S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study.
OBJECTIVE
To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.


RESULTS
In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.


CONCLUSIONS
In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.
Spijkerman
A M W
AM
Institute for Research in Extramural Medicine, VU VU University Medical Center, Amsterdam, The Netherlands.
Smulders
Y M
YM
Kostense
P J
PJ
Henry
R M A
RM
Becker
A
A
Teerlink
T
T
Jakobs
C
C
Dekker
J M
JM
Nijpels
G
G
Heine
R J
RJ
Bouter
L M
LM
Stehouwer
C D A
CD
D000368:Aged; D001916:Brachial Artery / Q000502:physiology; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000502:physiology; D012307:Risk Factors; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013763:Tetrahydrofolates / Q000378:metabolism*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage; D014805:Vitamin B 12 / Q000378:metabolism; D025101:Vitamin B 6 / Q000378:metabolism
D013763:Tetrahydrofolates; D014665:Vasodilator Agents; D006710:Homocysteine; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D005492:Folic Acid; D005996:Nitroglycerin; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate