ABSTRACTS

HAARLEM, NETHERLANDS. Dr. R. Dekkers a Dutch medical doctor and chemical engineer describes a novel method of removing gallstones. His wife apparently tried it with good results. She drank one liter of apple juice daily for six days and on the 7th day she drank a cup of olive oil just before going to bed. She lay on the left side during the night and the next morning found soft gallstones in the stool. The stones were recognized at the university hospital as fatty gallstones. Dr. Dekkers suggests that the stones can be more easily collected if an oral dose of magnesium sulfate (Epsom salt) is taken at noon on the 7th day and the evening meal is skipped.
Dekkers, R. Apple juice and the chemical-contact softening of gallstones. The Lancet, Vol. 354, December 18/25, 1999, p. 2171 (correspondence)

BOSTON, MASSACHUSETTS. There is increasing evidence that free radicals (reactive oxygen species) play a significant role in essential hypertension (high blood pressure). Now researchers at the Boston University School of Medicine report that daily supplementation with vitamin C (ascorbic acid) can significantly reduce blood pressure in people suffering from hypertension. Their randomized, placebo- controlled study involved 39 patients (average age of 49 years) 29 of whom were taking antihypertensive medication.
The study participants had diastolic blood pressure between 90 and 110 mm Hg and did not suffer from diabetes, coronary artery disease or heart failure. They also did not take estrogens or antioxidants within one month of the start of the study. After fasting overnight the patients had their blood pressures (systolic, mean, and diastolic) measured and had urine and blood samples collected. The measurements were repeated two hours after receiving a 2-gram oral dose of ascorbic acid or placebo and again after 30 days of oral supplementation with 500 mg/day of ascorbic acid or placebo.
The researchers found that blood pressures were similar at baseline and after the acute treatment (2- gram dose). At the end of the 30-day period, however, the average systolic pressure in the vitamin C group had decreased from 155 mm Hg to 142 mm Hg and the mean pressure had decreased from 110 to 100 mm Hg. No changes were observed in the placebo group. The average diastolic pressure in the vitamin C group also decreased, but the difference from the placebo group was not statistically significant. Blood plasma levels of ascorbic acid increased significantly in the vitamin C group during the study; from 50 micromol/L to 149 micromol/L two hours after ingesting the 2-gram dose and levelling out at 99 micromol/L at the end of the 30-day test period. The researchers conclude that oral supplementation with 500 mg/day of ascorbic acid is useful for blood pressure control in patients with high blood pressure.
Duffy, Stephen J., et al. Treatment of hypertension with ascorbic acid. The Lancet, Vol. 354, December 11, 1999, pp. 2048-49 (research letter)

PAMPLONA, SPAIN. Ichthyosis is a condition in which the skin is dry, rough, and scaly. It is caused by a fault in the control mechanism which governs the deposition of keratin (a fibrous protein) in the skin and is often present at birth (congenital). Ichthyosis can be ameliorated somewhat by the use of emollient creams, bath oils and ointments, but the condition is usually an ongoing problem. Medical doctors at the University Clinic of Navarra, School of Medicine now report the successful treatment of ichthyosis with a water-in-oil (silicone) emulsion containing 10 per cent of N-acetylcysteine (NAC). Their patient, a 33- year-old woman, had large patches of dark, scaly skin on her limbs, trunk, scalp, and neck and had been treated with conventional therapies without success. She was instructed to apply the NAC emulsion to one of her forearms and a placebo emulsion (without the NAC) to the other forearm twice a day. Five weeks later the skin on the arm treated with the NAC emulsion was essentially free of scales and roughness while no change was observed on the arm which had received the placebo treatment. The researchers conclude that a NAC-containing water-in-silicone emulsion may be useful in the treatment of hyperproliferative skin disorders and point out that NAC is hypoallergenic, non-toxic, and rarely has any side effects.
Redondo, Pedro and Bauza, Ana. Topical N-acetylcysteine for lamellar ichthyosis. The Lancet, Vol. 354, November 27, 1999, p. 1880 (research letter)

