ABSTRACTS

BOSTON, MASSACHUSETTS. Sudden cardiac death kills about 250,000 Americans every year and half of them have no known cardiovascular disease when they are suddenly struck down. Researchers at Brigham and Women's Hospital and the Harvard School of Public Health now report that men with a high intake of oils from fatty fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have an 81 per cent lower risk of sudden cardiac death than do men with a low intake. Their study involved a group of 15,000 male physicians aged 40 to 82 years when they enrolled in the study. Over a 17-year follow-up period 94 men with no known cardiovascular disease died suddenly from heart failure (sudden cardiac death). Blood samples taken from the men at enrollment were analyzed for fatty acids and the results compared to those obtained from 184 controls. The average age of both controls and cases was 58 years.
The researchers found that men whose blood levels of EPA and DHA constituted 6.87 per cent or more of their total fatty acid concentration had an 81 per cent lower risk of sudden cardiac death than did men whose level was 3.58 per cent or less. This correlation remained after adjusting for confounding factors such as diabetes, hypertension, exercise, aspirin usage, cholesterol levels, alcohol consumption, etc. The researchers conclude that their findings support the hypothesis that fish oils (EPA and DHA) are responsible for the inverse association between fish consumption and sudden death.
Dr. Irwin Rosenberg, MD of Tufts University comments that the study is further proof that striving for a daily intake of 1 gram per day of fish oils (from fatty fish) helps protect against sudden cardiac death.
Albert, Christine M., et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. New England Journal of Medicine, Vol. 346, April 11, 2002, pp. 1113-18
Rosenberg, Irwin H. Fish: food to calm the heart. New England Journal of Medicine, Vol. 346, April 11, 2002, pp. 1102-03

POMONA, CALIFORNIA. Diabetes has afflicted mankind for at least 3500 years and during that time many remedies have been used in traditional systems of medicine for keeping blood sugar under control. American pharmacists from the University of California and the Western University of Health Sciences have just completed a fascinating study of over 30 natural products traditionally used by diabetics. Following an extensive review of published literature they conclude the following:

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• Foods high in soluble fiber (nopal, fenugreek, aloe, flaxseed and psyllium) reduce postprandial (after meal) glucose concentrations. -
• Nopal or prickly pear cactus (Optunia fuliginosa) is widely used in Mexico and has been found highly effective in keeping glucose levels under control. -
• Fenugreek seed (Trigonella foenumgraecum) is widely used in Mediterranean countries and works in both type 1 and type 2 diabetics. -
• Karela or bitter melon (Momordica charantia) is the most popular plant used worldwide to treat diabetes. Karela is usually taken as a fresh juice (2-4 ounces daily) or in the form of a 4:1 tincture (1-3 ml twice daily). -
• Gymnema (Gymnema sylvestre) is native to central and southern India and has been used to treat diabetes for more than 2500 years. It is usually taken in the form of an extract of gymnema leaves known as GS4. GS4 (400 mg/day) has been found highly effective in controlling glucose levels in both type 1 and type 2 diabetics. -
• Other products that have been found useful for glucose control include ginseng (Panax quinquefolius), chromium picolinate (up to 1000 micrograms/day) and alpha-lipoic acid (600- 1800 mg daily in divided doses).

The pharmacists caution against the use of any of these products when hypoglycemia is present or suspected.
Shapiro, Karen and Gong, William C. Natural products used for diabetes. Journal of the American Pharmaceutical Association, Vol. 42, March/April 2002, pp. 217-26

