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c o s t + b l o o d + t e s t + q u i c k l y + r e v e a l s + i f + y o u + a r e + i n + a + d a n g e r + z o n e 8 % 2 c 9 % 0 d % 0 a m o s t + d o c t o r s + d o n % 2 7 t + t e s t + f o r + i t + a n d + c e r t a i n l y + d o n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 t + k n o w + h o w + e a s y + i t + i s + t o + t r e a t + h i g h + h o m o c y s t e i n e + w i t h + a + u n i q u e + f o r m + o f + f o l a t e + k n o w n + a s + 5 - m t h f % 0 d % 0 a d e v a s t a t i n g + i m p a c t + o f + h i g h + h o m o c y s t e i n e % 0 d % 0 a e l e v a t e d + h o m o c y s t e i n e + l e v e l s + % 2 8 h y p e r h o m o c y s t e i n e m i a % 2 9 + a r e + a n + i m p o r t a n t % 2 c + i n d e p e n d e n t + r i s k + f a c t o r + f o r + c a r d i o v a s c u l a r + d i s e a s e s + i n c l u d i n g + a t h e r o s c l e r o s i s + a n d + i t s + c o n s e q u e n c e s % 2 c + h e a r t + a t t a c k % 2 c + s t r o k e % 2 c 1 0 % 2 c 1 1 + a n d + p e r i p h e r a l + v a s c u l a r + d i s e a s e 5 % 2 c 1 2 % 2 c 1 3 % 0 d % 0 a h o m o c y s t e i n e + i s + a n + a m i n o + a c i d + t h a t % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + v e r y + s i m i l a r + t o + t h e + a m i n o + a c i d s + u s e d + b y + t h e + b o d y + t o + m a k e + p r o t e i n s 1 4 + b u t % 2 c + u n l i k e + t h e s e + b e n e f i c i a l + a m i n o + a c i d s % 2 c + h o m o c y s t e i n e + h a s + t o x i c + p r o p e r t i e s + t h a t + c o n t r i b u t e + t o + p o o r + h e a l t h 1 5 % 2 c 1 6 + h i g h + l e v e l s + o f + h o m o c y s t e i n e + h a v e + b e e n + a s s o c i a t e d + w i t h + n u m e r o u s + d e g e n e r a t i v e + d i s e a s e s 1 4 % 0 d % 0 a a c c o r d i n g + t o + o n e + s t u d y % 2 c + 4 2 % 2 5 + o f + p a t i e n t s + w i t h + c e r e b r o v a s c u l a r + d i s e a s e + % 2 8 s t r o k e + o r + n e a r + s t r o k e % 2 9 + h a d + h y p e r h o m o c y s t e i n e m i a % 2 c + 2 8 % 2 5 + o f + t h o s e + w i t h + p e r i p h e r a l + v a s c u l a r + d i s e a s e + % 2 8 o b s t r u c t i o n + o f + b l o o d + v e s s e l s % 2 c + e s p e c i a l l y + i n + t h e + l e g s % 2 9 + h a d + e l e v a t e d + l e v e l s % 2 c + a n d + 3 0 % 2 5 + o f + t h o s e + w i t h + c o r o n a r y + a r t e r y + d i s e a s e + % 2 8 o b s t r u c t i o n + o f + t h e + h e a r t % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + o w n + b l o o d + s u p p l y % 2 c + t h e + c o r o n a r y + a r t e r i e s % 2 9 + h a d + e l e v a t e d + h o m o c y s t e i n e + l e v e l s 1 7 % 0 d % 0 a i n + a + r e c e n t + s t u d y + o f + p a t i e n t s + w h o + h a d + s u r v i v e d + a + h e a r t + a t t a c k % 2 c + r e s e a r c h e r s + d i v i d e d + o v e r + 8 0 0 + s u b j e c t s + i n t o + t w o + g r o u p s - t h o s e + w i t h + h i g h + p l a s m a + h o m o c y s t e i n e + % 2 8 d e f i n e d + a s + g r e a t e r + t h a n + 1 5 + m i c r o m o l % 2 f l + i n + t h e + s t u d y % 2 9 + a n d + t h o s e + w i t h + l o w e r + l e v e l s 5 % 0 d % 0 a a f t e r + j u s t + 3 0 + d a y s % 2 c + r e s e a r c h e r s + f o u n d + t h e + r a t e s + o f + c o m p l i c a t i o n s + s u c h + a s + h e a r t + f a i l u r e % 2 c + h e a r t + r u p t u r e % 2 c + d e a t h % 2 c + a n d + t o t a l + a d v e r s e + c a r d i o v a s c u l a r + e v e n t s + w e r e + s i g n i f i c a n t l y + h i g h e r + i n + t h e + e l e v a t e d + h o m o c y s t e i n e + g r o u p + c o m p a r e d + w i t h + t h o s e + i n + t h e + g r o u p + w i t h + l o w e r + l e v e l s + a g a i n % 2 c + t h e + h i g h e r + t h e + h o m o c y s t e i n e + l e v e l % 2 c + t h e + g r e a t e r + t h e + i n c i d e n c e + o f + a d v e r s e + c a r d i o v a s c u l a r + e v e n t s % 0 d % 0 a w h y + h o m o c y s t e i n e + i s + s o + d a n g e r o u s % 0 d % 0 a s c i e n t i s t s + a r e + s t i l l + i n v e s t i g a t i n g + t h e + e x a c t + m e c h a n i s m + a s + t o + w h y + h o m o c y s t e i n e + c o n t r i b u t e s + t o + t h e s e + g r a v e + h e a l t h + r i s k s % 2 c + b u t + s e v e r a l + c o n v i n c i n g + m e c h a n i s m s + a r e + e m e r g i n g + t h e + m o s t + p r o m i n e n t + o n e s + i n v o l v e + h o m o c y s t e i n e % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + a b i l i t y + t o + e l e v a t e + o x i d a n t + s t r e s s % 2 c + a l t e r + l i p i d + % 2 8 f a t % 2 9 + m e t a b o l i s m % 2 c + a n d + p r o m o t e + e x c e s s i v e + b l o o d + c l o t t i n g 1 8 % 0 d % 0 a r e c e n t l y % 2 c + l i n k s + h a v e + b e e n + e s t a b l i s h e d + b e t w e e n + h o m o c y s t e i n e + a n d + v i t a l + s i g n a l i n g + i n f o r m a t i o n + u s e d + b y + a r t e r i e s + t o + c o n t r o l + b l o o d + p r e s s u r e 1 9 - 2 1 + t h e r e % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + a l s o + e v i d e n c e + t h a t + h o m o c y s t e i n e + h a s + d a m a g i n g + e f f e c t s + o n + t h e + h d l - a s s o c i a t e d + e n z y m e + p a r a o x o n a s e 1 % 2 c + o r + p o n 1 % 2 c + w h i c h + i s + r e q u i r e d + t o + p r o t e c t + l d l + f r o m + o x i d a t i o n 1 8 % 2 c 2 2 - 2 4 % 0 d % 0 a i t + i s + n o w + c l e a r + t h a t + r i s i n g + h o m o c y s t e i n e + l e v e l s + a r e + s i g n i f i c a n t l y + a s s o c i a t e d + w i t h + t h r e a t s + t o + t h e + c a r d i o v a s c u l a r + s y s t e m % 2 c + p a r t i c u l a r l y + t o + t h e + a g i n g + a d u l t + m a i n s t r e a m + m e d i c i n e + o f t e n + i g n o r e s + t h i s + i n f o r m a t i o n % 2 c 2 5 - 2 7 + a n d + f r e q u e n t l y + o f f e r s + l i t t l e + o r + n o + h e l p + t o + l o w e r + d e a d l y + h o m o c y s t e i n e + l e v e l s + i n + p a t i e n t s % 0 d % 0 a w h a t + y o u + n e e d + t o + k n o w % 3 a + l o w e r + h o m o c y s t e i n e + w i t h + h i g h - p o t e n c y + f o l a t e % 0 d % 0 a % 0 9 % 0 9 a + h i g h + l e v e l + o f + t h e + a m i n o + a c i d + h o m o c y s t e i n e + i s + a + s t r o n g + p r e d i c t o r + o f + c a r d i o v a s c u l a r + d i s e a s e s + s u c h + a s + h e