ABSTRACTS

BILTHOVEN, THE NETHERLANDS. In 1958 five European countries, Japan, and the United States began a study to determine the most important causes of premature death from various chronic diseases. The study involved 12,763 middle-aged men who completed questionnaires regarding their nutrient intake and smoking status at the start of the study. After 25 years of follow-up 5973 (47 per cent) of the men had died. The researchers evaluating the collected data noticed large differences in saturated fat intake ranging from 3.9 per cent of energy in Japan to 22.7 per cent in East Finland. An eight-fold difference in vitamin C intake (17 mg/day in Serbia versus 142 mg/day in the USA) was also observed. Smoking was found to be almost twice as prevalent in Japan (78 per cent) as in Serbia (44 per cent) and alcohol intake ranged from 1.8 grams/day in East Finland to 91.2 grams/day in Croatia.
After analyzing all the data the researchers concluded that a high intake of saturated fat, smoking, and a low vitamin C intake are the most important predictors of early death among middle-aged men. They estimate that a 5 per cent reduction in the intake of saturated fats, a 10 per cent decrease in the number of smokers, and a 20 mg/day increase in vitamin C intake would decrease the 25-year all-cause population mortality rate by an impressive 12.4 per cent.
The researchers cite Poland as an example of the enormous effect that dietary changes can have on overall mortality. After 20 years of rising coronary heart disease mortality a 25 per cent decrease was observed among men and women aged 45 to 64 years between 1991 and 1994. They credit a 23 per cent decrease in the intake of animal fats, a 48 per cent increase in vegetable fats, and a doubling in the imports of citrus fruits and bananas for this positive development.
Kromhout, Daan, et al. Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study. International Journal of Epidemiology, Vol. 29, April 2000, pp. 260-65

BERGEN, NORWAY. Elevated blood levels of homocysteine (a sulfur-containing amino acid) has been linked to a significantly higher risk of cardiovascular disease, stroke and heart attacks, and has also been implicated in Raynaud's phenomenon. Researchers at the universities in Bergen and Oslo now report that high homocysteine levels increase the risk of pregnancy complications and infant abnormalities. Their study evaluated 14,492 pregnancies that occurred between 1967 and 1996. The homocysteine levels of the 5883 mothers involved in the pregnancies were measured in 1992 or 1993 at which time the women were between the ages of 40 and 42 years. The researchers found that women with the highest levels of homocysteine (greater than 10.7 micromol/L) had an adjusted risk for preeclampsia (pregnancy- related hypertension) which was 38 per cent higher than the risk among the women with the lowest levels of homocysteine (3.6-7.5 micromol/L). The risk of giving birth to a very low birth weight baby (weight less than 1500 grams) was 101 per cent higher among high homocysteine women and the risk of stillbirth 103 per cent higher. The association between pregnancy complications and homocysteine levels was particularly pronounced when limiting the analysis to births after 1980. In this cohort high homocysteine levels were associated with an almost five-fold increase in the risk of preeclampsia and a doubling of the risk of premature delivery, stillbirth or the birth of a very low birth weight infant. There was also a significant association between the presence of malformations in the baby and high homocysteine levels in the mother. This was particularly pronounced for neural tube defects where a 3.57-fold increase in risk was observed. The researchers also noted that women with high homocysteine levels tended to smoke more, drink more coffee, have lower educational levels, and did not take vitamin supplements. Editor's Note: High homocysteine levels can be safely and effectively reduced by supplementation with folic acid, vitamin B6 and vitamin B12.
Vollset, Stein Emil, et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine Study. American Journal of Clinical Nutrition, Vol. 71, April 2000, pp. 962-68
Picciano, Mary Frances. Is homocysteine a biomarker for identifying women at risk of complications and adverse pregnancy outcomes? American Journal of Clinical Nutrition, Vol. 71, April 2000, pp. 857-58 (editorial)

