LE Magazine May 2001
Higher vitamin C levels related to lower mortality
In a study just published in the journal Lancet (2001; 357:657-63), researchers from Cambridge University in England sought to confirm the association between serum vitamin C levels and mortality from all causes as well as specifically from cardiovascular disease and cancer. They found that high levels of vitamin C resulted in a significant reduction in all cause mortality over a four year period. The study participants were part of a prospective population study of 19,496 men and women ranging in age from 45 to 79. At the beginning of the study participants were clinically examined and completed a health and lifestyle questionnaire and food intake diaries. Serum ascorbic acid levels were measured one year into the study. Causes of death were followed up and validated for four years.
In the group having the highest serum vitamin C concentrations, the risk of all-cause mortality in the four year period was half that of the group who had the lowest vitamin C concentrations. This relationship of ascorbic acid levels on mortality risk was consistent throughout the different levels of ascorbic acid concentration. Mortality from cardiovascular disease and ischemic heart disease was correlated with lower levels of ascorbic acid levels in men and women. High levels of vitamin C lowered the risk of cancer in men but not women over this four year study period. Researchers speculated this could be related to the different types of cancer diagnosed in men and women.
The increase in serum vitamin C was correlated with an increase in dietary consumption of fruits and vegetables. An increase in vitamin C equivalent to consuming one extra serving of a fruit or vegetable per day was determined to be associated with a 20% reduction in the risk of all-cause mortality. The researchers conclude that small changes in intake of vitamin C could have large effects on how long a person might live. By such processes as free radical scavenging, protecting lipid membranes and contributing to collagen production, several previous human epidemiological studies have shown that high amounts of vitamin C significantly cut mortality rates, with particularly striking reductions in a number of chronic diseases, including heart disease and cancer.
New findings on I3C
New discoveries have been made about indole-3-carbinol. Researchers report that the compound (found in cruciferous vegetables such as cabbage) upregulates tumor suppressor gene BRCA1 through an estrogen receptor. BRCA1 (breast cancer susceptibility gene) is mutated in some cases of breast cancer, especially in young women, and in some cases of prostate and ovarian cancer. More often, BRCA has methylation alterations that have silenced it. New research shows that BRCA1 is not just a tumor suppressor gene, but has roles in DNA repair as well. This important gene is found throughout the body.
The new findings on I3C show that the compound increases BRCA1. Both of them then work together to block estrogen from sending signals that enhance the growth of cancer. Also not previously known was that I3C blocks the estrogen receptor alpha from being made. This is like putting up a road block for estrogen. Estrogen is there, but it can’t do anything harmful.
These findings are the latest in a growing list of what I3C does to modulate estrogen. One of its most important actions is to change the way estrogen is metabolized. Instead of transforming into 16-a-hydroxyestrone, estrogen is converted to 2-hydroxyestrone when I3C is present. 2-hydroxyestrone is a weaker form of estrogen. Women with more 2-hydroxyestrone than 16-a-hydroxyestrone are at less risk for breast cancer than those with higher levels of the 16 metabolite. Another feat of I3C is to block carcinogens from causing cancer. In addition, I3C can prevent cervical cancer caused by human papilloma virus-16 in mice. I3C also causes apoptosis (cell death) in certain types of cancer cells.
Meng Q, et al. 2000. Indole-3-carbinol is a negative regulator of estrogen receptor- signaling in human tumor cells. J Nutr 130:2927-31.
Esteller M, et al. 2000. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92:564-9.
Ge X, et al. 1999. Induction of apoptosis in MCF-7 cells by indol-3-carbinol is independent of p53 and bax. Anticancer Res 19:3199-03.
Jin L, et al. 1999. Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res 59:3991-97.
Magdinier F, et al. 2000. Regional methylation of the 5’ end CpG island of BRCA1 is associated with reduced gene expression in human somatic cells. FASEB J 14:1585-94.
Muti P, et al. 2000. Estrogen metabolism and risk of breast cancer: a prospective study of the 2:16 -hydroxyestrone ratio in premenopausal and postmenopausal women. Epidem 11:635-40.
Sharma S, et al. 1994. Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer Res 54:5848-55.
Wang Y, et al. 2000. BASC, a super complex of BRCA-1 associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 14:927-39.
More fish means lower stroke risk in women
According to the latest findings, a higher dietary intake of fish and omega 3 polyunsaturated fatty acids can significantly decrease the risk of the most common form of stroke among middle-aged women, especially those who don’t take aspirin regularly (JAMA 2001 Jan; 285:304-312). The study, which tracked 79,839 women ages 34 to 59 over a 14-year period (1980-1994), showed that eating fish regularly reduced the risk of thrombosis (a blood clot that has built up on the wall of a brain artery), which causes 40% to 50% of strokes.
The study authors reported that, “Compared with women who ate fish less than once per month, those with higher intakes of fish had a lower risk of total stroke.” After adjusting for age, smoking and other cardiovascular risk factors, women who ate fish one to three times per month had a 7% lower risk than those who ate fish less than once per month. Stroke risk declined relative to how often women consumed fish, dropping by 22% when eating fish once a week, and 27% when dining on it two to four times a week. The risk of total stroke was reduced 52% for those who ate fish five or more times per week.
The study also found that, while regular use of aspirin can potentially lower stroke risk by reducing platelet aggregation, fish intake still reduced stroke risk in women who didn’t use aspirin as a means of stroke prevention. The authors suggest several mechanisms may be involved in the lower stroke risk associated with n3 fatty acids, namely their ability to reduce platelet aggregation, lower blood pressure and reduce plasma fibrinogen concentrations.
Veggies protect against lung cancer
A team of researchers from the United States and China has shown that isothiocyanates, found in cruciferous vegetables, offer significant protection against lung cancer, but that the degree of protection depends upon genetics, according to a report in a recent issue of the journal Lancet (Vol. 355, Issue 9231). Subjects in this prospective epidemiological study who lack glutathione S-transferase enzymes, which metabolize isothiocyanates, were about half as likely to get lung cancer as those who are homozygous for the genes, and who therefore quickly eliminate the protective isothiocyanates from their bodies. Prevalence of the genes varies from 32% to 55%, depending on ethnic group, says Stephanie London, PhD, of the National Institute of Environmental Health Sciences. This is the first study to link biological measures of isothiocyanates with reduced cancer risk. This study’s most important implication is for conduct of intervention studies, says London, who is the lead author. “Most clinical trials assume everybody is the same,” says London. Taking genetic differences into account would sharpen results, she says.
There are more than 20 different isothiocyanates, which are believed to combat cancer by boosting antioxidant production, but the details are a black box. “Just eat your vegetables,” says London. The study population included more than 18,000 males ages 45 to 64, in Shanghai, China. 232 cases of lung cancer occurred during the study. The local diet is high in cruciferous vegetables, and smoking is common in this population. —David Holzman