a r t + a t t a c k + a n d + s t r o k e % 2 c + t h e + l e a d i n g + k i l l e r s + o f + a m e r i c a n s % 0 d % 0 a % 0 9 % 0 d % 0 a % 0 9 % 0 9 f o l i c + a c i d + s u p p l e m e n t a t i o n + i s + r e c o m m e n d e d + a s + p a r t + o f + a + b - v i t a m i n + p a c k a g e + a i m e d + a t + r e d u c i n g + h o m o c y s t e i n e + l e v e l s % 0 d % 0 a % 0 9 % 0 d % 0 a % 0 9 % 0 9 b u t + m a n y + p e o p l e + f i n d + t h e i r + h o m o c y s t e i n e + l e v e l s + s t u b b o r n l y + r e s i s t + e v e n + h i g h + d o s e s + o f + f o l i c + a c i d % 0 d % 0 a % 0 9 % 0 d % 0 a % 0 9 % 0 9 s u c h + p e o p l e + m a y + c a r r y + a + g e n e + v a r i a n t + t h a t + w e a k e n s + t h e i r + a b i l i t y + t o + g e n e r a t e + t h e + a c t i v e + f o r m + o f + f o l a t e % 2 c + c a l l e d + 5 - m t h f % 2 c + r e s u l t i n g + i n + e l e v a t e d + h o m o c y s t e i n e + l e v e l s % 0 d % 0 a % 0 9 % 0 d % 0 a % 0 9 % 0 9 s u p p l e m e n t i n g + d i r e c t l y + w i t h + 5 - m t h f + e v a d e s + t h e + d e c r e a s e + i n + e n z y m e + a c t i v i t y + b e c a u s e + i t + r e q u i r e s + n o + f u r t h e r + m e t a b o l i s m + t o + a c h i e v e + h o m o c y s t e i n e - l o w e r i n g + e f f e c t s % 0 d % 0 a % 0 9 % 0 d % 0 a % 0 9 % 0 9 g e t + y o u r + h o m o c y s t e i n e + l e v e l s + c h e c k e d + a t + l e a s t + a n n u a l l y % 3 b + i f + y o u r + l e v e l s + r e s i s t + t h e r a p y + w i t h + s t a n d a r d + f o l i c + a c i d % 2 c + y o u + s h o u l d + s w i t c h + t o + t h e + a c t i v e % 2 c + 5 - m t h f + f o r m % 0 d % 0 a 5 - m t h f % 3 a + t h e + b e s t + f o r m + o f + f o l a t e + s u p p l e m e n t a t i o n % 0 d % 0 a i n + t h e + b o d y % 2 c + t h e + f o l a t e + m o l e c u l e + g o e s + t h r o u g h + s e v e r a l + e n z y m a t i c + s t e p s + t o + b e c o m e + t h e + a c t i v e + m o l e c u l e + 5 - m t h f 2 8 - 3 0 + i t + i s + t h e + a c t i v e + 5 - m t h f + f o r m + o f + f o l a t e + t h a t + p a r t i c i p a t e s + i n + t h e + h o m o c y s t e i n e - l o w e r i n g + s t e p + t h a t + r e s u l t s + i n + t h e + p r o d u c t i o n + o f + t h e + s a f e + a m i n o + a c i d % 2 c + m e t h i o n i n e 2 8 % 2 c 3 0 % 0 d % 0 a i t + m a k e s + s e n s e % 2 c + t h e n % 2 c + t h a t + l o w + l e v e l s + o f + f o l a t e + a r e + p r e d i c t i v e + o f + e l e v a t e d + h o m o c y s t e i n e + l e v e l s 3 1 % 0 d % 0 a i n + t h e o r y % 2 c + s u p p l e m e n t i n g + w i t h + f o l i c + a c i d - t h e + m o s t + c o m m o n + f o r m + o f + f o l a t e + i n + s u p p l e m e n t + f o r m - s h o u l d + p r o v i d e + t h e + b o d y + w i t h + t h e + f o l a t e + i t + n e e d s + t o + c o n v e r t + d a n g e r o u s + h o m o c y s t e i n e + i n t o + s a f e + m e t h i o n i n e + u n f o r t u n a t e l y % 2 c + t h i s + r e a d i l y + a v a i l a b l e + h o m o c y s t e i n e - l o w e r i n g + r e g i m e n + d o e s n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 t + w o r k + f o r + e v e r y o n e % 0 d % 0 a t h a t % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + b e c a u s e + i n + o r d e r + t o + m a k e + t h e + c o n v e r s i o n + f r o m + f o l a t e + t o + t h e + a c t i v e + 5 - m t h f % 2 c + a n + e n z y m e + c a l l e d + m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + o r + m t h f r + i s + n e c e s s a r y - a n d + n o t + e v e r y o n e + c a r r i e s + t h e + s a m e + v e r s i o n + o f + t h i s + i m p o r t a n t + e n z y m e + i t + i s + e s t i m a t e d + t h a t + b e t w e e n + 5 + a n d + 1 0 % 2 5 + o f + t h e + p o p u l a t i o n + h a s + a + g e n e + v a r i a n t + t h a t + r e d u c e s + m t h f r + a c t i v i t y + b y + 7 0 % 2 5 % 2 c 3 2 + w h i l e + n e a r l y + 5 0 % 2 5 + o f + p e o p l e + o f + e u r o p e a n + d e s c e n t + h a v e + a + g e n e t i c + v a r i a t i o n + t h a t + d e c r e a s e s + m t h f r + a c t i v i t y + b y + a s + m u c h + a s + 3 5 % 2 5 2 8 % 2 c 2 9 % 2 c 3 3 - 3 6 % 0 d % 0 a i f + y o u + f a l l + i n t o + t h e s e + c a t e g o r i e s % 2 c + y o u + a r e + l i k e l y + t o + b e + a + v i c t i m + o f + p e r s i s t e n t l y + h i g h + h o m o c y s t e i n e + l e v e l s - e v e n + i f + y o u + a r e + t a k i n g + h i g h + d o s e s + o f + f o l i c + a c i d 3 7 % 0 d % 0 a t h e + s o l u t i o n + i s + s i m p l e % 3 a + i n s t e a d + o f + r e l y i n g + o n l y + o n + t h e + f o l i c + a c i d + i n + y o u r + m u l t i n u t r i e n t + f o r m u l a % 2 c + s u p p l e m e n t + w i t h + 5 - m t h f + b y + d o i n g + t h i s % 2 c + y o u % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 l l + b y p a s s + t h e + e n z y m e + d e f e c t + a n d + p r o v i d e + y o u r + b o d y + w i t h + e x a c t l y + t h e + r i g h t + m o l e c u l e + i t + n e e d s + t o + b e g i n + l o w e r i n g + t h o s e + d a n g e r o u s + h o m o c y s t e i n e + l e v e l s 3 8 % 0 d % 0 a a + w e a l t h + o f + l a b o r a t o r y + a n d + h u m a n + s t u d i e s + d e m o n s t r a t e + t h a t + 5 - m t h f + i s + t h e + b e s t + f o r m + o f + f o l a t e + r e q u i r e d + f o r + l o w e r i n g + d a n g e r o u s + h o m o c y s t e i n e + l e v e l s % 0 d % 0 a 5 - m t h f % 3 a + m o r e + e f f e c t i v e + t h a n + f o l i c + a c i d % 0 d % 0 a n u m e r o u s + a n i m a l + a n d + h u m a n + s t u d i e s + h a v e + p r o v e n + t h a t + 5 - m t h f + i s + m o r e + e f f e c t i v e + t h a n + f o l i c + a c i d + a t + i n c r e a s i n g + s e r u m + a c t i v e + f o l a t e + l e v e l s % 0 d % 0 a i n + a + c o m p e l l i n g + a n i m a l + s t u d y % 2 c + m i c e + w e r e + b r e d + t o + h a v e + t w o + c o p i e s + o f + t h e + d e f e c t i v e + g e n e + f o r + m t h f r % 2 c + t h e + e n z y m e + i n v o l v e d + i n + m a k i n g + 5 - m t h f % 2 c + w h i c h + i n + t u r n % 2 c + c o n v e r t s + h o m o c y s t e i n e + i n t o + m e t h i o n i n e 3 9 + t h e + a n i m a l s + h a d + m a r k e d l y + e l e v a t e d + h o m o c y s t e i n e + l e v e l s + a s + a + r e s u l t % 2 c + a n d + a l m o