Vitamin A and iron as effective as hormone treatment for delayed puberty
A report appearing in the June 2004 issue of the journal Clinical Endocrinology detailed the findings of Israeli researchers that vitamin A and iron, often deficient in children, are as effective as hormone therapy for boys with delayed puberty.
One hundred two boys with short stature and delayed puberty were assigned to receive six months of treatment with oral oxandrolone, three months or six months of injectable testosterone, twelve months of supplementation with 600 international units per week vitamin A and 12 milligrams iron per day, oxandrolone plus vitamin A and iron, or no treatment. Height, weight, pubertal status and other measurements were ascertained before and after the treatment period. There were no differences between the groups in age, height or body mass index.
At the end of six months, boys who received vitamin A experienced an acceleration of growth that was similar to that of the boys who received oxandrolone or testosterone. All treatments elicited significantly greater growth than that experienced by the children in the untreated control group. The onset of puberty as measured by testicular volume was observed after six months in those receiving the nutritional supplements and at twelve months in those who received hormone treatment. The control group experienced no change in pubertal status at twelve months.
Vitamin A is involved in controlling cell replication, development and maturation, and iron levels have been found to be depleted in children during rapid growth periods. Retinoic acid, made in the body from vitamin A, has been shown to stimulate growth hormone in several experiments. The authors suggest that giving vitamin A as a medication rather than as a natural source rich in the vitamin ensures its consumption.
Indole-3-carbinol increases interferon response in human breast cancer cells
Research published in the July 2004 issue of the journal Carcinogenesis has identified a possible mechanism of action for indole-3-carbinol (I3C), a compound that occurs in the Brassica genus of vegetables, against breast cancer. Indole-3-carbinol, found in broccoli, cabbage and Brussels sprouts, has been found to reduce the incidence of tumors in rodents, and has elicited antiproliferative and apoptotic effects on human breast cells in vitro. Findings from the current study may help to explain how the compound provides these benefits.
The researchers treated cultured human breast cancer cells with I3C or a control substance for forty-eight hours. DNA microarrays found that I3C modified the expression of several genes involved in interferon signaling. The most significant of the gene-array results was I3C's stimulation of the interferon-gamma receptor 1 gene. Interferons are cytokines involved in immune response, apoptosis and antitumor activitiy . Interferon-gamma is used to treat various cancers, and has been shown to have antiproliferative effects in epithelial tumors and in cultured human cancer cells.
Treatment with the I3C and/or interferon-gamma for up to seven days resulted in a significant number of breast cancer cells arresting their growth in the G1 phase of the cell cycle, and stimulated the expression of the p21 cell cycle inhibitor. The combination of both agents was more effective than either agent alone.
The results of these experiments suggest that one of I3C's anticancer mechanisms is that of stimulating the expression of the interferon-gamma receptor 1 gene and increasing the response to interferon-gamma by human breast cancer cells. They note that their study shows a response when I3C is administered directly to cancerous tissue, and state that 300 milligrams indole-3-carbinol per day taken in capsule form is the minimum effective oral dose for breast cancer prevention.
Cost-induced prescription drug underuse results in poorer health
A study published in the July 2004 issue of the American Public Health Association journal Medical Care has found that middle aged and older Americans diagnosed with heart disease who had cut back on prescription drug use due to their high cost were 50 percent more likely to suffer angina, heart attacks and strokes than those who did not cut back on their medications. The longitudinal study, funded in part by the National Institutes on Aging, is the first of its kind to reveal the findings.
Michele Heisler, MD of the Veterans Affairs Ann Arbor Healthcare System and colleagues analyzed survey responses obtained from 7,991 middle-aged and older Americans who participated in the Health and Retirement Study or the Asset and Health Dynamics Among the Oldest Old (AHEAD) Study. All participants reported the use of prescription drugs, and 546 reported drug underuse due to their high cost. Over the two to three year follow-up period, 32 percent of those who had cut back on prescription drug use reported a decline in health status, compared to 21 percent who did not cut back on their drugs. Nonfatal heart attack or stroke was reported by 7.8 percent of those who had reduced prescription drug use compared to 5.3 of those who had not, and angina was reported by 11.9 percent of underusers compared to 8.2 percent of the rest. Depression was also more likely to worsen in older individuals economically pressured to reduce prescription drug use. There were no differences reported among individuals with diabetes and arthritis.