LONDON, UNITED KINGDOM. Raynaud's syndrome afflicts between 3 and 20 per cent of all adults and is more common by a ten to one ratio among women than among men. The condition is characterized by a disruption of the blood flow to fingers or toes resulting in cold, numbness, pain, and a characteristic white/blue colour of the affected parts. Avoidance of smoking, keeping warm, and the use of slow-acting calcium-channel-blockers are recommended, but not always successful therapies for the condition. There is some indication that Raynaud's syndrome involves an abnormality in the synthesis and inactivation of nitric oxide, a potent dilator of blood vessels.
Now researchers at St. Bartholomew's Hospital in London report that the application to the skin of a simple gel formulated to generate nitric oxide can markedly improve blood flow to the treated area. Their experiment involved 20 patients with severe, primary Raynaud's syndrome (Raynaud's disease) and 10 healthy volunteers. The nitric-oxide-generating system was prepared by mixing 0.5 mL of a jelly (KY jelly) containing 5 per cent sodium nitrite with 0.5 mL of a jelly containing 5 per cent ascorbic acid right on the skin or fingertip of the participants covering an area of about three square centimeters. The resulting reaction between the sodium nitrite and ascorbic acid was stopped after a few seconds by simply wiping the gel off with a paper tissue. The effect of the jelly on its own (placebo treatment) was tested in a similar way.
Blood flow in the treated areas was measured with infrared photoplethysmography and laser doppler fluxmetry. The researchers found no difference in baseline blood flow (microcirculatory volume and flux) in the forearm skin between the Raynaud's patients and the healthy controls. However, the Raynaud's patients had a significantly lower blood flow in the finger tips before application of the gel than did the controls. Application of the nitric-oxide-generating gel increased blood flow very significantly in both patients and controls. The increase in the treated forearm area was six- to ten-fold and on the fingertips about three-fold. The researchers conclude that application of the nitric-oxide-generating gel at the time of an attack is a simple, effective, and safe treatment of severe vasospasm associated with Raynaud's syndrome.
Tucker, A.T., et al. Effect of nitric-oxide-generating system on microcirculatory blood flow in skin of patients with severe Raynaud's syndrome: a randomised trial. The Lancet, Vol. 354, November 13, 1999, pp. 1670-75

MADRID, SPAIN. There have been sporadic case reports of bleeding disorders in patients taking selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). Now researchers at a Spanish medical research institute report that SSRIs do indeed increase the risk of upper gastrointestinal (stomach) bleeding. Their study involved 1651 cases of upper gastrointestinal bleeding occurring between April 1993 and September 1997. The cases were compared to 10,000 controls matched for age and sex.
The researchers found that people taking SSRIs were three times as likely to develop bleeding than were non-users. This corresponds to about one in 1300 users developing bleeding. They also found that patients who took both SSRIs and NSAIDs (non-steroidal anti-inflammatory drugs) had a 15 times greater risk of gastrointestinal bleeding than did people who took neither of the two classes of drugs. Even a combination of low-dose aspirin such as used for protection against heart attack and SSRIs significantly increased the risk of bleeding by a factor of seven.
The researchers conclude that SSRIs are associated with an increased risk of upper gastrointestinal bleeding and that this risk is vastly magnified if aspirin or NSAIDs are also taken. NOTE: This study was funded in part by Novartis, a major pharmaceutical company.
de Abajo, Francisco Jose, et al. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. British Medical Journal, Vol. 319, October 23, 1999, pp. 1106-09
Li Wan Po, Alain. Antidepressants and upper gastrointestinal bleeding: new results suggest a link. British Medical Journal, Vol. 319, October 23, 1999, pp. 1081-82 (editorial)