SYDNEY, AUSTRALIA. There is evidence that the development of cataracts, the most important cause of blindness worldwide, is associated with smoking, diabetes, and the use of corticosteroids. Now researchers at the University of Sydney report that a high salt (sodium chloride) intake is also associated with an increased risk of cataracts. Their study involved 2873 people between the ages of 49 and 97 years (median age of 65 years) who had photographs taken of their eyes (right and left lenses) and also completed a 145-item food intake questionnaire. Among the participants there were 620 cases of cortical cataracts, 350 of nuclear cataracts, and 160 of posterior subcapsular cataracts (the most disabling type). The researchers discovered a clear correlation between sodium intake and the incidence of posterior subcapsular cataracts. Study participants with a sodium intake of 3000 mg/day or more were twice as likely to have subcapsular cataracts than were participants with an intake of 1270 mg/day or less. This association held true even after adjusting for the effects of age, sex, smoking history, diabetes, hypertension, and the use of corticosteroids. The researchers found no correlation between sodium intake and the incidence of nuclear and cortical cataracts. They conclude that a reduced salt diet may help prevent cataracts in older individuals.
Cumming, Robert G., et al. Dietary sodium intake and cataract: the Blue Mountains Eye Study. American Journal of Epidemiology, Vol. 151, March 15, 2000, pp. 624-26

LONDON, UNITED KINGDOM. High body levels of aluminum are toxic and have been associated with Alzheimer's disease. There is some evidence that silica can bind to aluminum and safely excrete it from the body; however, not all studies have confirmed this effect. A team of Australian and British researchers believe that they have found the reason for the conflicting results. Most studies have used monomeric silica (orthosilicic acid) as the aluminum-binding compound. Silica, however, also occurs naturally as an oligomeric form (a polymer of orthosilicic acid) and this form apparently has a much greater affinity for aluminum than does the monomeric form. The researchers tested their hypothesis that the oligomeric form is the active one in a small experiment involving three healthy young men. The participants were given a drink containing isotope-labelled aluminum citrate with either monomeric or oligomeric silica. Subsequent blood and urine analyses showed that the concentrations of aluminum in both blood and urine were reduced by about 70 per cent in the case of oligomeric silica, but no change was observed with the monomeric form. The oligomeric silica was prepared by diluting a stock sodium silicate solution and neutralizing it to pH 7.2 with hydrochloric acid. The monomeric silica formed spontaneously from this solution by depolymerization over a seven-day period. The researchers conclude that oligomeric silica is highly effective in preventing the absorption of aluminum through the gastrointestinal tract.
Jugdaohsingh, Ravin, et al. Oligomeric but not monomeric silica prevents aluminum absorption in humans. American Journal of Clinical Nutrition, Vol. 71, April 2000, pp. 944-49

SALVADOR, BRAZIL. Aseptic (acute viral) meningitis is a known adverse effect of vaccination with the combined measles-mumps-rubella (MMR) vaccine. It is estimated that one out of every 10,000 children given the vaccine develops aseptic meningitis. Public health authorities in Salvador, the capital of the state of Bahia, now confirms this connection. In August 1997 about 450,000 children between the ages of one and eleven years of age were vaccinated against measles, mumps, and rubella using Pluserix vaccine (Smith-Kline Beecham Pharmaceuticals). Approximately three weeks after the vaccination 50 of the vaccinated children were diagnosed with aseptic meningitis and admitted to hospital. The health officials estimate that the rate of hospital admission for meningitis was 13.4 times higher three weeks after the vaccination than before the campaign started. The vast majority of cases involved children between the ages of one and eight years with children aged four to eight years being almost five times more likely to develop meningitis than children aged nine to eleven years. The officials conclude that the vaccination caused the outbreak of meningitis, but oddly enough their main concern is not this serious adverse effect, but rather how the public is going to perceive vaccination campaigns in the future. They note "The average citizen has started to behave as a health-care consumer, discussing official health policies, requesting more information, and questioning and even refusing governmental health measures."
Dourado, Ines, et al. Outbreak of aseptic meningitis associated with mass vaccination with a urabe- containing measles-mumps-rubella vaccine. American Journal of Epidemiology, Vol. 151, March 1, 2000, pp. 524-30

