|September 2002 |
New form of vitamin D grows bone
The September 30 2002 issue of the Proceedings of the National Academy of Sciences (http://www.pnas.org/) published research that showed that an analog of 1-alpha,25-dihydroxyvitamin D3 (the active form of vitamin D) was able to grow bone in vitro and in laboratory animals. The compound, known as 2MD, was synthesized by researchers at the University of Wisconsin in Madison, who conducted several successful experiments in human and mouse bone cell cultures, as well as two experiments utilizing rats.
In one experiment, the team administered 2MD to part of a group of rats who had their ovaries removed to create a menopausal condition, with its accompanying bone loss. In the rats who received the vitamin D analog, a 9 percent increase in bone mass compared to the group who did not receive the compound was observed, with an increase in long bone mass and a 25 percent increase in vetebral mass. Bone loss occurring in the vertebrae of the spine is a characteristic occurrence in human osteoporosis.
While vitamin D is necessary for maintaining blood levels of two important minerals for bone formation - calcium and phosphorous - there is little evidence to show that it has much additional involvement in building bone unless given in high concentrations. The new compound is the first vitamin D analog demonstrated to increase bone mass at a low dose without side effects. Lead researcher and international vitamin D authority Dr Hector F. DeLuca, stated, "We've got a compound that is very selective for bone. It is very effective in animals. From where I sit, this is the most promising vitamin D compound I've seen . . . There's nothing like it on the market now. We think it could become a major actor, but we haven't done any experiments in people."
Catechin polyphenol delays tumor onset in mice
Mice bred to spontaneously develop tumors experienced a delay in tumor onset when given catechin, one of the polyphenols found in red wine. The study, published in the October 2002 issue of the American Journal of Clinical Nutrition, utilized transgenic mice who received a nutritionally complete diet supplemented with various levels of catechin in two experiments, or the diet supplemented with alcohol-free solids from red wine in a third experiment. Control groups of mice received the same diet minus the catechins or red wine solids. Mice were examined daily for tumor formation and the age at which the first tumor appeared was recorded. Plasma levels of catechins and catechin metabolites were determined at the study's conclusion.
The researchers, from the University of California, Davis, and the University of Nebraska Medical Center in Omaha, observed a positive, linear relation between the amount of dietary catechin and age at first tumor onset in the first two experiments. A similar association was observed between age at tumor onset and plasma catechin and metabolite concentrations. The third experiment, which utilized a diet containing alcohol-free solids from red wine whose polyphenols included less than .22 micromoles catechin per kilogram, failed to delay tumor onset. However, previous research that provided animals with wine solids containing a similar amount of total polyphenols but four times as much catechin was found to significantly delay the onset of tumors compared to those receiving a control diet. No adverse effects were observed in the mice who received the catechin, nor were any observed in their offspring.
The study shows that genetically predisposed cancer onset can be delayed by dietary factors. The authors write that, "Concentrations of specific dietary polyphenols, such as catechin, may play a more important role in cancer prevention than does the total polyphenol concentration in the diet." (Ebeler SE, Brenneman CA, Kim GS et al, "Dietary catechin delays tumor onset in a transgenic mouse model," AJCN vol 76 No 4, 865-872)
Soy lowers dangerous estrogen
The September 2002 issue of Cancer Epidemiology, Biomarkers & Prevention, revealed the findings of a study of postmenopausal women in Singapore that showed regular consumption of soy based foods is associated with lower levels of the hormone estrone, a form of estrogen that is predominant following menopause, and which is associated with elevated breast cancer risk . One hundred forty-four healthy Chinese women between the ages of 50 and 74 were interviewed concerning the frequency of consumption and portion size for 165 food and beverage items as well as on reproductive history and various lifestyle factors. Six types of soy foods and one soy drink were included in the food items, and total soy as well as soy isoflavone intake was calculated. Blood samples were analyzed for levels of estrogens.
While little correlation was observed between diet and hormone levels, soy emerged as the one dietary factor that was associated with lower levels of estrone. Estrone levels did not decline in a linear fashion with increased soy, but were 15% lower only in those who were among the top 25% in soy consumption compared to the remaining participants. When isoflavone consumption was examined, high levels were also found to be associated with lower serum estrone.
Lead investigator and professor of preventive medicine at Keck School of Medicine of the University of Southern California, Los Angeles, Anna H. Wu, summarized, "Results from this study support the hypothesis that high soy intake may reduce the risk of breast cancer by lowering endogenous estrogen levels, particularly estrone. However, the effect of soy on the breast is controversial. There are some in vitro studies of breast cancer cells - animal studies, as well as short-term soy intervention studies in women - suggesting that soy isoflavones may have stimulatory effects."
