Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial

Choi, Hyung Jin; Yu, Juyoun; Choi, Hosanna; An, Jee Hyun; Kim, Sang Wan; Park, Kyong Soo; Jang, Hak Chul; Kim, Seong Yeon; Shin, Chan Soo

doi:10.2337/dc11-0551

Cited by 93 publications

(71 citation statements)

References 5 publications

(7 reference statements)

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“…Conflicting data were revealed in a recently published study, where vitamin K2 supplementation was found to increase insulin sensitivity in healthy young men. Interestingly, this effect was ascribed to an elevation of serum cOC levels (72).…”

Section: Clinical Evidence From Measurement Of Ucocmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Schwetz

Pieber²,

Obermayer-Pietsch

2012

European Journal of Endocrinology

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Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, b-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated. European Journal of Endocrinology 166 959-967

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Section: Clinical Evidence From Measurement Of Ucocmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Schwetz

Pieber²,

Obermayer-Pietsch

2012

European Journal of Endocrinology

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“…On the basis of these studies, it seems safe to argue that sex can also have a role in the relationships between OC and insulin resistance. In another study by Choi et al, 28 in which 42 healthy young men were studied, it was demonstrated that 30 mg of vitamin K2 supplementation for 4 weeks increased insulin sensitivity. Hence, it is suggested to compare the effects on male and female individuals in a study in order to shed more light on the relationship between osteocalcin and insulin resistance in the future studies.…”

Section: Resultsmentioning

confidence: 96%

The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: a double-blind randomized controlled clinical trial

et al. 2015

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“…Given calcium's dependency on K2 assisted carboxylation with respect to osteocalcin and matrix GLA proteins, further study may show that K2 is similarly involved in activation of salivary signaling and composition. It has already been demonstrated with insulin [46] and the exocrine secretions of the pancreas [47]. Saliva is a significant factor in the mineralization and demineralization of the erupted tooth's enamel as pH changes.…”

Section: The Systemic Approach Reveals the Overlooked Importance Of Amentioning

confidence: 92%

A hypothetical role for vitamin K2 in the endocrine and exocrine aspects of dental caries

Southward¹

2015

Medical Hypotheses

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The growing interest in oral/systemic links demand new paradigms to understand disease processes. New opportunities for dental research, particularly in the fields of neuroscience and endocrinology will emerge. The role of the hypothalamus portion of the brain cannot be underestimated. Under the influence of nutrition, it plays a significant role in the systemic model of dental caries. Currently, the traditional theory of dental caries considers only the oral environment and does not recognize any significant role for the brain. The healthy tooth, however, has a centrifugal fluid flow to nourish and cleanse it. This is moderated by the hypothalamus/parotid axis which signals the endocrine portion of the parotid glands. High sugar intake creates an increase in reactive oxygen species and oxidative stress in the hypothalamus. When this signaling mechanism halts or reverses the dentinal fluid flow, it renders the tooth vulnerable to oral bacteria, which can now attach to the tooth's surface. Acid produced by oral bacteria such as Strep Mutans and lactobacillus can now de-mineralize the enamel and irritate the dentin. The acid attack stimulates an inflammatory response which results in dentin breakdown from the body's own matrix metalloproteinases. Vitamin K2 (K2) has been shown to have an antioxidant potential in the brain and may prove to be a potent way to preserve the endocrine controlled centrifugal dentinal fluid flow. Stress, including oxidative stress, magnifies the body's inflammatory response. Sugar can not only increase oral bacterial acid production but it can concurrently reduce the tooth's defenses through endocrine signaling. Saliva production is the exocrine function of the salivary glands. The buffering capacity of saliva is critical to neutralizing the oral environment. This minimizes the de-mineralization of enamel and enhances its re-mineralization. K2, such as that found in fermented cheese, improves salivary buffering through its influence on calcium and inorganic phosphates secreted. Data collected from several selected primitive cultures on the cusp of civilization demonstrated the difference in dental health due to diet. The primitive diet group had few carious lesions compared to the group which consumed a civilized diet high in sugar and refined carbohydrates. The primitives were able to include the fat soluble vitamins, specifically K2, in their diet. More endocrine and neuroscience research is necessary to better understand how nutrition influences the tooth's defenses through the hypothalamus/parotid axis. It will also link dental caries to other inflammation related degenerative diseases such as diabetes.

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Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial

Cited by 93 publications

References 5 publications

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: a double-blind randomized controlled clinical trial

A hypothetical role for vitamin K2 in the endocrine and exocrine aspects of dental caries

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