Dr Heisler commented, "Medications have been getting more and more effective at preventing or slowing the progression of health problems, but at the same time patients have increasingly been bearing the costs."
Atorvastatin lowers coQ10 levels in patients at risk of cardiovascular disease
A study published in the June 2004 issue of the American Medical Association journal Archives of Neurology ( http://archneur.ama-assn.org/ ) has found that even brief exposure to the statin drug atorvastatin markedly lowers blood plasma levels of coenzyme Q10 (coQ10). Coenzyme Q10 is an antioxidant made in the body whose production declines with age. In addition its role as an antioxidant, coenzyme Q10 is a component of the mitochondrial respiratory chain and acts as a cell membrane stabilizer. Therefore, anything that reduces coenzyme Q10 levels could have significant adverse effects.
Researchers from Columbia University College of Physicians and Surgeons in New York studied 45 men and women with elevated low-density lipoprotein levels (a risk factor for cardiovascular disease) who received 80 milligrams oral atorvastatin for thirty days. After two weeks and at the study's conclusion, the participants were examined for changes in liver enzymes, kidney function and any adverse effects, including muscle pain or weakness. Plasma levels of coenzyme Q10 were measured at the beginning of the study, and at 14 and 30 days.
In all participants, coenzyme Q10 levels were lower at both fourteen and thirty days than at the beginning of the study. Following two weeks of treatment with atorvastatin , plasma coenzyme Q10 levels in thirty-two participants were reduced by 49 percent. After thirty days, the mean coenzyme Q10 concentration was reduced from 1.26 micrograms per milliliter to 0.62 micrograms per milliliter.
The findings could explain the most common adverse effects of statins, particularly muscle pain, exercise intolerance and myoglobinuria. The authors recommend that, “it may be reasonable to add coQ10 in patients receiving long-term treatment with statins in general, and atorvastatin in particular. This recommendation is strengthened by the general experience that oral coQ10—even in high doses—is well tolerated by patients.” ( Rundek T et al, “ Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke,” Arch Neur , vol 16, June 2004, p 884-92.)
Antioxidants may help protect unborn children from maternal alcohol abuse
A study conducted by researchers at the University of North Carolina at Chapel Hill, published online in the journal FASEB ( Federation of American Societies for Experimental Biology ), has found that antioxidants can protect the fetuses of women who abuse alcohol during their pregnancies from fetal alcohol spectrum disorders (FASD). Fetal alcohol spectrum disorders are a group of birth defects caused by prenatal alcohol exposure that can result in effects on the central nervous system, facial abnormalities and limb malformations.
The researchers gave the synthetic superoxide dismutase plus catalase mimetic known as EUK-134 to pregnant mice in combination with ethyl alcohol. ( Superoxide dismutase and catalase are two antioxidants made by the body.) Other groups of mice received ethyl alcohol or EUK-134 alone, or saline. Within fifteen hours of alcohol exposure, forelimb damage was observed in the fetuses. After nine days, 67.3 percent of the ethanol exposed fetuses that were examined showed forelimb defects. Mice who received EUK-134 with alcohol had 36 percent less forelimb malformations than those who received alcohol without the antioxidant.
Study coauthor and professor of cell and developmental biology Kathleen K Sulik , PhD, commented, "The nutritional status of alcoholics isn't the best. People who are alcoholic by definition can't control their drinking and often cannot quit drinking during pregnancy. And so the practical point of this paper is that perhaps we can diminish some of the problems that might exist if the nutritional status of alcoholic mothers improves. It would be great if these women would supplement their diets with a daily multivitamin. The idea of possibly adding antioxidants to alcoholic beverages has been proposed as a way of helping the situation, at least a little, for those women who are unable to quit drinking alcohol."
Antioxidant supplement use associated with lower inflammatory markers regardless of exercise levels
A study funded by the National Institute on Aging, published in the July 2004 issue of the Journal of the American Geriatrics Society, examined the effects of exercise and antioxidant supplements on the inflammatory markers C-reactive protein, interleukin-6 and tumor necrosis factor alpha (TNF-alpha). Inflammation is related to a large number of chronic diseases and is associated with obesity and increased age. Bouts of intense or prolonged exercise may stimulate an inflammatory response according to many studies, but the effect of regular exercise on inflammation has been less well researched.
