Lancet recommends vitamin D supplements for children and pregnant women
A seminar article published in the October 25 2003 issue of The Lancet documents the global resurgence of rickets, a childhood disease caused by a deficiency of vitamin D, which had been believed by many to no longer be a present threat. Rickets causes severe skeletal malformations, an increased tendency toward bone fractures, dental deformities and impaired growth. Lack of exposure to sunlight due to a legitimate fear of increasing skin cancer risk, breastfeeding, and the replacement of vitamin D fortified milk with sodas and nonnutritious drinks in some societies have been blamed for the reemergence of the disease.
The article discusses the effects of genes, stage of child development and environment on the expression of the disease. Although diseases of the digestive tract, liver, kidney and pancreas can cause rickets, a deficiency of vitamin D is the primary culprit. The promotion of breastfeeding, while providing many benefits over vitamin D fortified cow's milk, may be responsible for part of the problem, particularly in mothers who are vitamin D deficient. Additionally, the campaign to encourage the use of sunscreens while helping to prevent against skin cancer later in life may prevent the sunscreen wearer from forming adequate vitamin D in their skin. Immigrants to temperate zones have been particularly afflicted.
Coauthor and Professor of Paediatric Bone Disease at the University of Sheffield in Sheffield, England, Nick J Bishop, commented, "A safety net of extra dietary vitamin D should be re- emphasised , not only for children but also for pregnant women. The reason why many immigrant children in temperate zones have vitamin D deficiency is unclear. We speculate that in addition to differences in genetic factors, sun exposure, and skin pigmentation, iron deficiency may affect vitamin D handling in the skin or gut or its intermediary metabolism."
Ginger compound prevents growth of colorectal cancer cells
Research results presented on October 28, 2003 at the American Association for Cancer Research's Second Annual International Conference on Frontiers in Cancer Prevention Research showed that gingerol, a compound found in ginger that gives the spice its flavor, slowed the growth of human colorectal cancer cells. Ann Bode and Zigang Dong of the University of Minnesota's Hormel Institute in Austin, Minnesota fed 500 micrograms -gingerol three times weekly to a group of twenty mice before and after injecting them with human colorectal tumor cells. Control mice injected with the cancerous cells received no -gingerol . Tumors began to appear fifteen days after the mice received the cancer cells, with 13 tumors appearing in the control mice compared to four in the group that received -gingerol . Twenty-eight days after receiving the injections, all the mice in the control group had measurable tumors, compared to thirty-eight days for the treatment group. After forty-nine days, 12 of the 20 treated mice still did not have tumors that had reached the size of one cubic centimeter, with tumors averaging half this size, while all of the control mice had already reached this point.
Dr Bode summarized, “Plants of the ginger family have been credited with therapeutic and preventive powers and have been reported to have anticancer activity. The substance called -gingerol is the main active compound in ginger root and the one that gives ginger its distinctive flavor . . . These results strongly suggest that ginger compounds may be effective chemopreventive and/or chemotherapeutic agents for colorectal carcinomas. It's difficult to know if the ginger-treated mice would have lived longer if left to die of their tumors, but it looks that way.”
A new study is being planned that will administer ginger to mice after their tumors have progressed to a certain size.
Healthy hearts equal healthy aging
The October 27 2003 issue of the American Medical Association Journal Archives of Internal Medicine published the results of research carried out at the University of Pittsburgh which found that older individuals without subclinical cardiovascular disease (the presence of heart disease without apparent symptoms) were more able to “age successfully” over an eight year period than those in whom the disease was detected. The study involved participants in the multisite Cardiovascular Health Study, and involved 2,932 health men and women ages and older at the beginning of the investigation.
The subjects received ultrasound and electrocardiogram examinations at the study's onset to test for the presence of subclinical cardiovascular disease. At the end of the eight year follow-up period, 51 percent of the men and 56 percent of the women in the group in whom subclinical cardiovascular disease was not detected were found to have aged successfully—defined as remaining free of cancer, chronic obstructive pulmonary disease, cardiovascular disease, cognitive decline or new physical disabilities. The group consisting of those in whom subclinical cardiovascular disease was confirmed experienced only a 40 percent rate of successful aging, with a decline in health similar to subjects who were five years older that did not have the condition.
Lead investigator and associate professor of geriatric medicine and epidemiology at the University of Pittsburgh , Anne B. Newman, MD, stated, "Our study is a picture of what the future of older people could be like - the ideal golden years – if they keep heart disease risk factors in check. Older healthy people can maintain better-than-average quality of life, with lower rates of physical and cognitive decline, when they refrain from smoking, lower their blood lipids, watch blood pressure and avoid obesity through diet and exercise."
