|May 2003 |
Hesperidin strengthens bone, lowers lipids in animal study
In the June 2004 issue of Journal of Nutrition, a mouse model of osteoporosis was used to ascertain the benefit of hesperidin, a citrus bioflavonoid, on bone mineral density and lipids. Osteoporosis, a disease characterized by low bone mineral density and an increase in fracture risk, is most frequently found in women following menopause, when the ovaries’ production of estrogen has declined. An increase in serum lipids, such as cholesterol and triglycerides, is also a concern among aging women and men. Mice in this study had their ovaries removed to mimic the endocrine status of postmenopausal females.
The Japanese researchers removed the ovaries of thirty-two mice. Eight rats serving as controls received sham surgeries which left the ovaries intact. The ovariectomized rats were divided into groups who received a diet containing hesperidin, alpha-glucosylhesperidin (hesperidin enzymatically modified to be more water soluble), or a control diet without hesperidin for four weeks. Some of the ovarietctomized mice who received the control diet additionally received subcutaneous estrogen replacement.
When the femurs of the mice were examined after four weeks, bone mineral density was much lower in the mice without ovaries on the control diet than in those who received the sham surgeries. However, ovariectomized mice who received the diets enhanced with hesperidin had bone mineral density measurements similar to the mice with intact ovaries at all femur sites measured. Estrogen administration also prevented bone loss in the mice lacking ovaries. When serum lipids were measured, total cholesterol and triglycerides were lower in the groups who received hesperidin than in the ovariectomized mice who received the control diet, although high density lipoprotein levels were similar.
The authors hypothesize that hesperidin acts on bone by the same mechanism as that of statin drugs: that of producing bone morphogenic protein. They recommend studies of the bioflavanoid’s effect on bone metabolism in humans.
Ovarian cancer risk decreases with greater plant food intake
The June 1 2003 issue of the Journal of Nutrition published the findings of research funded in part by the National Cancer Institute that a higher dietary intake of fiber, carotenoids, lignans (which are phytoestrogens), stigmasterols, poultry and vegetables is associated with a lower incidence of ovarian cancer in 820 women studied. The study utilized datab obtained as part of a series of studies of diet and reproductive system cancers in Western New York.
There were 124 women with ovarian cancer among the cases studied. Dietary questionnaires revealed that women diagnosed with the disease consumed significantly fewer total carotenoids and had slightly higher intakes of calories, carbohydrates, protein, fats and cholesterol. Consumption of fiber, folate, and alcohol was lower in women with ovarian cancer than in healthy women. Among phytochemicals examined, women who had the highest intakes of stigmasterol and total lignan precursors had a significantly lower risk of ovarian cancer compared to those with the lowest intakes. Vegetable and poultry consumption were also associated with a reduced risk of the disease, when women whose consumption of these foods was the highest were compared to those whose intake was the lowest.
The authors, from the University of Buffalo and the Roswell Park Cancer Institute, in Buffalo, New York, write that this is the first study, to their knowledge, to report an association with phytoestrogen intakes in relation to ovarian cancer, and state that “the evidence toward a protective effect of a plant-based diet on hormone-related cancers continues to accumulate.” They explain that modulation by diet of endogenous hormone levels, which play a role in the development of reproductive system cancers, may be one of the mechanisms by which diet influences the risk of cancer of the ovary. (McCann SE et al, “Risk of human ovarian cancer is related to dietary intake of selected nutrients, phytochemicals and food groups,” J Nutr 2003 133: 1937-1942.)
Fish oil mechanism elucidated
The May 26 2003 issue of Circulation: Journal of the American Heart Association published a review detailing the mechanism of fish oil in preventing sudden cardiac death. Last year the journal published the results of the GISSI-Prevenzione trial which found that taking a daily fish oil supplement for three months reduced sudden cardiac death by half compared to a placebo group. (See What’s Hot, April 12 2002)
Following a trial conducted in 1989 that showed a reduction in mortality in subjects who consumed fish two times per week compared to those advised to consume fat or fiber, a series of observational studies and clinical trials provided similar results for omega-3 polyunsaturated fatty acids (n-3 PUFA) from fish. Because over half of the sudden cardiac deaths in heart disease patients are due to abnormal heart rhythms called ventricular arrhythmias, researchers believed that prevention of this dangerous condition may be responsible for the decrease in mortality observed.