EDINBURGH, UNITED KINGDOM. Cachexia (abnormal weight loss) is a major problem in many types of cancer especially cancer of the pancreas. Preliminary research has shown that supplementing the diet with fish oils, about 2.2 grams of EPA (eicosapentaenoic acid) and 1.4 grams of DHA (docosahexaenoic acid) daily, will stabilize weight in patients with inoperable pancreatic cancer. Now researchers at the Royal Infirmary of Edinburgh report that patients with pancreatic cancer can actually gain weight by consuming a nutritional supplement fortified with fish oils. The experiment involved 20 patients with inoperable pancreatic cancer (aged 18 to 80 years). The participants were asked to ingest two cans of fish oil-enriched nutritional supplement per day in addition to their normal food intake. The nutritional supplement provided 310 kcal per can and contained 16.1 g protein, 49.7 g carbohydrate, 6.5 g fat, 1.09 g EPA, 0.46 g DHA, and 28 essential vitamins and minerals.
After three weeks the patients had gained an average (median) of 1 kg in weight and at seven weeks an average of 2 kg. A significant improvement in performance status and appetite was also noted after three weeks on the supplement. Other research has shown that EPA inhibits the growth of pancreatic cancer cells in vitro. It is therefore of interest to note that the average survival time among the patients was over eight months. This compares very favourably with the normal survival time of 4.1 months and is at least as good as the survival time that can be obtained with aggressive chemotherapy.
The researchers conclude that a fish oil-enriched nutritional supplement has the potential to be a safe and effective means of preventing weight loss in cancer patients and may even increase survival time in patients with cancer of the pancreas. NOTE: This study was partially funded by Abbott Laboratories, the maker of the nutritional supplement.
Barber, M.D., et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. British Journal of Cancer, Vol. 81, No. 1, September 1999, pp. 80- 86

AMSTERDAM, NETHERLANDS. The healing of fractures, injuries, and other forms of trauma are often complicated by the reflex sympathetic dystrophy (RSD) syndrome which involves pain, swelling, decreasing joint mobility, and large temperature swings in the affected part. A team of Dutch medical doctors have just completed a study aimed at proving their hypothesis that RSD is associated with oxidative stress and can be prevented by vitamin C supplementation.
The study involved 115 patients with a total of 119 wrist fractures (some had fractures on both wrists). After initial treatment (application of a plaster cast) the patients were randomly assigned to receive one 500 mg capsule of vitamin C or a placebo capsule daily for 50 days. The patients were assessed after 1 week, 4-5 weeks (at removal of plaster cast), 6-7 weeks, 12 weeks, and 26 weeks and were interviewed by telephone after one year. All told there were about three times as many cases of RSD (22 per cent of all fractures vs. 7 per cent) in the placebo group as in the vitamin C group.
The researchers conclude that oxidative stress (free radicals) is indeed an important contributing factor to RSD and recommend vitamin C supplementation as a simple, safe, and inexpensive way of preventing it. They believe that vitamin C may be effective not only in the prevention of RSD in connection with wrist fractures, but also in connection with other fractures and lesions.
Zollinger, Paul E., et al. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures; a randomised trial. The Lancet, Vol. 354, December 11, 1999, pp. 2025-28

ROTTERDAM, NETHERLANDS. Macular degeneration (age-related maculopathy) and Alzheimer's disease are both chronic neurodegenerative disorders which are characterized by extracellular plaque deposits either in the macula of the retina or in the brain. Both disorders are more prevalent among smokers and people with atherosclerosis.
A team of medical doctors from the Erasmus University Medical School has just released the results of a major study into a possible connection between age-related macular degeneration and Alzheimer's disease. The study involved 1438 Dutch men and women aged 75 years or older. The participants underwent a thorough medical and ophthalmologic examination and were screened for signs of dementia at the beginning of the study and after two years of follow-up.
At baseline, 43.6 per cent of the participants were diagnosed with age-related maculopathy of varying severity; none had signs of Alzheimer's disease at this stage. Two years later, 62 of the participants had developed Alzheimer's disease. This corresponds to an incidence rate of 14 per 1000 person-years in the 75 to 84 year age group and 41.6 per 1000 person-years in those aged 85 years or older. The researchers discovered a clear relationship between the presence of moderate to severe (stage 3 and 4) maculopathy at baseline and the incidence of Alzheimer's disease two years later. The incidence of Alzheimer's was found to be twice as high among participants with moderate to severe maculopathy as among participants with no or less severe maculopathy. The risk factor was reduced to 1.5 (a 50 per cent excess risk) when the data was adjusted for age, gender, smoking, and atherosclerosis.
The researchers conclude that macular degeneration and Alzheimer's disease may have a common origin and that both diseases may be causally linked to smoking and atherosclerosis.
Klaver, Caroline C.W., et al. Is age-related maculopathy associated with Alzheimer's disease? American Journal of Epidemiology, Vol. 150, November 1, 1999, pp. 963-68