Scientists end trade-off between long life and active life
In a research collaboration between Nuno Arantes-Olivera , Jennifer R Berman and Cynthia Kenyon, genetic manipulation of Caenorhabditis elegans enabled the roundworm to live six times its normal lifespan and to be active most of its life. Previous research had discovered mutations that conferred a long life with the metabolic trade-off of extreme lethargy. The current research enabled the worms to live the human equivalent of an active, healthy 500 year old. The findings were published in the October 24 2003 issue of Science (http://www.sciencemag.org/), the journal of the American Association for the Advancement of Science.
Prior research had found that mutations that inhibit insulin/insulin-like growth factor 1 signaling can double the experimental animal's lifespan. Strong reduction of daf-2 insulin/IGF1 receptor activity causes young animals to enter a dormant state called dauer, whereas partial loss of function of daf-2 allows the animal to grow to adulthood and live a long life. The researchers found that further reduction of daf-2 activity through RNA interference in roundworms with the weaker loss of daf-2 function led to a large increase in lifespan without dauer formation. When the reproduction systems of these animals were removed, their lifespans were extended by a factor of six. This allowed the worms to live 124 days, compared to a lifespan of 20 days for normal roundworms.
Dr Kenyon and colleagues conclude “These findings in C. elegans show that remarkable life-span extensions can be produced with no apparent loss of health or vitality by perturbing a small number of genes and tissues in an animal. These life-span extensions, which are the longest mean life-span extensions ever produced in any organism, are particularly intriguing because the insulin/IGF-1 pathway controls longevity in many species, including mammals.” ( Arantes -Oliveira N et al, “Healthy Animals with Extreme Longevity”, Science, vol 302 Oct 24 2003 )
Alpha-tocopherol supplementation reduces gamma and delta-tocopherol levels
Researchers at Johns Hopkins University in Baltimore , Maryland have found a possible reason for the conflicting results obtained from vitamin E supplementation in cardiovascular and cancer trials. Clinical research has most often utilized alpha-tocopherol, one of four tocopherols that combined with four tocotrienols, form the full complement of vitamin E fractions. Although the major form of vitamin E found in the blood is alpha-tocopherol, a typical American diet provides over two-thirds of its vitamin E in the form of gamma-tocopherol. Recent research has found that the other tocopherols and tocotrienols, particularly gamma-tocopherol, have disease preventive benefits. In the current study, Han-Yao Huang and Lawrence J Appel found that supplementation with alpha-tocopherol lowered concentrations of both gamma and delta-tocopherols.
One hundred eighty-four adult nonsmokers were randomized to receive 400 international units alpha-tocopherol or a placebo daily for a two month period. Enrolled individuals who were users of vitamin E supplements were asked to stop supplementing during the two months prior to the trial. Nevertheless, this group had higher serum levels of alpha-tocopherol and lower levels of gamma-tocopherol than those who had not used the supplements prior to the study's onset.
Predictably, alpha-tocopherol supplementation increased serum levels of the vitamin in the group that received it. However, at the study's conclusion, participants who received alpha-tocopherol experienced a reduction in serum gamma-tocopherol levels of approximately 58 percent. While delta-tocopherol concentrations were detectable in half of the subjects in each group at the study's onset, alpha-tocopherol supplementation for two months reduced detectable levels to 13 percent.
The authors sugest that alpha-tocopherol supplements may compete with gamma and delta-tocopherols for hepatic transfer, thereby lowering their concentrations. Although they did not test for beta-tocopherols or the tocotrienols, serum levels of these fractions may also be reduced by supplementing with only alpha-tocopherol.
Aged garlic combats atherosclerosis in vitro and vivo
A study conducted by Y K Lee and Yu-Yan Yeh PhD of Pennsylvania State University has found a mechanism of action for garlic's ability to lower lipids. The duo tested aged garlic extract (A GE ) and some of the sulfur containing compounds found in garlic in garlic (S-allyl cysteine, S-ethyl cysteine, S-propyl cysteine, and gamma-glutamyl S-alk(en)yl cysteines) on a human liver cell line. They found that aged garlic and particularly aged garlic with the addition of S-allyl cysteine lowered cholesterol formation by reducing the production of the liver enzyme HMG-CoA, which is necessary for cholesterol synthesis. Since this is the same mechanism of action as statin drugs, aged garlic extract may be a promising therapy for cholesterol reduction without the side effects of statins.
Dr Yeh, who is a professor of Nutritional Biochemistry of Penn State's Department of Nutritional Sciences, commented, “AGE can help people who are working to reduce their cholesterol levels in conjunction with drug treatments. Aged garlic extract can be useful for the general public to help achieve the desired cholesterol level of 200 or less.”
In a separate study currently under review for publication, UCLA researchers conducted a double blind randomized trial on 19 patients who consumed aged garlic extract or a placebo for one year. Participants underwent electron bean tomography to determine their atherosclerotic plaque burden at the study's onset and at twelve months. While the placebo group experienced an average progression in plaque of 22.2 percent, progression in the garlic supplemented group was 7.5 percent. Blood testing revealed an improvement in high density lipoprotein and homocysteine status in the supplemented group. The researchers recommend larger studies to asses the impact of aged garlic on atherosclerosis and the prevention of coronary events.
