Effect of vitamin K supplementation on insulin resistance in older men and women.
Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg C, Dawson-Hughes B, Dallal G, Booth SL.
Diabetes Care. 2008 Nov;31(11):2092-6. Epub 2008 Aug 12.
OBJECTIVE: Vitamin K has a potentially beneficial role in insulin resistance, but evidence is limited in humans. We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women.
RESEARCH DESIGN AND METHODS: This was an ancillary study of a 36-month, randomized, double-blind, controlled trial designed to assess the impact of supplementation with 500 microg/day phylloquinone on bone loss. Study participants were older nondiabetic men and women (n = 355; aged 60-80 years; 60% women). The primary outcome of this study was insulin resistance as measured by homeostasis model assessment (HOMA-IR) at 36 months. Fasting plasma insulin and glucose were examined as the secondary outcomes.
RESULTS: The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex x treatment interaction P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women.
CONCLUSIONS: Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men.
PMID: 18697901 [PubMed – indexed for MEDLINE]PMCID: PMC2571052
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Excerps from the article:
Limited evidence from human and animal studies suggests that vitamin K may be inversely associated with insulin resistance (1– 4). In an observational study, higher dietary and supplemental vitamin K intakes were associated with greater insulin sensitivity and better glycemic status in a community-based cohort of men and women (3). In a small metabolic study of young men (n 12), short-term (1-week) vitamin K supplementation improved the insulin response after an oral glucose challenge (2).
Although these studies support a potential novel role for vitamin K in insulin resistance, the available human data are limited. Furthermore, biological mechanisms behind the association be- tween vitamin K and insulin and glucose metabolism are uncertain. Vitamin K and vitamin K–dependent proteins (pro- thrombin and protein S) have been identified in organs important for glucose and insulin metabolism, such as liver and pancreas (5,6). However, the function of vitamin K is not well understood beyond its role as an enzyme cofactor for gamma-carboxylation of certain glutamic acid residues in vitamin K– dependent proteins (7).
CONCLUSIONS — The major finding of this study was that daily supplementation with 500 ug of phylloquinone for 36 months had a protective effect on progression of insulin resistance in older men.
In an animal study, rats fed a low vitamin K diet had impaired early insulin response and subsequent increased insulin secretion after intravenous administration of glucose (1).
Higher vitamin K intake was cross-sectionally associated with reduced insulin resistance in both men and women in the Framingham Off- spring cohort (3).
A metabolic study of young men showed a significant association between vitamin K and post-glucose challenge measures, but not fasting measures (2).
In our study, a beneficial effect of vitamin K supplementation for 36 months was observed using fasting measures of insulin resistance.
Recent studies proposed that the un-carboxylated form of osteocalcin, a vitamin K– dependent bone protein, may improve insulin sensitivity and increase beta-cell insulin secretion partially through the enhancement of beta-cell proliferation, energy expenditure, and adiponectin ex-pression in mice (16,17).
In our study, men receiving vitamin K supplementation had less uncarboxylated osteocalcin than the control group, which does not support the findings of the animal studies.
Alternatively, it is plausible that vitamin K may improve insulin sensitivity through suppression of inflammation.
In vivo and in vitro studies have shown that vitamin K reduced lipopolysaccharide-induced inflammation (18,19).
More recently, it was reported that biochemical and dietary measures of vitamin K status were inversely associated with inflammatory markers in an observational study (20).
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This study indicates that Vitamin K, a fat soluble vitamin, has an important role in blood sugar control. The dose for supplementation of phylloquinone is 500 ug/day.