AUCKLAND, NEW ZEALAND. Medical researchers in New Zealand provide convincing evidence that an increased consumption of fish oils helps reduce the risk of developing prostate cancer. Their study involved 317 men who had been diagnosed with prostate cancer during 1996-97 and 480 age-matched controls. Blood samples were obtained from all participants and the erythrocyte (red blood cell) phosphatidylcholine fraction of the plasma was analyzed for EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), the two main components of fish tissue oils.
Evaluation of the collected data showed a clear correlation between blood level of EPA and DHA and the presence of prostate cancer. Study participants with levels in the highest quartile were found to have a 40 per cent lower incidence than participants with levels in the lowest quartile. This relationship held true even when adjusted for age, height, use of NSAIDs (non-steroidal anti-inflammatory drugs), socio- economic status, and estimated intake of lycopene and polyunsaturated fats.
The researchers also found that men with low socio-economic status, a low intake of lycopene, and non- regular use of NSAIDs were more likely to develop prostate cancer. They did not, however, find any correlation between self-reported intake of EPA and DHA indicating that food frequency questionnaires are not an accurate method for estimating fish oil intake. The researchers speculate that fish oils may prevent the progression of prostate cancer by inhibiting the biosynthesis of eicosanoids from arachidonic acid.
Norrish, A.E., et al. Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case- control study. British Journal of Cancer, Vol. 81, No. 7, December 1999, pp. 1238-42

BETHESDA, MARYLAND. The relationship between blood levels of alpha-tocopherol (the most active form of vitamin E) and the risk of lung cancer is not clear. Some studies have found higher levels of alpha-tocopherol protective while other studies have found no such effect. A team of researchers from the National Cancer Institute and the National Public Health Institute in Helsinki, Finland has just released a report which concludes that high alpha-tocopherol levels are indeed protective. The study (ATBC Study) involved 29,102 white, male, Finnish smokers aged 50 to 69 years. The men had blood samples drawn for alpha-tocopherol analysis at entry to the study and were then followed up for a median period of 7.7 years. The study was designed to examine the effects of beta-carotene and vitamin E supplementation on lung cancer incidence.
At the end of the follow-up period 1144 of the study participants had developed lung cancer. A 19 per cent reduction in incidence was observed among participants with the highest baseline blood levels (highest quintile) of alpha-tocopherol as compared to those with the lowest levels. The inverse association was particularly strong among younger men (60 years or younger), among men with less tobacco exposure (less than 40 years of smoking), and possibly among men receiving alpha-tocopherol supplementation.
The researchers conclude that high levels of alpha-tocopherol may inhibit lung cancer development if present during the early stages of tumour formation. They go on to say that "While it is tempting, based on the present data, to speculate that the administration of greater quantities of alpha-tocopherol (i.e. more than 50 mg daily) might have produced a substantial reduction in lung cancer incidence in the ATBC Study, only future studies, and controlled trials in particular, can shed light on this question." Editor's Note: 50 mg/day of synthetic alpha-tocopherol as used in the ATBC Study would correspond to about 25 IU of natural vitamin E, a far lower level than the 200-400 IU/day found to have beneficial effects in regard to cardiovascular disease.
Woodson, Karen, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. Journal of the National Cancer Institute, Vol. 91, October 20, 1999, pp. 1738-43

