February 27 2002
In a study reported in the premier issue of the journal, Cancer Cell, published February 26 2002, research at Hebrew University in Jerusalem showed that some chemotherapy drugs damage the chromosomes of healthy cells which could lead to new tumor growth. Previous research conducted by two of the authors showed that the drugs may cause normal cells to develop what are called fragile sites, on which the mechanism for DNA replication is disturbed, leading to breakage and rearrangement of the chromosomes which is found typically in cancer cells. This can amplify the action of genes known as oncogenes which promote tumor formation. Five of approximately one hundred fragile sites on the human genome are currently being studied.
In this study, the researchers found that recurrent breaks within fragile sites of chromosomes amplified the MET oncogene in human stomach cancer.
Study coauthor and Hebrew University Associate Professor of Genetics Batsheva Karem hopes that the research will lead to the development of less damaging chemotherapy drugs. She commented, "Our work creates a better understanding of how drugs used against cancer work, which will lead to the creation of the next generation of drugs, which can halt the growth of cancerous cells without inducing fragile sites."
Longterm vitamin C consumption lowers early-onset cataract incidence
The March 2002 issue of the American Journal of Clinical Nutrition was the site of the publication of a report showing that longterm consumption of ascorbic acid, or vitamin C, prevented the formation of cortical and posterior subcapsular cataracts in women under sixty. Cortical cataracts are a type of cataract involving the inner and outer cortical tissue of the cortex of the lens, while posterior subcapsular opacities are found in the lens's outmost layers. Nuclear cataracts form in the central zone of the lens. The study examined the eyes of 492 nondiabetic participants enrolled in the Nurse's Health Study cohort, whose diet and health information has been tracked since 1976. The women had completed food frequency questionnaires every other year for the past thirteen to fifteen years, which detailed diet and nutritional supplement intake.
Although no associations between antioxidant intake and either type of cataract was observed in the entire sampling consisting of women between the ages of 53 and 73, women sixty years of age and younger had a 57% lower risk of developing a cortical cataract if the amount of vitamin C consumed per day was greater than or equal to 362 milligrams, compared to those whose intake of the vitamin was 140 milligrams per day or less. Ten years or more of vitamin C supplementation provided a 60% lower risk than no use of the supplements. For posterior subcapsular cataracts, risk of their development was inversely related to folate, alpha-carotene, beta-carotene and total carotenoid intake in nonsmokers.
The researchers believe that the results of the study contribute to the evidence that antioxidants can alter the rates of development of these age-related lens opacities, and note that smoking diminishes their benefits.
New England Journal of Medicine recommends hypothermia for cardiac arrest patients
Two studies appearing in the February 21 2002 issue of New England Journal of Medicine have demonstrated favorable outcomes for the use of hypothermia in patients experiencing cardiac arrest. In the first study, conducted by the Hypothermia after Cardiac Arrest Study Group at several centers over a five year period, 136 patients who had been resuscitated after cardiac arrest were cooled to a body temperature of 32 to 34 degrees celsius for twenty-four hours followed by an approximately eight hour rewarming period. This group was compared to a control group of 138 patients who received standard care after cardiac resuscitation. In the hypothermia group, 59% of the patients were alive after six months, whereas 45% remained in the group not receiving it. Of the group receiving the hypothermia treatment, 55% experienced a favorable neurologic outcome, compared to 39% in the group who did not receive the treatment.
In the second study, comatose survivors of cardiac arrest out of the hospital were randomized to receive cooling as soon as admitted to a participating hospital or to receive treatment without cooling. Of the group treated with hypothermia, 49% survived and were discharged to their homes or to rehabilitation facilities. Only 26% of the group not receiving hypothermia experienced similar outcomes.
An editorial in the same issue of the journal notes that therapeutic hypothermia has been in use since the 1950s. In the 1990s, hypothermia provided positive outcomes for dogs experiencing a lack of blood flow for ten to twelve minutes. The editorialists, Peter J Safar, MD and Patrick M. Kochanek, MD, write, "The dismal outcomes after cardiac arrest call for novel therapeutic approaches," and they "recommend the use of mild hypothermia in survivors of cardiac arrest - as early as possible and for at least 12 hours."
Happy medium best with iron
A study published in the February 19 2002 issue of the Proceedings of the National Academy of Sciences, showed that too much as well as too little iron increases oxidative damage. Iron is a mineral essential to life, but high levels have been linked with increased incidences of cancer and heart disease.
