Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation

Westerman, Kenneth; Kelly, Jennifer; Ordovás, José M.; Booth, Sarah L.; DeMeo, Dawn L.

doi:10.1080/15592294.2020.1734714

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…Nevertheless, levels of each K vitamers at each tissue/system might depend on the considered vertebrate species, gender, population, and/or the daily dietary uptake [ 1 , 16 , 26 ]. Furthermore, a variable response to VK1 dietary supplementation in humans was recently associated to differences in DNA methylation in multiple genomic regions [ 27 ].…”

Section: Vitamin K Metabolites Sources and Metabolismmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.

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Section: Vitamin K Metabolites Sources and Metabolismmentioning

confidence: 99%

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

2020

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“…Given the observation that Vitamin K1 levels can be increased in seven days and diminished in 28 days or less, it is clear that the potential benefits of GLV might require sustained consumption. Estimating a minimally therapeutic dose of GLV is warranted, though it is already established that a number of genetic variants affect Vitamin K1 absorption and metabolism [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

A Dietary Intervention High in Green Leafy Vegetables Reduces Oxidative DNA Damage in Adults at Increased Risk of Colorectal Cancer: Biological Outcomes of the Randomized Controlled Meat and Three Greens (M3G) Feasibility Trial

et al. 2021

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Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) > 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p < 0.001) increased, while circulating 8OHdG (−8.52 ± 19.05 ng/mL, p < 0.001), fecal 8OHdG (−6.78 ± 34.86 ng/mL, p < 0.001), and TNFα (−16.95 ± 60.82 pg/mL, p < 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted.

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“…These results link a nutrient and possible direct, or indirect [133], mTOR inhibitor, in possible agerelated metabolic pathologies. In another diet-related EWAS study, blood-based differential methylomes comparing responders and non-responders to vitamin K1 supplementation (identified in a 3-year supplementation test) revealed multiple regions with previously unknown relationships to Vitamin K1 absorption and metabolism, such as at the TMEM263 locus [135], coding a gene previously reported to be involved in skeletal dysplasia [136]. Finally, in another study, differential methylome was examined after bariatric surgery.…”

Section: Ewas Studies In Human Lifespan and Healthspan: Links To Diet?mentioning

confidence: 98%

Nutrient-Response Pathways in Healthspan and Lifespan Regulation

Dabrowska

Kumar

Rallis

2022

Cells

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Cellular, small invertebrate and vertebrate models are a driving force in biogerontology studies. Using various models, such as yeasts, appropriate tissue culture cells, Drosophila, the nematode Caenorhabditis elegans and the mouse, has tremendously increased our knowledge around the relationship between diet, nutrient-response signaling pathways and lifespan regulation. In recent years, combinatorial drug treatments combined with mutagenesis, high-throughput screens, as well as multi-omics approaches, have provided unprecedented insights in cellular metabolism, development, differentiation, and aging. Scientists are, therefore, moving towards characterizing the fine architecture and cross-talks of growth and stress pathways towards identifying possible interventions that could lead to healthy aging and the amelioration of age-related diseases in humans. In this short review, we briefly examine recently uncovered knowledge around nutrient-response pathways, such as the Insulin Growth Factor (IGF) and the mechanistic Target of Rapamycin signaling pathways, as well as specific GWAS and some EWAS studies on lifespan and age-related disease that have enhanced our current understanding within the aging and biogerontology fields. We discuss what is learned from the rich and diverse generated data, as well as challenges and next frontiers in these scientific disciplines.

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Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation

Cited by 13 publications

References 45 publications

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species

A Dietary Intervention High in Green Leafy Vegetables Reduces Oxidative DNA Damage in Adults at Increased Risk of Colorectal Cancer: Biological Outcomes of the Randomized Controlled Meat and Three Greens (M3G) Feasibility Trial

Nutrient-Response Pathways in Healthspan and Lifespan Regulation

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