DNA-damaging effects of folate deficiency comparable to that of high dose radiation
A report published online on November 3 2003 in the Federation of the American Societies for Experimental Biology ( FASEB http://www.fasebj.org/ ), has revealed that a deficiency in the B vitamin folate is more damaging as ionizing radiation in regard to its effect on DNA strand breaks. DNA damage can lead to chromosomal aberrations and cancer. Folate and other vitamin and mineral deficiencies can cause DNA double-strand breaks, which are the most serious DNA lesion caused by ionizing radiation.
Bruce N Ames of the Children's Hospital Oakland Research Institute and colleagues irradiated human lymphocytes (white blood cells) at several doses, and cultured other lymphocytes in low concentrations of folate for ten days. They found that folate deficiency and high doses of ionizing radiation caused DNA breaks and apoptosis. Ionizing radiation and folate deficiency also caused changes in cell cycle and gene expression. While radiation activated DNA double-strand break repair genes, folate deficiency was not found to do the same.
The authors concluded that folate deficiency may be more detrimental than low doses of radiation and noted that insufficient dietary folate causes sperm damage. Because most individuals' exposure to radiation is relatively low, radiation may pose a smaller cancer risk than that incurred by a poor diet. They write, “Our results suggest that research on the biological effects of low-dose radiation, in humans, should take into account the nutritional status of the subjects, because folate (and other vitamin and mineral) deficiency could confound the effects of low-dose radiation or could even have a synergistic effect and increase the sensitivity of cells to radiation.” ( Courtemanche C et al, “ Folate deficiency and ionizing radiation cause DNA breaks in primary human lymphocytes: a comparison,” FASEB November 3 2003 )
Betaine supplementation lowers homocysteine in healthy men and women
A study published in the December 2003 issue of the Journal of Nutrition found that supplementing with betaine, also known as trimethylglycine, lowered homocysteine both immediately and long term in a group of seventy-six healthy men and women. Participants were divided into four groups who received 1.5 grams betaine, 3 grams betaine, 6 grams betaine, or a daily placebo for six weeks. Homocysteine levels were ascertained with fasting homocysteine blood tests and with methionine loading tests. The methionine loading test is considered the more accurate method of determining homocysteine levels, because the more commonly used fasting homocysteine level blood test does not find elevated homocysteine in 27 to 40 percent of individuals who have the condition. Subjects were tested before receiving their treatment regimens, at several points during the study, and at the study's conclusion.
After one day of betaine supplementation, the methionine loading test determined that the group receiving 1.5 grams betaine had homocysteine levels that were 16 percent lower than the placebo group, and those who received 6 grams had homocysteine levels 35 percent less. After six weeks, homocysteine levels further declined to levels 23% and 40% than placebo in the groups receiving 1.5 grams and 6 grams, respectively. Fasting plasma homocysteine levels were 12% less in the group receiving 1.5 grams and 20% less in the group receiving 6 grams at the end of six weeks. This demonstrates an immediate as well as longterm ability ofr betaine to lowering homocysteine.
The authors note that this is the first placebo-controlled study to demonstrate that supplementing with betaine at a dose as low as 1.5 grams per day can lower homocysteine levels in healthy adults. Their findings also show that betaine is quickly available as a methyl donor.
Fiber intake associated with slowed progression of atherosclerosis
The December 2003 issue of the American Journal of Clinical Nutrition published findings obtained from the Los Angeles Atherosclerosis Study, a prospective study which is investigating factors involved in atherosclerosis progression, on the ability of fiber to help combat atherosclerosis. Five hundred men and women between the ages of forty and sixty with no history of cardiovascular events received baseline examinations and were followed for three years. Dietary information was obtained through oral and telephone interviews at the beginning of the study and at the first follow up at eighteen months. Intima -media thickness of the common carotid arteries (a measure of atherosclerosis) was determined by ultrasound examination at the study's onset, at eighteen months and at three years. Blood samples taken at all three examinations provided data on serum lipids.
