NattoPharma to conduct highest-dosage K2 study in cardio clinical trial

08 Jun 2021 --- An 18 month clinical trial using NattoPharma’s MenaQ7 Vitamin is registered to kick off this September using the highest dosage of vitamin K2 as MK-7 to date: 1 mg daily.

The trial will examine arterial stiffness and the occurrence of cardiovascular events in peritoneal dialysis (PD) patients with chronic kidney disease (CKD), a state of progressive vascular calcification and cardiovascular disease.

“This study will add to the already substantial evidence that MenaQ7 vitamin K2 is an important cardiovascular-support nutrient, and it presents great hope for an at-risk patient population,” says Dr. Hogne Vik, chief medical officer with NattoPharma.

“People with kidney problems exhibit low vitamin K status, which has been shown to increase cardiovascular disease as well as mortality risk.”

The project represents two important firsts, according to Dr. Vik. It will be the first trial in PD patients, and it will be the highest dosage studied, which supports the safety profile of the nutrient. 

“Vitamin K2 supplementation has shown to be effective to improve vitamin K status in kidney patients to some extent. However, none of these trials have been conducted in PD patients, but only in pre-dialysis CKD, hemodialysis subjects or kidney transplant patients.”

People with kidney problems exhibit low vitamin K status, according to NattoPharma.A Greek and Dutch collaboration
The investigators at Aristotle University of Thessaloniki in Greece will study the effect of K2 supplementation through normalization of desphospho-uncarboxylated matrix Gla (dp-ucMGP), which is associated with arterial stiffness.

Long-time NattoPharma research partner Maastricht University will also collaborate by evaluating vitamin K status.

The multi-center, placebo-controlled, randomized, open-label intervention clinical trial will be entitled “The Effect of Vitamin K2 Supplementation on Arterial Stiffness and Cardiovascular Events in PEritonial DIAlysis (VIKIPEDIA).”

“Several studies have shown that hemodialysis patients have vitamin K depletion and accelerated vascular calcification, and this finding led to the initiation of several randomized controlled trials exploring the effect of vitamin K2 supplementation on vascular calcification in hemodialysis patients,” explains lead researcher Stefanos Roumeliotis, MD, PhD. 

“VIKIPEDIA is the first study to assess whether the high dosage of Menaquinone-7 could improve arterial stiffness, mortality, cardiovascular disease, 24-hour ambulatory blood pressure and dialysis efficacy in patients with PD.”

At baseline, all eligible patients who have provided a written, informed consent will be enrolled in the study. Αortic stiffness and vitamin K status will be assessed by PWV and plasma dp-ucMGP levels respectively. 

Before randomization, the investigators will draw blood (serum and plasma) and PD fluid samples from all patients to measure blood count and routine biochemical parameters These include urea, creatinine, potassium, sodium, calcium, phosphorus, c-reactive protein, alkaline phosphatase, albumin, parathormone, 25-OH D3, magnesium, glycated hemoglobin and thyroid function hormones.

Patients with vitamin D or magnesium depletion will be treated with oral supplements before randomization.Setting the baseline with critical nutrients
Since both vitamin D and magnesium are considered of utmost importance in vitamin K metabolism, after baseline, patients with vitamin D and/or magnesium depletion will be treated with oral supplements to achieve normal levels of both elements before randomization. 

It is important to note, says Dr. Vik, that researchers recognized the importance of optimal levels of vitamin D and magnesium to support the function of vitamin K2. 

“That is why patients deficient with vitamin D or magnesium will be treated with these nutrients to reach normal levels before randomization.”

The cohort will then be categorized into one of the two groups (placebo or active group), and the treatment period will last 1.5 years. 

To ensure that the two parallel groups will include patients that will not differ significantly in vitamin K and stiffness, patients will be accordingly stratified. 

After randomization, all patients will continue their routine, standard medical treatment and patients in the treatment group will additionally receive daily, per 1 mg of vitamin K2 (NattoPharma’s MenaQ7). VIKIPEDIA is currently registered on ClinicalTrials.gov. 

Increasing demand for K2
Vitamin K2 has earned its place in the nutraceutical spotlight for its role in activating matrix Gla proteins in synergy with vitamin D3, as highlighted by KappaBioscience, resulting in calcium being diverted from arteries and into bones. 

This mechanism of action makes vitamin K2 a top contender to address bone, heart health and other forms of calcification in the body. 

The MK-7 form of K2 has also been investigated for its potential link to less severe COVID-19 outcomes. 

As new research illuminates vitamin K2’s potential, demand is on the rise. Earlier this year, Norway-based Kappa Bioscience announced it was expanding its vitamin K2 business to the US, where “the number of clients and projects require dedicated local resources.”

By Missy Green