BOSTON, MASSACHUSETTS. Surgery-induced arteriosclerosis is a serious problem in heart transplant patients and is now the single most important factor in determining long-term survival. Researchers at the Brigham and Women's Hospital and the Linus Pauling Institute in Oregon believe that the accelerated arteriosclerosis is due to oxidative stress initiated at the transplant operation. They speculated that, if this is indeed the case, then supplementing heart transplant patients with vitamins C and E should prevent or slow the development of arteriosclerosis. Their clinical trial included 40 recent transplant patients who were randomly assigned to receive either a placebo or 500 mg of vitamin C plus 400 IU of vitamin E twice daily for a year. The degree of thickening (intimal index) of the coronary artery was measured using intravascular ultrasonography at the beginning and end of the study. The researchers found that the intimal index had increased by only 0.8 per cent in the vitamin group as compared to 8 per cent in the placebo group. They conclude that supplementing with vitamins E and C may not only prevent transplant-induced arteriosclerosis, but may also be helpful in kidney, lung and liver transplants.
Fang, James C., et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. The Lancet, Vol. 359, March 30, 2002, pp. 1108-13

HOBART, TASMANIA. Researchers at the University of Tasmania have developed a novel way of determining a person's risk of developing melanoma or skin cancer. Their experiment included 244 patients with cutaneous malignant melanoma, 220 with basal cell carcinoma, 195 with squamous cell carcinoma, and 483 healthy controls. All participants were of northern European descent. The researchers measured the participants' melanin density in skin of the upper inner arm using a handheld spectrophotometer. They found that men with a low melanin density had a 6.2-fold greater incidence of melanoma, a 6.3-fold greater incidence of basal cell carcinoma, and a 4.2-fold greater incidence of squamous cell carcinoma than did men with a high level. The corresponding figures for women were a 1.9, 1.4 and 0.7 fold increase.
The researchers point out that melanin absorbs ultraviolet light and is found in greater density in the skin of racial groups (dark-skinned people) that have the lowest incidence of skin cancers. They cannot explain why women show a poorer correlation between melanin density and skin cancer risk, but speculate that it could be due to a higher general degree of sun avoidance among women. They conclude that spectrophotometric measurement of melanin content could be used to identify people of high risk for developing melanoma or skin cancer.
Dwyer, Terence, et al. Cutaneous melanin density of Caucasians measured by spectrophotometry and risk of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin. American Journal of Epidemiology, Vol. 155, April 1, 2002, pp. 614-21

DENVER, COLORADO. Researchers at the University of Colorado School of Pharmacy warn that prolonged use of acid-suppressing drugs such as cimetidine (Tagamet), ranitidine (Zantac) and omeprazole (Losec) can lead to a serious vitamin B12 deficiency. They cite the case of a 78-year-old non-vegetarian, white woman with GERD (gastroesophageal reflux disease) who had been taking cimetidine or ranitidine for 4.5 years. She was started on cimetidine (300 mg four times daily) in February 1990, which was changed to ranitidine (150 mg twice daily) in April 1993. Her vitamin B12 level was normal (413 pg/mL) in August 1992, but by June 1994 it had decreased to 256 pg/mL and her homocysteine level had increased dramatically to 27.3 micromol/L. Note: A homocysteine level above 10 micromol/L vastly increases the risk of atherosclerosis and stroke with a 5 micromol/L increase corresponding to a 70 per cent increase in the risk of heart disease and a 50 per cent increase in stroke risk.
The patient was started on 1000 micrograms/day of sublingual vitamin B12 supplementation and by November 1994 her level was back up to 517 pg/mL and her homocysteine level was down to 20.3 micromol/L. Further improvements were observed in March 1998 when her vitamin B12 level was up to 629 pg/mL and homocysteine was down to 13.9 micromol/L. The researchers point out that other studies have shown that omeprazole also lowers vitamin B12 levels and conclude that older people on long-term acid- suppressing drugs should be monitored for vitamin B12 deficiency and supplement if necessary.
Ruscin, J. Mark, et al. Vitamin B12 deficiency associated with histamine2-receptor antagonists and a proton-pump inhibitor. Annals of Pharmacotherapy, Vol. 36, May 2002, pp. 812-16