The median total fiber intake in the highest fifth of the study population was found to be twice that of the lowest fifth. Intima -media thickness progression declined with an increase in fiber intake. The trend was significant for viscous (soluble) fiber found particularly in fruit and vegetables, and pectin. Controlling for the intake of fruit and vegetables, which have other antiatherogenic constituents, did not alter the findings.
Increased high density lipoprotein levels were correlated with an increase in total fiber, viscous fiber and pectin. Additionally, the ratio of total to HDL cholesterol was inversely related to total fiber, viscous fiber and pectin intake. These findings support the hypothesis that fiber retards the progression of cardiovascular disease through its effect on lipids.
The authors conclude that “The present study suggests that increased dietary fiber intake has significant cardiovascular benefit and that the regulation of serum lipids by dietary fiber may be partially involved in the process of slowing the progression of atherosclerosis.” Wu H et al, “Dietary fiber and progression of atherosclerosis: the Los Angeles Atherosclerosis Study,” Am J Clin Nutr 2003; 78:1085-91.)
Modified citrus pectin associated with improved PSA doubling time
A phase II pilot study published in the Nature groups journal Prostate Cancer and Prostatic Diseases (volume 6 2003), has found that modified citrus pectin (MCP) slowed prostate-specific antigen doubling time (PSADT) in a small group of prostate cancer patients. Prostate-specific antigen, or PSA, is a blood marker of prostate cancer, and the time it takes for PSA to double is used to predict the progression of prostate cancer to metastatic disease.
Ten patients who had experienced a rise in PSA after having received loca liz ed treatments for prostate cancer were given eighteen 800 milligram capsules of Pecta-Sol modified citrus pectin per day, to be taken in divided doses with liquid for one year. Blood samples were obtained each month to determine PSA values. The participants' previous PSA levels and doubling times were used to compare with those obtained during the trial.
Although none of the men experienced a reversal of PSA values, PSA doubling time significantly increased in seven of the ten subjects, demonstrating a deceleration of disease progression.
Modified citrus pectin appears to bind to a lectin known as galectin-3, expressed in metastatic cells. Galectins permit greater clumping of cancer cells at the site of metastasis. By binding to galectin-3, modified citrus pectin blocks the ability of tumor cells to adhere and aggregate at metastasis sites.
An earlier study, summarized in “What's Hot” on April 28 of this year, reached a similar conclusion concerning the benefit of modified citrus pectin in prostate cancer. Coauthor Stephen B Strum, MD, commented, “ It is hoped that by slowing the PSADT with MCP we can delay the need for more aggressive therapy and perhaps enhance the quality of life of those patients exhibiting PSA recurrence after surgery or radiation therapy.”
Synthetic progestins likely culprit in HRT downside
Female hormone replacement therapy, once widely popular, has recently been determined to increase the risk of breast cancer, cardiovascular disease, stroke and dementia. A new study conducted by researchers at the University of South Florida , published in the most recent issue of Climacteric, the Journal of the International Menopause Society , has found that synthetic progestins such as those combined with estrogen in the female hormone replacement drug Prempro , may be responsible for some of HRT's harmful effects.
The researchers developed a novel imaging technique combining video microscopy with fluorescence and electron microscopy to observe blood vessel structure, blood flow and the activities of blood cells in rats. They found that medroxyprosterone acetate, the synthetic progestin commonly used in oral contraceptives hormone replacement, caused damage to peripheral and brain blood vessels and endothelial and smooth muscles. In addition, the researchers observed an increase in inflammation, blood clot formation and blood flow impedence . Estrogen alone, or natural progesterone (identical to what is manufactured in the body), were not found to cause these damaging effects. On the contrary, estrogen was shown to be protective of blood vessels in the brain and surrounding areas, as well as helping to prevent inflammation and blood clot formation.
In another study, published this year in the Journal of Alzheimer's Disease (volume 5, 2003), the duo demonstrated that estrogen may protect brain blood vessels from beta- amyloid , a substance believed to be involved in the loss of memory that occurs in Alzheimer's disease.