s t + a l l + d i e d + i n + i n f a n c y + f r o m + h o m o c y s t e i n e + t o x i c i t y % 0 d % 0 a h o w e v e r % 2 c + w h e n + t h e i r + m o t h e r s + % 2 8 w h o + s u r v i v e d + b e c a u s e + t h e y + c a r r i e d + o n e + n o r m a l + a n d + o n e + a b n o r m a l + g e n e % 2 9 + w e r e + f e d + 5 - m t h f + d u r i n g + p r e g n a n c y % 2 c + 6 4 % 2 5 + o f + t h e + o f f s p r i n g + s u r v i v e d % 2 c + c o m p a r e d + w i t h + t h e + 9 5 % 2 5 + m o r t a l i t y + r a t e + s e e n + i n + p u p s + o f + m o t h e r s + s u p p l e m e n t e d + w i t h + f o l i c + a c i d + e n c o u r a g i n g l y % 2 c + t h e + p u p s + f r o m + m o t h e r s + s u p p l e m e n t e d + w i t h + 5 - m t h f + a l s o + s h o w e d + i m p r o v e d + a p p e a r a n c e + o f + s t r u c t u r e s + i n + t h e i r + b r a i n s + t h a t + w e r e + p r e v i o u s l y + a f f e c t e d + b y + f o l a t e + d e f i c i e n c y % 0 d % 0 a h u m a n + s t u d i e s + v a l i d a t e + t h e + s u p e r i o r i t y + o f + 5 - m t h f + o v e r + f o l i c + a c i d % 0 d % 0 a o n e + c r o s s o v e r + s t u d y + e v a l u a t e d + c a r d i o v a s c u l a r + p a t i e n t s + k n o w n + t o + h a v e + t w o + c o p i e s + o f + t h e + g e n e + f o r + t h e + w e a k e n e d + m t h f r + e n z y m e 3 8 + s u b j e c t s + r e c e i v e d + a + s i n g l e + 5 + m g + o r a l + d o s e + o f + e i t h e r + f o l i c + a c i d + o r + 5 - m t h f % 2 c + a n d + t h e n + a f t e r + a + w a s h o u t + p e r i o d % 2 c + e a c h + p a t i e n t + r e c e i v e d + t h e + o p p o s i t e + s u p p l e m e n t + f r o m + w h a t + t h e y + o r i g i n a l l y + r e c e i v e d + r e s e a r c h e r s + f o u n d + t h a t + t h e + s u b j e c t s % 2 7 + p e a k + s e r u m + f o l a t e + l e v e l s + w e r e + n e a r l y + 7 + t i m e s + h i g h e r + w h e n + t a k i n g + t h e + a c t i v e + 5 - m t h f + a s + t h e y + w e r e + w h e n + t h e y + t o o k + t h e + f o l i c + a c i d + s u p p l e m e n t % 2 c + d e m o n s t r a t i n g + s u p e r i o r + b i o a v a i l a b i l i t y + o f + t h e + 5 - m t h f + f o r m % 0 d % 0 a a n o t h e r + c r o s s o v e r + s t u d y + i n v o l v e d + a + g r o u p + o f + h e a l t h y + w o m e n % 2 c + o n e - t h i r d + o f + w h o m + h a d + t h e + t y p i c a l + g e n e + v a r i a n t + f o r + m t h f r % 2 c + a n d + t w o - t h i r d s + o f + w h o m + h a d + t h e + w e a k e r + g e n e + v a r i a n t 3 5 + e a c h + w o m a n + r e c e i v e d + e i t h e r + 4 0 0 + m c g + o f + f o l i c + a c i d + o r + 4 1 6 + m c g + o f + 5 - m t h f + % 2 8 t h e + s l i g h t l y + h i g h e r + d o s e + i n + m i c r o g r a m s + r e f l e c t s + c h e m i c a l + d i f f e r e n c e s + b e t w e e n + f o l i c + a c i d + a n d + 5 - m t h f % 3 b + i t + r e p r e s e n t s + t h e + s a m e + d o s e + o f + f o l a t e + a t + t h e + c e l l u l a r + l e v e l % 2 9 + a f t e r + t h e + f i r s t + p h a s e + o f + t h e + s t u d y % 2 c + t h e + d o s i n g + r e g i m e n + w a s + r e v e r s e d % 2 c + a n d + e a c h + w o m a n + r e c e i v e d + t h e + o p p o s i t e + s u p p l e m e n t + f r o m + t h e + f i r s t % 0 d % 0 a r e g a r d l e s s + o f + t h e + w o m e n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + g e n e t i c + m a k e u p % 2 c + t h e + t o t a l + a m o u n t + o f + f o l a t e + i n + b l o o d % 2 c + a s + w e l l + a s + t h e + m a x i m u m + c o n c e n t r a t i o n + r e a c h e d % 2 c + w e r e + s i g n i f i c a n t l y + h i g h e r + w h e n + t h e + w o m e n + w e r e + t a k i n g + 5 - m t h f + c o m p a r e d + t o + w h e n + t h e y + w e r e + t a k i n g + f o l i c + a c i d 3 5 % 0 d % 0 a 5 - m t h f + l o w e r s + h o m o c y s t e i n e + l e v e l s % 0 d % 0 a t h e + s u p e r i o r i t y + o f + 5 - m t h f + f o r + i n c r e a s i n g + b l o o d + l e v e l s + o f + f o l a t e + d i r e c t l y + t r a n s l a t e s + t o + l o w e r + h o m o c y s t e i n e + l e v e l s % 0 d % 0 a t h i s + w a s + f i r s t + s h o w n + i n + a + s t u d y + o f + h e a l t h y + p e o p l e 4 0 + f o r + t h e + s t u d y % 2 c + a + l o w + d o s e + o f + 5 - m t h f + % 2 8 1 1 3 + m c g + p e r + d a y % 2 9 + w a s + c o m p a r e d + w i t h + a + l o w + d o s e + o f + f o l i c + a c i d + % 2 8 1 0 0 + m c g + p e r + d a y % 2 9 + a f t e r + s i x + m o n t h s % 2 c + t h e + m e a n + t o t a l + h o m o c y s t e i n e + w a s + r e d u c e d + b y + 1 4 6 % 2 5 + i n + t h e + 5 - m t h f + g r o u p % 2 c + c o m p a r e d + w i t h + o n l y + 9 3 % 2 5 + i n + t h e + f o l i c + a c i d + g r o u p % 0 d % 0 a f u r t h e r + s u p p o r t + f o r + t h e + s u p e r i o r i t y + o f + 5 - m t h f + a s + a + h o m o c y s t e i n e - l o w e r i n g + s u p p l e m e n t + c o m e s + f r o m + a + s t u d y + o f + p a t i e n t s + w i t h + k i d n e y + d i s e a s e + o n + d i a l y s i s 4 + t h i s + g r o u p + o f + p e o p l e + i s + a t + v e r y + h i g h + r i s k + f o r + e l e v a t e d + h o m o c y s t e i n e + l e v e l s % 2 c 4 1 % 2 c 4 2 + a s + w e l l + a s + h i g h + r a t e s + o f + c o m p l i c a t i o n s + a n d + c a r d i o v a s c u l a r + d i s e a s e + t h a t + o c c u r + a s + a + r e s u l t + i n + f a c t % 2 c + 9 3 % 2 5 + o f + t h i s + g r o u p + o f + p e o p l e + h a d + h o m o c y s t e i n e + l e v e l s + a b o v e + t h e + u p p e r + l i m i t + o f + n o r m a l % 2 c + w h i c h + i s + c o n s i d e r e d + i n + t h i s + s t u d y + t o + b e + 1 2 + m i c r o m o l % 2 f l % 0 d % 0 a s u b j e c t s + w e r e + d i v i d e d + i n t o + t w o + t r e a t m e n t + g r o u p s % 3 a + t h e + f i r s t + o n e + r e c e i v e d + 5 0 + m g + o f + i n t r a v e n o u s + 5 - m t h f + a t + t h e + e n d + o f + e a c h + d i a l y s i s + s e c t i o n + a n d + t h e + s e c o n d + r e c e i v e d + 5 + m g + p e r + d a y + o f + f o l i c + a c i d % 2 c + o r a l l y + b o t h + g r o u p s + r e c e i v e d + t h e + s a m e + i n t r a v e n o u s + d o s e + o f + v i t a m i n s + b 6 + a n d + b 1 2 + a f t e r + s i x + m o n t h s % 2 c + h o m o c y s t e i n e + l e v e l s + w