MANCHESTER, UNITED KINGDOM. It is estimated that irritable bowel syndrome (IBS) affects about 15-20 per cent of the population in western countries. It accounts for approximately half of the workload of the average gastroenterologist and engenders a significant amount of lost work hours. The syndrome is about twice as common among women as among men. The most common symptoms are abdominal distension (bloating), abdominal pain, altered bowel habits (diarrhea or constipation), backache, urinary symptoms, and flatulence. IBS can also lead to anxiety and depression and an overall reduction in the quality of life. Several studies have found that hypnotherapy is effective in alleviating IBS. The National Health Service (UK) has just set up the first Hypnotherapy Unit devoted exclusively to the treatment of IBS patients. The Unit has six therapists on staff and has treated several hundred patients since its inception.
Medical researchers at the University Hospital of South Manchester have just completed a major study to evaluate the effect of hypnotherapy (12 sessions over a three-month period and "homework" in between) in the first 250 people treated at the Unit. They found that the overall IBS score (sum of score for pain severity and frequency, bloating, bowel habits and interference with life; maximum score of 500) had decreased from 300 for male IBS patients and 343 for females to 178 and 151 respectively; this corresponds to a 56 per cent improvement in females and a 40 per cent improvement in males. An impressive 78 per cent of all participants had significantly improved bowel habits after treatment. The observed reductions in anxiety score (33 per cent) and depression score (43 per cent) were also impressive. The researchers conclude that hypnotherapy is an extremely effective treatment for IBS.
Gonsalkorale, Wendy M., et al. Hypnotherapy in irritable bowel syndrome: a large-scale audit of a clinical service with examination of factors influencing responsiveness. American Journal of Gastroenterology, Vol. 97, April 2002, pp. 954-61

SANTA MARIA IMBARO, ITALY. A group of Italian researchers (GISSI) reported in 1999 that supplementation with fish oil reduces the mortality among patients who have survived a first heart attack. Their study involved over 11,000 heart attack survivors who supplemented with 1 gram/day of fish oil (580 mg of eicosapentaenoic acid [EPA] and 290 mg of docosahexaenoic acid [DHA]) for 3.5 years.
The researchers have now re-analyzed their data in an attempt to determine how the fish oil exerts its protective effect. The reduced mortality was apparent after only three months of supplementation (1.1 per cent versus 1.6 per cent in the placebo group) and continued for the duration of the study. The reduction in the incidence of sudden cardiac death accounted for about 57 per cent of the total improvement in mortality rates. At the end of the study 2.7 per cent of the placebo group participants had died from sudden cardiac death as compared to only 2.0 per cent in the fish oil group. Overall, cardiovascular death (including stroke) at the end of the study was 6.5 per cent in the placebo group versus 5.5 per cent in the fish oil group. There was no statistical significant difference in the incidence of non-fatal heart attacks between the fish oil and placebo groups.
The researchers conclude that fish oils exert their protective effect by preventing fatal ventricular arrhythmias rather than through an improvement in cholesterol profile. They did note a small (4.6 per cent) drop in triglyceride levels in the fish oil group, but found no significant differences in LDL (low-density lipoprotein) and HDL (high-density lipoprotein) cholesterol between the two groups. They also point out that the number of lives (per 1000 patients) which could be saved every year by giving heart attack survivors fish oil exceeds the number of lives (per 1000 patients) estimated to be saved by treating heart disease patients with high cholesterol levels with pravastatin. This puts fish oils squarely in the category of highly effective heart "drugs".
Marchioli, Roberto, et al. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Lipids, Vol. 36, Supplement 2001, pp. S119-S126
Marchioli, Roberto, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of GISSI-Prevenzione. Circulation, Vol. 105, April 23, 2002, pp. 1897-1903
Leaf, Alexander. On the reanalysis of the GISSI-Prevenzione. Circulation, Vol. 105, April 23, 2002, pp. 1874-75 (editorial)