Lead author of Tom Thomas, MD, PhD, commented, "This is experimental evidence that supports scientists who believe estrogen with the right formulation is good for some women, depending on their other risk factors."
Despite these positive findings for estrogen, the use of estrogen alone would still be dangerous for women who have had or who have an increased risk of breast cancer.
Fiber plus vitamin D reduces colon cancer risk
In a study that has been called one of the most comprehensive to date on colon cancer risk, researchers from Harvard University , Veterans Affairs and the National Cancer Institute have found that the consumption of vitamin D and fiber from cereal are associated with a lower risk of serious colon polyps, which can be a precursor to colon cancer. The report was published in the December 10 2003 issue of the Journal of the American Medical Association.
The study involved 3121 individuals who were examined at VA medical Centers between 1994 and 1997. Questionnaires were administered to determine dietary intake, and medical history was ascertained. Colonoscopic examinations found 329 cases of advanced neoplasia , defined as a polyp of 10 millimeters or more, a villous adenoma (often a precursor of of adenocarcinoma ), adenoma with high grade dysplasia, or invasive cancer.
Men who consumed more than 4 grams of cereal fiber per day, and over 645 international units of vitamin D per day experienced a significantly reduced risk of developing serious colon polyps. Taking aspirin on a daily basis lowered the risk by one-third. Having a first degree relative with colon cancer, smoking, and moderate to heavy alcohol use emerged as factors that increased risk. A separate analysis that studied those whose worst lesions were hyperplastic polyps (small benign polyps) produced similar findings.
Lead investigator and chief of gastroenterology at the Portland VA Medical Center and Oregon Health and Science University , David Lieberman, MD, stated, "The finding that may surprise the scientific community is the vitamin D data . . . . These data support relatively simple and safe recommendations that may reduce the risk of colon cancer. Stop smoking, reduce alcohol and red meat consumption, take a multivitamin, exercise regularly, and consume vitamin D, calcium and cereal fiber in your diet."
Hypertension another inflammatory disorder?
A report published in the December 10 2003 Journal of the American Medical Association has found a link between elevated levels of the inflammatory marker C-reactive protein and the development of hypertension, and suggests that the condition may be inflammatory in part. Hypertension is a strong risk factor for heart attack and stroke, and high levels of C-reactive protein have also been linked to these events.
The researchers, led by Howard D S esso , Sc.D , of Brigham and Women's Hospital and Harvard Medical School in Boston , analyzed data obtained from 20,525 participants in the ongoing Women's Health Study. Blood samples obtained in 1992 were assayed for levels of C-reactive protein and the subjects' coronary risk factors were collected. While the group examined in the current study were free of high blood pressure at enrollment, 5,365 women developed incident hypertension (defined as systolic blood pressure of at least 140 mm Hg and diastolic of at least 90 mm Hg) during the 7.8 year follow up period.
The team discovered a positive association between C-reactive protein levels and hypertension risk. Women whose C-reactive protein levels were the highest were twice as likely to develop hypertension as those whose levels were the lowest. The association was valid even among those whose blood pressure was initially very low and for those who had no traditional coronary risk factors.
C-reactive protein increases with the chronic activation of the immune system, known as an inflammatory response. C-reactive protein may increase blood pressure by reduce endothelial cell production of nitric oxide, causing the blood vessels to constrict. In turn, inflammation has been associated with endothelial dysfunction. The authors conclude that the study's findings “provide evidence that inflammation may be an important mechanism through which hypertension develops.”
Calcium and vitamin D: partners in colon cancer prevention
A report published in the December 3 2003 Journal of the National Cancer Institute detailed the findings of Maria V Grau, MD, of the Dartmouth Medical School in Lebanon, New Hampshire and colleagues that calcium and vitamin D work together to reduce colorectal cancer risk. The study analyzed data provided by 803 participants in the Calcium Polyp Prevention Study, which found that supplementation with 1200 milligrams calcium were day was associated with a lower risk of recurrence of colorectal adenomas, or polyps, which can be a precursor of colorectal cancer. In the current study, the researchers analyzed serum 25-hydroxyvitamin D levels from blood samples obtained at the beginning and end of the trial. They also examined the subjects' cells for the presence of changes in the vitamin D receptor gene.