KUMAMOTO, JAPAN. Heart failure (congestive heart failure) is the end stage of heart disease; it affects more than 2 million people in the United States alone. Simply defined, heart failure (CHF) occurs when the output of the heart is insufficient to meet the demands of the body. Left ventricular dysfunction is a common feature of heart failure and recent research has shown that blood plasma levels of A- and B-type natriuretic peptides are elevated in CHF patients.
Researchers at the Kumamoto University School of Medicine now report that there is a close association between blood levels of dehydroepiandrosterone sulfate (DHEAS) and the severity of CHF. The more severe the CHF the lower the DHEAS levels. The study involved 49 male patients (mean age of 61 years, range 38-75 years) with left ventricular dysfunction and 32 age-matched controls with no heart disease. The researchers confirmed that DHEAS levels decline markedly with age, but noted that this decline was only present in healthy controls. In CHF patients DHEAS levels were low regardless of age. The average DHEAS level in the CHF patients was 79 micrograms/dL as compared to 132 micrograms/dL in the controls. DHEAS levels in patients with severe CHF were significantly lower than in patients with a milder grade of CHF. There were no significant differences in plasma levels of cortisol between the patients and the controls. The plasma cortisol/DHEAS ratio was significantly associated with the levels of A-type natriuretic peptide and the levels of thiobarbituric acid-reactive substances (TBARS). TBARS are a powerful indicator of oxidative stress.
The researchers conclude that oxidative stress may play a role not only in CHF, but also in the lowering of DHEAS levels in CHF patients. They also mention that glutathione, a powerful antioxidant, may help reverse the suppression of DHEAS synthesis observed in CHF patients.
Moriyama, Yasushi, et al. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. Journal of Clinical Endocrinology & Metabolism, Vol. 85, April 2000, pp. 1834-40

NEW YORK, NY. The bacterial flora in the gastrointestinal tract exists in a finely-tuned balance which can easily be disturbed by antibiotics, infections, chemotherapy, and radiation. Antibiotics in particular destabilize the flora leading to serious impairments in the absorption and metabolism of vitamins and other nutrients. Treatment with antibiotics can produce sprue-like symptoms, can reduce the absorption or synthesis of carotenes, iron, calcium, vitamin B12 and vitamin K, and can produce gastritis (inflammation of the stomach lining), diarrhea, itching, bleeding, increased susceptibility to infections by salmonella and overgrowth by resistant organisms.
Dr. Joseph Levy, MD of Columbia University warns that, while antibiotics are useful in combating some infections, they are definitely not without serious side effects. His recommendation is to "minimize antibiotic use whenever it is clinically reasonable to do so." He also cautions that wide-spectrum antibiotics should be avoided and that antibiotics should be administered at the lowest effective dose for the shortest possible duration. Dr. Levy is optimistic that the use of lactobacilli and nonpathogenic yeasts to recolonize the gastrointestinal tract will prove effective in decreasing the side effects of antibiotics.
Levy, Joseph. The effects of antibiotic use on gastrointestinal function. American Journal of Gastroenterology, Vol. 95 (suppl), January 2000, pp. S8-S10