Grape seed blocks fat absorption
A study published in the October 2003 issue of the journal Nutrition found that grape seed extract inhibited the pancreatic enzyme lipase as well as lipoprotein lipase, an enzyme responsible for the hydrolysis of triglycerides from plasma lipoproteins, suggesting that the extract could be helpful to prevent the absorption of dietary fat. This could benefit individuals attempting to lose weight or those who need to limit fat consumption for other health reasons.
The U.S. researchers tested an extract of crushed grape seeds on pancreatic lipase and lipoprotein lipase activity in vitro. They found that the extract contained lipase inhibitors that act in a dose-dependent manner. A one milligram per milliliter concentration of the extract caused an 80 percent inhibition of lipase activity during a five minute incubation period. When lipoprotein lipase activity was tested, the same concentration of grape seed extract elicited a 30 percent inhibition of the enzyme.
In the Discussion, the authors state that the effect of grape seed extract may be due to a synergistic action of its flavonoid procyanidins rather than being caused by a single component. They recommend further studies to determine whether grape seed extract may be a weight loss treatment in addition to improving plasma lipid profiles, thus reducing the risk of heart disease.
The currently available prescription drug Orlistat works via lipase inhibition and has been shown to decrease dietary fat absorption in adults by approximately 30 percent. Grape seed extract may prove to be an effective natural alternative.
In-hospital medical injuries put patients at risk, elevate costs
A report published in the October 8 issue of the Journal of the American Medical Association found that medical injuries acquired during hospitalization “posed a significant threat to patients and incur substantial costs to society.”
Researchers Chunliu Zhan, MD, PhD, of the Agency for Healthcare Research and Quality (AHRQ) in Rockville, Maryland, and Marlene R. Miller, MD, of Johns Hopkins University examined data collected in the AHRQ's 2000 Healthcare Cost and Utilization Project Nationwide Inpatient Sample. The data provided information on medical injuries documented in 7.45 million hospital discharge records from 994 hospitals, representing approximately 20 percent of U.S. acute care hospitals. The most dangerous and costly medical injury was postoperative sepsis, or infection of the bloodstream, that incurred excess costs of up to $57,727 and carried an excess mortality risk of nearly 22 percent compared to matched controls. Following sepsis in seriousness was the re-opening of a sutured incision, which necessitated $40,323 in excess charges and conferred a 9.63 percent risk of death. While this condition could necessitate 9.42 extra days of hospitalization, postoperative sepsis required up to10.89 extra hospital days. Infection due to medical care ranked third in excess charges and mortality.
In an editorial accompanying the report, Saul N Weingart, MD PhD and Lisa I Iezzoni, MD, MSc, write, “ . . . given their staggering magnitude, these estimates are clearly sobering . . . measuring preventable harm will require a comprehensive and far-reaching approach. Many inpatient injuries and errors that appear most prevalent based on chart review studies, such as adverse drug events, diagnostic errors, and problems with adequate monitoring and follow-up, require sources other than administrative data. Capturing safety information reliably and efficiently may become easier with electronic monitoring algorithms of clinical databases and computerized text searches of electronic medical records." (Weingart SN, Iezzoni LI, “Looking for Medical Injuries Where the Light is Bright”, JAMA vol 290 no 14 p 1917-1919)
Silibinin increases apoptosis and inhibits angiogenesis in advanced prostate cancer
A “short communication” published in Cancer Epidemiology, Biomarkers & Prevention’s September 2003 issue described how researchers at the University of Colorado Health Sciences Center in Denver discovered the mechanisms of action for silibinin in a mouse model of prostate cancer. Previous research conducted by coauthor Rana P Singh and colleagues found that silibinin, an active ingredient in milk thistle, inhibited advanced human prostate cancer growth in nude mice. The current study sought to determine why.
The researchers fed dietary concentrations of 0.05 percent and 0.1 percent silibinin, or a control diet to athymic mice who had received advanced human prostate tumor grafts. After sixty days the tumors were assessed for cell proliferation, apoptosis (programmed cell self-destruction) and angiogenesis (the formation of new blood vessels by the tumors which facilitates their growth). They found that while cell proliferation and angiogenesis were reduced, apoptosis increased. They also found an increase in insulin-like growth factor-binding protein 3 expression. Increased plasma levels of insulin-like growth factor (IGF-1) have been found to be associated with an elevation in prostate cancer risk, and upregulation of insulin-like growth factor binding protein 3 might have an inhibitory effect on IGF-1’s cancer-promoting action. The binding protein has also been found to have its own apoptotic and antiproliferative effects. No signs of toxicity from silibinin were observed in the mice.
As the effect of silibinin on angiogenesis, apoptosis and tumor cell proliferation was greater in the group receiving the higher dose, the authors of the study believe that there is a strong possibility that higher doses of the compound could even provide complete prostate cancer growth inhibition. A trial in humans with prostate cancer is underway.