Antioxidant vitamins prevent homocysteine-induced memory impairment in animals
A study published in the journal Metabolic Brain Research, has found that the administration of vitamins C and E completely prevents the impairment of memory induced by homocysteine administration in rats. The researchers, from the Universidade Federal do Rio Grande do Sul, in Porto Alegre, Brazil, pretreated adult rats with vitamins C and E, or saline daily for seven days. One hour before a training session, one hour before testing, or directly following training, the rats were injected with homocysteine. A control group received saline in lieu of homocysteine. Current research data indicates that homocysteine administration impairs memory.
The rats were trained and tested in two tasks. Pretraining, pre-test and post-training administration of homocysteine as opposed to saline was demonstrated to cause amnesia for the task in the animals who received it. Administration of vitamins C and E along with the homocysteine completely prevented amnesia in all groups receiving it. This indicates that oxidative stress is most likely involved in homocysteine's inhibition of memory, which agrees with previous findings demonstrating that elevated blood levels of homocysteine stimulates the formation of the oxidants superoxide and hydrogen peroxide.
Vitamin E, while trapping free radicals, requires vitamin C for its regeneration back to reduced tocopherol. Studies have shown that vitamin E may slow Alzheimer's disease progression and reverse memory and learning deficits in aging animals.
The authors, led by Dr Angela T S Wyse, suggest that antioxidant therapy be administered to patients with homocystinuria, an inherited metabolic disorder that leads to high tissue levels of homocysteine, causing neurologic dysfunction.
Allergy benefit found for green tea
The October 9 2002 issue of the American Chemical Society's Journal of Agricultural and Food Chemistry will reveal the latest findings of Japanese research, that a compound found in green tea, epigallocatechin gallate, or EGCG, blocks one of the receptors involved in the allergic response. Previous studies in rodents have shown that orally administered EGCG helped prevent the allergic response, but its mechanism of action remained unknown. Although other compounds in green tea have been demonstrated to fight allergies, EGCG appears to be the most potent.
EGCG has been discovered to block the formation of two compounds involved in allergic reactions: histamine and immunoglobulin E (IgE). By studying the human white blood cells that release histamine called basophils, the researchers found that a methylated form of EGCG blocks the IgE receptor, involved in the allergic response. Methylated EGCG provides a stronger response than normal EGCG against allergies, and the researchers state that it is the has the strongest anti-allergy effect of all of the compounds in green tea.
The scientists do not yet know how which varieties of green tea are the best for individuals with allergies to consume, or how much tea it is necessary to drink to have a therapeutic benefit. They are currently seeking additional compounds in green tea that may have similar effects.
Research team leader and associate professor of chemistry at Kyushu University in Fukuoka, Japan, Dr Hirofumi Tachibana, stated, "Green tea appears to be a promising source for effective anti-allergenic agents. If you have allergies, you should consider drinking it."
This study reveals yet another of green tea's promising health benefits, in addition to its ability to combat heart disease, cancer, tooth decay and arthritis.
Vitamin E improves bone in old animals
An report published in The Journal of Nutritional Biochemistry, September 2002, provides evidence to support to the theory that the decline in the rate of bone formation observed in older animals may be due to an increase in oxygen-derived free radicals. Six month old and twenty-four month old male mice were each divided into groups receiving adequate (30 milligrams per kilogram diet) or high (500 milligrams per kilogram diet) levels of the antioxidant vitamin E for thirty days. Following this period, the mice were examined for bone volume, density and strength. Expression of compounds involved in bone formation: insulin-like growth factor-I, osteocalcin, and type 1 alpha-collagen, were determined.
In the older mice receiving the high dose of vitamin E, dry weight of the femur (leg bone) and tibial mean total protein content was higher than in old mice who received an adequate dose of the vitamin. High dose vitamin E significantly enhanced femoral strength and improved material properties of bone in old, but not young animals. In the both groups, the higher vitamin E dose significantly increased the expression of osteocalcin and IGF-1, while type 1 alpha-collagen was increased with high dose vitamin E only in the older group of animals.
Vitamin E may help to protect the body's ability to form bone by preventing oxidative stress to the osteoblasts: bone forming cells that contain substantial amounts of polyunsaturated fatty acids, making them highly susceptible to oxidation. Vitamin E may also suppress the rise in prostaglandin E2 production that occurs with age which stimulates bone resorption in high concentrations. The authors recommend the need for clinical studies to evaluate the ability of vitamin E to improve bone health in older humans.
