Health effects of trans-fatty acids: experimental and observational evidence.
OBJECTIVE
Growing evidence indicates that trans-fatty acids (TFA) adversely affect cardiovascular health. As part of the World Health Organization (WHO) Scientific Update on TFA, we reviewed the evidence for effects of TFA consumption on coronary heart disease (CHD).


METHODS
We searched Medline publications examining TFA consumption and CHD risk factors or outcomes, emphasizing results of studies in humans. We evaluated and synthesized evidence from both controlled feeding trials evaluating risk factors and long-term observational studies evaluating risk factors or clinical outcomes, each of which have complementary strengths and limitations, to enable the most robust and reliable inferences of effects.


RESULTS
The effects of TFA consumption on risk factors most consistently seen in both controlled trials and observational studies included adverse lipid effects (for example [upward arrow] low-density lipoprotein cholesterol, [downward arrow] high-density lipoprotein cholesterol (HDL-C), [upward arrow] total/HDL-C ratio), proinflammatory effects (for example [upward arrow] tumor necrosis factor-alpha activity, [upward arrow] interleukin-6, [upward arrow] C-reactive protein) and endothelial dysfunction. These effects were most prominent in comparison with cis unsaturated fats; adverse effects on total/HDL-C and endothelial function were also seen in comparison with saturated fatty acids (SFA). TFA may also worsen insulin sensitivity, particularly among individuals predisposed to insulin resistance; possible effects on weight gain and diabetes incidence require further confirmation. Five retrospective case-control studies and four prospective cohort studies demonstrated positive associations between TFA consumption and CHD events. A meta-analysis of prospective studies indicated 24, 20, 27 and 32% higher risk of myocardial infarction (MI) or CHD death for every 2% energy of TFA consumption isocalorically replacing carbohydrate, SFA, cis monounsaturated fatty acids and cis polyunsaturated fatty acids, respectively. The differential effects of specific TFA isomers may be important but are less well established. The available evidence indicates that trans-18:1 and particularly trans-18:2 isomers have stronger CHD effects than trans-16:1 isomers. The limited data suggest that the experimental effects of ruminant and industrial TFA are similar when consumed in similar quantities, but very few persons consume such high levels of ruminant TFA, and observational studies do not support adverse CHD effects of ruminant TFA in amounts actually consumed.


CONCLUSIONS
Controlled trials and observational studies provide concordant evidence that consumption of TFA from partially hydrogenated oils adversely affects multiple cardiovascular risk factors and contributes significantly to increased risk of CHD events. The public health implications of ruminant TFA consumption appear much more limited. The effects of specific TFA isomers require further investigation.
Mozaffarian
D
D
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. dmozaffa@hsph.harvard.edu
Aro
A
A
Willett
W C
WC
D000818:Animals; D003327:Coronary Disease / Q000209:etiology* / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance; D007536:Isomerism; D050356:Lipid Metabolism / Q000187:drug effects*; D009203:Myocardial Infarction / Q000209:etiology; D012307:Risk Factors; D044242:Trans Fatty Acids / Q000009:adverse effects*
D004041:Dietary Fats; D044242:Trans Fatty Acids