The study, conducted at the University of California, Berkeley, and coauthored by nutritional researcher Bruce Ames, examined the effects of iron deficiency and supplementation on rats in two separate experiments. In the first study, iron deficient rats and rats with normal iron levels had their mitochondrial function and white blood cell oxidant levels measured. The rats who were deficient in iron were found to have lower liver mitochondrial respiratory control ratios, a measure of mitochondrial function, and white blood cells showed increased amounts of oxidants. When both groups were given high levels of iron for thirty-four days, both mitochondrial function impairment and DNA damage in either group were increased to levels above those in rats with normal iron status.
The second experiment found that an every third day dose of iron to rats deficient in the mineral induced less mitochondrial DNA damage than those supplemented on a daily basis.
Both iron deficiency and elevated iron increased lipid peroxidation, demonstrating that either condition is favorable to oxidative stress. The results of the second experiment suggest that intermittent supplementation may be a desirable way to take iron, if one is deficient. The researchers propose several mechanisms of action for iron deficiency's ability to cause damage to the mitochondria, including increased mitochondrial superoxide release, increased copper absorption, loss of iron-containing repair enzymes, and changes in the cellular iron homeostasis system. They conclude that iron deficiency has the potential to be more damaging than had been previously suspected and urge its prevention and treatment.
Another study implicates HRT in breast cancer
A study published in the February 3 2002 issue of the Journal of the American Medical Association has reconfirmed the link between hormone replacement therapy and breast cancer risk. In an attempt to determine the association between various hormone replacement therapies and breast cancer type, researchers conducted a study of 705 postmenopausal women diagnosed with invasive breast cancer and 692 aged-matched controls enrolled in the Group Health Cooperative of Puget Sound. A computerized database with information about prescriptions dispensed to the women was the source of information on the types of hormone replacement therapies used by the participants. The data was analyzed for the five years prior to one year before a diagnosis of breast cancer. Information was collected on risk factors for the disease, such as age, reproductive history, family history of breast cancer, and years of oral contraceptive use.
Current use of estrogen and progestin pills was found to be associated with an increased breast cancer risk. Past use of hormone replacement did not appear to increase risk. Participants who used hormone replacement for the longest period of time had a greater risk than those who had not used hormone replacement during the five year period. These results were similar for various types of hormone replacement therapy, such as oral estrogens alone, combination therapy, sequential and continuous combined therapy. All hormone replacement had a stronger association with lobular breast cancer than with nonlobular cancer, with recent hormone replacement use of fifty-seven or greater months associated with three times the risk of this type of cancer. An especially high risk was found with current use of combination therapy.
In conclusion the authors emphasized the growing body of evidence that longterm hormone replacement therapy use in women is associated with an elevation in breast cancer risk.
Cool study underway
Stanford University Medical Center, in Palo Alto, California, is conducting a new study involving four hundred patients at twenty-five centers to test the benefits of inducting hypothermia in heart attack patients. Acting on the knowledge that cooling can prevent the damage that occurs to cells deprived of oxygen due to the lack of blood flow following a heart attack, Stanford and other medical centers will be lowering the body temperature of heart attack patients treated with angioplasty. Within thirty minutes of hospital arrival, physicians will place a small catheter into the patient's leg vein, which is connected to a device that cools the body to over seven degrees lower than normal body temperature. Drugs to prevent shivering are administered, and the patient is warmed following a three hour period. If the technique is begun early enough, previous studies have indicated that the release of toxic substances may be prevented and permanent heart tissue damage avoided.
Cooling has been successfully used during cardiac surgical procedures, as well as on stroke patients to protect the brain from ischemic damage. Stanford researchers earlier discovered that cooling the brain prevented stroke damage even two hours after the event.
Stanford University interventional cardiologist David Lee, MD, stated, "This is a promising procedure that could revolutionize the way we treat heart attacks. I have great hope that therapeutic cooling can preserve heart muscle and significantly improve a patient's long-term prospects.... Cooling is not a novel idea. It's an attractive concept - you can cool a patient down and lower the metabolism of the cells.... Basically, we're stealing heat from the body and sending it to a machine."
