vitamin b6 and b12 intakes in relation to risk of 叶酸维生素b6和b12摄入量关系风险课件

Folate, Vitamin B6, and B12 Intakes in Relation to Risk of Stroke Among Men Ka He, MD;Anwar DMD; Eric B;. Rimm, ScD;Bernard A. Rosner, PhD; Meir J. Stempfer, MD;Walter C. Willett, MD; Alberto Ascherio, MD Stroke. 2004;35:169-174 Folate Intake and Risk of Stroke Among Wemen Wael K. Al-Delaimy, MD, PhD;Kathryn M. Rrxrode, MD, MPH; Frank B. HU, MD, PhD; Christine M. Albert, MD, MPH; Meir J. Stampfer, MD, DrPH; Walter C. Willett, MD, DrPH; John E. Manson, MD, DrTH Stroke. 2004;35:1259-1263 翁履珍 IntroductionIntroduction Folate (Folic acid) Water Soluble Functions i. Red blood cell formation ii. New cell division iii. Protein metabolism Deficiencies Anemia, diarrhea, depression, heartburn Toxicity Insomnia, irritability, diarrhea, may mask B12 deficiency Recommended Intakes (RDA): 400 g/day for adults Food Sources Green leafy vegetables, liver, legumes, seeds, and enriched breads, cereals, rice, and pasta. /cs/supplements/l/blvitbfolate.htm Homocysteine ) Elevated homocysteine level Genetic defects (Brattstrom, et al.1998) Low intake of folate, vitamin B6 vitamin B12 (Verhoef, et al.1996) Homocysteine Folate metabolism /maladies/homocystinurie.html Study 1 Examining the relationship between prospectively intakes of folate and vitamin B6 and vitamin B12 and incidence of ischemic and hemorrhagic stroke in a large cohort of US men with an average 14 years of follow-up. Subjects and MethodsSubjects and Methods The Health Professional Follow-up Study Established in 1986 51529 male US health professionals 40-75 years old Questionnaire on medical history, lifestyle and diet Mailed questionnaire in every other year Potential risk factors and Identify new cases of diseases Excluded Have a history of CVD and DM Inadequate dietary data 4200kcal/day, or 70 blank items Dietary Assessment Assessed in 1986, 1990, and 1994 Semiquantitative food frequency questionnaires (FFQ) Commenly used portion size Never or autopsy reports A search of National Death Index death certificates Subcategorized by National Survey of Stroke Ischemic ( embolism or thrombosis) stroke Hemorrhagic (subarachnoid and intracerebral) stroke Unknown type of stroke Statistical Analyses Divided into quintiles according to intakes of B vitamins Incident rate = Case number person time (follow-up in each quintile) Relative Risk (RR) = The incident of stroke in a particular quintile compare with the lowest one Cumulative average of nutrient intakes Represent long-term dietary intake Reduce within-subject variation Statistical Analyses (cont.) The different effect between long-term and short-term diet intake Baseline diet and the most recent diet Stop updating DM, CHD, TIA, peripheral arterial disease Incident rates and 95% CI ( Mantel-Haenszel methods) Adjusted covariate Stratify age(5-year categories) and cigarette smoking status Relative Risk( COX proportional hazards models) (i) Cigarette smoking; body mass index; physical activity; history of hypertention and hypercholesterolemia; aspirin use (ii) Intake of alcohol, fiber, potassium, vitamin E All nutrition intakes were energy-adjusted, and total energy intake was included in all regression models. ResultsResults 725 incident cases 455 ischemic stroke 125 hemorrhagic stroke 145 unknown type stroke No significantly association between Dietary or supplemental folate and ischemic stroke No apparent jointly relation of alcohol consumption and folate intake to risk of ischemic or hemorragic stroke DiscussionDiscussion Inversely related to risk of ischemic stroke Folate intake (30% ) Vitamin B12 But not Vitamin B6 No significant associations with risk of hemorrhagic stroke were observed. In this large prospective follow-up study Other health-related factors Healthier lifestyle of higher folate intake Source of folate Other constituents of the supplement Inaccurate dietary assessment Inverse association between intakes of folate, vitamin B6, B12 and risk of CHD Repeated measurements Excluded participants with intermediate diseases Cumulative average diet The amount of vitamin B6 in the ref. group 1.8mg/d in ref. group 2mg/d of RDA Previous Study Inverse relation between folate intake and risk of stroke in the NHANE I RR=0.79 may be diluted by cases of hemorragic stroke (Salhub et al) Inversely associated with blood homocysteine Toxic accumulate in endothelial vascular damage Generation of free radical (Verhoef et al; Harker et al.) Regular intake 100g folic acid/d lower homocysteine (Salhub et al) In the Framingham Heart Study (Salhub et al) Homocysteine plasma folate plasma B12 MI, myocardial infarction. 