e r e + r e d u c e d + t o + a n + a v e r a g e + o f + 2 0 7 + m i c r o m o l % 2 f l + i n + t h e + 5 - m t h f + g r o u p % 2 c + c o m p a r e d + w i t h + s t u b b o r n l y + h i g h + l e v e l s + o f + 3 5 0 + m i c r o m o l % 2 f l + i n + t h e + f o l i c + a c i d + g r o u p 4 + a l o n g + w i t h + t h e + g r e a t e r + h o m o c y s t e i n e + r e d u c t i o n % 2 c + a f t e r + 2 4 + m o n t h s % 2 c + t h o s e + i n + t h e + 5 - m t h f + g r o u p + a l s o + h a d + s i g n i f i c a n t l y + l o w e r + l e v e l s + o f + t h e + i n f l a m m a t o r y + m a r k e r + c - r e a c t i v e + p r o t e i n % 2 c + o r + c r p % 0 d % 0 a m o s t + i m p o r t a n t l y % 2 c + h o w e v e r % 2 c + w a s + t h e + i m p a c t + 5 - m t h f + h a d + o n + s u r v i v a l + s u b j e c t s + i n + t h e + 5 - m t h f + g r o u p + s u r v i v e d + o n + a v e r a g e + 3 6 2 + m o n t h s + a f t e r + b e g i n n i n g + t r e a t m e n t % 2 c + w h i l e + t h o s e + i n + t h e + f o l i c + a c i d + g r o u p + s u r v i v e d + a n + a v e r a g e + o f + o n l y + 2 6 1 + m o n t h s - t h a t % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + a + 3 9 % 2 5 + i n c r e a s e + i n + s u r v i v a l + i n + t h e + 5 - m t h f + g r o u p % 2 1 4 + i n t e r e s t i n g l y % 2 c + t h e + d o c t o r s + w h o + c o n d u c t e d + t h i s + s t u d y + a t t r i b u t e d + t h e + i m p r o v e d + s u r v i v a l + o n + t h e + r e d u c t i o n + i n + c r p + o b s e r v e d + i n + t h e + 5 - m t h f + g r o u p % 0 d % 0 a 5 - m t h f + a n d + d e p r e s s i o n % 0 d % 0 a 5 - m t h f + i s + c l e a r l y + a + s u p e r i o r + w a y + t o + a c h i e v e + o p t i m a l + b l o o d + l e v e l s + o f + a c t i v e + f o l a t e % 2 c + a s + w e l l + a s + t h e + b e s t + m e a n s + k n o w n + f o r + l o w e r i n g + d a n g e r o u s + h o m o c y s t e i n e + l e v e l s + b u t + i t + h a s + o t h e r + b e n e f i t s + a s + w e l l + b e c a u s e + f o l a t e + i s + r e q u i r e d + i n + p r o c e s s e s + t h a t + p r o d u c e + t h e + b r a i n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + n e u r o t r a n s m i t t e r s % 2 c 4 3 + 5 - m t h f + h a s + a l s o + a t t r a c t e d + t h e + i n t e r e s t + o f + r e s e a r c h e r s + t h a t + i n v e s t i g a t e + m a j o r + d e p r e s s i o n % 2 c + a + c o n d i t i o n + t h a t + r e f l e c t s + i m b a l a n c e s + i n + n e u r o t r a n s m i t t e r + q u a n t i t y + o r + e f f e c t 4 4 % 0 d % 0 a m a j o r + d e p r e s s i o n + i s + a + d e b i l i t a t i n g + i l l n e s s + t h a t + i s + v e r y + d i f f i c u l t + t o + t r e a t % 3 a + o n l y + a b o u t + 3 0 % 2 5 + o f + p a t i e n t s + t r e a t e d + w i t h + a + s i n g l e + a n t i d e p r e s s a n t + d r u g + a c h i e v e + r e m i s s i o n + o f + t h e i r + s y m p t o m s % 2 c + a + f i g u r e + t h a t + o n l y + r i s e s + t o + 5 0 + t o + 5 5 % 2 5 + w h e n + a + s e c o n d + d r u g + i s + a d d e d 4 5 % 2 c 4 6 + a s + a + r e s u l t % 2 c + t h e r e + h a s + b e e n + a + m a j o r + p u s h + t o + f i n d + n o n - p h a r m a c o l o g i c a l + t h e r a p i e s + t h a t + c o u l d + i m p r o v e + r e s p o n s e + r a t e s + o n c e + r e s e a r c h e r s + d i s c o v e r e d + t h a t + p e o p l e + w i t h + l o w + s e r u m + a n d + r e d + b l o o d + c e l l + l e v e l s + o f + f o l a t e + h a v e + p o o r e r + r e s p o n s e s + t o + a n t i d e p r e s s a n t + t h e r a p y % 2 c + t h e y + d e c i d e d + t o + s e e + i f + a d d i n g + 5 - m t h f + t o + a n t i d e p r e s s a n t + d r u g s + c o u l d + i m p r o v e + r e s p o n s e + r a t e s 4 5 + t h e + r e s u l t s + h a v e + b e e n + d r a m a t i c % 0 d % 0 a i n + o n e + s t u d y % 2 c + 1 9 % 2 5 + o f + p a t i e n t s + t a k i n g + 5 - m t h f + p l u s + a + r e g u l a r + a n t i d e p r e s s a n t + d r u g + e x p e r i e n c e d + m a j o r + i m p r o v e m e n t + o n + a + s t a n d a r d + d e p r e s s i o n + s c o r e % 2 c + c o m p a r e d + w i t h + j u s t + 7 % 2 5 + o f + t h o s e + w h o + o n l y + t o o k + a n + a n t i d e p r e s s a n t + d r u g 4 7 + t h a t + r e s p o n s e + r a t e + w a s + e v e n + h i g h e r + a m o n g + p a t i e n t s + w i t h + t h e + w o r s t + d e g r e e + o f + i m p a i r m e n t + f r o m + d e p r e s s i o n % 2 c + w i t h + 4 0 % 2 5 + o f + t h o s e + t a k i n g + 5 - m t h f + i n + a d d i t i o n + t o + t h e i r + r e g u l a r + a n t i d e p r e s s a n t s + e x p e r i e n c i n g + m a j o r + i m p r o v e m e n t + v e r s u s + j u s t + 1 6 % 2 5 + o f + t h o s e + t a k i n g + a n t i d e p r e s s a n t s + o n l y % 0 d % 0 a i n + a d d i t i o n % 2 c + t h e + 5 - m t h f + g r o u p + e x p e r i e n c e d + t h e s e + i m p r o v e m e n t s + s i g n i f i c a n t l y + f a s t e r + t h a n + t h e + c o n t r o l + g r o u p - i n + 1 7 7 + d a y s + v e r s u s + 2 3 1 + d a y s + o n c e + a g a i n % 2 c + t h o s e + w i t h + t h e + m o s t + s e v e r e + d e p r e s s i o n + e x p e r i e n c e d + t h e + m o s t + d r a m a t i c + r e s u l t s % 2 c + w i t h + t h e + m e d i a n + t i m e + t o + i m p r o v e m e n t + i n + t h e + 5 - m t h f + g r o u p + b e i n g + 8 5 + d a y s % 2 c + c o m p a r e d + w i t h + 1 5 0 + d a y s + i n + c o n t r o l + s u b j e c t s + i m p r e s s i v e l y % 2 c + n e a r l y + t w i c e + a s + m a n y + p e o p l e + i n + t h e + a n t i d e p r e s s a n t - o n l y + g r o u p + s t o p p e d + t h e r a p y + b e c a u s e + o f + a d v e r s e + e v e n t s + % 2 8 3 4 % 2 5 % 2 9 + v e r s u s + t h e + 5 - m t h f + g r o u p + % 2 8 1 7 9 % 2 5 % 2 9 % 2 c + a + t e s t a m e n t + t o + t h e + s u p p l e m e n t % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + s a f e t y % 0 d % 0 a n u m e r o u s + o t h e r + s t u d i e s + h a v e + a c h i e v e d + s i m i l a r + r e s u l t s + w h e n + 5 - m t h f + i s + a d d e d + t o + a + s t a n d a r d + a n t i d e p r e s s a n t + d r u g % 3 b + d o s e s + u s e d + a r e + t y p i c a l l y + 1 5 + m g + d a y 4 8 - 5 0 + a n + a b n o r m a l + g e n e + v a r i a n t + f o r + 5 - m t h