Circulating B-Vitamins and Smoking Habits Are Associated with Serum Polyunsaturated Fatty Acids in Patients with Suspected Coronary Heart Disease: A Cross-Sectional Study

Skeie, Eli; Strand, Elin; Pedersen, Eva Ringdal; Bjørndal, Bodil; Bohov, Pavol; Berge, Rolf K.; Svingen, Gard Frodahl Tveitevåg; Seifert, Reinhard; Ueland, Per Magne; Midttun, Øivind; Ulvik, Arve; Hustad, Steinar; Drevon, Christian A.; Gregory, Jesse F.; Nygård, Ottar

doi:10.1371/journal.pone.0129049

Cited by 8 publications

(10 citation statements)

References 55 publications

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“…Tobacco smoke contains a substantial number of reactive oxygen species that could trigger oxidative stress in the brain 60 , blood-brain-barrier 66 and periphery 67 , leading to vitamin B6 deficiency 67 . Of note, in humans, smoking reduced circulating plasma vitamin B6 and PLP levels 68,69 , with concentrations increasing significantly after a few days of smoking cessation 70 . This suggests that cigarette smoking could deplete circulating vitamin B6 and PLP levels by modifying the activity of the brain antioxidant defense triggered by PLP enzymatic interaction with SRR.…”

Section: Discussionmentioning

confidence: 99%

Integrating Human Brain Proteomic Data with Genome-Wide Association Study Findings Identifies Novel Brain Proteins in Substance Use Traits

Toikumo

Kember

et al. 2022

Preprint

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Background: Despite the growing number of genetic risk loci identified for substance use traits (SUTs), the impact of these loci on protein abundance and their potential as therapeutic targets are unknown. Methods: To address this, we performed a proteome-wide association study (PWAS) by integrating human brain proteomes from discovery (Banner; N = 152) and validation (ROSMAP; N = 376) datasets with genome-wide association study (GWAS) summary statistics for 4 SUTs. The sample comprised 4 GWAS of European-ancestry individuals for smoking initiation [Smk] (N = 1,232,091), alcohol use disorder [AUD] (N = 313,959), cannabis use disorder [CUD] (N = 384,032), and opioid use disorder [OUD] (N = 302,585). We conducted transcriptome-wide association studies (TWAS) with human brain transcriptomic data to examine the overlap of genetic effects at the proteomic and transcriptomic levels and tested significant genes for causality through Colocalization analysis. Results: Twenty-seven genes (Smk=21, AUD=3, CUD=2, OUD=1) were significantly associated with cis-regulated brain protein abundance. There was evidence for causality in 6 genes (Smk: NT5C2, GMPPB, NQO1, SRR, and ACTR1B; AUD: CTNND1), which act by regulating brain protein abundance. Cis-regulated transcript levels for 8 genes (Smk=6, CUD=1, OUD=1) were associated with SUTs, indicating that genetic loci could confer risk for these SUTs by modulating both gene expression and proteomic abundance. Conclusions: Functional studies of the high-confidence risk proteins (SRR for Smk and CTNND1 for AUD) identified here are needed to determine whether they are modifiable targets and useful in developing medications and biomarkers for these SUTs.

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Section: Discussionmentioning

confidence: 99%

Integrating Human Brain Proteomic Data with Genome-Wide Association Study Findings Identifies Novel Brain Proteins in Substance Use Traits

Toikumo

Kember

et al. 2022

Preprint

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“…Tsuge et al [ 8 ] further showed the lower contents of eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and AA in plasma total lipids in B6-deficient male rats compared to pair-fed controls. Moreover, epidemiologic studies have indicated that low levels of circulating pyridoxal 5′-phosphate (PLP) change the compositions of PUFA in serum or plasma [ 9 , 10 , 11 , 12 ]. A clinical study with 23 healthy men and women combined (20–40 years) found that marginal vitamin B6 deficiency (plasma PLP concentration between 20 and 30 nmol/L), which was induced by a 28 day B6-restricted diet, reduced plasma concentrations of EPA, DHA, and AA and increased slightly plasma n-6/n-3 PUFA ratio [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…A clinical study with 23 healthy men and women combined (20–40 years) found that marginal vitamin B6 deficiency (plasma PLP concentration between 20 and 30 nmol/L), which was induced by a 28 day B6-restricted diet, reduced plasma concentrations of EPA, DHA, and AA and increased slightly plasma n-6/n-3 PUFA ratio [ 10 ]. Thus, the data from animal and human studies thus far suggest that vitamin B6 deficiency may adversely affect PUFA compositions [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Gender Differences in the Associations of Plasma Pyridoxal 5′-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003–2004