BELLEVUE, WASHINGTON. Several psychiatrists have argued that it is unethical for clinical trials of antidepressants to include placebo controls when an effective treatment (antidepressants) is available. A group of researchers from the Northwest Clinical Research Center and Brown University in Providence, Rhode Island now thoroughly debunks this notion. The researchers evaluated the results of 45 studies aimed at evaluating the effectiveness of seven new antidepressants (Prozac, Zoloft, Paxil, Effexor, Serzone, Remeron, and Wellbutrin SR). They obtained their data directly from the Food and Drug Administration (FDA). Among the 19,639 study participants (moderately to severely depressed) 34 committed suicide (0.8 per cent/year) and 130 (2.9 per cent/year) attempted suicide during the studies. There were no significant differences in suicide rates among drug takers and placebo takers. Annual rates of suicide were 0.4 per cent for placebo takers, 0.7 per cent for patients taking established tricyclic antidepressants (imipramine, amitriptyline or trazodone), and 0.8 per cent among patients taking the new antidepressants. Annual rates of attempted suicide were 2.7 per cent, 3.4 per cent, and 2.8 per cent respectively. The researchers conclude that omitting the placebo group in tests of antidepressants cannot be justified on the grounds that they are more likely to commit suicide than are treated patients.
Analysis of the FDA database also led to the surprising conclusion that placebos were nearly as effective as both established and new antidepressants in reducing the symptoms of depression. Using the Hamilton Depression Rating Scale as a yardstick the researchers concluded that the average extent of symptom reduction was 40.7 per cent with the new antidepressants, 41.7 per cent with the tricylics, and 30.9 per cent with the placebo. So less than 10 per cent improvement separated the new antidepressants from the placebo. As a matter of fact, 15 studies out of 42 found placebos to be more effective than active drugs compared to 18 studies which found the new antidepressants more effective.
Khan, Arif, et al. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials. Archives of General Psychiatry, Vol. 57, April 2000, pp. 311-17

SAN FRANCISCO, CALIFORNIA. It is estimated that 20 million Americans have cholesterol-based gallstones. These stones form when bile acid supersaturated with cholesterol is destabilized. Animal experiments have shown that guinea pigs that are deficient in vitamin C (ascorbic acid) frequently develop gallstones. Now researchers at the University of California report that vitamin C can help prevent gallbladder disease in women. Their study involved 7042 women and 6088 men enrolled in the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III). All participants had their blood serum levels of ascorbic acid determined and were evaluated for gallbladder disease. Among the women 761 (11 per cent) reported a history of gallbladder disease (symptomatic gallstones or cholecystectomy) while 408 (8 per cent) were found to have asymptomatic gallstones. Corresponding figures among the men were 235 (4 per cent) and 274 (6 per cent) respectively.
In the women a clear association was found between the prevalence of both clinical gallbladder disease and asymptomatic gallstones and the blood level of ascorbic acid. For every 27 micromol/L increase in ascorbic acid level the incidence of gallbladder disease and asymptomatic gallstones decreased by 13 per cent. The protective effect of ascorbic acid was particularly impressive among the women who supplemented with vitamin C. In this group the incidence of clinical gallbladder disease was 34 per cent lower than among women who did not supplement. No association between gallbladder disease or asymptomatic gallstones and vitamin C level was observed for the men.
The researchers recommend larger clinical trials specifically aimed at investigating the effect of vitamin C in preventing gallbladder disease among women. NOTE: This study was partially funded by Roche Vitamins, Inc.
Simon, Joel A. and Hudes, Esther S. Serum ascorbic acid and gallbladder disease prevalence among US adults. Archives of Internal Medicine, Vol. 160, April 10, 2000, pp. 931-36

BUFFALO, NEW YORK. Medical doctors at the State University of New York report five cases of vitamin D deficiency which debilitated its victims to such as extent that they became wheelchair-bound due to severe myopathies (muscle disease) involving shoulder and hip muscles. The five patients had been given various diagnoses for their conditions ranging from diabetic neuropathy to osteoporosis. Detailed clinical investigations showed that all five patients suffered from a severe vitamin D deficiency accompanied by elevated parathyroid hormone concentrations. The patients were treated with 50,000 IU of oral ergocalciferol (vitamin D2) once a week for six weeks. At the end of the treatment all patients were fully mobile and no longer needed their wheelchairs.
The doctors speculate that myopathies caused by chronic vitamin D deficiency contribute to immobility and ill health in a significant number of patients in the northern United States and Canada. Vitamin D deficiency is also common in the United Kingdom and in Northern Europe and is attributed to a lack of sun exposure. The doctors point out that a vitamin D deficiency should be suspected in patients complaining of muscle weakness and aches and pains in their bones. They also report that they have seen milder cases of vitamin D deficiency which had been diagnosed as fibromyalgia, depression or chronic fatigue syndrome. Editor's Note:Excessive use of sunscreens undoubtedly contributes to vitamin D deficiencies as sunscreens prevent the skin from generating vitamin D (80 per cent of the body's vitamin D supply is generated in the skin).
Prabhala, Anu, et al. Severe myopathy associated with vitamin D deficiency in western New York. Archives of Internal Medicine, Vol. 160, April 24, 2000, pp. 1199-1203

