Research
JPEN J Parenter Enteral Nutr. 2006 Mar-Apr;30(2):108-14.
Antioxidant Supplementation With Or Without B-Group Vitamins After Acute Ischemic Stroke: A Randomized Controlled Trial.
Ullegaddi R, Powers HJ, Gariballa SE.
Sheffield Institute for Nutritional Studies on Ageing and the Human Nutrition Unit, University of Sheffield,
Northern General Hospital, Sheffield S5 7AU, UK.
BACKGROUND: Evidence shows that there is a rapid increase in the production of markers of oxidative damage
immediately after acute ischemic stroke and that endogenous antioxidant defenses are rapidly depleted, thus
permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a
pro-oxidant effect of elevated total plasma homocysteine (tHcy). METHODS: To test whether supplementary antioxidants with or without B-group vitamins during this critical period enhance antioxidant capacity or mitigate oxidative damage, ninety-six acute ischemic stroke patients within 12 hours of symptom onset were randomly assigned to receive either daily oral 800 IU (727 mg) vitamin E and 500 mg vitamin C (n = 24), or B-group vitamins (5 mg folic acid, 5 mg vitamin B(2), 50 mg vitamin B(6), and 0.4 mg of vitamin B(12); n = 24), both vitamins together (n = 24), or no supplementation (n = 24) for 14 days. Treatment groups and controls were matched for stroke subtype and age. Blood was obtained before treatment, at day 7, and day 14 for measurements of plasma or blood vitamin status, plasma total antioxidant capacity (TAOC), malondialdehyde (MDA), tHcy and C-reactive protein (CRP). RESULTS: Supplementation with antioxidant vitamins and B-group vitamins separately or together significantly increased the plasma concentration of vitamin C, E, pyridoxal phosphate (B(6) status), red blood cell folate, and improved a measure of B(2) status (red cell glutathione reductase activation coefficient [EGRAC]), compared with the control group. Plasma TAOC increased significantly in the antioxidant treatment groups compared with the nonsignificant decline seen in the control group. tHcy concentrations decreased in subjects who received B-group vitamins and the control group compared with the rise seen in those who received antioxidants alone. There was a significant reduction in plasma MDA concentration in the 3 treatment groups, in contrast to the increase seen in the control group; however, the changes were most evident in antioxidant groups. CRP concentrations (a marker of tissue inflammation) were significantly lower in the 3 treatment groups compared with the control group. There were no additive or synergistic effects of antioxidants and B-group vitamins together on any outcome measure. CONCLUSIONS: Antioxidants supplementation with or without B-group vitamins enhances antioxidant capacity, mitigates oxidative damage, and may have an anti-inflammatory effect immediately postinfarct in stroke disease.
PMID: 16517955 [PubMed - in process]
Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):443-8.
Folate, Vitamin B(6), And Vitamin B(12) Intake And The Risk Of Breast Cancer Among Mexican Women.
Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I.
Instituto Nacional de Salud Publica, Av. Universidad 655, Col. Santa Maria Ahuacatitlan, Cuernavaca, Morelos 62508,
Mexico.
BACKGROUND: High intake of folate, vitamin B(6), and vitamin B(12) have been hypothesized to lower the risk for
breast cancer. We conducted a population-based case-control study to evaluate the risk for breast cancer among
Mexican women with relatively low vitamin intakes. METHODS: We included 475 women (median age, 53 years; range,
23-87 years) diagnosed with incident breast cancer through six hospitals in Mexico City and interviewed them to
obtain data on breast cancer risk factors and their usual diet using a food frequency questionnaire. We selected
1,391 (median age, 49 years; range, 18-82 years) controls from the Mexico City population using a national sampling frame. RESULTS: Compared with women in the lowest quartile, the odds ratio for breast cancer for women in the highest quartile of folate intake was 0.64 [95% confidence intervals (CI), 0.45-0.90; P, test for trend = 0.009] and 0.32 (95% CI, 0.22-0.49; P, test for trend < 0.0001) for vitamin B(12) intake. Among postmenopausal women, intakes of folate and vitamin B(12) were associated with a lower risk of breast cancer and those associations were stronger than among premenopausal women. The inverse association of folate and breast cancer was stronger among women who consumed a high level of vitamin B(12) as compared with women consuming diets low in vitamin B(12). No association was observed for vitamin B(6) intake. CONCLUSIONS: In this population, high intakes of folate and vitamin B(12) were independently associated with decreased breast cancer risk, particularly among postmenopausal women.
Can J Cardiol. 2006 Jan;22(1):47-53.
Rationale, Design And Baseline Characteristics Of A Large, Simple, Randomized Trial Of Combined Folic Acid And
Vitamins B6 And B12 In High-Risk Patients: The Heart Outcomes Prevention Evaluation (HOPE)-2 Trial.
Lonn E, Held C, Arnold JM, Probstfield J, McQueen M, Micks M, Pogue J, Sheridan P, Bosch J, Genest J, Yusuf S
HOPE-2 Investigators.
Hamilton Health Sciences Corporation, Hamilton, Ontario. lonnem@mcmaster.ca
BACKGROUND: Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration
is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial--the Heart Outcomes Prevention Evaluation (HOPE)-2 study--is being conducted to evaluate this therapy in patients at high risk for CV events.
OBJECTIVES: To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke.
METHODS: A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005.
RESULTS: The patients'' baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention.
PMID: 16450017 [PubMed - indexed for MEDLINE]
Stroke. 2006 Feb;37(2):547-9. Epub 2005 Dec 22.
Efficacy Of B Vitamins In Lowering Homocysteine In Older Men: Maximal Effects For Those With B12 Deficiency
And Hyperhomocysteinemia.
Flicker L, Vasikaran SD, Thomas J, Acres JM, Norman P, Jamrozik K, Hankey GJ, Almeida OP.
School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. leonflic@cyllene.uwa.edu.au
BACKGROUND AND PURPOSE: A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels.
METHODS: We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged > or =75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 microg of B12 or placebo. The study groups were balanced regarding age (mean+/-SD, 78.9+/-2.8 years), B vitamins, and tHcy at baseline.
RESULTS: Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 micromol/L (95% CI, 3.94 to 9.55 micromol/L) compared with 2.88 micromol/L (95% CI, 0.07 to 5.69 micromol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 micromol/L (95% CI, 0.6 to 4.9 micromol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=-0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group.
CONCLUSIONS: The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.
PMID: 16373648 [PubMed - indexed for MEDLINE]
Am J Clin Nutr. 2005 Dec;82(6):1320-6
Randomized Controlled Trial Of Homocysteine-Lowering Vitamin Treatment In Elderly Patients With Vascular Disease.
Stott DJ, MacIntosh G, Lowe GD, Rumley A, McMahon AD, Langhorne P, Tait RC, O''Reilly DS, Spilg EG, MacDonald JB, MacFarlane PW, Westendorp RG.
Division of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom. d.j.stott@clinmed.gla.ac.uk
BACKGROUND: Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function.
OBJECTIVE: We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function. DESIGN: This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y. RESULTS: The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4).
CONCLUSION: Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.
PMID: 16332666 [PubMed - indexed for MEDLINE]