et al. 2021

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Vitamin B6-restricted diets and low plasma pyridoxal 5′-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20–59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (β) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (β = 0.138, b = 0.104, p = 0.0004), DHA (β = 0.101, b = 0.058, p = 0.036), EPA + DHA (β = 0.125, b = 0.073, p = 0.005), EPA/AA (β = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (β = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

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“…Vitamin B family members with antioxidant activity—folic acid, vitamin B2 (riboflavin), and vitamin B6 (pyridoxine)—are reduced in SMK compared with nonsmokers. 32 , 33 In this study, urinary levels of Vitamin B2- and B6-associated metabolite (pyridoxate) were increased following product switching to either VS Original or VS Menthol. Vitamin B2 acts as a cofactor for glutathione (GSH) reductase.…”

Section: Discussionmentioning

confidence: 59%

Metabolomic Analysis Identified Reduced Levels of Xenobiotics, Oxidative Stress, and Improved Vitamin Metabolism in Smokers Switched to Vuse Electronic Nicotine Delivery System

Liu

Lin

Yates³

et al. 2020

Nicotine &Amp; Tobacco Research

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Introduction Switching to non-combustible tobacco products presents an opportunity for cigarette smokers to potentially reduce the health risks associated with smoking. Electronic Nicotine Delivery Systems (ENDS) are one such product since the vapor produced from ENDS contains far fewer toxicants than cigarette smoke. To investigate the biochemical effects of switching from smoking to an ENDS, we assessed global metabolomic profiles of smokers in a 7-day confinement clinical study. Methods In the first 2 days of this clinical study, the subjects used their usual brand of cigarettes and then switched to exclusive ENDS ad libitum use for 5 days. Urine and plasma samples were collected at baseline and 5 days after switching. The samples were analyzed using a mass spectrometry-based metabolomics platform. Results Random forest analyses of urine and plasma metabolomics data revealed excellent predictive accuracy (>97%) of a 30-metabolite signature that can differentiate smokers from 5-day ENDS switchers. In these signatures, most biomarkers are nicotine-derived metabolites or xenobiotics. They were significantly reduced in urine and plasma, suggesting a decreased xenobiotic load on subjects. Our results also show significantly decreased levels of plasma glutathione metabolites after switching, which suggests reduced levels of oxidative stress. In addition, increased urinary and plasma levels of vitamins and anti-oxidants were identified, suggesting enhanced bioavailability due to discontinuation of cigarette smoking and switching to ENDS use. Conclusions Our results suggest reduced toxicant exposure, reduced oxidative stress, and potential beneficial changes in vitamin metabolism within 5 days in smokers switching to an ENDS.

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Circulating B-Vitamins and Smoking Habits Are Associated with Serum Polyunsaturated Fatty Acids in Patients with Suspected Coronary Heart Disease: A Cross-Sectional Study

Cited by 8 publications

References 55 publications

Integrating Human Brain Proteomic Data with Genome-Wide Association Study Findings Identifies Novel Brain Proteins in Substance Use Traits

Integrating Human Brain Proteomic Data with Genome-Wide Association Study Findings Identifies Novel Brain Proteins in Substance Use Traits

Gender Differences in the Associations of Plasma Pyridoxal 5′-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003–2004

Metabolomic Analysis Identified Reduced Levels of Xenobiotics, Oxidative Stress, and Improved Vitamin Metabolism in Smokers Switched to Vuse Electronic Nicotine Delivery System

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