BERLIN, GERMANY. Children with cystic fibrosis are often underdeveloped for their age in stature and muscle mass. They also have a significantly lower exercise capacity (peak oxygen uptake) than do healthy children. Researchers at the Free University Berlin now report that treatment with growth hormone can markedly increase height, lean muscle mass, and peak oxygen uptake in children with cystic fibrosis. Their clinical trial involved 10 prepubertal children between the ages of 9.7 and 14.3 years (3 girls and 7 boys). The children were randomly assigned to receive standard therapy (high caloric diet, pancreatic enzymes and vitamins) or standard therapy plus growth hormone injections every night between 7 and 8 pm (0.11 to 0.14 IU per kg body weight). After six months the protocol was reversed so that the children on growth hormone received only the standard therapy and vice versa.
Children on growth hormone increased their height by an average 4.3 cm during the six-month period as compared to an increase of only 2.3 cm in the control group. Lean body mass increased by 2.9 kg as compared to no change in the control group. Exercise capacity as measured by peak oxygen uptake declined by an average 44 mL in the control group, but increased by 214 mL in the hormone group. The researchers conclude that growth hormone treatment clearly improves exercise capacity through its combined beneficial effect on muscular, cardiovascular and pulmonary capacity.
Hutler, Matthias, et al. Effect of growth hormone on exercise tolerance in children with cystic fibrosis. Medicine & Science in Sports & Exercise, Vol. 34, April 2002, pp. 567-72

SYDNEY, AUSTRALIA. Leukemia is the most common cancer among children in developed countries. The causes of childhood leukemia are largely unknown, but there is some indication that environmental factors and exposure to radiation could play a role. Researchers at the Cancer Foundation of Western Australia now report the results of a comprehensive study aimed at determining the risk factors for acute lymphoblastic leukemia. The researchers compared 83 children under the age of 14 years with leukemia with 166 healthy children matched for sex, date of birth, and broad region of residence. They interviewed both the mother and father of each child and also determined the child's exposure to various expected risk factors. As an add-on they also asked the mothers about their use of medicines and supplements during pregnancy.
Not unexpectedly, they found that children who had been exposed to pesticides and x-rays had a three-fold increased risk of leukemia. A mother's exposure to agricultural chemicals, glues or resins during pregnancy increased the risk by a factor of three or four. A father's exposure to paints or pigments (at work) or to solvents, degreasers or cleansing agents or other industrial chemicals, in the five-year period prior to the child's birth, was associated with a three-fold risk increase. Completely unexpected was the finding that children born to women who had supplemented with iron and folic acid during pregnancy had a three times (0.37 odds ratio) lower risk of developing leukemia than did children born to mothers who had not supplemented.
The researchers believe that the folic acid is responsible for the protective effect, but could not separate the effects of iron and folic acid as they were always taken together. They point out though that folic acid has been associated with a reduced risk of colon cancer. The researchers conclude that folic acid supplementation during pregnancy reduces the risk of childhood leukemia. NOTE: The RDA for iron and folic acid during pregnancy is 30 mg/day and 400 micrograms/day respectively.
Thompson, Judith R., et al. Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukemia in childhood: a case-control study. The Lancet, Vol. 358, December 8, 2001, pp. 1935-40

ATLANTA, GEORGIA & PERTH, AUSTRALIA. It is estimated that infertility now affects about 10 per cent of the reproductive age population in the United States. In medical terms a couple is considered infertile if the woman fails to conceive after a year of trying to do so. The growing incidence of infertility has led to the development of various assisted reproduction schemes; the most widely used being in vitro fertilization and intracytoplasmic sperm injection. It has long been known that the use of assisted reproduction technology vastly increases the chance of having twins or even triplets. This, in turn, leads to an increase in the number of low birth weight children.
Researchers at the National Institutes of Health now report that the incidence of low birth weight in single children conceived with assisted reproduction is 6.5 per cent as compared to 2.5 per cent among children conceived naturally. Artificially conceived children are also more likely to be born with major birth defects. Australian researchers found that 9 per cent of children conceived with assisted reproductive technology had a major birth defect diagnosed by one year of age as compared to a rate of 4.2 per cent among naturally conceived infants.
Dr. Allen Mitchell, MD of Boston University warns that the number of clinics providing assisted reproductive services is growing rapidly and that they are aggressively promoting their services. He recommends that prospective parents "keep trying a little longer" rather than rush into an artificial conception, which may produce a low birth weight infant or one with a birth defect.
Schieve, Laura A., et al. Low and very low birth weight in infants conceived with use of assisted reproductive technology. New England Journal of Medicine, Vol. 346, March 7, 2002, pp. 731-37
Hansen, Michele, et al. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. New England Journal of Medicine, Vol. 346, March 7, 2002, pp. 725-30
Mitchell, Allen A. Infertility treatment: more risks and challenges. New England Journal of Medicine, Vol. 346, March 7, 2002, pp. 769-70 (editorial)

