In this large randomized trial by SEARCH group, no benefit of homocysteine lowering treatment was obsreved among MI survivors

1. www.pronutritionist.net
Effects of Homocysteine-Lowering
With Folic Acid Plus Vitamin B12
vs Placebo
on Mortality and Major Morbidity
in Myocardial Infarction Sur vivors
A Randomized Trial
SEARCH
Collaborative Group. JAMA.
2010;303(24):2486-2494
Page 1 SEARCH
Collaborative Group. JAMA. 2010;303(24):2486-2494

2. Page 2
Background (1/2)
• Intake of folic acid is low in many developed countries like
Finland. In USA flour and grain products are fortified with folic
acid since 1998
• Lack of dietary folic acid is associated neural tube defects of
offspring and increased cardiovascular risk
• Vitamin B12 is found only in foods from animal origin. Usual intake
of vitamin B12 is on adequate level in most developed countries
• Lack of vitamin B12 is not connected with increased
cardiovascular risk in most studies
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Collaborative Group. JAMA. 2010;303(24):2486-2494

3. Page 3
Background (2/2)
• Both folic acid and vitamin B12 decrease homocysteine levels
• High serum homocysteine levels are associated with increased
cardiovascular risk in cohort and cross sectional studies
• In a Norwegian randomized trial, lowering homocysteine with
folic acid, vitamin B12 and vitamin B6 did not bring any benefit for
CAD patients (Ebbing et al. 2008)
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Collaborative Group. JAMA. 2010;303(24):2486-2494

4. Methods
• n=12 064 MI survivors from UK (83 % males)
• Randomized controlled trial, 2x2 factorial
• Duration: 6.7 years
• Primary outcome: First major vascular event, defined as
major coronary event (coronary death, myocardial
infarction, or coronary revascularization), fatal or nonfatal
stroke, or noncoronary revascularization.
• Secondary outcome: cognitive function, cancers, blood
pressure, hearing loss, fractures
• Intervention: 2 mg folic acid plus 1 mg vitamin B daily vs
matching placebo.
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Collaborative Group. JAMA. 2010;303(24):2486-2494

5. Results, primary outcomes
• 11 945 patients completed study (drop out rate 1 %)
• Allocation to the study vitamins reduced homocysteine by
28 % (a mean of 3.8 µmol/L
• Risk of any major vascular event after folic acid and
vitamin B12 was 1.04 vs placebo
• No effect was seen in stroke, coronary events or
noncoronary revascularizations either
• Number of deaths were equal in both groups
• The results were consistent across all the sub-populations
analysed
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Collaborative Group. JAMA. 2010;303(24):2486-2494

6. Results, secondary outcomes
• No difference in blood pressure was seen
• No difference in cognitive function was seen
• Occurrence of dementia was similar in both groups
• Occurrence of non-traumatic fractures was similar in
both groups
• Occurrence of hearing loss was similar in both groups
• Occurrence of cancers were similar in both groups
21.12.146 SEARCH
Collaborative Group. JAMA. 2010;303(24):2486-2494

7. Discussion
• In this study no benefit at all was found with
homocysteine lowering treatment with folic acid and
vitamin B12
• Unlike in some previous studies, no deleterious effect on
incidence of cancers was observed
• There is no evidence that homocysteine lowering
treatments decrease cardiovascular morbidity or mortality
in randomized controlled trials
• Safety of high dose folic acid and vitamin B12 was good, no
detrimental effects on health were observed
• Adequate folic acid intake remains essential to prevent
neural tube defects
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Collaborative Group. JAMA. 2010;303(24):2486-2494