f + s y n t h e s i s + a n d + m e t a b o l i s m + m a y + p r e d i c t + r e s i s t a n c e + t o + a n t i d e p r e s s a n t + t h e r a p y + a n d + h e l p + i d e n t i f y + p a t i e n t s + w h o + m a y + b e + r e s p o n s i v e + t o + a d j u n c t i v e + t h e r a p y + w i t h + 5 - m t h f 5 1 % 0 d % 0 a 5 - m t h f + a n d + d i a b e t i c + p e r i p h e r a l + n e u r o p a t h y % 0 d % 0 a d i a b e t i c + p e r i p h e r a l + n e u r o p a t h y + i s + a n o t h e r + c o n d i t i o n + t h a t + r e f l e c t s + i m b a l a n c e s + i n + n e u r o t r a n s m i t t e r + q u a n t i t y + o r + e f f e c t % 2 c 5 2 + l e a d i n g + r e s e a r c h e r s + t o + i n v e s t i g a t e + 5 - m t h f + a s + a + p o t e n t i a l + t r e a t m e n t + d i a b e t i c + p e r i p h e r a l + n e u r o p a t h y + i s + a + p a i n f u l + c o n d i t i o n + t h a t + c a u s e s + s l o w i n g + a n d + a b n o r m a l + t r a n s m i s s i o n + o f + n e r v e + i m p u l s e s % 2 c 5 3 + w h i c h + r e s u l t s + i n + b o t h + p a i n + a n d + l o s s + o f + s e n s i t i v i t y + t o + n o r m a l + t o u c h 5 4 % 0 d % 0 a t h e + c o m b i n a t i o n + o f + 5 - m t h f + w i t h + v i t a m i n + b 1 2 + % 2 8 m e t h y l c o b a l a m i n % 2 9 + a n d + a n + a c t i v e + f o r m + o f + v i t a m i n + b 6 + % 2 8 p y r i d o x a l - 5 % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 - p h o s p h a t e % 2 9 + h a s + b e e n + u s e d + t o + t r e a t + e n d o t h e l i a l + d y s f u n c t i o n % 2 c + a n d + i s + n o w + u n d e r + a c t i v e + e x p l o r a t i o n + f o r + u s e + i n + d i a b e t i c + n e u r o p a t h y % 0 d % 0 a a n + a n i m a l + s t u d y + s h o w e d + t h a t + t h i s + c o m b i n a t i o n % 2 c + a t + a + h u m a n + e q u i v a l e n t + d o s e % 2 c + i n c r e a s e d + t h e + d e n s i t y + o f + n e r v e + f i b e r s + i n + t h e + s k i n + a n d + i m p r o v e d + n e r v e + s e n s o r y + c o n d u c t i o n + a n d + r e s p o n s e s + t o + t e m p e r a t u r e + a n d + m e c h a n i c a l + t o u c h 5 5 + t h e s e + i m p r o v e m e n t s + o c c u r r e d + i n + t h e + a b s e n c e + o f + c h a n g e s + i n + b l o o d + s u g a r % 0 d % 0 a s t u d i e s + h a v e + s h o w n + t h a t + w h e n + h u m a n s + w i t h + d i a b e t i c + p e r i p h e r a l + n e u r o p a t h y + a r e + t r e a t e d + w i t h + t h i s + s u p p l e m e n t + c o m b i n a t i o n % 2 c + t h e y + e x p e r i e n c e + i m p r o v e m e n t s + o f + s k i n + s e n s i t i v i t y + t o + t o u c h + a n d + r e d u c t i o n + i n + p a i n f u l + s y m p t o m s 5 6 % 2 c 5 7 + o n e + s u c h + t r i a l + a l s o + s h o w e d + i m p r o v e m e n t s + i n + t h e + d e n s i t y + o f + n e r v e + f i b e r s + i n + t h e + s k i n % 2 c 5 7 + a n d + a + d i f f e r e n t + t r i a l + a l s o + n o t e d + a + s i g n i f i c a n t + d e c r e a s e + i n + h o m o c y s t e i n e + l e v e l s + c o m p a r e d + w i t h + a + s m a l l + i n c r e a s e + i n + p l a c e b o + r e c i p i e n t s 5 6 % 0 d % 0 a t e s t i n g + f o r + h o m o c y s t e i n e % 0 d % 0 a y o u r + h o m o c y s t e i n e + l e v e l s + c a n + b e + d e t e r m i n e d + b y + a + s i m p l e + b l o o d + t e s t + k n o w i n g + y o u r + h o m o c y s t e i n e + s t a t u s + w i l l + a l l o w + y o u + t a k e + t h e r a p e u t i c + a c t i o n + i f + y o u r + l e v e l s + a r e + t o o + h i g h + r e m e m b e r + t o + f a s t + f o r + e i g h t + t o + 1 2 + h o u r s + b e f o r e + t h e + b l o o d + t e s t + d o + n o t + e a t + a n y + f o o d + o r + d r i n k + l i q u i d s + o t h e r + t h a n + w a t e r + b e f o r e + t h e + t e s t + a n d + t a k e + a n y + m e d i c a t i o n s + a s + p r e s c r i b e d + d o + n o t + t a k e + y o u r + s u p p l e m e n t s + t h e + m o r n i n g + o f + t h e + t e s t % 0 d % 0 a s u m m a r y % 0 d % 0 a h i g h + l e v e l s + o f + t h e + a m i n o + a c i d + h o m o c y s t e i n e + a r e + a + m a j o r + t h r e a t + t o + a n + a g i n g + p e r s o n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 s + h e a l t h % 2 c + r a i s i n g + t h e + r i s k + f o r + c a r d i o v a s c u l a r + d i s o r d e r s + s u c h + a s + h e a r t + a t t a c k + a n d + s t r o k e + f o l a t e + i s + k n o w n + t o + b e + e f f e c t i v e + i n + l o w e r i n g + h o m o c y s t e i n e + l e v e l s % 2 c + b u t + a + l a r g e + p r o p o r t i o n + o f + p e o p l e + f i n d + t h a t + t h e i r + h o m o c y s t e i n e + l e v e l s + r e m a i n + s t u b b o r n l y + h i g h % 2 c + e v e n + o n + f o l i c + a c i d + s u p p l e m e n t s % 0 d % 0 a t h i s + c o u l d + b e + c a u s e d + b y + t h e + f a c t + t h a t + 5 + t o + 1 0 % 2 5 + o f + t h e + p o p u l a t i o n + a n d + n e a r l y + h a l f + o f + p e o p l e + o f + e u r o p e a n + d e s c e n t + c a r r y + a + g e n e + v a r i a n t + t h a t + r e d u c e s + t h e + a c t i v i t y + o f + t h e + e n z y m e + r e q u i r e d + t o + e f f i c i e n t l y + c o n v e r t + f o l i c + a c i d + i n t o + t h e + a c t i v e % 2 c + h o m o c y s t e i n e - l o w e r i n g + f o r m + o f + t h e + v i t a m i n % 2 c + 5 - m t h f % 0 d % 0 a f o r + p e o p l e + w i t h + p e r s i s t e n t l y + h i g h + h o m o c y s t e i n e + l e v e l s % 2 c + h i g h - d o s e + 5 - m t h f + i s + n o w + a v a i l a b l e + a s + a + s u p p l e m e n t % 0 d % 0 a p u b l i s h e d + s t u d i e s + s h o w + t h a t + 5 - m t h f + n o t + o n l y + l o w e r s + h o m o c y s t e i n e + a n d + c r p % 2 c + b u t + a l s o + i m p r o v e s + h u m a n + s u r v i v a l % 0 d % 0 a i f + y o u r + h o m o c y s t e i n e - l o w e r i n g + r e g i m e n + s e e m s + s t a l l e d % 2 c + d o n % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 9 t + s i m p l y + r a i s e + y o u r + d o s e + o f + f o l i c + a c i d + i n s t e a d % 2 c + s w i t c h + t o + 5 - m t h f % 2 c + t h e + a c t i v e + f o r m + o f + t h e + s u p p l e m e n t + t h e n + t e s t + y o u r + h o m o c y s t e i n e + l e v e l s + a g a i n + i n + 3 0 + d a y s + t o + e n s u r e + y o u + a r e + t a