Researchers examined data from the Health, Aging and Body Composition Study which provided information on body mass index, exercise and activity levels, and medication and nutritional supplement intake for 2,964 men and women recruited from two locations in the United States. Blood samples were analyzed for serum levels of C-reactive protein and interleukin-6, and plasma levels of TNF-alpha.
In this study, individuals who reported higher levels of exercise and higher levels of nonexercise physical activity had lower levels of C-reactive protein, interleukin-6 and TNF-alpha. As revealed in previous studies, body mass index was positively related to levels of all three inflammatory markers. The use of multivitamin supplements, beta carotene, vitamin C and/or vitamin E, was associated with lower levels of C-reactive protein and interleukin-6 regardless of whether the participant reported high or low exercise levels. The authors wrote that “taking an antioxidant supplement was associated with CRP levels similar to those seen in those who exercised 180 minutes/week or more and did not take supplements.”
The authors note that differences in body fat level explained some but not all of the association found between exercise levels and reduction in inflammatory markers in this study.
Exercise fails to slow atherosclerosis progression in men taking statins
The well known benefits of exercise in retarding the progression of atherosclerosis failed to manifest in a six year study reported on in the June 15 2004 issue of the Annals of Internal Medicine. The DNASCO study, a six year randomized, controlled clinical trial, examined the effects of low to moderate intensity aerobic exercise on inflammation and atherosclerosis in 140 middle aged men. One group of participants was assigned to five weekly sessions of up to an hour of aerobic exercise, while the remaining participants remained at their usual activity levels. Ultrasound examinations monitored atherosclerosis progression by measuring carotid artery intima-media thickness at the second and sixth year of the trial, and blood samples provided C-reactive protein levels that reflected the amount of inflammation experienced by the subjects.
At the trial’s conclusion, ventilatory aerobic threshold was increased by 19.5 percent in the group of men who exercised, however carotid intima-media thickness progression was the same as the nonexercisers and C-reactive protein levels were only slightly lowered. Yet a small group of men in the study who were not taking a class of cholesterol-reducing drugs known as statins appeared to benefit from exercise, as demonstrated by 40 percent less carotid intima-media progression than that of nonexercising men at the end of the study.
Peter H. Langsjoen, MD, of Coenzyme Q10 Laboratory, Inc., offered an interpretation of the findings: “We know that intermittent exercise enhances Q10 biosynthesis resulting in higher endogenous Q10 levels and it may be hypothesized that this is a factor in the well-known health benefits of exercise. This study makes perfect sense in showing that statins block the beneficial effect of exercise, probably through their blocking of coQ10 biosynthesis.”
Vitamin E helps protect smokers from atherosclerosis
A study published in the May 2004 issue of Nutrition Research found that alpha-tocopherol , the primary form of vitamin E found in the body, is important in the inhibition of low-density lipoprotein (LDL) oxidation in smokers. Oxidation of low-density lipoprotein is one of the phenomena involved in atherosclerosis, and antioxidants such as vitamin E help protect against this.
Sixty-two nonsmokers and twenty-seven smokers participated in the current study conducted by Taiwanese researchers, which sought to determine smoking's effect on plasma water soluble (vitamin C) and fat soluble (vitamin E) antioxidants and LDL alpha- tocopherol . Blood samples were analyzed for plasma levels of the vitamins, and levels of alpha-tocopherol within LDL.
Values for vitamins C and E were comparable between both groups, but LDL alpha-tocopherol levels were significantly higher for nonsmokers. Lag time for LDL peroxidation was greater for nonsmokers and the oxidation rate was lower.