Review author and Jackson Professor of Clinical Medicine Emeritus at Harvard Medical School, Alexander Leaf, MD, explained that studies of individual heart cells have shown that omega-3 fatty acids block excessive sodium and calcium currents in the heart, which cause erratic changes in heart rhythm. Dr Leaf stated, “Animal experiments show that fatty acids from n-3 fish oils are stored in the cell membranes of heart cells and can prevent sudden cardiac death or fatal arrhythmias.”
In an editorial in the same issue, David S. Siscovick, MD, and colleagues write, “For clinicians, it is time to implement the current American Heart Association dietary guidelines . . . For policymakers, there is a need to consider a new indication for treatment with low-dose n-3 PUFA supplements – the prevention of sudden cardiac death in patients with a prior [heart attack]. For researchers, there is a need to continue both clinical studies and studies that explore the mechanism through which n-3 PUFAS influence the risk of sudden cardiac death.”
Blood pressure “normal” not normal
The “Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure,” published in the May 21 2003 issue of the Journal of the American Medical Association, has revised the “normal” values for blood pressure downward, from 120/80 mm Hg to 115/75. Individuals with blood pressure readings of 120/80 should be considered prehypertensive and should adopt lifestyle modifications to prevent cardiovascular disease. The report also identified systolic blood pressure of 140 mm Hg or greater as a much more important cardiovascular disease risk factor than diastolic blood pressure in people 50 years of age or older. Systolic blood pressure is the upper number in a blood pressure reading, and is a measure of pressure during the heart’s contracting phase, while diastolic pressure, the bottom number, reflects pressure during the heart’s resting phase.
Among other findings the committee determined that cardiovascular disease risk doubles with each increment of 20/10 mm Hg over the new normal of 115/75. They recommend drug combinations for most individuals with hypertension and emphasize the importance of patient motivation. Lifestyle modifications recommended are weight reduction, implementing the Dietary Approaches to Stop Hypertension (DASH) diet, which is high in calcium and potassium; reducing dietary sodium, increasing physical activity and moderating alcohol consumption.
The committee noted that antihypertensive therapy lowered heart attack incidence by 20 to 25 percent and stroke incidence by 35 to 40 percent in clinical trials. In patients with additional cardiovascular risk factors whose systolic blood pressure ranged from 140 to 159 mm Hg and/or diastolic blood pressure from 90 to 99 mm Hg, lowering systolic blood pressure would prevent one death out of every eleven patients treated over a ten year period.
Selenium may help prevent esophageal cancer in Barrett’s esophagus
The May 21 2003 issue of the Journal of the National Cancer Institute published the findings of researchers at Fred Hutchinson Cancer Research Center in Seattle, Washington that the trace mineral selenium may inhibit the progression of Barrett’s esophagus toward esophageal cancer. Barrett’s esophagus is a precancerous condition of the esophagus that is linked to chronic gastroesophageal reflux. Patients diagnosed with Barrett’s esophagus are thirty to seventy-five times more likely to develop esophageal cancer than those without the condition.
The researchers analyzed data from 399 Barrett's esophagus patients and found that higher selenium levels were associated with fewer biological markers of progression toward cancer compared to those with lower levels. High selenium levels were associated with a three-fold decreased risk of aneuploidy, which is the accumulation of cells with abnormal amounts of DNA, and indicates progression toward cancer. There was also a two-fold lower risk of loss of the p53 gene, which functions as a tumor suppressor.
Lead author and researcher in Fred Hutchinson's Public Health Sciences Division, Rebecca Rudolph, MD, MPH, commented, "Our research suggests that low blood levels of selenium are a risk factor for progression of Barrett's esophagus. We found that Barrett's patients with low selenium levels had a two- to three-fold greater risk of advanced precancerous changes than patients with selenium levels in the middle or high end of the normal range . . . Most Barrett's patients will never get esophageal cancer, but since it is such a rapidly fatal cancer once you get it, it's really important to figure out ways to prevent it. This research gives us hope that we will be able to develop medical means by which to lower Barrett's-related cancer risk and perhaps even reverse the risk among people who already show signs of progression toward esophageal cancer."
