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[Gender differences in serum homocysteine levels and associated factors]
1Centrum preventivní medicíny LF UK, II. interní klinika, Plzen.
Insights
Men have higher homocysteine (Hcy) levels than women, particularly within normal ranges. This difference is linked to factors beyond B vitamins, possibly involving methionine metabolism and creatinine production.
Area of Science:
- Biochemistry
- Clinical Medicine
- Vascular Biology
Context:
- Homocysteine (Hcy) is a recognized risk factor for vascular diseases.
- Hcy levels are influenced by genetics and nutrition.
- Previous studies indicate higher Hcy levels in males, but the clinical significance is unclear.
Purpose:
- To investigate gender differences in Hcy levels.
- To identify associated factors contributing to these differences.
- To determine the specific Hcy ranges where gender disparities are most pronounced.
Summary:
- A study of 500+ individuals found significantly higher Hcy levels in males (13.1 vs. 11.5 µmol/l).
- This gender difference was prominent in normal Hcy ranges (up to 15 µmol/l) but not in mild hyperhomocysteinemia.
- Males with normal Hcy showed higher methionine and creatinine, and lower folate/B12 levels compared to females.
Impact:
- Findings suggest that higher Hcy in males is not solely due to B vitamin differences.
- Increased methionine demethylation and creatinine production in males may play a role, potentially influenced by sex hormones.
- Understanding these gender-specific Hcy variations is crucial for targeted vascular disease prevention strategies.
Background:
Homocysteine (Hcy) is an important independent risk factor for vascular diseases. Its level is determined by genetic polymorphism of several enzymes in association with nutritional factors. Higher Hcy levels were found in men than in women, however the clinical significance of this phenomenon remains to be elucidated. The aim of this study was to analyze the gender differences in Hcy levels in relation to associated factors and to assess in which range of Hcy these differences are mainly expressed.
Methods And Results:
The series comprised of 257 males and 239 females, mean age 52.9 and 52.3 years, resp., selected from the population study Pils II. All subjects were examined by a standard protocol, to assess clinical, anthropometrical and laboratory variables. Hcy and methionine levels were estimated by ion exchange chromatography, other laboratories using standard kits. The methods were validated by a reference laboratory. Statistical analyses were done by Wilcoxon's unpaired test and multiple linear regression. We found in males significantly higher Hcy levels (13.1 vs. 11.5 mumol/l, p < 0.0001) than in females. This difference persisted only in the range of normal Hcy levels (11.1, 10.2 mumol/l, p < 0.0001), i.e. up to 15 mumol/l (1st-4th quintile of the Hcy distribution) and not in the top quintile, considered as mild hyperhomocysteinaemia. We found in males, with normal Hcy levels, significantly higher serum methionine (23.8 vs. 22.4 mumol/l, p < 0.0001), creatinine (91.5 vs 80.9 mumol/l, p < 0.0001) and a lower methionine/creatinine ratio (0.25 vs. 0.27, p < 0.01). Plasma folates and B12 vitamin in males were also lower than in females, however these differences were only of a borderline statistical significance. On the other hand, in subjects with MHHcy (5th quintile) no gender differences were observed, except in creatinine.
Conclusions:
Higher Hcy levels in males cannot be explained by differences in folate and B12 levels only. We considered also other factors, namely higher demethylation of methionine associated with higher creatinine production in males, which may be influenced by sex hormons.