The results suggest that alpha-tocopherol in LDL is more sensitive to smoking-induced oxidative stress than the alpha-tocopherol and ascorbic acid that exist in plasma, which could help contribute to the understanding of smoking's promotion of atherosclerosis. For smokers, alpha-tocopherol in LDL helps prevent LDL from being oxidized, and the authors conclude that “it seems reasonable to propose that the presence of alpha- tocopherol in LDL from diets is especially crucial for the prevention of LDL oxidation for smokers. Furthermore, enhancement of LDL alpha-tocopherol levels via diets is important for the prevention of smoking-associated oxidative stress, which may contribute to atherosclerosis.” (Liu CS et al, “alpha- Tocopherol is important to inhibit low-density lipoprotein oxidation in smokers,” Nutrition Research 24 (2004) p 361-371.)
Some teens vitamin D deficient
A study published in the June 2004 issue of the American Medical Association journal, Archives of Pediatrics & Adolescent Medicine, has found a deficiency of vitamin D in city dwelling African American adolescents. Vitamin D is essential for calcium absorption and bone growth during childhood and adolescence, and for preventing rickets in children. In addition, vitamin D may be involved in the prevention of diabetes type 1, hypertension, multiple sclerosis and some cancers.
Catherine M. Gordon, MD, of Children's Hospital in Boston, and colleagues analyzed blood test results for serum 25-hydroxyvitamin D from 307 adolescents recruited to participate in the study between July 2001 and June 2003. Nutritional intake and physical activity levels were also assessed. They found that 24 percent of the participants were deficient in vitamin D, and among these, 4.6 percent were classified as being severely deficient. When a broader definition of vitamin D deficiency was used, 42 percent were discovered to be lacking in the vitamin. There was no difference between the prevalence of deficiency in male or female participants.
Deficiency in the vitamin was most often found in winter and spring. Because populations with increased skin pigmentation absorb less sunlight the amount of vitamin D made from exposure to the sun's rays is less in these groups. African American women of reproductive age have a higher prevalence of nutritional rickets in their breastfed infants, coinciding with a greater incidence of low vitamin D levels.
The authors conclude, "Vitamin D deficiency was present in many U.S. adolescents in this urban clinic-based sample. The prevalence was highest in African American teenagers and during winter, although the problem seems to be common across sex, season, and ethnicity."
Untreated early stage prostate cancer risks becoming aggressive after fifteen years
A study published in the June 9 2004 issue of the Journal of the American Medical Association ( http://jama.ama-assn.org/ ) found that early stage prostate cancer that is untreated carries a significant long term risk of progressing to a more aggressive form of the disease. Without treatment, only a small percentage of prostate cancer patients that have been diagnosed early die of the disease within fifteen years.
Jan-Erik Johansson, MD, PhD, of Örebro University Hospital in Örebro , Sweden, and colleagues followed 223 early-stage prostate cancer patients who were undergoing "watchful waiting", which involves monitoring the disease without aggressive therapy. During the twenty-one year follow-up period, any patients who developed tumor progression with symptoms were treated with estrogens or orchiectomy.
The researchers found that during the initial ten to fifteen years most cancers progressed slowly, but after fifteen years there was an increase in tumor progression, metastases and death from the disease, with prostate cancer mortality increasing three-fold compared to the first fifteen years. At the study's conclusion, 40 percent of the participants had experienced disease progression, and of these, 17 percent had developed local progression of the disease (defined as tumor growth through the prostate capsule) with distant metastases.
The authors conclude, "Our data may be important for counseling and clinical management of individual patients. Postponement of death is not the only treatment objective because local progression may create substantial suffering. In conclusion, our data indicate that the probability of progression to a more aggressive and lethal phenotype may increase after long-term follow-up of prostate cancers that are diagnosed at an early stage and initially left without treatment. These findings argue for early radical treatment of patients with long life expectancy."
Carotenoid levels inversely related to stroke risk
A study published online on June 3 2004 in the American Heart Association journal Stroke ( http://stroke.ahajournals.org/ ) found an inverse correlation between levels of alpha-carotene, beta-carotene and lycopene and the risk of ischemic stroke. Ischemic stroke is caused by the blockage by a blood clot of a blood vessel that feeds the brain and accounts for the majority of strokes.