Indole-3-carbinol byproduct acts as antiandrogen to halt prostate cancer cell growth
In a study funded in part by the National Institutes of Health, to be published in the June 6 2003 issue of the Journal of Biological Chemistry, University of California, Berkeley researchers have found that a digestive product of indole-3-carbinol, which occurs naturally in broccoli and other cruciferous vegetables, halts the growth of prostate cancer cells in vitro. The compound, 3,3’-diindolymethane (DIM), inhibits androgenic hormones that fuel prostate cancer growth. Although androgen is important for the normal development of the prostate, it is believed to be involved in the early stages of prostate cancer.
The researchers administered DIM to androgen dependent and androgen independent prostate cancer cells and found that androgen-dependent cells experienced a 70 percent reduction in growth compared to those that did not receive the compound. Androgen-independent prostate cancer cells were not affected by DIM. The scientists went on to discover that DIM inhibited dihydrotestosterone, the primary androgenic hormone that is believed to be the culprit in prostate cancer. Dihydrotesterone stimulates prostate specific antigen, or PSA, which is elevated in prostate cancer. When DIM was administered to the androgen-dependent prostate cancer cells, PSA levels dropped.
A study of the molecular structure of DIM showed that it is similar to the androgen-blocking drug Casodex. Lead author Hien Le, PhD, explained, “DIM works by binding to the same receptor that DHT uses, so it's essentially blocking the androgen from triggering the growth of the cancer cells."
Principle researcher and professor nutritional sciences and toxicology at UC Berkeley's College of Natural Resources, Leonard Bjeldanes, summarized, "As far as we know, this is the first plant-derived chemical discovered that acts as an antiandrogen. This is of considerable interest in the development of therapeutics and preventive agents for prostate cancer."
Heat shock proteins slow aging and diseases of aging
Cynthia Kenyon, PhD of the University of California, San Francisco, has unveiled a link between the aging process and the diseases that occur with aging with the discovery in worms that molecules called small heat shock proteins prevent the accumulation of the abnormal proteins found in Alzheimer’s, Huntington’s, Parkinson’s, and prion diseases, and, additionally, extend life. These harmful aggregates disrupt brain cell function, leading to the abnormal movements and behavior found in these diseases. Heat shock proteins assemble into complexes that bind to damaged proteins and prevent the harmful aggregation from occurring. Dr Kenyon announced, "We think we've found an important physiological explanation for both aging and age-related disease. The question of why older people are more susceptible to so many diseases has been a fundamental, unsolved problem in biology. Our findings suggest a beautiful molecular explanation, at least for this protein-aggregation disease. By preventing damaged and unfolded proteins from aggregating, this one set of proteins may be able to stave off both aging and age-related disease. The small heat-shock proteins are the molecular link between the two."
The report, published in the May 16 2003 issue of Science, detailed research conducted on the roundworm C elegans. Prior research by Dr Kenyon showed that modifying the gene daf-2, which encodes the hormone insulin-like growth factor and the insulin receptor, doubled the worm’s lifespan. Subsequent research by others found that the worms with mutated daf-2 accumulated the harmful protein aggregates later in life. Kenyon’s current research discovered that the expression of genes for four small heat-shock proteins were significantly increased in these animals.
To determine whether the heat-shock proteins lengthened life span, the scientists partially disabled their genes and found that the roundworm’s lifespan was shortened by approximately 25 percent, demonstrating the genes’ involvement in longevity. Research by pharmaceutical companies is seeking ways to increase heat-shock protein activity, which could potentially benefit humans suffering from several of the diseases associated with aging.
Vitamin B6 stops pancreatic cancer growth
A study published in the May 2003 issue of the journal Nutrition Research provided evidence that vitamin B6 significantly inhibited the growth of pancreatic cancer in a human cell line. Researches from Brigham and Women’s Hospital/Harvard Medical School in Boston tested a human pancreatic carcinoma cell line with six different concentrations of pyridoxine, the most well known form of vitamin B6, and six varying concentrations of pyridoxal, another form of the vitamin. Control groups of cells did not receive the vitamin. Each experiment was carried out three times.
At concentrations of 2.5 micromoles and greater, pyridoxine inhibited pancreatic cell growth in a dose dependent manner. Lower concentrations of pyridoxine did not product this effect. From the second day of treatment, pyridoxal inhibited cancer growth at concentrations of 0.5 micromoles and greater but not at 0.1 micromoles.