The team found that calcium supplements reduced the risk of polyp recurrence only among individuals whose vitamin D levels were higher than the median at the study's onset, and that serum vitamin D levels were associated with a lower risk of polyps reoccurring only among participants who were taking calcium supplements. When polymorphisms in the vitamin D receptor gene were analyzed in relation to the risk of colorectal adenoma recurrence, no association was found.
In an accompanying editorial in the JNCI , Elizabeth T Jacobs et al speculate that the presence of adequate calcium might allow for the diversion of 1,25-hydroxyvitamin D3 to antitumor activities. 1,25-hydroxyvitamin D3 is produced from 25-hydroxyvitamin D, and is the form of vitamin D found to have antiproliferative effects in colon cancer.
The authors concluded that the findings "provide a strong indication that vitamin D and calcium have a joint antineoplastic effect in the large bowel," and recommend further investigation to understand the mechanistic basis of their interaction.
Vitamin D supplements recommended for elderly women
The results of a first-of-its-kind study published in the November 2003 issue of the Journal of the American Geriatrics Society have revealed that a vitamin D deficiency is associated with falls and injuries in elderly women. Researchers at the University of Melbourne in Australia measured the serum vitamin D levels of 667 women in low-level care residential facilities and 952 women in high-level care facilities and determined the presence of other risk factors for falls. Low level care residents were tracked for 145 days and high level care residents for 168 days, with falls recorded by the residential care staff.
The investigating team discovered that 22 percent of low level care residents and 45 percent of nursing home residents were deficient in vitamin D. Low levels of the vitamin were found to be a predictor of falls, even after adjustment for weight and other factors. Statistical analysis determined a 20% reduction in the risk of experiencing a fall with a doubling of vitamin D levels. Lead investigator and University of Melbourne P rofessor John Wark , explained, “The solution to vitamin D deficiency may simply be supplying safe and readily available vitamin D supplements. Most of us are able to get our daily requirement for vitamin D from sun exposure plus a small amount from our diets. For elderly people in residential care, this is more problematic as most have impaired mobility, therefore more difficulty getting outdoors. In addition, the skin of elderly people is less effective at producing vitamin D, further compounding the problem. In Australia , there are few dietary sources for vitamin D, so it is very difficult to make up for the lack of vitamin D production in the skin of people with very restricted sunlight exposure. Vitamin D supplements should generally prevent this problem and should be used more widely.”
Vitamin B12 helps depression treatments work better
A report published online this week in Biomed Central Psychiatry found that individuals who have high serum levels of vitamin B12 have a better response to treatment for depression. The research was conducted at Kuopio University Hospital in Finland , and involved 45 male and 70 female outpatients suffering from depression between the ages of 21 and 69 years.
The researchers measured the participants' serum folate and vitamin B12 levels, in addition to rating their level of depression, at the study's onset and at six months. Patients were classified as not responding to treatment, partially responding or fully responding.
It was found that the participants who fully responded to treatment had the highest serum vitamin B12 levels at the beginning and end of the study. When smoking, drinking habits, type of treatment, and family history were included in the analyses, the association between B12 levels and treatment responsiveness was still significant.
The authors noted that low vitamin B12 levels may result in elevated levels of homocysteine , which may lead to exitotoxic reactions that enhance depression. Additionally, vitamin B12 is necessary for the formation of S- adenosylmethionine ( SAMe ) in the body, which has an antidepressant action. Another possible reason for vitamin B12's role in alleviating depression is its involvement in the synthesis of monoamines such as serotonin and dopamine. Several antidepressant drugs' mechanism of action is to keep monamines from breaking down.
"As far as we know, there have been no previous studies that have suggested a positive relationship between vitamin B12 and the treatment outcome in patients with major depressive disorder who have normal or high vitamin B12 levels,” the authors announced. An earlier study found that older depressed individuals responded better to treatment when taking a supplement containing vitamins B1, B2 and B6.