In an effort to identify the nutrients found in fruits and vegetables that are responsible for the lower incidence of stroke associated with their consumption, Harvard School of Public Health researchers analyzed data from the Physicians' Health Study, which enrolled 22,071 male physicians in 1982. For the current analysis, 297 participants who had experienced ischemic stroke during the follow-up period were matched with control subjects for age and smoking status. Food frequency questionnaires administered at the beginning of the study provided information concerning nutrient intake. Blood samples were analyzed for plasma levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, retinol, alpha-tocopherol and gamma tocopherol, and stroke patients compared to controls.
It was found that levels the carotenoids alpha- and beta-carotene and lycopene were inversely related to the risk of stroke. Men whose plasma levels of alph a-carotene was in the top four-fifths of the participants had a 41 percent lower risk of ischemic stroke than subjects whose levels were in the lowest fifth. Beta-carotene and lycopene lowered stroke risk similarly, while beta-cryptoxanthin had a small, insignificant effect. No association was found for the other nutrients analyzed, or with dietary intake of alpha-carotene, beta-carotene or lycopene.
Because the increased risk of ischemic stroke was determined only for those who carotenoid levels were in the lowest fifth, only those with low levels of these nutrients may be at risk.
Insulin's role in aging further defined
A study conducted by researchers at Brown University in Providence, Rhode Island, published in the June 3 2004 issue of the journal Nature ( http://www.nature.com/nature/ ), has found an increase in life expectancy of 50 percent in fruit flies when messages sent by an insulin-like hormone in fat cells are reduced. Previous research uncovered a similar effect in worms, but this is the first time it has been observed in fruit flies, a species that has more genes similar to those of humans. Research has found that a nimals live longer when on calorie restriction regimens, which reduce insulin production.
Brown University biology professor Marc Tatar and colleagues fed a copy of the hormone progesterone known as mifepristone to a group of flies that had the protein dFOXO, controlled by the fly equivalent of insulin, inserted into the genetic material of fat cells near their brains. Mifepristone activated a switch attached to dFOXO which repressed insulin signals in the cells, unexpectedly resulting in lowered body-wide insulin production. The treated flies lived an average of 50 days, which was 18 days longer than untreated flies.
The study revealed that in addition to regulating its own production, insulin directly regulates tissue aging. Keeping insulin levels low should help strengthen cells and protect against age-related diseases such as cancer and dementia.
Dr Tatar explained, “Think of the body like a car. We knew insulin controlled the car's speed by regulating things like the gas pedal and the fuel injectors. Now we know that insulin is also the fuel that makes the engine go. We now know that insulin is a direct player in the aging process. So the research fits some key puzzle pieces together. And it should change the way we think about aging.”
Chromium supplementation lowers depression-associated carbohydrate cravings
A double-blind placebo-controlled study presented on June 2 2004 at a conference of the National Institutes of Mental Health New Drug Evaluation Unit found that supplementation with chromium picolinate decreased carbohydrate cravings in people with atypical depression. Atypical depression is a frequently undiagnosed type of depression characterized by carbohydrate cravings, mood swings and weight gain among other symptoms.
One hundred thirteen atypical depression sufferers at several centers received 400 micrograms chromium in the form of chromium picolinate for two weeks followed by four weeks of 600 micrograms chromium, or a placebo. Individuals who reported the highest level of carbohydrate craving experienced the greatest reduction in symptoms. They found that carbohydrate cravings were significantly reduced among those who received chromium. Mood swings and fatigue were improved among the chromium takers as well.
Researchers have hypothesized that chromium's role in insulin function may be its link with carbohydrate cravings and atypical depression. Insulin's effect on metabolic function may improve brain serotonin levels that, when low, are associated with carbohydrate cravings and depression. Carbohydrate consumption may be an attempt to stimulate insulin, which elevates brain serotonin levels. Chromium, however, increases the body's insulin response, which may fight carbohydrate craving and depression.
Lead investigator and president of Comprehensive NeuroScience, Inc, John Docherty MD, stated, “This is the first indication that chromium picolinate may play an important role in the reduction of carbohydrate cravings in people with atypical depression. It also may offer a new treatment option for atypical depressed patients with carbohydrate cravings who find it difficult to stay on current prescription medication because of the common side effects of sexual dysfunction and weight gain. This study suggests that carbohydrate cravings may be a key and idependent marker of atypical depression and might predict how patients will respond to chromium picolinate therapy.”