Scope of the talk. Riboflavin, other dairy B vitamins and cardiovascular health. Epidemiology of milk consumption and CVD

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1 Riboflavin, other dairy B vitamins and cardiovascular health Professor Hilary J Powers University of Sheffield United Kingdom Scope of the talk Importance of dairy products to B vitamin intakes Epidemiological evidence linking B vitamins with cardiovascular disease The mechanistic basis for such links Epidemiology of milk consumption and CVD Ischaemic heart disease or stroke cohort studies High degree of consistency Pooled OR for highest v lowest consumers IHD.7 (.7-.3) Stroke.3 (.77-.9) Elwood et al () Contribution of milk and milk products to B vitamin intake Vitamin Preschool children (-y) Children and young people (-y) Adults Older (-y) adults (5+y) Thiamin 9 (B ) Riboflavin (B ) Pyridoxine 5 5 (B ) Cobalamin 7 (B ) 7 Barker () Riboflavin intakes according to age Vitamin B intakes according to age.... riboflavin intake (mg/day).... -y 7-y -y 5-y vitamin B µg/day y 7-y -y 5-y

2 Pyridoxine intake according to age intake according to age pyridoxine intake mg/day y 7-y -y 5-y folate intake (µg/day) y 7-y -y 5-y A metabolic basis for a link between B vitamin and cardiovascular disease Elevated Plasma Total Homocysteine is a Risk Factor for CVD Meta-analysis of 7 studies: (Boushey et al (995) JAMA 7: 9-57 OR for CAD for 5µmol/l thcy was M.; F. Estimated % of CAD risk attributed to Hcy 5µmol/l increment in thcy increased CAD risk by as much as.5 mmol/l cholesterol Elevated Plasma Total Homocysteine is a Risk Factor for Cardiovascular Disease Prospective Studies: The Physician s Health Study Stampfer et al (99) JAMA &: 77 Tromso Study (Arneson et al (995) Int J Epidemiol : 7 BUPA Study (Perry et al (995) Irish J Med Sci : Top 5% for thcy had a RR for MI of 3. RR of. for µmol/l thcy RR of stroke =.5 for top quartile v bottom quartile of thcy Variable Dietary determinants of plasma homocysteine Vitamin B Vitamin B Riboflavin B Vitamin supplements Jacques et al Range (per day) P* (trend for regression coefficient) <9->37 µg <.* <3.5->7.57µg.* <.5->. mg <.* <.->.mg.3* Yes or No <.

3 Does increasing B vitamin intake lower homocysteine? homocysteine (µmol/l) intake and plasma total homocysteine 5mg Total folate or added folate (µg/day) Boushey et al (995) JAMA 7:9-57 Vitamin B lowers plasma thcy Food folate lowers plasma thcy Plasma thcy µmol/l pre post P. control treatment homocysteine µmol/l baseline P<. post intervention exclusion food folate supplement Ashfield-Watt et al Breakfast cereal increases B vitamin status.and lowers plasma homocysteine Variable Treatment group Control group. nmol/l Vitamin B pmol/l Vitamin B nmol/l.7 (.7) 3.* (.7) 9 () 35* (3) 5. (.9).3* (5.5).7 (.7). (.7) 93 () 9 () 5 9 (.). (.) Homocysteine µmol/l baseline P<. post intervention breakfast control Tucker et al 3

4 Riboflavin is an independent predictor of homocysteine 5, methylene THF 5 methyl THF MTHFR (FAD) Epidemiological evidence for a link between B vitamin intake and CVD Case control studies Friso et al OR.9 for B - Cattaneo et al OR. for B - Robinson et al 99 OR for folate.5,. for B Prospective cohort Rimm et al 99 RR for highest quintiles,.9 for folate,.7 for B. -Merchant et al 3 RR for highest quintile for folate.7 Low plasma vitamin B associated with increased CAD risk Intakes of folate and B associated with CHD risk Unadjusted Model Model Model 3 Quartiles of intake 3 5 P for trend OR (95% CI).7 (.-.3). (.5-.5) Model : adjusted for major risk factors Model : plus inflammatory markers Model 3: plus thcy, vitamin B, folate.73 (.-.7).9 (.- 3.3) RR Vitamin B RR Friso et al Rimm et al 99 Acute coronary events according to homocysteine and folate status B vitamin interventions and clinical outcomes Very few trials Usually patient groups and moderate to high B vitamin intakes (usually folate and B ) Vermeulen et al ; showed folate plus B lowered markers of atherosclerosis Doshi et al showed improved endothelial function in CAD patients, with high dose folate Voutilainen et al

5 Flow-Mediated Dilatation Following Methionine Loading Do B vitamins have homocysteineindependent effects on CVD? Usui et al (999) Clin Sci 9: 35 methionine + folic acid methionine P<. pre 3-H -H -H Time High dose folate and endothelial function Hcy independent effects of folate on endothelial function Participants Design Protocol Endpoint Result Doshi et al 5 CAD patients double-blind placebo-controlled crossover weeks of 5mg folic acid or placebo with weeks washout endothelial function (FMD) impaired FMD improved, and increased plasma folate but also reduction in thcy CAD patients 5-MeTHF infused at 5µg/min for 3 mins Endothelial function measured as FMD FMD improved over 3 mins, no reduction in plasma thcy acts directly on endothelial function, independent of homocysteine lowering effect Doshi et al Low vitamin B is associated with stroke independent of thcy Conclusions Milk makes a useful contribution to the dietary intake of B vitamins Milk intake declines with increasing age in young people, pyridoxine, riboflavin, and vitamin B all contribute to homocysteine metabolism Homocysteine-lowering may have vascular protective effects There may be homocysteine-independent protective effects of some B vitamins Kelly et al 3