The authors note that similar findings have been obtained with melanoma and liver cancer cells. They also noted that vitamin B6 added to the diet of mice suppressed tumors, and that the vitamin may inhibit colon cancer in some models of the disease. Additionally, supplementation with a multivitamin that included 100 milligrams pyridoxine per day reduced the risk of bladder cancer in one double-blind clinical trial.
The relatively high amounts of vitamin B6 needed in this study to inhibit cancer cell growth may raise some questions concerning safety, however, the authors cite a study in which 400 milligrams vitamin B6 per day was given to physically active men for twelve weeks during which no side effects were reported. Further studies are needed to determine the effect of megadose vitamin B6 treatment for cancer of the pancreas in human subjects.
Low folate levels associated with depression
A study published in the March-April 2003 issue of the journal Psychotherapy and Psychosomatics found an association with low levels of folate in depressed individuals. Folate is the natural form of the vitamin folic acid that occurs in the body and in many plant-based foods. The association was strongest in those who had recently recovered from the condition.
Two thousand nine hundred forty-eight subjects, ages 15 to 39 years, who were participants in the third US National Health and Nutrition Examination Survey (NHANES III) were interviewed for assessment of major depression and dysthymia (mild depression), and information concerning physical health, socioeconomic status and nutrition. Fasting blood samples were analyzed for serum folate as well as red blood cell folate, considered to be a better indicator of body folate stores than serum levels which fluctuate with dietary intake. Serum total homocysteine was also measured.
Of the total participants in this study, 301 reported major depression and 121 reported dysthymia. While red blood cell folate levels in subjects who reported never having been depressed averaged 365 nanomoles per liter, levels for depressed subjects were significantly lower at 320 nanomoles per liter for dysthymic individuals and 340 nanomoles per liter for those with major depression. When serum folate levels were examined, both dysthymic subjects and subjects with major depression had similarly low levels compared to participants who had never been depressed. Participants who reported depressive symptoms occurring six to twelve months prior to the study had the lowest folate levels. Serum homocysteine levels, which can be inversely related to folate levels, were not found to be associated with lifetime depression.
The authors write, “Our results should provide greater impetus for supplementing depressed people with folate, in that we have shown that folate status after a depressive episode may be very low.” (Morris MS et al, “Depression and folate status in the US population,” Psychother Psychosom 2003;72:80-87)
TMG lowers mildly elevated homocysteine in men and women
The May 2003 issue of the Journal of Nutrition published the results of a trial of betaine, or trimethylglycine (TMG) on men and women who had mildly elevated plasma levels of the amino acid homocysteine. Homocysteine, a breakdown product of the amino acid methionine, is considered to be a risk factor for cardiovascular disease when even slightly elevated. Homocysteine can be remethylated into methionine via TMG or folate.
Thirty-six participants were divided into three groups and given one of three daily regimens for six weeks: 6 grams TMG, 800 micrograms folic acid with 6 grams placebo, or 6 grams placebo. Blood samples were obtained at the study’s onset, and fasting total plasma homocysteine and folate levels ascertained. Before and after the six week regimen, the subjects ingested 100 milligrams methionine per kilograms body mass as a methionine loading test.
Before treatment, homocysteine levels in the three groups did not differ, however after the six week regimens, the placebo group experienced an elevation of 4 percent compared to an 11 percent decrease in the group receiving TMG and an 18 percent decline in the folic acid group. Methionine loading also produced similar responses among the groups at the study’s onset, with plasma homocysteine levels peaking within six to nine hours before declining. While the curve for the folate-takers was not significantly different from that of the placebo group, for the TMG group, the curve was significantly lower, demonstrating lower homocysteine levels in response to methionine.
The authors note that the 800 microgram folic acid dose may have been too low to achieve an optimal response to methionine loading. It remains to be seen whether homocysteine elevation is a cause or an effect of cardiovascular disease.
Large studies confirm high fiber diets slash colon cancer risk
A new study published in the May 3 2003 issue of The Lancet contradicts the findings of recent studies that concluded that fiber consumption has no impact on the development of colon cancer. Results from the European Prospective Investigation into Cancer (EPIC), the largest study to ever investigate the association between diet and cancer risk, show that individuals who consume the highest amount of fiber have almost half the risk of colon cancer than those who consume the least amount. Another study in the same issue of the journal obtained similar results.