AUCKLAND, NEW ZEALAND. There is considerable evidence that calcium supplementation reduces bone loss and hip fractures in postmenopausal women. Researchers at the University of Auckland now report that calcium supplementation may also reduce the risk of cardiovascular disease by increasing the level of HDL (high-density lipoprotein) cholesterol, the "good" kind. The study involved 223 postmenopausal women who were randomized to receive either a placebo or 1 gram of elemental calcium in the form of calcium citrate. Two 200 mg tablets were taken before breakfast and three in the evening. Fasting serum levels of triglycerides, total cholesterol and HDL cholesterol were measured at baseline and after 2, 6, and 12 months of supplementation.
The researchers found that women taking the calcium citrate decreased their LDL cholesterol levels (the "bad" cholesterol) and increased their HDL levels by an average 6 per cent corresponding to a 20 to 30 per cent reduction in cardiovascular events. There was no significant change in triglyceride or total cholesterol levels. The researchers point out that this highly beneficial effect of supplementation with calcium citrate is in sharp contrast to the lack of beneficial cardiovascular effects observed with increased milk consumption. They conclude that postmenopausal women should be encouraged to supplement with calcium.
Reid, Ian R., et al. Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial. American Journal of Medicine, Vol. 112, April 1, 2002, pp. 343-47

DALLAS, TEXAS. There is considerable epidemiologic evidence that being physically fit reduces the risk of having a stroke. Most of the studies reaching this conclusion have been based on self-reported physical activity rather than on actual evaluation of physical fitness. Researchers at the Cooper Institute and the West Texas A & M University recently released the results of a 10-year study aimed at determining the risk of stroke as a function of physical fitness actually measured during a treadmill test.
The study involved 16,878 men between the ages of 40 and 87 years who entered the study group between 1971 and 1994. The men's cardiorespiratory fitness was determined through a maximal treadmill exercise test. The men were divided into three groups based on their performance – the least fit group (bottom 20 per cent), the moderately fit (middle 40 per cent), and the most fit (highest 40 per cent). After an average 10 years of follow-up 32 stroke deaths had occurred among the 16,878 men. The researchers found that the most fit men had a 68 per cent and the moderately fit men a 63 per cent lower risk of dying from a stroke than did the least fit men even after correcting for other know risk factors such as smoking, alcohol consumption, hypertension, diabetes, body mass index, and parental history of coronary heart disease. It is interesting to note that the overall absolute risk of dying from a stroke within a 10-year period was only 0.2 per cent in this group.
Lee, Chong Do and Blair, Steven N. Cardiorespiratory fitness and stroke mortality in men. Medicine & Science in Sports & Exercise, Vol. 34, April 2002, pp. 592-95

NEWSBRIEFS

Birth control pills increase risk of stroke
A major class action suit has been launched against the manufacturers of third generation contraceptive pills (Femodene, Minulet, Marvelon and Mercilon) introduced in the 1980s. The suit claims that more than 100 women suffered harmful side effects from the pills. A spokeswoman for Wyeth acknowledges that the stroke risk for women taking the pills is five times higher than it is for women not taking the pill (25 versus 5 cases per 100,000 women). The health problems caused by the pills were first discovered in 1995 and since then many women have switched to other brands.
Reuters Health Information, March 4, 2002