WORCESTER, MASSACHUSETTS. Both total and bioavailable testosterone levels decline as men age and the decrease is often accompanied by a decline in sexual function, loss of bone density and muscle mass, and an increase in cholesterol level. The decline in bioavailable testosterone is partially due to an age-related increase in sex hormone-binding globulin (SHBG) which removes the free testosterone from circulation.
Researchers at the University of Massachusetts Medical School have just completed a major study aimed at determining the relationship between diet and the level of SHBG in middle-aged men. The study was carried out in 1987-1989 as part of the Massachusetts Male Aging Study and involved 1522 men aged 40 to 70 years. All study participants were interviewed in person, had blood samples drawn and were evaluated for height, weight, and waist and hip circumferences. They also completed the Willett semiquantitative 1-year food frequency questionnaire.
Multiple regression analysis of the collected data showed that a high intake of protein corresponded to a lower level of SHBG and thus by inference, a higher level of free testosterone. A high fiber intake, on the other hand, was clearly correlated with a high SHBG level. Other research has shown that vegetarians tend to have higher SHBG levels than do non-vegetarians. The data analysis also found that advanced age and a high serum testosterone level were associated with higher SHBG levels whereas a greater body mass index and waist/hip ratio both correlated with a lower SHBG level. No correlation was found with total calorie intake or intakes of fats and carbohydrates. The researchers conclude that elderly men can increase their bioavailable testosterone levels by increasing their protein intake.
Longcope, C., et al. Diet and sex hormone-binding globulin. Journal of Clinical Endocrinology and Metabolism, Vol. 85, January 2000, pp. 293-96

MILAN, ITALY. A group of Italian researchers recently reported that consumption of whole-grain foods helps protect against cancer, particularly cancers involving the digestive system. This adds to the evidence that diet is an important factor in cancer prevention. Diets high in fruits and vegetables have also been found to be protective while alcohol consumption and smoking are risk factors for certain cancers, particularly those involving the mouth, esophagus, and lungs (smoking).
Now the same researchers report that while whole-grain foods protect against cancer, foods based on processed grains, e.g. pasta and bread, may actually increase the risk of cancer. Their study involved 3336 patients diagnosed with cancer at various sites and 3526 people without cancer.
Based on food frequency questionnaires completed two years before the diagnosis of cancer the researchers conclude that people with a high consumption of bread, pasta, and rice have a 60 per cent higher risk of developing cancer of the oral cavity, pharynx, esophagus or larynx than do people who consume only one serving or less per day of refined cereal products. The estimated risk increase for stomach and colon cancer was 50 per cent and for thyroid cancer it was 100 per cent.
The researchers point out that a high consumption of refined sugar produces similar increases in cancer risk and speculate that the detrimental effect of refined cereals is due to their rapid digestion. This tends to cause glycemic overload and a subsequent increase in insulin and IGF-1 (insulin-like growth factor 1) which is known to stimulate tumour growth. They also suggest that the substantial increase in thyroid cancer observed among frequent consumers of refined cereals may be due to the low iodine content of these foods.
The researchers conclude that replacing meat and fat with refined cereals in the diet may not have the intended effect of reducing cancer risk.
Chatenoud, Liliane, et al. Refined-cereal intake and risk of selected cancers in Italy. American Journal of Clinical Nutrition, Vol. 70, December 1999, pp. 1107-10

BRUSSELS, BELGIUM. Oral supplementation with creatine monohydrate is widely used among athletes in order to improve their performance and maximize the effect of intense training sessions. Individual doses of 1 to 20 grams of creatine may be taken up to four times a day. Creatine contains 32 per cent nitrogen and some concern has been expressed that its excretion may put an added burden on the kidneys.
Researchers at the University of Brussels have recently released the results of a study which concludes that long-term supplementation with creatine is quite safe, at least among healthy athletes. The study involved eight young men and one woman aged between 21 and 27 years. The participants had been taking creatine daily for periods ranging from 10 months to 5 years. Blood plasma levels and urine excretion rates for creatine, urea, and albumin were compared between the creatine users and a control group of 85 male students who did not use creatine. No differences were found. The researchers conclude that glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups and that daily creatine supplementation for up to five years is safe in healthy athletes. They caution though that people with suspected renal dysfunction should not take creatine.
Poortmans, Jacques R. and Francaux, Marc. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medicine and Science in Sports and Exercise, Vol. 31, August 1999, pp. 1108-10

