Safety assessment of menaquinone-7 for use in human nutrition

Ravishankar, B; Dound, Yogesh Arun; Mehta, Dilip; Ashok, B K; Souza, Anselm de; Pan, Min‐Hsiung; Ho, Chi Tang; Badmaev, Vladimir; Vaidya, Ashok D.B.

doi:10.1016/j.jfda.2014.03.001

Cited by 16 publications

(13 citation statements)

References 21 publications

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“…Nevertheless, a number of preclinical and clinical studies confirmed the safety of VK consumption. Several times higher dose levels than the estimated dietary intake for MK-7 did not show any toxicity in experimental animals [35]. In clinical studies, very high doses of MK-4 were used in the treatment of osteoporosis with no side effects [36].…”

Section: Introductionmentioning

confidence: 96%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

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As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.

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Section: Introductionmentioning

confidence: 96%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

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“…It was reported that MK-7 is a component of microbial plasma membranes and plays an important role in electron transport and oxidative phosphorylation [ 4 , 5 ]. Owing to its good bioavailability, MK-7 functions in protecting human health [ 6 ] by preventing osteoporosis [ 7 ], arterial calcification, cardiovascular disease, and Parkinson disease [ 8 , 9 ]. The cost of treating osteoporosis and cardiovascular diseases is high and will likely increase with the aging of populations.…”

Section: Introductionmentioning

confidence: 99%

Site-directed mutagenesis of the quorum-sensing transcriptional regulator SinR affects the biosynthesis of menaquinone in Bacillus subtilis

Zhao

et al. 2021

Microb Cell Fact

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Background Menaquinone (MK-7) is a highly valuable vitamin K2 produced by Bacillus subtilis. Common static metabolic engineering approaches for promoting the production of MK-7 have been studied previously. However, these approaches caused an accumulation of toxic substances and reduced product yield. Hence, dynamic regulation by the quorum sensing (QS) system is a promising method for achieving a balance between product synthesis and cell growth. Results In this study, the QS transcriptional regulator SinR, which plays a significant role in biofilm formation and MK production simultaneously, was selected, and its site-directed mutants were constructed. Among these mutants, sinR knock out strain (KO-SinR) increased the biofilm biomass by 2.8-fold compared to the wild-type. SinRquad maximized the yield of MK-7 (102.56 ± 2.84 mg/L). To decipher the mechanism of how this mutant regulates MK-7 synthesis and to find additional potential regulators that enhance MK-7 synthesis, RNA-seq was used to analyze expression changes in the QS system, biofilm formation, and MK-7 synthesis pathway. The results showed that the expressions of tapA, tasA and epsE were up-regulated 9.79-, 0.95-, and 4.42-fold, respectively. Therefore, SinRquad formed more wrinkly and smoother biofilms than BS168. The upregulated expressions of glpF, glpk, and glpD in this biofilm morphology facilitated the flow of glycerol through the biofilm. In addition, NADH dehydrogenases especially sdhA, sdhB, sdhC and glpD, increased 1.01-, 3.93-, 1.87-, and 1.11-fold, respectively. The increased expression levels of NADH dehydrogenases indicated that more electrons were produced for the electron transport system. Electrical hyperpolarization stimulated the synthesis of the electron transport chain components, such as cytochrome c and MK, to ensure the efficiency of electron transfer. Wrinkly and smooth biofilms formed a network of interconnected channels with a low resistance to liquid flow, which was beneficial for the uptake of glycerol, and facilitated the metabolic flux of four modules of the MK-7 synthesis pathway. Conclusions In this study, we report for the first time that SinRquad has significant effects on MK-7 synthesis by forming wrinkly and smooth biofilms, upregulating the expression level of most NADH dehydrogenases, and providing higher membrane potential to stimulate the accumulation of the components in the electron transport system.

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“…The adverse effects of menaquinones, including Menaquinone-7 has been investigated in several animal and in vitro toxicity studies. Findings from animal studies for acute, chronic, and genotoxicity and in vitro studies for mutagenicity and carcinogenicity showed no significant risks associated with exposure to menaquinones [3]. The absence of adverse effects or death suggest that the minimum lethal dose of Menaquinone-7 is greater than 2000 mg/kg bw [4].…”

Section: Menaquinone-7 Safetymentioning

confidence: 95%

Menaquinone-7: Wide Ranging Physiological Relevance in Muscle and Nerve Health

Mehta¹,

Souza²,

Jadhav³

2022

Biochemistry

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Menaquinone-7 plays a significant role in cardiovascular and bone health. In recent times there is a growing interest in understanding the role of Menaquinone-7 in health and diseases. Several population-based studies have reported specific health effects of the long-chain menaquinones, notably MK-7, MK-8, and MK-9. There are several epidemiological studies, clinical trials, along with in vivo and in vitro studies confirming the role of Menaquinone-7 in health and diseases. More recently, research group at Synergia Life Sciences has discovered a wider role for Menaquinone-7 in energy homeostasis (VO2max), peripheral neuropathy, muscle cramps and mitochondrial respiration not only through improvement of the electron transport but also the perfusion improving oxygen availability. In the current chapter, the authors have discussed the wider physiological role of Menaquinone-7 highlighting the recent research with Menaquinone-7 in the areas of Muscle and Nerve Health.

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Safety assessment of menaquinone-7 for use in human nutrition

Cited by 16 publications

References 21 publications

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

Site-directed mutagenesis of the quorum-sensing transcriptional regulator SinR affects the biosynthesis of menaquinone in Bacillus subtilis

Menaquinone-7: Wide Ranging Physiological Relevance in Muscle and Nerve Health

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