ISTANBUL, TURKEY. Paroxysmal (intermittent) atrial fibrillation is an increasingly common heart arrhythmia. The condition may be associated with heart disease or it may have no known cause in which case it is classified as lone, primary or idiopathic atrial fibrillation (AF). It is believed that the arrhythmia is initiated by irregularities in autonomic tone (imbalances between the sympathetic and parasympathetic nervous systems) which causes a slowed and nonuniform progression of the atrial impulse. This progression is represented by the so-called P-wave dispersion on a standard 12-lead electrocardiogram.
Researchers at the Istanbul Faculty of Medicine now report that the P-wave dispersion during an atrial fibrillation attack is much longer than in normal controls (60 milliseconds vs. 37 milliseconds). Their clinical study involved 27 patients with AF and 27 controls with no history of heart problems. Almost half (48 per cent) of the patients suffered from lone atrial fibrillation. All participants had their electrocardiograms taken before, during, and after performing the Valsalva maneuver (exhaling into a mercury manometer with enough force to reach 35 mm Hg pressure and sustaining this pressure for 20 seconds). The AF patients were evaluated during an attack.
The researchers noted that the P-wave dispersion increased markedly in the controls after performing the Valsalva maneuver (from 37 ms to 47 ms). On the other hand, in the patients the P-wave dispersion declined from 60 to 45 ms indicating a pronounced decrease in sympathetic activity. They conclude that the Valsalva maneuver normalizes the P-wave duration and dispersion in AF patients and suggest that medications that decrease sympathetic tone may be beneficial in converting AF to sinus rhythm.
Tukek, Tufan, et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. American Journal of Cardiology, Vol. 85, April 1, 2000, pp. 896-99

TORONTO, CANADA. Ginseng is one of the most popular herbal remedies and has been used in China for thousands of years. Asian ginseng is known to combat stress, fatigue, and memory loss while American ginseng (Panax quinquefolius L) is believed to enhance sex drive and improve memory and learning. There is also evidence from animal experiments that American ginseng helps regulate the digestion and protects the liver.
Researchers at the University of Toronto's Faculty of Medicine now report that American ginseng also helps control blood glucose levels. Their randomized, placebo-controlled clinical trial involved 10 non- diabetic subjects (6 males and 4 females) and 9 patients with type 2 diabetes (5 males and 4 females). The trial consisted of two parts. In part one subjects were given either a 3-gram capsule of American ginseng or a placebo capsule (containing 3 grams of corn flour) 40 minutes before drinking 100 ml of a glucose solution containing 25 grams of glucose. In part two the ginseng and placebo capsules were swallowed together with the glucose solution. Blood samples were taken before the start of the test, immediately before swallowing the glucose solution, and then 15, 30, 45, 60 and 90 minutes later. The diabetics also had a blood sample drawn after 120 minutes.
In the non-diabetic subjects who took the ginseng and glucose solution simultaneously no differences were found in blood glucose levels between ginseng and placebo. When ginseng was taken 40 minutes before the glucose challenge a significant change in blood glucose response was noted (an 18 per cent reduction in area under the glycemic curve [AUC]). In the patients with diabetes improved glucose control (over placebo) was noted regardless of when the ginseng was taken (19 per cent reduction in AUC if taken before glucose challenge and 22 per cent if taken with glucose solution). The researchers conclude that American ginseng may be useful in improving glycemic control in patients with type 2 diabetes and also speculate that it may help prevent diabetes from developing in non-diabetics. They caution that non-diabetics prone to hypoglycemia should take ginseng with a meal in order to avoid an unintended drop in blood sugar. NOTE: This study was partially funded by Chai-Na-Ta Corp, a producer of American ginseng products.
Vuksan, Vladimir, et al. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Archives of Internal Medicine, Vol. 160, April 10, 2000, pp. 1009-13