NEWSBRIEFS

Toddlers join the drug scene.
Scientists are voicing mounting concern about the increasing use of pharmaceutical drugs in the treatment of psychological disorders such as attention-deficit/hyperactivity disorder (ADHD) in very young children. Marsha Rappley of Michigan State University found that 223 Michigan children aged three and under had been diagnosed with ADHD and that 57 per cent of them were being treated with drugs which have never been evaluated for safety in such young children. The ADHD toddlers had been prescribed 22 different drugs in a total of 30 combinations. Many were taking two to three drugs at the same time. Among the more popular drugs used was Ritalin which has not been proven safe for toddlers. Says Richard Todd, a psychiatrist who treats children with ADHD "This [the toddler stage] is a very important developmental period. The effects of medications on these processes are not well understood."
Boyce, Nell. Too young? New Scientist, November 6, 1999, p. 17

Parasites may not be all bad.
It is generally believed that parasites (worms) in the intestines are bad for you and should be eliminated. Now researchers at the University of Iowa question this assumption. Joel Weinstock the leader of the team noticed that the increase in inflammatory bowel disease (ulcerative colitis and Crohn's disease) was preceded by a decline in intestinal worm infections. Dr. Weinstock believes that inflammatory bowel disease is caused by an overactive immune system and that the presence of worms in the intestines somehow dampens this overactivity. Says Dr. Weinstock "The worms living in the gastrointestinal tract have been with us for 3 million years or longer and our immune systems have grown used to their presence." To test the hypothesis the Iowa researchers gave six patients with severe inflammatory bowel disease a drink containing eggs of a species of intestinal worm that doesn't normally infect people and is eliminated naturally after a couple of months. The results were dramatic, five of the six patients went into complete remission with a single dose of worms easing symptoms for about a month. A larger scale trial is now underway.
Coghlan, Andy. Wonderful worms. New Scientist, August 7, 1999, p. 4

Schizophrenia and vitamin D.
Dr. John McGrath of the University of Queensland in Australia has made the fascinating discovery that children born in an El Nino year are less likely to develop schizophrenia in later life. El Nino brings drought and increased sunshine to eastern Australia. Dr. McGrath speculates that the additional sunshine helps pregnant women develop adequate stores of vitamin D. He believes that low levels of vitamin D may increase the risk of schizophrenia as the vitamin is important in the development of fetus's central nervous system. Dr. McGrath admits that his hypothesis is very speculative at this point and says "I'm keen to get feedback."
Sun and schizophrenia. New Scientist, November 13, 1999, p. 27

Gulf War syndrome: is it drug related?
About 100,000 Gulf War veterans developed the so-called Gulf War syndrome which involves memory loss, insomnia, joint pain, fevers, and fatigue. The disorder has been blamed on everything from depleted uranium shells to oil fires, but now the US Department of Defense admits that the problem may well have been caused by a drug given to the soldiers to protect them against nerve gas attacks. The drug, pyridostigmine bromide (PB) was developed 10 years ago at Britain's main chemical defense laboratory at Porton Down. PB works by binding temporarily to an enzyme which is required for the nerve gases sarin and soman to do their devastating damage. Although PB was tested (at the cost of 25 lives and 400 cases of long-term health damage) for its effectiveness in counteracting the nerve gases, it was never monitored for its long-term health effects. Chemical weapons expert Alastair Hay of the University of Leeds says that soldiers were under orders to take PB tablets three times a day, but that some soldiers may have forgotten and then taken two or three pills at a time. This could presumably create symptoms similar to those caused by a sub-lethal exposure to sarin and soman.
Perils of prevention. New Scientist, October 30, 1999, p. 16