August 15, 2008 — Vitamin K supplementation for 36 months at doses that could be achieved through dietary intake may reduce progression of insulin resistance in older men, according to the results of a study reported in the August 12 Online First issue of Diabetes Care.

"Vitamin K has a potentially beneficial role on insulin resistance, but evidence is limited in humans," write Makiko Yoshida, PhD, from the Jean Mayer US Department of Agriculture Human Nutrition Research Center at Tufts University in Boston, Massachusetts, and colleagues. "We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women."

This was an ancillary study of a 36-month, randomized, double-blind, controlled clinical trial in which the primary objective was to determine the effect of supplementation with 500 μg/day of phylloquinone (vitamin K) on bone loss. The study sample consisted of 355 nondiabetic adults aged 60 to 80 years; 60% were women. The main endpoint was insulin resistance, measured by the homeostasis model (HOMA-IR) evaluated at 36 months, and secondary endpoints were fasting plasma insulin and glucose.

The affect on the HOMA-IR of 36-month vitamin K supplementation was different in men and in women (sex-by-treatment interaction: P = .02). Compared with men in the control group, men in the supplement group had statistically significantly lower HOMA-IR at 36 months (P = .01), after adjustment for baseline HOMA-IR, body mass index (BMI), and body weight change. Women in the 2 intervention groups did not differ significantly in HOMA-IR or in other outcome measures.

"Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men," the study authors write. "There was an inverse association between plasma phylloquinone concentrations and BMI in the women suggestive of an impaired response to vitamin K supplementation."

Limitations of this study include analyses of data obtained from a study designed to determine the effect of vitamin K supplementation on changes in bone mineral density and vascular calcification in older men and women; possible lack of generalizability to the overall population; measures presented not necessarily obtained by optimal techniques; limited statistical power to detect differences in HOMA-IR in response to vitamin K supplementation; and predominantly Caucasian sample.

"In summary, 36 months of vitamin K supplementation had a beneficial effect on insulin resistance in older men, but not older women," the study authors conclude. "As the parent study was not designed to test this hypothesis, these findings need to be replicated in a study designed specifically to test the hypothesis that vitamin K plays a protective role in insulin resistance in older adults."

Hermes Arzenemittel GMBH, Munich, Germany, donated the supplements used for this study. The US Department of Agriculture and American Heart Association supported this study. The Ministry of Education, Culture, Sports, and Technology in Japan supported one author and the American Diabetes Association supported another author.

Diabetes Care. Published online August 12, 2008.

Clinical Context

Study Highlights

• Included were men and women aged 60 to 80 years who were part of a vitamin K supplementation trial to reduce age-related bone loss and vascular calcification. The primary outcome was femoral neck bone mineral density.
• Excluded from this study were those with coronary artery disease, renal disease, osteoporosis, use of medications affecting bone, and diabetes.
• Diabetes was defined as fasting glucose of 126 mg/dL or higher or use of hypoglycemic agents.
• Participants maintained their usual diets and were told to avoid dietary supplements other than those provided.
• Participants had BMI, percentage body fat, and other laboratory measures taken.
• Total body fat was measured by dual energy x-ray absorptiometry scan.
• Physical activity was assessed using the Physical Activity for Elderly questionnaire.
• Dietary intake was assessed using the Harvard food frequency questionnaire.
• Adherence was assessed by self-reported pill count.
• Primary outcome was insulin resistance measured by the HOMA-IR at 36 months.
• Secondary outcomes were fasting plasma insulin and glucose.
• 355 participants (142 men) were assigned to either 500 μg/day of phylloquinone (vitamin K) or a control multivitamin without vitamin K daily for 36 months.
• Both groups received 600 mg of elemental calcium and 400 IU of vitamin D daily.
• 60% were women, mean age was 68 years, and 59% to 74% were overweight or obese.
• In both men and women, plasma phylloquinone levels were significantly increased in the treatment group vs the control group at 36 months, indicating adherence to the supplementation.
• In men, HOMA-IR and plasma insulin levels were significantly lower at 36 months in the vitamin K group vs the control group even after controlling for BMI and weight changes.
• There were no significant differences in HOMA-IR or plasma insulin in men at 6 months.
• Fasting plasma glucose did not differ among men in the 2 groups at any point.
• There were no significant differences in HOMA-IR, plasma insulin, or fasting glucose among women in the 2 groups at any point.
• Percentage body fat was not correlated with plasma phylloquinone levels in men or women.
• Among women, there was a significant increase in mean percentage body fat of 0.6% during the 36 months (P = .002), but body weight did not change.
• In men, the mean body weight decreased by 0.5 kg (P = .02) from baseline, and body fat increased by 0.5% (P = .001).
• The authors concluded that daily supplementation with 500 μg of vitamin K for 36 months had a protective effect on progression of insulin resistance in older men, but not older women.
• This level of vitamin K supplementation is also attainable in the diet.
• However, the authors speculated that because women in this study were more likely to be obese or overweight, adipose tissue may have rendered the vitamin K less bioavailable in women.

Pearls for Practice

• In older men, use of vitamin K supplements (500 μg/day of phylloquinone) for 36 months is associated with reduced insulin resistance and insulin levels and no change in fasting glucose.
• In older women, use of vitamin K supplements (500 μg/day of phylloquinone) for 36 months is not associated with significant reduction in insulin resistance, insulin levels, or fasting glucose.

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