The EPIC study followed 519,978 European participants from ten countries, aged 24 to 75 for four and a half years. During this period, 1065 cases of colon cancer were diagnosed. The researchers discovered that those whose dietary fiber consumption was in the top 20 percent, at 35 grams per day, experienced a 40 percent lower risk of developing colon cancer than subjects who consumed an average of 15 grams per day. The second study, which was part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, compared 33,971 patients without polyps with 3591 patients who had one or more polyp and found that those whose fiber intake was highest had a 27 percent lower risk of polyps than those whose intake was lowest. Colon polyps are frequently precursors of colon cancer.
It was noted by the American Institute for Cancer Research that a study appearing in the International Journal of Epidemiology which found no association between fiber intake and colon cancer incidence in women involved a population with low fiber intake. Women who consumed the highest amounts of fiber in this study had intakes equivalent to those in the EPIC study’s low fiber group.
In an accompanying commentary in The Lancet, authors Lynnette Ferguson and Philip Harris of the University of Auckland, New Zealand, write, "Whatever the reasons for the results reported by the two studies, eating a diet rich in plant foods, in the form of fruit, vegetables, and whole-grain cereals, probably remains the best option for reducing the risk of colon cancer, and for more general health protection."
Chromium supplements improve glycemic control in type 2 diabetics
A double-blind, cross-over study published in the November 2002 issue of The Journal of Nutritional Biochemistry, found that administration of chromium picolinate twice daily to men and women with diabetes increased chromium levels glycemic control. Fifty diabetics were age and sex matched with 50 healthy, nondiabetic control subjects by researchers led by Basudev Bhattacharya from Calcutta India’s University College of Medicine. Serum chromium levels in the diabetics were found to be lower than those of the controls, and body mass index, waist to hip ratio, systolic and diastolic blood pressures, and blood glucose values were higher. The diabetic subjects were given 200 micrograms chromium or a placebo to be taken twice daily for 12 weeks, followed by a four week wash out period and a twelve week cross-over period (during which the chromium group received a placebo and the placebo group received supplements containing chromium). Participants were monitored every four weeks, blood samples were taken at the twelfth and sixteenth week, and at the study’s conclusion. Forty-three of the 50 diabetics completed the study.
Participants experienced a significant rise in serum chromium values following supplementation. Both fasting glucose levels and glucose levels following a meal decreased in participants after the chromium phase. While levels of glycated hemoglobin increased after the placebo phase, they did not rise in the subjects receiving chromium. Since fasting serum insulin levels declined following the chromium phase, chromium’s mechanism of lowering glucose appears to be caused by enhancement of insulin’s action rather than stimulation of insulin secretion.
"The overwhelming majority of studies using chromium picolinate supplementation for impaired glucose tolerance and diabetes have shown a positive effect. This study by Bhattacharya and colleagues is exciting and substantiates earlier studies conducted in the U.S., China and other countries," enthused Richard Anderson, PhD, of the U.S. Department of Agriculture's Beltsville Human Nutrition Research Center.
Genistein reduces PSA in untreated prostate cancer
In findings announced at the 2003 meeting of the American Urological Association on April 30 by researchers from the University of California Davis Cancer Center, prostate cancer patients who consumed the soy isoflavone genistein for six months experienced a drop in prostate specific antigen (PSA) levels of up to 61 percent. Prostate specific antigen is a marker for prostate tumors, and levels in prostate cancer patients are monitored to evaluate disease progression.
The study involved 62 men with prostate cancer who received 5 grams of genistein concentrated polysaccharide daily for six months. Forty-six of the subjects had undergone treatment for the disease, which involved radiation, androgen deprivation therapy or surgery, and the remainder were on watchful waiting. Watchful waiting is often advised for prostate cancer patients who are asymptomatic with small, contained tumors. The majority of participants on watchful waiting experienced a decline in PSA levels while all but one of the men who had been treated saw a rise in PSA.
University of California Davis Cancer Center director and UC Davis School of Medicine professor of Urology, Ralph deVere White, stated, "This study must be interpreted cautiously because the numbers of men enrolled are small. However, the findings do stimulate us to do a larger, placebo-controlled trial in patients who are on watchful waiting."
The results of the study, which found an increase in PSA among only 38 percent of the watchful waiting group compared to 98 percent in the treated group, indicate that genistein may help prevent prostate cancer progression in men who have not elected to undergo treatment. The authors conclude, "Patients on watchful waiting may do better due to grade of disease or distribution and concentration of genistein within the prostate. Further research is needed to determine this."