Once on statins always on statins?
Statins such as pravastatin (Pravachol) and simvastatin (Zocor) are effective in lowering cholesterol levels and are often prescribed for people with heart disease. German researchers now warn that statin therapy should not be withdrawn in heart patients hospitalized with chest pain. A study of 1612 patients admitted with coronary artery disease and chest pain found that those whose statin therapy was discontinued after admission had a three times higher rate of fatal and non- fatal heart attacks during a 30-day follow-up period than did patients whose statin therapy was maintained. Patients whose therapy was discontinued actually had a 69 per cent higher event rate than did patients who did not take statins at all (controls). Continued statin therapy was found to be beneficial with a 50 per cent lower event rate than the controls.
Circulation, Vol. 105, March 26, 2002, pp. 1446-52, e9085-90

Diabetes drug linked to vitamin B12 deficiency
A Wisconsin doctor reports a case of a 63-year- old man who developed a severe vitamin B12 deficiency after having taken metformin (Glucophage) for five years. Replacing the metformin with sulfonylurea and taking 1000 mg of cyanocobalamin (vitamin B12) for two months reversed the deficiency. Dr. Mary Ann Gilligan estimates that 10 to 30 per cent of patients on metformin develop a vitamin B12 deficiency and points out there is some evidence that calcium supplementation will prevent it.
Archives of Internal Medicine, Vol. 162, February 25, 2002, pp. 484-85

Newspapers biased on mammography
In 1993 the National Cancer Institute concluded that there is insufficient evidence to recommend routine mammography screening for women aged 40 to 49 years. Other organizations have also questioned the benefits of screening in this age group. Yet despite this evidence most newspaper articles on the topic still push screening. Researchers at the University of Maryland reviewed 187 articles on mammography published in six American high-circulation newspapers between 1990 and 1997. They found that mammography screening was recommended twice as often as no screening for women aged 40 to 49 years. They conclude that newspapers tend to over-represent support for screening in this age group and often do not provide the sources of their information and recommendations.
Annals of Internal Medicine, Vol. 135, December 18, 2001

Magnetic storms can affect health
Solar winds can interact with the earth's magnetic field to cause magnetic storms. Russian researchers have found that these storms can have a profound effect on cardiovascular parameters such as blood viscosity, coagulation and adrenaline levels. The storms are imperceptible to people, but can be detected with magnetometers. One of the researchers suggests that intensive-care wards be equipped with magnetometers so that doctors can give patients anticoagulation medicine when a storm approaches. The storms can happen two to three times a month and it is estimated that about 13 per cent of all heart attacks in Moscow are connected to magnetic storms.
Reuters Health Information, April 5, 2002

Gender-benders are everywhere
The so-called gender-bending chemicals are turning up everywhere. A team of German researchers found nonylphenols, which strongly mimics estrogen, in every food product they tested from pasta to butter. They estimate that the average German adult takes in about 7.5 micrograms of nonylphenols every day. Formula-fed infants take in 1.4 micrograms/day or seven times more than they would get if they were breastfed. Nonylphenols are used in the manufacture of paint, pesticides and cleaning products.
New Scientist, March 30, 2002, p. 23

Irritable male syndrome
Studies involving male sheep, deer, reindeer and elephants have clearly shown that these animals become grumpy, irritable and withdrawn when their testosterone levels decline. Gerald Lincoln of the Scottish Medical Council believes that a similar "irritable male syndrome" occurs in men when their testosterone levels fall. He points out that stress causes testosterone to plummet. Richard Anderson, another Edinburgh researcher, has found that men on testosterone replacement therapy become irritable and depressed when they stop the therapy. Dr. David Abbott, an American researcher, believes that doctors often miss the connection between stress (high cortisol levels) and depression and do not even consider falling testosterone levels as a potential cause of depression.
New Scientist, March 2, 2002, p. 4