2622232222 Current hormone replacement use (%) 44444444 44 Postmenopausal (%) 2020212020 65 y (%) 2525273037 Current smokers (%) 65554 History of high cholesterol (%) 1616161514 History of high blood pressure (%) 2.01.5 History of diabetes (%) 5151474235 Regular physical activity (%) 5148454544 Current aspirin use (%) 5149484949 Oral contraceptive pill ever-user (%) Prevalence 5 4 3 2 1 Folate Intake Quintiles TABLE I. Age-Adjusted Characteristics of Women According to Energy-Adjusted Total Folate Intake Quintiles in 1980 (cont.) 1140 incident cases during 1379614 preson- years TABLE II. Multivariable*-Adjusted Relative Risks of Developing Stroke According to the Categories of Dietary and Supplemental Folate Intake Type of Stroke Dietary Folate Intake Quintiles (Excluding Supplements) and Their Range (g/d) P for trend Cases 1 37194 2 195235 3 2362734 2743255 325 (Total stroke) RR11401.001.03 (0.851.25)1.08 (0.891.31)1.01 (0.821.24)1.06 (0.851.32)P =0.7 (Ischemic) RR6011.000.91 (0.701.18)1.03 (0.791.35)0.85 (0.631.13)0.93 (0.691.25)P =0.6 (Thrombotic) RR3231.001.17 (0.811.69)1.43 (1.002.06)0.96 (0.641.46)1.19 (0.781.81)P =0.8 (Embolic) RR1101.000.79 (0.421.49)1.00 (0.541.86)0.77 (0.391.52)0.71 (0.341.52)P =0.4 (Subarachnoid) RR1661.001.05 (0.641.72)1.26 (0.772.07)1.00 (0.581.72)0.82 (0.451.49)P =0.4 (Hemorrhagic) RR1141.001.98 (1.073.66)1.65 (0.853.18)1.49 (0.743.02)1.44 (0.692.99)P =0.8 Type of Stroke Supplement Folate Intake Categories CasesNonusers0.1149 g/d150249 g/d250399 g/d400 g/d (Total stroke) RR11401.001.17 (0.951.45)0.93 (0.721.21)1.02 (0.751.37)1.02 (0.821.27)P =0.9 (Ischemic) RR6011.001.30 (0.981.74)0.93 (0.651.33)1.08 (0.721.63)1.08 (0.801.48)P =0.8 (Thrombotic) RR3231.001.38 (0.961.99)0.75 (0.451.24)0.69 (0.371.30)1.01 (0.661.53)P =0.5 (Embolic) RR1101.001.23 (0.642.37)1.16 (0.562.43)1.36 (0.593.09)0.82 (0.381.76)P =0.8 (Subarachnoid) RR1661.001.59 (0.942.68)1.06 (0.562.01)1.37 (0.682.74)0.99 (0.561.76)P =1.0 (Hemorrhagic) RR1141.000.94 (0.412.15)2.53 (1.255.11)2.16 (0.865.41)1.30 (0.592.85)P =0.2 *Covariates are the same as in Table 1. DiscussionDiscussion In this prospective cohort study Total, dietary, and supplement folate intake were not associated with total stroke or its subtypes This finding is consistent when using different definition of folate intake during 5 years Inaccurate dietary assessment Good validity Folate associated with CHD Folate fortification cannot account Residual or unmeasured confounding Have no power Extreme value of folate intake in relation to risk of stroke Nonlinear relation between folate and stroke Fewer women intake very low folate Previous study Folate supplement lows homosysteine levels (Kang, et al; Diaz-Arrastia, et al.) Homocysteine levels and stroke Risk reduced 19% 24% when homocysteine were lower by 3mol/L (Wald, et al) High homocysteine RR=1.37 of ischemic stroke (Bautista, et al) However 4 cohort dont find the positive association (Stehouwer, et al; Fallon, et al; Verhoef, et al; Alfthan, et al) A randomized controlled trial failed to find the difference between high and low-dose homocysteine in recurrence of stroke through lowing homocysteine levels (Toole, et al) In NHANE I (Bazzano et al) Small and nonsignificant elevation the risk of stroke Folate serum level 9.2nmol compare with 9.2nmol The NHANE I (Bazzano et al) RR= 0.79 Baseline folate intake 24-hour recall questionnaire Age Gender Previous study (cont.) Conclusion Folate intake does not have an important relation to the risk