k i n g + t h e + p r o p e r + d o s e + o f + 5 - m t h f + s o m e + p e o p l e + w i t h + h i g h + h o m o c y s t e i n e + m a y + o n l y + n e e d + 5 + m g + % 2 8 5 % 2 c 0 0 0 + m c g % 2 9 + o f + 5 - m t h f + o n c e + d a i l y + w h i l e + o t h e r s + w i l l + n e e d + t o + t a k e + 5 + m g + o f + 5 - m t h f + t w i c e + a + d a y % 0 d % 0 a % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 r e f e r e n c e s % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + l a m e r s + y % 2 c + p r i n z - l a n g e n o h l + r % 2 c + b r a m s w i g + s % 2 c + p i e t r z i k + k + r e d + b l o o d + c e l l + f o l a t e + c o n c e n t r a t i o n s + i n c r e a s e + m o r e + a f t e r + s u p p l e m e n t a t i o n + w i t h + % 5 b 6 s % 5 d - 5 - m e t h y l t e t r a h y d r o f o l a t e + t h a n + w i t h + f o l i c + a c i d + i n + w o m e n + o f + c h i l d b e a r i n g + a g e + a m + j + c l i n + n u t r + 2 0 0 6 + j u l % 3 b 8 4 % 2 8 1 % 2 9 % 3 a 1 5 6 - 6 1 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + p i e t r z i k + k % 2 c + b a i l e y + l % 2 c + s h a n e + b + f o l i c + a c i d + a n d + l - 5 - m e t h y l t e t r a h y d r o f o l a t e % 3 a + c o m p a r i s o n + o f + c l i n i c a l + p h a r m a c o k i n e t i c s + a n d + p h a r m a c o d y n a m i c s + c l i n + p h a r m a c o k i n e t + 2 0 1 0 + a u g % 3 b 4 9 % 2 8 8 % 2 9 % 3 a 5 3 5 - 4 8 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + c a r u s o + r % 2 c + c a m p o l o + j % 2 c + s e d d a + v % 2 c + e t + a l + e f f e c t + o f + h o m o c y s t e i n e + l o w e r i n g + b y + 5 - m e t h y l t e t r a h y d r o f o l a t e + o n + r e d o x + s t a t u s + i n + h y p e r h o m o c y s t e i n e m i a + j + c a r d i o v a s c + p h a r m a c o l + 2 0 0 6 + a p r % 3 b 4 7 % 2 8 4 % 2 9 % 3 a 5 4 9 - 5 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + c i a n c i o l o + g % 2 c + l a + m a n n a + g % 2 c + c o l i + l % 2 c + e t + a l + 5 - m e t h y l t e t r a h y d r o f o l a t e + a d m i n i s t r a t i o n + i s + a s s o c i a t e d + w i t h + p r o l o n g e d + s u r v i v a l + a n d + r e d u c e d + i n f l a m m a t i o n + i n + e s r d + p a t i e n t s + a m + j + n e p h r o l + 2 0 0 8 % 3 b 2 8 % 2 8 6 % 2 9 % 3 a 9 4 1 - 8 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + m a + y % 2 c + l i + l % 2 c + g e n g + x b % 2 c + e t + a l + c o r r e l a t i o n + b e t w e e n + h y p e r h o m o c y s t e i n e m i a + a n d + o u t c o m e s + o f + p a t i e n t s + w i t h + a c u t e + m y o c a r d i a l + i n f a r c t i o n + a m + j + t h e r + 2 0 1 4 + n o v + 1 7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + m a r t % c 3 % 8 3 % c 2 % a d - c a r v a j a l + a j % 2 c + s o l % c 3 % 8 3 % c 2 % a 0 + i % 2 c + l a t h y r i s + d + h o m o c y s t e i n e - l o w e r i n g + i n t e r v e n t i o n s + f o r + p r e v e n t i n g + c a r d i o v a s c u l a r + e v e n t s + c o c h r a n e + d a t a b a s e + s y s t + r e v + 2 0 1 5 + j a n + 1 5 % 3 b 1 % 3 a c d 0 0 6 6 1 2 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + v o l l s e t + s e % 2 c + r e f s u m + h % 2 c + t v e r d a l + a % 2 c + e t + a l + p l a s m a + t o t a l + h o m o c y s t e i n e + a n d + c a r d i o v a s c u l a r + a n d + n o n c a r d i o v a s c u l a r + m o r t a l i t y % 3 a + t h e + h o r d a l a n d + h o m o c y s t e i n e + s t u d y + a m + j + c l i n + n u t r + 2 0 0 1 + j u l % 3 b 7 4 % 2 8 1 % 2 9 % 3 a 1 3 0 - 6 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + a v a i l a b l e + a t % 3 a + h t t p % 3 a % 2 f % 2 f w w w m e d i c i n e n e t c o m % 2 f h o m o c y s t e i n e % 2 f p a g e 3 h t m + a c c e s s e d + f e b r u a r y + 1 1 % 2 c + 2 0 1 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + a v a i l a b l e + a t % 3 a + h t t p % 3 a % 2 f % 2 f e l c a m i n o g m i d n a d i r e c t c o m % 2 f g r c % 2 f p a t i e n t - s i t e % 2 f m t h f r - p r e g n a n c y - c o m p l i c a t i o n s % 2 f t e s t i n g - f o r - h i g h - h o m o c y s t e i n e h t m l + a c c e s s e d + f e b r u a r y + 1 1 % 2 c + 2 0 1 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + t a s c i l a r + n % 2 c + e k e m + s % 2 c + a c i m a n + e % 2 c + e t + a l + h y p e r h o m o c y s t e i n e m i a + a s + a n + i n d e p e n d e n t + r i s k + f a c t o r + f o r + c a r d i o e m b o l i c + s t r o k e + i n + t h e + t u r k i s h + p o p u l a t i o n + t o h o k u + j + e x p + m e d + 2 0 0 9 + a u g % 3 b 2 1 8 % 2 8 4 % 2 9 % 3 a 2 9 3 - 3 0 0 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + a s h j a z a d e h + n % 2 c + f a t h i + m % 2 c + s h a r i a t + a + e v a l u a t i o n + o f + h o m o c y s t e i n e + l e v e l + a s + a + r i s k + f a c t o r + a m o n g + p a t i e n t s + w i t h + i s c h e m i c + s t r o k e + a n d + i t s + s u b t y p e s + i r a n + j + m e d + s c i + 2 0 1 3 + s e p % 3 b 3 8 % 2 8 3 % 2 9 % 3 a 2 3 3 - 9 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + b o u s h e y + c j % 2 c + b e r e s f o r d + s a % 2 c + o m e n n + g s % 2 c + m o t u l s k y + a g + a + q u a n t i t a t i v e + a s s e s s m e n t + o f + p l a s m a + h o m o c y s t e i n e + a s + a + r i s k + f a c t o r + f o r + v a s c u l a r + d i s e a s e % 3 a + p r o b a b l e + b e n e f i t s + o f + i n c r e a s i n g + f o l i c + a c i d + i n t a k e s + j a m a + 1 9 9 5 % 3 b 2 7 4 % 3 a 1 0 4 9 - 5 7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + f o w l e r + b + h o m o c y s t e i n e % c 3 % a 2 % c 2 % 8 0 % c 2 % 9 4 a n + i n d e p e n d e n t + r i s k + f a c t o r + f o r + c a r d i o v a s c u l a r + a n d + t h r o m b o t i c + d i s e a s e s + t h e r + u m s c h + 2 0 0 5 + s e p % 3 b 6 2 % 2 8 9 % 2 9 % 3 a 6 4 1 - 6 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + g a n g u l y + p % 2 c + a l a m + s f + r o l e + o f + h o m o c y s t e i n e + i n + t h e + d e v e l o p m e n t + o f + c a r d i o v a s c u l a r + d i s e a s e + n u t r + j + 2 0 1 5 + j a n + 1 0 % 3 b 1 4 % 2 8 1 % 2 9 % 3 a 6 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + j a k u b o w s k i + h + m o l e c u l a r + b a s i s + o f + h o m o c y s t e i n e + t o x i c i t y + i n + h u m a n