Antioxidants may slow TSE progression
A case report published in the February 2002 issue of Journal of the American College of Nutrition documented an early reversal of neurologic decline in a patient diagnosed with Creutzfeldt-Jakob disease, the human form of spongiform encephalitis. The patient was a 69 year old woman who experienced a rapid onset of anxiety, insomnia and an inability to coordinate voluntary muscle movements. Her initial rapid deterioration of cognitive and motor function led to a prognosis of death within a couple of months. Upon admission to the University of Kansas Medical Center, the patient's family provided her with a multivitamin supplement, fresh fruit and vegetable puree, NADH, mixed tocopherols and alpha-lipoic acid. The woman regained limited speech, became more responsive and expressed that she felt better. Following a course of dilantin upon which the patient became comatose, she again lost her ability to speak. After discharge her family continued providing the nutrients via a stomach tube, and added coenzyme Q10, vitamin C, B complex, L-glutamine, omega-3 fatty acids and magnesium. Glutathione and vitamin C were administered intravenously. The therapy appeared to reduce episodes of apnea as well as rigidity. The patient survived on the regimen for twenty-two months subsequent to the onset of her symptoms.
Author Jeanne A Drisko, MD of the University of Kansas, told Life Extension, "In the group of diseases known as transmissible spongiform encephalopathies (TSE) such as Creutzfeldt-Jakob disease, mad cow disease, and the others, the immune system has been ignored. Inflammatory cytokines and other inflammatory mediators produced by the immune cells of the brain - the glial cells- are largely responsible for destruction of brain tissue in TSE. Research into ways to couple agents that could treat the infection with high dose antioxidant therapy to quell the inflammation could provide tools to change the course of these fatal diseases. Research dollars have been largely funneled into prion protein research in TSE. Federal dollars should also be targeted to antioxidant research."
Lifestyle changes win over metformin in lowering diabetes risk
A study published in the February 7 2002 issue of the New England Journal of Medicine reported that results of a study of 3,234 individuals at risk for diabetes who were given either standard lifestyle recommendations along with a placebo or the drug metformin, or were prescribed an intensive lifestyle modification program consisting 150 minutes or more of exercise per week with the goal of at least 7% weight loss. Elevation of fasting and post-load plasma glucose concentrations qualified participants as being at risk of developing the disease. The trial was conducted at 27 centers and participants were followed up for an average of 2.8 years.
Those who received metformin, sold under the name Glucophage, received 850 mg twice per day. Standard lifestyle recommendations consisted of recommendations to follow the Food Guide Pyramid and a cholesterol-lowering diet to reduce their weight, and to increase exercise. The intensive lifestyle intervention involved a low calorie low fat diet, plus 150 minutes of exercise per week of moderate intensity, such as brisk walking.
During the follow up period, the incidence of diabetes was 31% lower in the group receiving metformin than the group receiving the placebo. However, in the lifestyle modification program, diagnoses of diabetes were 58% lower than those who received a placebo - 39% lower than the metformin group. Metformin and lifestyle intervention restored normal fasting glucose levels to a similar extent, but the lifestyle intervention more greatly improved post-load glucose levels. It was concluded that it should be possible to delay diabetes and its complications, reducing individual and public health burdens caused by this disease.
Intravenous vitamin C safe
Vitamin C is a well known antioxidant that can, under some circumstances and particularly in high doses, function as a pro-oxidant. In a study to be reported at the 2002 Nutrition Week forum to be held later this month, which was published in the February 2002 number 2(S) issue of the American Journal of Clinical Nutrition, researchers in Stuttgart and Frankfurt, Germany found that high dose vitamin C administered intravenously is not pro-oxidative.
In a cross-over study, six healthy men received intravenous vitamin C in the amount of 750 milligram or 7.5 grams per day for a six day period. On the first day of the study, serum concentrations of vitamin C were measured at five intervals as well as concentrations of ascorbyl radicals, free radicals created by the oxidation of vitamin C. On the first and sixth days of the study, urine concentrations of 8-oxoguanosine and plasma levels of thiobarbituric acid reactive substances, which are both indicators of oxidation, were measured.
Participants' plasma vitamin C levels rose from fasting levels when measured at varying intervals subsequent to the infusions. Levels of thiobarbituric acid reactive substances decreased by the end of the study. The researchers' analysis of the data, including levels of ascorbyl radicals and 8-oxoguanosine, determined that there was no evidence for pro-oxidative effects of intravenous high dose vitamin C when tested in healthy subjects.
