Mortality folic acid

Johnson and colleagues made a provocative observation in the course of exploratory preclinical toxicological studies of vincristine, namely, that folinic acid (Leucovorin citrovorum factor 5-formyl-5,6,7,8-tetrahy-drofolic acid) was able to protect mice from the toxicity of high doses of vincristine lb). Vincristine, at a dose of 2.5 mg/kg administered intravenously, resulted in a mortality of 90% over a period of 30 days, but treatment with folinic acid lowered the mortality to 25%. The protection against vincristine toxicity did not occur when folic acid was substituted for folinic acid. A report has appeared (45) indicating that there is no specific protective effect of folinic acid against vincristine toxicity in mice and that the protection can be observed by comparable treatment with isotonic saline solution. As discussed in Section Vll, there is not conclusive evidence that folinic acid is able to ameliorate vincristine toxicity in humans (46). 

Patients with PAD have increased mortality risk from cardiovascular causes (4,5), which is significantly increased in the subgroup of patients with high serum homocysteine concentration (33,34). Association of a low ABI and high homocysteine level could be useful for identifying patients at excess risk for cardiovascular death (34). In spite of the efficacy in lowering homocysteine level with a folic acid supplement there is no evidence that reducing homocysteine concentration is beneficial in patients with CHD and PAD (26,35),... 

Centers for Disease Control and Prevention Knowledge and use of folic acid by women of childbearing age—United States. Morbidity and Mortality Weekly Report 46, 721 (1997). 

One of the most prevalent clinical problems observed in the elderly is anemia, although it is not an inevitable outcome of aging. The anemia is associated with an increased risk of mortality, poor health, and decreased physical functioning. Those with iron deficiency may have concurrent folic acid or vitamin B12 deficiency. 

In addition, cancer incidence and mortality was reported in seven of the eight randomized controlled trials in CVD prevention (Clarke et al. 2010). It appeared that supplementation with folic acid (0.8-40 mg/d) had no effect on overall cancer incidence (RR 1.05 95% Cl 0.98-1.13) and mortality (RR 1.00 95% Cl 0.85-1.18). It has to be noted that none of these trials was specifically designed to investigate cancer incidence or mortality, and that there was no analysis for specific cancers. A combined analysis of two of these trials... 

Ebbing, M., Bonaa, K.H., Nygard, O., Arnesen, E., Ueland, P.M., Nordrehaug, J.E., Rasmussen, K., Njolstad, I., Refsum, H., Nilsen, D.W., Tverdal, A., Meyer, K., and Vollset, S.E., 2009. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA, the Journal of the American Medical Association. 302 2119-2126. 

Albert, C.M., Cook, N.R., Gaziano, J.M., Zaharris, E., MacFadyen, J., Danielson, E., Buring, J.E., and Manson, J.E., 2008. Elfect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease a randomized trial. JAMA, the Journal of the American Medical Association. 299 2027-2036. 

Armitage, J.M., Bowman, L., Clarke, R.J., Wallendszus, K., Bulbulia, R., Rahimi, K., Haynes, R., Parish, S., Sleight, P., Peto, R., and Collins, R., 2010. Elfects of homocysteine-lowering with folic acid plus vitamin B vs placebo on mortality and major morbidity in myocardial infarction survivors a randomized trial. JAMA, the Journal of the American Medical Association. 303 2486 494. 

Daily intake of folic acid and B vitamins and risk of cardiovascular events and total mortality... 

In addition, it is interesting to consider the issue of folic acid fortification. In the US and Canada, folic acid fortification of enriched grain products was fully implemented by 1998. Yang et al. (2006) evaluated trends in stroke-related mortality before and after folic acid fortification in the US and Canada and, as a comparison, during the same period in England and Wales, where fortification is not required. They observed a trend consistent with the hypothesis that folic acid fortification is contributing to a reduction in stroke deaths. 

The evidence supports both folic acid supplementation and fortification as effective in reducing neonatal mortality from NTDs. A review by Ray et al. (2004) of the prevalence of folic acid supplement use both pre- and peri-conceptionally in community programmes worldwide found that fewer than 50% of women appeared to take folic acid periconceptionally and noted that the rate continues to be much lower than desired. In some programmes, users of supplement tend to take higher than recommended doses. 

The comparisons were intention-to-treat analyses of first events during the scheduled treatment period in all participants allocated to folic acid-based B vitamins or control (irrespective of any other treatment allocated factorially). The main outcomes were coronary heart disease events, stroke, cancer and allcause mortality. Coronary heart disease events were defined as the first occurrence of non-fatal myocardial infarction or coronary death although for several trials the definition of coronary events was restricted to fatal or non-fatal myocardial infarction. Stroke was defined as the first occurrence of either ischemic or hemorrhagic or unspecified strokes. Cancer was defined as any cancer, excluding non-melanoma skin cancers. 

Figure 45.4 Effects of folic acid on all-cause mortality in published studies.

Large trials of folic acid have demonstrated that lowering blood homocysteine levels for an average of five years had no significant effect on risk of heart disease, stroke, cancer or all-cause mortality. 

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