Effect of vitamin K2 on body fat and body mass in humans-Results of a 3-year study
The pathophysiology of fat metabolism and its related changes in body composition has since long been a widely studied domain among medical professionals. Recent research has put the focus on the interlink between fat metabolism and hemostasis of bone in humans. (1, 2)
In the last decade, extensive research has highlighted the fact that osteocalcin, an osteoblast-specific protein, plays an important role in fat as well as glucose metabolism in humans. (3,4) Previous studies, both in vivo and in vitro, have proved that uncarboxylated osteocalcin(Ucoc) helps in the breakdown of fat, thus reducing the body mass(5); whereas an increase in the levels of carboxylated osteocalcin reduces the rate of fat metabolism (6) leading to obesity. Contrary to such results, a few other studies have suggested regular supplementation with Vitamin K2 reduced total fat accumulation and serum triglycerides in rats (7). To date, human trials have provided contradicting results regarding the role of osteocalcin in fat metabolism.
Vitamin K2 has long been identified to help in the carboxylation of osteocalcin (8), playing a pivotal role in altering the fat metabolism, fat accumulation and the glucose status of individuals kept on regular supplements.
Keeping in view the fact that recent studies have shown the beneficial effects of vitamin K2 supplementation in humans, specifically in body fat and body weights in humans, a study was conducted by MHJ Knapen et al (8), from the Maastricht University, Maastricht, The Netherlands, in 2017, to verify whether high vitamin K intake influences body weight or composition in apparently healthy women. The research team tested the hypothesis that increased vitamin K intake decreases body fat or fat distribution.
The findings were put forth in the European Journal of Clinical Nutrition.
The study design consisted of a randomized placebo-controlled human intervention trial, where 214 postmenopausal women, 55–65 years of age, with a body mass index <30 kg/m2, not using medication known to affect calcium and bone metabolism and/or vitamin K-containing supplements, who received either 180 mcg/day of vitamin K2 (menaquinone-7, MK-7) or placebo for 3 years. Osteocalcin (OC) carboxylation was used as a marker for vitamin K status, and fat distribution was assessed by dual-energy X-ray absorptiometry total body scan.
There were no dietary restrictions and participants were asked to continue their regular diet and physical activities throughout the study. No side effects have been reported of long-term use of MK-7 in the study dose.
The waist-to-hip ratio was calculated by taking the ratio between the waist and hip circumference (both in cm), with a precision of 0.5 cm.
Data analysis highlighted the following facts.
• In the total cohort, MK-7 supplementation increased circulating carboxylated OC (cOC) but did not affect body composition.
• In those with an above-median response in OC carboxylation ('good responders', who were defined as those who had increased their circulating cOC concentration with a value above the 50th percentile of the 3-year change of this variable), MK-7 treatment resulted in a significant increase in total and human molecular weight adiponectin and a decrease in abdominal fat mass and the estimated visceral adipose tissue area compared with the placebo group and the poor responders.
Focusing on the results, the research team arrived at some important opinions, as has been summarized below.
1. Poor vitamin K status at baseline (as deduced from low serum cOC concentrations) is associated with a higher waist circumference and a higher fat mass in the android region in healthy women between 55 and 65 years. Further, the researchers found that poor vitamin K status (low cOC) is associated with higher levels of the pro-inflammatory marker hsCRP.
2. A major finding noted was that increasing cOC at the expense of ucOC by vitamin K supplements was paralleled by a decreased ratio between the android/gynoid fat mass ratio and a decreased estimated visceral fat area.
3. Inverse associations were noted between cOC and insulin, and leptin, pointing towards the involvement of cOC in the endocrine pathways as well as in glucose homeostasis. This fact is supported by previous studies where phylloquinone supplementation improved the glycemic status independent of the effects of adiponectin levels in premenopausal women with prediabetes.
4. This study also highlighted the anti-inflammatory effect of vitamin K2, observing that as the levels of cOC increased, there was a fall in the levels of CRP, a biomarker of low-grade chronic inflammation.
5. No significant associations were found between the vitamin K-induced change in cOC and several biomarkers for fat and glucose metabolism.
Taking a cue from the observations, the team concluded that," In this trial, we demonstrate the beneficial effects of vitamin K supplementation on fat mass and body composition. Our data suggest that cOC rather than ucOC is a key component in the interplay between bone and energy metabolism, but the precise mechanism underlying this effect remains to be determined in future studies. The fact that changes in body composition measures or markers for fat or glucose metabolism were not associated with changes in uncarboxylated OC (ucOC) does not support the assumption that ucOC stimulates fat metabolism in humans. Instead, high vitamin K2 intake may support reducing body weight, abdominal and visceral fat, notably in subjects showing a strong increase in cOC. A causal relationship between the changes in cOC and body fat or distribution cannot be concluded from these data."
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Vitamin K, click here
References
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2. Shapses, S. A., & Sukumar, D. (2012). Bone metabolism in obesity and weight loss. Annual review of nutrition, 32, 287–309. https://doi.org/10.1146/annurev.nutr.012809.104655
3. Kanazawa I. (2015). Osteocalcin as a hormone regulating glucose metabolism. World journal of diabetes, 6(18), 1345–1354. https://doi.org/10.4239/wjd.v6.i18.1345
4. Booth, S. L., Centi, A., Smith, S. R., & Gundberg, C. (2013). The role of osteocalcin in human glucose metabolism: marker or mediator?. Nature reviews. Endocrinology, 9(1), 43–55. https://doi.org/10.1038/nrendo.2012.201
5. Schafer, A. L., Sellmeyer, D. E., Schwartz, A. V., Rosen, C. J., Vittinghoff, E., Palermo, L., Bilezikian, J. P., Shoback, D. M., & Black, D. M. (2011). Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). The Journal of clinical endocrinology and metabolism, 96(12), E1982–E1989. https://doi.org/10.1210/jc.2011-0587
6. Patti, A., Gennari, L., Merlotti, D., Dotta, F., & Nuti, R. (2013). Endocrine actions of osteocalcin. International journal of endocrinology, 2013, 846480. https://doi.org/10.1155/2013/846480
7. Sogabe N, Maruyama R, Baba O, Hosoi T, Goseki-Sone M. Effects of long-term vitamin K(1) (phylloquinone) or vitamin K(2) (menaquinone-4) supplementation on body composition and serum parameters in rats. Bone. 2011 May 1;48(5):1036-42. doi: 10.1016/j.bone.2011.01.020. Epub 2011 Feb 2. PMID: 21295170.
8. Gundberg, C. M., Lian, J. B., & Booth, S. L. (2012). Vitamin K-dependent carboxylation of osteocalcin: friend or foe?. Advances in nutrition (Bethesda, Md.), 3(2), 149–157. https://doi.org/10.3945/an.112.001834
9. Knapen, M., Jardon, K. & Vermeer, C. Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. Eur J Clin Nutr 72, 136–141 (2018). https://doi.org/10.1038/ejcn.2017.146
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