Broccoli ingredient fights more than cancer
Researchers at Johns Hopkins University have discovered that sulforaphane, a cancer-fighting substance in broccoli, has antioxidant capabilities that provide protection against other human diseases. The research, published in the December 18 2001 issue of Proceedings of the National Academy of Sciences, revealed that sulforaphane may help protect cells from oxidants for several days after being treated with the compound.
The researchers pretreated adult retinal pigment epithelial cells for twenty-four hours with varying concentrations of sulforaphane and exposed the cells to four different oxidative stressors. Sulforaphane provided protection to the cells in proportion to the concentration used. The cells continued to be protected from the compounds for two to three days after the sulforaphane was removed.
The study's authors believe that sulforaphane's ability to prevent oxidative damage as well as fight cancer are attributable to its ability to manufacture phase 2 enzymes that can detoxify oxidants. Study coauthor and Johns Hopkins Professor of Pharmacology Paul Talalay, MD commented, "Our work with sulforaphane has focused on cancer, but now it assumes wider significance for human disease because the compound also helps prevent oxidative damage. The finding that a compound from the diet can provide powerful, chemically versatile and prolonged protection against oxidative stress may particularly impact human retinal disease. There are many dangers to cells, and it makes sense that cells have protection against these dangers, which include oxidants. Elevating these intrinsic protection mechanisms by administering a wide variety of chemicals, many of which are in the diet already, can be an effective way to prevent disease. This adds to already good evidence that eating large quantities of vegetables -- and cruciferous ones play a special role -- is one thing that really works to fight disease."
Aged garlic lowers oxidative stress in humans
A study published in the February 2002 issue of The Journal of Nutrition showed that dietary supplementation with aged garlic lowered a marker of oxidative stress in human volunteers. The study examined the effects of Kyolic brand aged garlic on twenty healthy men and women, divided into two groups consisting of smokers and nonsmokers. Data concerning age, height, weight, alcohol consumption and number of cigarettes smoked daily was obtained from each participant, and blood and urine samples taken.
Study participants were given 5 milliliters of aged garlic extract once daily for fourteen days. No lifestyle changes were requested of the volunteers. After fourteen days and twenty-eight days, blood and urine samples were recollected. Urine and plasma levels of free 8-iso-prostaglandin F2-alpha, a measure of lipid peroxidation, were determined.
At the study's onset, blood plasma concentrations of 8-iso-PGF2-alpha in smokers were 58% higher than that of age and sex-matched nonsmokers, and 85% higher in the urine. After fourteen days of aged garlic supplementation, the nonsmokers experienced a 29% drop in the plasma concentration of the oxidative stress marker while smokers experienced at 35% drop. Urinary concentrations fell by 37% in the nonsmoking group and 48% in smokers. When levels were remeasured two weeks following the last dose of aged garlic, they were found to have returned to those measured at the study's onset, before supplementation was initiated.
A discussion of the results noted the confirmation of the increased oxidative stress observed in smokers compared to nonsmokers, and the authors conclude that dietary supplementation with aged garlic may help prevent diseases associated with oxidative stress, such as atherosclerosis.
Beta-carotene and other antioxidant levels associated with lower breast cancer risk
A case control study published in the February 2002 issue of The Journal of Nutrition found an association between serum levels of beta-carotene, vitamin A, and total antioxidant status with a lower risk of breast cancer. The study examined serum samples taken from 153 Australian women newly diagnosed with breast cancer prior to treatment, who were matched with 153 women without the disease. Samples were analyzed for total antioxidant status, albumin, bilirubin, uric acid, vitamin A, vitamin E, lycopene, alpha-carotene and beta-carotene. Both groups were interviewed to obtain lifestyle, demographic and reproductive history information.
Analysis of the data adjusted for age at menarche, number of children, alcohol intake, and fat consumed. Of the serum levels analyzed, beta-carotene showed the strongest association with a reduction in the risk of breast cancer. Vitamin A, bilirubin and total antioxidant status followed beta-carotene in association, with the group showing the highest levels experiencing approximately half the risk of the group with the lowest levels. In regard to bilirubin's positive association with breast cancer risk reduction, recent research has indicated that bilirubin has antioxidant properties and may protect against atherosclerosis and inflammation, but no studies have been conducted to determine its relevance to cancer.
This study confirms the anticancer benefit of beta-carotene and other antioxidants demonstrated by numerous other studies. While many other studies have relied on the participants' recall of foods consumed in order to calculate nutrient levels, this study had the advantage of measuring them directly in the subjects' serum.