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Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched
Jamal Golbahar1, Golamreza Rezaian, Z Fathi
1Department of Biochemistry, Faculty of Medicine, Cardiovascular Unit, Shiraz University of Medical Sciences, Iran. golbaharj@sums.ac.ir
Insights
Low red blood cell 5-methyltetrahydrofolate (5-MTHF) is a stronger predictor of coronary artery disease (CAD) than plasma homocysteine. This suggests RBC 5-MTHF is a more reliable marker for homocysteine pathway disturbances in Iranians.
Area of Science:
- Cardiovascular Disease Research
- Nutritional Biochemistry
- Metabolic Pathway Analysis
Background:
- Coronary artery disease (CAD) risk factors are not fully understood, particularly the role of homocysteine and its remethylation pathway.
- Investigating the association between plasma/red blood cell (RBC) levels of vitamin B12, 5-methyltetrahydrofolate (5-MTHF), and total homocysteine (tHcy) in CAD etiology.
Purpose of the Study:
- To test the hypothesis that RBC 5-MTHF, reflecting long-term folate status, is a more reliable marker for homocysteine remethylation pathway disturbances.
- To determine if 5-MTHF deficiency is associated with CAD in an Iranian population.
Main Methods:
- Measured plasma tHcy, vitamin B12, plasma and RBC 5-MTHF in 200 CAD patients and 200 matched controls.
- Utilized logistic regression and quartile analysis to assess associations with CAD prevalence.
Main Results:
- Plasma tHcy was higher in CAD patients, while RBC 5-MTHF and vitamin B12 were higher in controls.
- RBC 5-MTHF independently predicted plasma tHcy.
- Lowest quartile of RBC 5-MTHF showed a 2.5-fold increased CAD prevalence, remaining significant after adjustments.
- Association between CAD and plasma tHcy weakened significantly when adjusted for RBC 5-MTHF.
Conclusions:
- Low RBC 5-MTHF demonstrated a stronger association with CAD than plasma 5-MTHF or plasma tHcy.
- RBC 5-MTHF appears to be a more stable and reliable marker for homocysteine remethylation pathway disturbances in the Iranian population.
Background:
It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians.
Methods:
Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age.
Results:
In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11).
Conclusion:
In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.
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