s + c e l l + m o l + l i f e + s c i + 2 0 0 4 + f e b % 3 b 6 1 % 2 8 4 % 2 9 % 3 a 4 7 0 - 8 7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + b o l d y r e v + a a + m o l e c u l a r + m e c h a n i s m s + o f + h o m o c y s t e i n e + t o x i c i t y + b i o c h e m i s t r y + % 2 8 m o s c % 2 9 + 2 0 0 9 + j u n % 3 b 7 4 % 2 8 6 % 2 9 % 3 a 5 8 9 - 9 8 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + c l a r k e + r % 2 c + d a l y + l % 2 c + r o b i n s o n + k % 2 c + e t + a l + h y p e r h o m o c y s t e i n e m i a % 3 a + a n + i n d e p e n d e n t + r i s k + f a c t o r + f o r + v a s c u l a r + d i s e a s e + n + e n g l + j + m e d + 1 9 9 1 + a p r + 2 5 % 3 b 3 2 4 % 2 8 1 7 % 2 9 % 3 a 1 1 4 9 - 5 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + e r e n + e % 2 c + e l l i d a g + h y % 2 c + a y d i n + o % 2 c + y i l m a z + n + h o m o c y s t e i n e % 2 c + p a r a o x o n a s e - 1 + a n d + v a s c u l a r + e n d o t h e l i a l + d y s f u n c t i o n % 3 a + o m n i b u s + v i i s + r o m a m + p e r v e n i t u r + j + c l i n + d i a g n + r e s + 2 0 1 4 + s e p % 3 b 8 % 2 8 9 % 2 9 % 3 a c e 0 1 - 4 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + k i m + c s % 2 c + k i m + y r % 2 c + n a q v i + a % 2 c + e t + a l + h o m o c y s t e i n e + p r o m o t e s + h u m a n + e n d o t h e l i a l + c e l l + d y s f u n c t i o n + v i a + s i t e - s p e c i f i c + e p i g e n e t i c + r e g u l a t i o n + o f + p 6 6 s h c + c a r d i o v a s c + r e s + 2 0 1 1 + d e c + 1 % 3 b 9 2 % 2 8 3 % 2 9 % 3 a 4 6 6 - 7 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s c h i f f r i n + e l % 3 b + c a n a d i a n + i n s t i t u t e s + o f + h e a l t h + r e s e a r c h + m u l t i d i s c i p l i n a r y + r e s e a r c h + g r o u p + o n + h y p e r t e n s i o n + b e y o n d + b l o o d + p r e s s u r e % 3 a + t h e + e n d o t h e l i u m + a n d + a t h e r o s c l e r o s i s + p r o g r e s s i o n + a m + j + h y p e r t e n s + 2 0 0 2 + o c t % 3 b 1 5 % 2 8 1 0 + p t + 2 % 2 9 % 3 a 1 1 5 s - 1 2 2 s % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s p i e k e r + l e % 2 c + f l a m m e r + a j % 2 c + l % c 3 % 8 3 % c 2 % b c s c h e r + t f + t h e + v a s c u l a r + e n d o t h e l i u m + i n + h y p e r t e n s i o n + h a n d b + e x p + p h a r m a c o l + 2 0 0 6 % 3 b % 2 8 1 7 6 + p t + 2 % 2 9 % 3 a 2 4 9 - 8 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + r o z e n b e r g + o % 2 c + r o s e n b l a t + m % 2 c + c o l e m a n + r % 2 c + s h i h + d m % 2 c + a v i r a m + m + p a r a o x o n a s e + % 2 8 p o n 1 % 2 9 + d e f i c i e n c y + i s + a s s o c i a t e d + w i t h + i n c r e a s e d + m a c r o p h a g e + o x i d a t i v e + s t r e s s % 3 a + s t u d i e s + i n + p o n 1 - k n o c k o u t + m i c e + f r e e + r a d i c + b i o l + m e d + 2 0 0 3 + m a r + 1 5 % 3 b 3 4 % 2 8 6 % 2 9 % 3 a 7 7 4 - 8 4 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + e f r a t + m % 2 c + a v i r a m + m + p a r a o x o n a s e + 1 + i n t e r a c t i o n s + w i t h + h d l % 2 c + a n t i o x i d a n t s + a n d + m a c r o p h a g e s + r e g u l a t e + a t h e r o g e n e s i s + - + a + p r o t e c t i v e + r o l e + f o r + h d l + p h o s p h o l i p i d s + a d v + e x p + m e d + b i o l + 2 0 1 0 % 3 b 6 6 0 % 3 a 1 5 3 - 6 6 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s a m p s o n + m j % 2 c + b r a s c h i + s % 2 c + w i l l i s + g % 2 c + a s t l e y + s b + p a r a o x o n a s e - 1 + % 2 8 p o n - 1 % 2 9 + g e n o t y p e + a n d + a c t i v i t y + a n d + i n + v i v o + o x i d i z e d + p l a s m a + l o w - d e n s i t y + l i p o p r o t e i n + i n + t y p e + i i + d i a b e t e s + c l i n + s c i + % 2 8 l o n d % 2 9 + 2 0 0 5 + a u g % 3 b 1 0 9 % 2 8 2 % 2 9 % 3 a 1 8 9 - 9 7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + j a c o b s e n + d w % 2 c + g a t a u t i s + v j % 2 c + g r e e n + r % 2 c + e t + a l + t o t a l + p l a s m a + h o m o c y s t e i n e % 3 a + t h e + m e d i a t o r % 2 f m a r k e r + c o n t r o v e r s y + c o n t i n u e s + 1 9 9 4 + c l i n + c h e m + 2 0 0 9 + s e p % 3 b 5 5 % 2 8 9 % 2 9 % 3 a 1 7 4 2 - 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s c h a f f e r + a % 2 c + v e r d o i a + m % 2 c + c a s s e t t i + e % 2 c + m a r i n o + p % 2 c + s u r y a p r a n a t a + h % 2 c + d e + l u c a + g + r e l a t i o n s h i p + b e t w e e n + h o m o c y s t e i n e + a n d + c o r o n a r y + a r t e r y + d i s e a s e + r e s u l t s + f r o m + a + l a r g e + p r o s p e c t i v e + c o h o r t + s t u d y + t h r o m b + r e s + 2 0 1 4 + a u g % 3 b 1 3 4 % 2 8 2 % 2 9 % 3 a 2 8 8 - 9 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s m u l d e r s + y m % 2 c + b l o m + h j + t h e + h o m o c y s t e i n e + c o n t r o v e r s y + j + i n h e r i t + m e t a b + d i s + 2 0 1 1 + f e b % 3 b 3 4 % 2 8 1 % 2 9 % 3 a 9 3 - 9 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + o b e i d + r % 2 c + h o l z g r e v e + w % 2 c + p i e t r z i k + k + i s + 5 - m e t h y l t e t r a h y d r o f o l a t e + a n + a l t e r n a t i v e + t o + f o l i c + a c i d + f o r + t h e + p r e v e n t i o n + o f + n e u r a l + t u b e + d e f e c t s % 3 f + j + p e r i n a t + m e d + 2 0 1 3 + s e p + 1 % 3 b 4 1 % 2 8 5 % 2 9 % 3 a 4 6 9 - 8 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + l e e m a n s + l + d o e s + 5 - m e t h y l t e t r a h y d r o f o l a t e + o f f e r + a n y + a d v a n t a g e + o v e r + f o l i c + a c i d % 3 f + j + p h a r m + b e l g + 2 0 1 2 + d e c + % 2 8 4 % 2 9 % 3 a 1 6 - 2 2 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + b a i l e y + l b % 2 c + g r e g o r y + j f + 3 r d + f o l a t e + m e t a b o l i s m + a n d + r e q u i r e m e n t s + j + n u t r + + 1 9 9 9 + a p r % 3 b 1 2 9 % 2 8 4 % 2 9 % 3 a 7 7 9 - 8 2 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + k l e e + g g + c o b a l a m i n + a n d + f o l a t e + e v a l u a t i o n % 3 a + m e a s u r e m e n t + o f + m e t h y l m a l o n i c + a c i d + a n d + h o m o c y s t e i n e + v s + v i t a m i n + b % 2 8 1 2 % 2 9 + a n d + f o l a t e + c l i n + c h e m + 2 0 0 0 + a u g % 3 b 4 6 % 2 8 8 + p t + 2 % 2 9 % 3 a 1 2 7 7 - 8 