Folate deficiency impairs melatonin secretion
The September 2002 issue of Journal of Nutrition published a report authored by researchers from the Hopital Neuro-Cardiologique and Laboratoire de Physiologie de L'Environnement in Lyon, France that demonstrated a significant alteration in melatonin by rats who were deficient in the B vitamin folate. Melatonin, a hormone involved in sleep and other functions, is synthesized via a pathway involving methylation of N-acetyl-serotonin as the final step. The methyl donor needed for methylation is S-adenosylmethionine, which is provided by a pathway involving homocysteine and methionine. Folate is necessary for the remethylation of homocysteine to methionine.
In the study, twelve rats received a diet containing no folate and twelve rats received a control diet containing 8 milligrams folic acid per kilogram body weight. Twenty-four hour urine samples were collected for the day before the study's onset, at two weeks and at four weeks, and blood samples were collected weekly. Blood was tested for homocysteine, folate and other factors. At the end of the study, the rats' pineal glands (the glands in the brain that secrete melatonin) and urine samples were analyzed for levels of melatonin or the melatonin metabolite 6 sulfatoxymelatonin.
The folate deficient group predictably had lower erythrocyte folate and plasma total homocysteine concentrations than the group that received folate in their diets. Pineal melatonin and urinary melatonin as well as 6 sulfatoxymelatonin were markedly lower in the rats receiving the folate deficient diet than in the control group. The authors remark that this is the first study to their knowledge to demonstrate a direct influence of folate deficiency of the synthesis of melatonin in the body. They note that this could explain why melatonin declines with age, when elderly populations are deficient in folate, and could also explain why treatment with folate may be effective for insomnia.
Study finds polyphenols account for red wine benefits
Many studies over the past decade have uncovered benefits associated with moderate consumption of alcoholic beverages. Wine drinking, in particular, has been touted as the reason for the "French paradox", a term used to describe the fact that the French, who consume a diet high in saturated fat and cholesterol, paradoxically have less cardiovascular disease compared to other developed countries. A study in the September 2002 Journal of Nutrition (www.nutrition.org) that tested the ability of the polyphenols derived from wine as well as ethanol (alcohol) in inhibiting high density lipoprotein (HDL) and low density lipoprotein (LDL) oxidation, found a benefit for the polyphenols but none for ethanol alone. Oxidation of LDL and its uptake by macrophages in the arterial walls is believed to contribute to atherosclerotic plaque formation, while oxidation of HDL negatively effects cholesterol transport, also potentially contributing to atherosclerosis.
The researchers, from the Robert Wood Johnson Medical School in New Brunswick, New Jersey, initially tested HDL and LDL samples from four healthy subjects. The LDL and HDL were incubated with and without mouse macrophages, in the presence and absence of red wine, polyphenols in ethanol in concentrations comparable to those found in red wine, as well as in ethanol alone. Copper was included to induce oxidation. It was found that the polyphenol mixtures were as effective as red wine in inhibiting LDL and HDL oxidation, suggesting that these polyphenols may be responsible for red wine's antioxidant activity. Ethanol at a one gram per liter concentration failed to inhibited HDL or LDL oxidation, indicating that its presence in red wine is not responsible for inhibiting oxidation.
When each polyphenol used in the mixture was separately analyzed for its ability to inhibit LDL oxidation, catechin and epicatechin were found to be the major antioxidants in red wine. In one concentration studied, epicatechin, catechin and quercetin had greater oxidation inhibiting activity than vitamin E.
Vitamin B6 inhibits platelet aggregation
Research has documented the ability of pyridoxal-5'-phosphate, the major form of vitamin B6 found in the blood, to inhibit platelet aggregation in vitro, however the concentrations found to provide this benefit were much higher than those normally found in the blood. A new study, published in the September 2002 issue of journal Nutrition Research, has shown that relatively low concentrations of pyridoxine hydrochloride, a form of vitamin B6 widely available in supplement form, was able to inhibit platelet aggregation when added to platelets separated from human blood.
Venous blood was drawn from fifteen healthy volunteers. The researchers, from the Tallinn Technical University in Tallinn, Estonia, added several concentrations of pyridoxine HCl to platelet-rich plasma samples and to washed platelets separated from plasma before inducing platelet aggregation by the addition of adenosine diphosphate.
Although plasma samples from some individuals were less sensitive to pyridoxine than others, pyridoxine HCl was found in to inhibit platelet aggregation in platelet-rich plasma and washed platelets in a concentration-dependent manner, in micromolar concentrations. The concentrations of pyridoxine used were three orders of magnitude less than those earlier found for pyridoxal-5'-phosphate, and approximately two orders of magnitude higher than the concentration of pyridoxine in the blood. The researchers remark that in vivo, the ability of pyridoxine HCl to prevent platelet aggregation could be enhanced by other dietary components having a similar activity in the body. They also note that a mechanism of action of pyridoxine on platelets could be the blockage of calcium channels, so that calcium ions do not enter platelets, therefore inhibiting their aggregation.
