TReVasc-HDK Trial examined the efficacy of K2 supplementation in reducing vascular calcification progression in hemodialysis patients, offering new insights on appropriate dosing.
Gnosis by Lesaffre is eager to share that Kidney International Reports has published a new study using MenaQ7® Vitamin K2 as MK-7 that explored the relationship between vitamin K2 menaquinone-7 (MK-7) supplementation on coronary artery calcification progression in 138 kidney dialysis patients. The study concluded that 360 mcg MK-7 thrice weekly for 18 months was not enough to provide statistically significant improvement in slowing vascular calcification progression in this population.
It has been established that individuals on hemodialysis have impaired function of matrix GLA protein (MGP), a powerful vitamin K-dependent inhibitor of vascular calcification. MK-7 activates MGP, and increased activated MGP helps protect arteries from calcification. The researchers hypothesized that oral menaquinone-7 (MK-7) would enhance the carboxylation of MGP, reduce levels of undercarboxylated (inactive) MGP, and therefore reduce coronary artery calcification (CAC) in the hemodialysis (HD) population.
The kidney population participating in the Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K (TReVasc-HDK) study,1 a single-center, prospective, open-label interventional clinical trial on HD patients at the National University Hospital, Singapore, represented a multiethnic Asian population with an extremely low extrahepatic K status represented by high dp-ucMGP, inactive form of MGP. They were randomized to vitamin K2 supplementation or standard care between July 2016 and February 2019.
After 18 months, the researchers found that there was no statistical difference between the supplementation group and placebo group in CAC scores, although K2 supplementation was found to reduce undercarboxylated MGP. The researchers concluded, “TReVasc-HDK does not suggest a beneficial effect of oral vitamin K2 supplementation in attenuating VC or arterial stiffness at a dose of 360 µg 3x/week despite a significant reduction in dp-ucMGP. Our findings are consistent with three priors smaller RCTs on vitamin K supplementation which reported progression of VC in HD patients.”
They added that there may be a possibility that K2 supplementation at higher doses or provided earlier in the development of vascular calcification may provide a quantifiable benefit in this population. Further, many other factors might contribute to the initiation and progression of VC via non-vitamin K-dependent mechanisms.
“This study found that vitamin K2 supplementation did not attenuate vascular calcification or arterial stiffness at a dose of 360 mcg three times per week, which strongly suggests that kidney patients on dialysis would need higher doses to achieve protection benefit against arterial calcification,” says Sophie Legrain-Raspaud, Gnosis Research & Application Director.
While the dose of 360 mcg of vitamin K2 as MK7 three times a week was able to produce a 20% reduction in dpucMGP in this trial, the dose was too low to optimally improve extrahepatic K status.
Two previous studies of MenaQ7® in kidney patients yielded some promising data. Kurnatowska et al. published the first clinical trial in kidney patients in 2015, which yielded positive results with just 90 mcg daily combined with 10 mcg of vitamin D3.2 Mansour et al. showed an improvement in arterial elasticity in kidney transplant patients with 360 mcg/daily in 2017.3 These outcomes were repeated by others in 2022.4
“There is a clear need for the optimization of vitamin K status in kidney patients, and this study is critically important in helping to understand what doses will ultimately work to provide protective cardiovascular benefits to individuals on hemodialysis,” adds Legrain-Raspaud. “In the progress of researching an ingredient, some studies will not find a conclusive benefit due to any number of reasons. This knowledge gained helps guide future trials that could yield the hypothesized results, particularly once a beneficial dose range is pinpointed.”
Other K2 research has yielded many important insights since this study was initiated in 2016. To that end, other MenaQ7® trials have considered higher dosages, such as the VIKIPEDIA trial in Greece,5 which will study the effects using the highest dosage to date: 1 mg MK-7 daily. Further, outside of the optimization of extrahepatic K status, VIKIPEDIA will optimize vitamin D, vitamin K2, and magnesium levels – three nutrients known to support vascular health.
“While the present study findings might be characterized as ‘unsuccessful”, it should not hinder enthusiasm to proceed forward as this is integral to a sound exploratory scientific method,” adds Marc Philouze, Gnosis by Lesaffre General Manager. “Rather, the insights gained help design future trials to answer clinically highly relevant questions. The pursuit of scientific knowledge and discovery is not always so straightforward.”
References
Published June 15, 2024
About Gnosis by Lesaffre
Gnosis by Lesaffre harnesses the power of microorganisms and biotransformation processes like fermentation to cultivate nutritional actives, probiotics, and nutritional and functional yeasts that benefit human health and well-being. The team draws on its focused research and application capabilities to collaborate with nutraceutical and pharmaceutical brands to develop game-changing products for their customers.
Gnosis by Lesaffre – Exploring Life to Improve Living. http://www.GnosisByLesaffre.com
About Lesaffre
A key global player in fermentation for more than a century, Lesaffre, with a 2,7 billion euro turnover, and established on all continents, counts 11,000 employees and more than 90 nationalities. On the strength of this experience and diversity, we work with customers, partners, and researchers to find ever more relevant answers to the needs of food, health, naturalness, and respect for our environment. Thus, every day, we explore and reveal the infinite potential of microorganisms.
To nourish 9 billion people, in a healthy way, in 2050 by making the most of our planet’s resources is a major and unprecedented issue. We believe that fermentation is one of the most promising answers to this challenge.
Lesaffre – Working together to better nourish and protect the planet. www.lesaffre.com