Daily rhythms in plasma levels of homocysteine

Lavie, Lena; Lavie, Peretz

doi:10.1186/1740-3391-2-5

Cited by 24 publications

(17 citation statements)

References 23 publications

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“…For example, the tryptophan concentrations observed in the afternoon and at night were significantly decreased in comparison with those detected in the morning (Table S3 and Figure S3), and these differences might have been due to the effects of diet and/or daily activity. Previous studies have also demonstrated intra-day and inter-day variance in the levels of some amino acids [10], [11], [12]. Therefore it is important to evaluate the inter-day and intra-day variances of serum metabolite levels in metabolomic research, and blood samples collected before breakfast were used in this study.…”

Section: Discussionmentioning

confidence: 99%

A Novel Serum Metabolomics-Based Diagnostic Approach for Colorectal Cancer

et al. 2012

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BackgroundTo improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer.Methodology/Principal FindingsWe performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0–2 colorectal cancer (82.8%).Conclusions/SignificanceOur prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

A Novel Serum Metabolomics-Based Diagnostic Approach for Colorectal Cancer

et al. 2012

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“…Hcy concentrations are influenced slightly by a circadian variation but not necessarily by food consumption. (42)(43)(44) It has even been suggested that the preferred way of analyzing Hcy should be in the nonfasting state. (45) Nonfasting samples were fracture predictive in another study.…”

Section: Figmentioning

confidence: 99%

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

Gerdhem

Ivaska

Isaksson

et al. 2007

Journal of Bone and Mineral Research

106

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Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.Introduction: Recently, the association between high serum homocysteine (Hcy) levels and an increased risk of fracture has been described. Materials and Methods: Hcy levels were measured at baseline in 996 women, all 75 years old. Vitamin B 12 , folate, serum cross-linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin, urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound (QUS), and physical performance were assessed at baseline. Fractures and mortality were recorded during a mean follow-up of 7.0 years. Results: Bone marker levels were higher in women with Hcy in the highest quartile compared with all other women (p < 0.05). The most evident correlation between Hcy and a bone marker was seen with CTX (r ‫ס‬ 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest quartile compared with the other women (p < 0.05). During the follow-up, 267 women sustained at least one low-energy fracture (including 69 hip fractures). When women in the highest Hcy quartile were compared with all other women, the hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89-1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for confounders did not substantially change these associations. Adjustment for PTH increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B 12 or folate was not associated with increased fracture risk or mortality. Conclusions: High Hcy levels were associated with higher bone turnover, poor physical performance, and lower BMD. There was no clear association to fracture risk. The increased mortality among women with high Hcy levels indicates that a high Hcy level may be a marker of frailty.

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“…One factor involved might be homocysteine. Only limited studies with small sample sizes and without taking gender differences into account have analyzed circadian rhythms of homocysteine levels (Guttormsen et al, 2004;Jordan et al, 2004;Lavie & Lavie, 2004, 2006. In rats, plasma homocysteine concentration varies spontaneously with ontogenic development and during the estrous cycle, and shows 24 h variation in young rats with lower levels during the night (Martins et al, 2005).…”

Section: Introductionmentioning

confidence: 97%

Daily Variations of Homocysteine Concentration May Influence Methylation of DNA in Normal Healthy Individuals

Bönsch

Hothorn

Krieglstein

et al. 2007

Chronobiology International

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The regulation of genetic expression is tightly controlled and well balanced in the organism by different epigenetic mechanisms such as DNA methylation and histone modifications. DNA methylation occurring after embryogenesis is seen mainly as an irreversible event. Even small changes in genomic DNA methylation might be of biological relevance, and several factors influencing DNA methylation have been identified so far, one being homocysteine. In this study, genomic DNA methylation was analyzed and homocysteine plasma levels were measured over a 24 h period in 30 healthy students (15 males and 15 females) exposed to a standard 24 h regime of daytime activity alternating with nighttime sleep. Plasma homocysteine concentrations were measured using HPLC detection. DNA was extracted from whole EDTA blood, and genomic DNA methylation was assessed by fluorescently labeled cytosine extension assay. Both homocysteine and DNA methylation showed 24 h variation. Homocysteine showed a significant daily rhythm with an evening peak and nocturnal nadir in all subjects (p<0.001). Males showed higher overall homocysteine levels compared to females (p=0.002). Genomic DNA methylation showed a significant rhythm with increased levels at night (p=0.021), which was inverse to plasma homocysteine levels.

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Daily rhythms in plasma levels of homocysteine

Cited by 24 publications

References 23 publications

A Novel Serum Metabolomics-Based Diagnostic Approach for Colorectal Cancer

A Novel Serum Metabolomics-Based Diagnostic Approach for Colorectal Cancer

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

Daily Variations of Homocysteine Concentration May Influence Methylation of DNA in Normal Healthy Individuals

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