Psyllium benefits diabetics
Psyllium seed husks have long been in use as a source of water soluble fiber and are found in several over the counter formulas. A study published in the September 2002 issue of the European Journal of Clinical Nutrition found that psyllium lowers glucose and total and LDL cholesterol in a small population of type 2 diabetics.
Twelve men and eight women with type two diabetes participated in the study. The first phase of the study consisted of one week during which the participants received a standard diabetic diet and the drug sulphonylurea, which all volunteers had been previously using to treat the disease. Subjects then received 3.5 grams psyllium mixed with water before breakfast, lunch, afternoon snack and dinner for six weeks, along with the drug and diet. Following this phase and a two week washout interval, the next phase consisted of four weeks during which participants received only the drug and diet. The amount of water consumption before meals remained the same during all phases of the trial.
Blood samples were drawn to measure glucose, uric acid, total, HDL and LDL cholesterol and several vitamins and minerals. Analysis of the bloodwork results showed that glucose was significantly reduced following each meal preceded by psyllium consumption. Mean total cholesterol was reduced by 7.7% and LDL reduced by 9.2% by psyllium. Vitamin and mineral levels were not altered by psyllium consumption, with the exception of sodium, which inexplicably rose. The authors, from the University of Leon in Spain, state that these results indicate a beneficial therapeutic effect of psyllium in the control of type 2 diabetics and in lowering heart disease risk, without affecting mineral or vitamin A and E concentrations.
CLA regulates oncogenes in breast cancer cells
In a study published in the July 18 2002 issue of The Federation of American Societies for Experimental Biology (FASEB) Journal, researchers have found that conjugated linoleic acid (CLA), a fatty acid found in dairy products and some vegetable oils, regulates genes that control cell proliferation and apoptosis in benign breast cells and in an estrogen receptor positive and estrogen receptor negative breast cancer cell line. The researchers cultured the three cell lines and treated them with four different concentrates of CLA. RNA and protein were extracted from the cells and changes in expression of oncogenes p53, p21WAF1/CIP1 and BCL-2 were determined.
Higher concentrations of CLA increased expression of wild-type p53 in the estrogen-receptor positive cancer cell line. p53 is a gene that promotes apoptosis (programmed cell death) and has an antiproliferative effect in its nonmutated, or "wild" state. The gene is found to be mutated in many cancers. CLA completely suppressed the expression of mutant p53 in the estrogen receptor cancer cell line. Higher concentrations of CLA also induced an increase in the p21WAf1/CIP1 protein in all of the cell lines. This protein also has an antiproliferative and proapoptotic effect.
The bcl-2 gene is associated with an anti-apoptotic effect. CLA reduced the expression of this gene in the benign as well as one of the cancer cell lines.
These observations support the anti-tumor effect of CLA found in animals and "clearly indicate that their mechanism of action is through regulation of major genes involved in apoptosis." The authors announced that, "This is the first indication that deleterious mutations can be regulated by fatty acids commonly found in the human diet." (Majumder B, et al, "Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells", FASEB J, July 18 2002)
Longterm study shows genotype associated with cognitive decline
The August 29 2002 issue of the journal Nature published an article under "Brief Communications" which showed that individuals positive for the APOE e4 gene experienced greater cognitive decline later in life independent of the known predisposition toward Alzheimer's disease associated with this genotype. The Scottish Mental Survey of 1932 tested the cognitive ability of 87,498 people who were born in 1921 and attended school in Scotland in June of 1932. Of the 206 male and 285 female surviving participants , 190 men and 276 women without symptoms of dementia as determined by Mini-Mental State Examination scores completed cognitive function tests at age 80, and had their APOE genotype determined. One hundred twenty-one participants were found to have the APOE e4 allele while 345 did not.
At eleven years of age, the cognitive function scores were similar for both APOE e4 positive and APOE e4 negative participants. However, when comparing the eighty-year-old subjects' test scores, the APOE e4 negative group scored significantly higher than those with the APOE e4 genotype. In order to rule out the possibility that the greater loss of cognitive function could be caused by incipient Alzheimer's dementia, the researchers excluded in their analysis a group of patients with Mini-Mental State Examination scores borderlining on those used to exclude dementia patients, but found an even greater association between the APOE E4 genotype and cognitive decline.
The researchers, from the University of Edinburgh, and Royal Victoria Hospital, Western General Hospital in Edinburgh, and the University of Aberdeen in Scotland. , conclude that the possession of APOE e4 is not related to differences in cognitive function in youth but is significantly associated with cognitive function in old age.