbits were treated with 150 milligrams vitamin C twenty four hours and one hour before surgery, their platelet activating factor activity was much lower than that of untreated animals. Platelet activating factor has been shown in vitro to result from the formation of oxidized phospholipids. When DNA damage was assessed, that in the vitamin C-treated animals was significantly less than the intense kidney DNA oxidation observed in untreated animals. A marker of inflammation was also lower in the vitamin C treated rabbits.
In another experiment with ischemic rats, those who received vitamin C beforehand had less functional and histological damage to the kidneys than those who did not receive the vitamin. Rats who did not receive vitamin C experienced severe renal failure during the three day follow-up, while rats treated with the vitamin showed continued improvement.
The authors conclude that ischemia-reperfusion injury generates oxygen free radicals resulting in PAF-like lipids and an inflammatory state. They suggest an active role of PAF in initiating the inflammatory response and hypothesize that vitamin C protects the kidneys against ischemic insult.