NEWSBRIEFS Herbal remedies for Alzheimer's disease.
The Greek physician Hippocrates used wormwood to treat memory loss. In Shakespeare's time the herbs sage and lemon balm were recommended for the same purpose. Medical researchers are now revisiting these ancient remedies as a possible treatment for Alzheimer's disease. It is well-established that Alzheimer's patients have lower levels of the neurotransmitter acetylcholine in their brains and that this deficiency is associated with memory loss and other cognitive problems. Now Dr. Elaine Perry and her colleagues at the University of Newcastle report that lemon balm (Melissa officinalis), pineapple sage (Salvia elegans), and wormwood (Artemisia absinthium) are effective in blocking the reuptake of acetylcholine in the brain and thereby increasing its concentration. A clinical trial is underway at the University to test the effectiveness of lemon balm and sage in the treatment of Alzheimer's disease. The herbs are being administered in the form of aromatherapy as the active components have been found to be quite volatile.
New Scientist, January 22, 2000, p. 19

Mammography controversy continues.
The reaction to the publication of a study by the Nordic Cochrane Centre which concluded that breast cancer screening with mammography "is unjustified" has been swift and predictable. Harry de Koning of Erasmus University in Rotterdam believes that screening has clearly cut breast cancer deaths in the Netherlands, Finland, and the United Kingdom. Nils Bjurstam of the University of Gothenburg in Sweden points out that death rates from breast cancer are twice as high in Denmark as in Sweden even though the incidence is much the same in the two countries. He believes the main reason for this is that Sweden has a screening program whereas Denmark does not.
New Scientist, January 15, 2000, p. 18

Hazelnuts - a new source of cancer drugs?
Taxol (paclitaxel) is a powerful cancer drug which has been found particularly useful in the treatment of cancers of the breast and ovaries. It is also being tested for possible use in combating other cancers, multiple sclerosis, and Alzheimer's disease. Unfortunately, Taxol is extracted from the endangered Pacific yew tree and could eventually become in short supply. Dr. Angela Hoffman, a chemist at the University of Portland in Oregon, recently announced that she has discovered another source of paclitaxel. Apparently hazelnut trees produce the compound in their leaves, twigs, and nuts although at a level which is only 10 per cent of that found in the yew tree. Dr. Hoffman also discovered that a fungus living on hazelnut trees produce paclitaxel. Says David Houck of Phytera, a drug company in Worcester, MA "If a fungus could be coaxed into churning out the drug in vats it would definitely have value."
Science, April 7, 2000, pp. 27-28

Cocaine is bad for the heart.
Snorting cocaine may wreck your health in more ways than one. It can cause coronary arteries to go into a spasm which closely mimics a heart attack. Now researchers at the University of Michigan report that cocaine also encourages the immune system to attack healthy heart tissue eventually leading to permanent damage. Dr. Larry Alexander of the Baylor Medical Center in Dallas, TX is concerned that cocaine users may not be aware of what damage they are doing to their hearts. Says he "At the weekend I saw three young males in their early twenties with chest pains, and all three were positive for cocaine." He points out that there are almost 200,000 cocaine-related emergency room incidents in the United States every year putting an extra burden on an already overextended health care system. The situation is similar in the United Kingdom. Dr. John Henry, an expert on drug abuse at St. Mary's Hospital in London, estimates that 10 per cent of emergency admissions for chest pain is caused by cocaine abuse.
New Scientist, January 22, 2000, p. 14