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + b e z o l d + g % 2 c + l a n g e + m % 2 c + p e t e r + r u + h o m o z y g o u s + m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + c 6 7 7 t + m u t a t i o n + a n d + m a l e + i n f e r t i l i t y + n + e n g l + j + m e d + 2 0 0 1 + a p r + 1 2 % 3 b 3 4 4 % 2 8 1 5 % 2 9 % 3 a 1 1 7 2 - 3 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + f u k u d a + n % 2 c + h a m a j i m a + n % 2 c + w a k a i + k % 2 c + s u z u k i + k + a + c r o s s - s e c t i o n a l + s t u d y + t o + f i n d + o u t + t h e + r e l a t i o n s h i p + o f + m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + % 2 8 m t h f r % 2 9 + c 6 7 7 t + g e n o t y p e + w i t h + p l a s m a + l e v e l s + o f + f o l a t e + a n d + t o t a l + h o m o c y s t e i n e + b y + d a i l y + f o l a t e + i n t a k e + i n + j a p a n e s e + j + n u t r + s c i + v i t a m i n o l + % 2 8 t o k y o % 2 9 + 2 0 1 4 % 3 b 6 0 % 2 8 4 % 2 9 % 3 a 2 3 1 - 8 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + l o v r i c e v i c + i % 2 c + f r a n j i c + b d % 2 c + t o m i c i c + m % 2 c + e t + a l + 5 % 2 c + 1 0 - m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + % 2 8 m t h f r % 2 9 + 6 7 7 + c + - - % 3 e + t + g e n e t i c + p o l y m o r p h i s m + i n + 2 2 8 + c r o a t i a n + v o l u n t e e r s + c o l l + a n t r o p o l + 2 0 0 4 + d e c % 3 b 2 8 % 2 8 2 % 2 9 % 3 a 6 4 7 - 5 4 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + p r i n z - l a n g e n o h l + r % 2 c + b r a m s w i g + s % 2 c + t o b o l s k i + o % 2 c + e t + a l + % 5 b 6 s % 5 d - 5 - m e t h y l t e t r a h y d r o f o l a t e + i n c r e a s e s + p l a s m a + f o l a t e + m o r e + e f f e c t i v e l y + t h a n + f o l i c + a c i d + i n + w o m e n + w i t h + t h e + h o m o z y g o u s + o r + w i l d - t y p e + 6 7 7 c - - % 3 e t + p o l y m o r p h i s m + o f + m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + b r + j + p h a r m a c o l + 2 0 0 9 + d e c % 3 b 1 5 8 % 2 8 8 % 2 9 % 3 a 2 0 1 4 - 2 1 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + y a f e i + w % 2 c + l i j u n + p % 2 c + j i n f e n g + w % 2 c + x i a o y i n g + z + i s + t h e + p r e v a l e n c e + o f + m t h f r + c 6 7 7 t + p o l y m o r p h i s m + a s s o c i a t e d + w i t h + u l t r a v i o l e t + r a d i a t i o n + i n + e u r a s i a % 3 f + j + h u m + g e n e t + 2 0 1 2 + d e c % 3 b 5 7 % 2 8 1 2 % 2 9 % 3 a 7 8 0 - 6 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + s h o j a e i + m h % 2 c + d j a l a l i + m % 2 c + s i a s s i + f % 2 c + k h a t a m i + m r % 2 c + b o r o u m a n d + m a % 2 c + e s h r a g i a n + m r + s e r u m + l e v e l s + o f + l i p o p r o t e i n % 2 8 a % 2 9 + a n d + h o m o c y s t e i n e + i n + p a t i e n t s + o n + h e m o d i a l y s i s + w h o + t a k e + h y d r o x y m e t h y l g l u t a r y l - c o a + r e d u c t a s e + i n h i b i t o r s % 2 c + v i t a m i n + b 6 % 2 c + a n d + f o l i c + a c i d + i r a n + j + k i d n e y + d i s + 2 0 0 9 + j u l % 3 b 3 % 2 8 3 % 2 9 % 3 a 1 4 1 - 4 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + w i l l e m s + f f % 2 c + b o e r s + g h % 2 c + b l o m + h j % 2 c + a e n g e v a e r e n + w r % 2 c + v e r h e u g t + f w + p h a r m a c o k i n e t i c + s t u d y + o n + t h e + u t i l i s a t i o n + o f + 5 - m e t h y l t e t r a h y d r o f o l a t e + a n d + f o l i c + a c i d + i n + p a t i e n t s + w i t h + c o r o n a r y + a r t e r y + d i s e a s e + b r + j + p h a r m a c o l + 2 0 0 4 + m a r % 3 b 1 4 1 % 2 8 5 % 2 9 % 3 a 8 2 5 - 3 0 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + l i + d % 2 c + k a r p + n % 2 c + w u + q % 2 c + e t + a l + m e f o l i n a t e + % 2 8 5 - m e t h y l t e t r a h y d r o f o l a t e % 2 9 % 2 c + b u t + n o t + f o l i c + a c i d % 2 c + d e c r e a s e s + m o r t a l i t y + i n + a n + a n i m a l + m o d e l + o f + s e v e r e + m e t h y l e n e t e t r a h y d r o f o l a t e + r e d u c t a s e + d e f i c i e n c y + j + i n h e r i t + m e t a b + d i s + 2 0 0 8 + j u n % 3 b 3 1 % 2 8 3 % 2 9 % 3 a 4 0 3 - 1 1 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + v e n n + b j % 2 c + g r e e n + t j % 2 c + m o s e r + r % 2 c + m a n n + j i + c o m p a r i s o n + o f + t h e + e f f e c t + o f + l o w - d o s e + s u p p l e m e n t a t i o n + w i t h + l - 5 - m e t h y l t e t r a h y d r o f o l a t e + o r + f o l i c + a c i d + o n + p l a s m a + h o m o c y s t e i n e % 3 a + a + r a n d o m i z e d + p l a c e b o - c o n t r o l l e d + s t u d y + a m + j + c l i n + n u t r + 2 0 0 3 + m a r % 3 b 7 7 % 2 8 3 % 2 9 % 3 a 6 5 8 - 6 2 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + b o s t o m + a g % 2 c + s h e m i n + d % 2 c + l a p a n e + k l % 2 c + h u m e + a l % 2 c + y o b u r n + d % 2 c + n a d e a u + m r % 2 c + b e n d i c h + a % 2 c + s e l h u b + j % 2 c + r o s e n b e r g + i h + h i g h + d o s e - b - v i t a m i n + t r e a t m e n t + o f + h y p e r h o m o c y s t e i n e m i a + i n + d i a l y s i s + p a t i e n t s + k i d n e y + i n t + 1 9 9 6 + j a n % 3 b 4 9 % 2 8 1 % 2 9 % 3 a 1 4 7 - 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7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + f a r a h + a + t h e + r o l e + o f + l - m e t h y l f o l a t e + i n + d e p r e s s i v e + d i s o r d e r s + c n s + s p e c t r + 2 0 0 9 + j a n % 3 b 1 4 % 2 8 1 + s u p p l + 2 % 2 9 % 3 a 2 - 7 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + w a d e + r l % 2 c + k i n d e r m a n n + s l % 2 c + h o u + q % 2 c + t h a s e + m e + c o m p a r a t i v e + a s s e s s m e n t + o f + a d h e r e n c e + m e a s u r e s + a n d + r e s o u r c e + u s e + i n + s s r i % 2 f s n r i - t r e a t e d + p a t i e n t s + w i t h + d e p r e s s i o n + u s i n g + s e c o n d - g e n e r a t i o n + a n t i p s y c h o t i c s + o r + l - m e t h y l f o l a t e + a s + a d j u n c t i v e + t h e r a p y + j + m a n a g + c a r e + p h a r m + 2 0 1 4 + j a n % 3 b 2 0 % 2 8 1 % 2 9 % 3 a 7 6 - 8 5 % 0 d % 0 a % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 % c 3 % 8 2 % c 2 % a 0 + g i n s b e r g + l d % 2 c + o u b r e + a y % 2 c + d a o u d + y a + l - 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