Essential vitamins A, C, D and E have been common components of multivitamin formulations for decades, but a relative newcomer has seen its stock steadily rising: vitamin K.
 
Important for optimal bone and cardiovascular health, vitamin K comprises a number of structurally related compounds, including phylloquinones (vitamin K1) and menaquinones (vitamin K2).
 
“Vitamin K1 is known for its role in blood coagulation (clotting),” noted Eric Anderson, senior vice president of global marketing and business development, NattoPharma USA, Inc., Edison, NJ, supplier of branded MenaQ7 Vitamin K2 as MK-7. “Vitamin K2 also contributes to coagulation, but more importantly, it is now recognized for its essential role in building and maintaining strong bones, as well as inhibiting calcium deposits in the arteries and blood vessels.”
 
All K vitamins are similar in structure, but differ in the length of the “side chain”—the longer the side chain, the better effect and efficiency, Mr. Anderson explained. “Consequently, the long-chain menaquinones (especially MK-7) are the most desirable as they are nearly completely absorbed and stay in the blood for the longest time. This makes vitamin K2 also available for tissues outside the liver, namely bones, arteries, and soft tissues.”
 
In fact, studies consistently show that vitamin K2 as MK-7 is more effective compared to MK-4, mainly due to MK-7’s significantly greater absorption and half-life, accumulation in the serum, and efficacy.
 
Understanding about the vitamin K forms has come a long way since the 1950s, said Dan Murray, vice president, business development, Xsto Solutions, LLC, Morristown, NJ, which supplies K2VITAL brand vitamin K2 MK-7 from Kappa Bioscience. “The challenge for K1 was the strong coagulation properties were beneficial for some, but not for all. The second generation was vitamin K2 MK-4, (menaquinone 4) offering some bone benefit with less powerful coagulation properties, but it has stability challenges and literally requires 1,000-times the dose of the more advanced form K2 MK-7. The current form of K2 MK7 (menaquinone 7) offers a more optimum package of stability, bone and heart benefits, but with reduced negative blood clotting aspects.” 
 
Fermented foods like natto are the primary food source of vitamin K2, as well as certain cheeses and animal products, like egg yolks.
 
Market Success
Thanks to recent clinical research, growing consumer awareness, manufacturing efficiencies, and lower price-points, the market for vitamin K2 has been accelerating, according to experts.
 
“We would conservatively estimate the global ingredient market for vitamin K2 is in the $30-35 million range, which as a specialty ingredient equates to about $300 million at retail,” said Mr. Anderson. “Importantly, most products today are in the bone health segment. The strength of NattoPharma’s MenaQ7 cardiovascular science is now driving heart health products globally. And the ultimate goal is multivitamins for prenatals, infant nutrition, kids, teens, and adults. This will ultimately grow the market exponentially.”
 
The vitamin K2 market has already been growing at a “tremendous pace,” essentially doubling annually over the past few years, said Mr. Murray. “When an ingredient is new and relatively small volume this is not so difficult, but at current volumes this is impressive growth.”
 
Several factors are coming together to support the growth trajectory of vitamin K2, he added, principally a strong body of science. “Consumer awareness for bone health started years ago with calcium. Followed by the explosive growth of vitamin D, K2 is now appreciated for the cardiovascular benefit in addition to the bone benefit. With this significant growth, manufacturers are realizing some production efficiencies and that has helped bring down raw material prices. The trifecta of good science, growing awareness, and falling prices is pulling K2 into more and more formulas.”
 
NattoPharma has been focused on driving awareness by educating the market about the importance of vitamin K2 for human health; finished product brands have played an important role toward that end, said Mr. Anderson. “As the leader in vitamin K2 research and development, we have worked to cultivate an understanding—down to the consumer level—of the substantial evidence supporting vitamin K2 as a vital nutrient for bone and cardiovascular health. As the sponsor of this important research, these studies have utilized our branded MenaQ7 Vitamin K2 as MK-7.”
 
Primary Beneficiaries
In terms of consumer demographics, Luke Bucci, PhD CCN CNS, vice president of R&D for the supplement brand Ritual, noted that people age 50 and up might stand to benefit most from supplementation with vitamin K. “But all adults and children would derive a stronger, lifelong benefit. Women with a family history of bone loss and cardiovascular issues would probably benefit the most.” Ritual’s Essential for Women multivitamin/mineral includes nine essential nutrients women lack the most.
 
“We started out with a blank slate,” Dr. Bucci said of the product’s development. “Something from which every adult woman could derive life-long benefit. We wanted a lean and efficient MVM without frills, window dressing, or herbs/foodstuffs that have microbial concerns and focusing on essentials. We set out to see what essential nutrients are needed the most, which ones have gaps between healthy and unhealthy intakes, and what is already satisfied by the available science. We also sought vegan/vegetarian sources, non-GMO, organic when possible, bioidentical/food form sources and doses to bring up intakes to those seen in healthy diets (that is, diets that help extend quality lifespan, maintain mental functions and decrease risk of major causes of mortality).”
 
Mr. Murray agreed that with the two primary benefits being bone health and heart health, “We tend to think of the middle-age to senior population as the target market for vitamin K2. In fact, if people in their 30s take a preventive approach to healthy living, this population may be able to significantly reduce typical age-related health issues such as osteopenia/osteoporosis and cardiovascular disease.”
 
Speaking about research trends, Mr. Anderson said numerous human clinical trials have confirmed the health benefits of vitamin K2. “NattoPharma currently has more than 20 human studies, including 19 published clinical trials confirming the benefits of vitamin K2 as MK-7 in both patient and healthy populations, with more underway.”
 
“Most significantly, our three-year studies have shown an unprecedented impact on the health of postmenopausal women,” he added. For example, three years of daily 180 mcg MenaQ7 led to statistically significant improvement in bone mineral content and bone mineral density, leading to improved bone strength.
 
In addition three years of daily 180 mcg MenaQ7 not only inhibited age-related stiffening of the artery walls, but also made a statistically significant improvement in vascular elasticity, he added. “This is so very significant because, to date, no other compound has demonstrated these benefits. Our studies have also confirmed that children have the greatest need for vitamin K2—8-10 times higher need than in adults (as measured by inactive osteocalcin, the K-dependent protein that binds calcium to the bone mineral matrix).
 
Bones grow and develop most intensively during childhood and adolescence, with up to 90% of peak bone mass acquired by age 18 in girls and by age 20 in boys, Mr. Anderson noted. “Without adequate vitamin K2 to activate the bone-building osteocalcin, calcium cannot be properly used to build healthy, strong bones. Further, a two-year study in healthy prepubertal children showed that just 45-50 mcg of MenaQ7 daily improved K status, resulting in stronger, denser bones.
 
In just the last year, several studies have expounded on the benefits of vitamin K. “The medical community has been paying attention, and drug studies are already underway using menaquinone-7,” he added.  The studies look at progression of coronary artery calcification, valve calcification, and the progression of bicuspid aortic valve stenosis.
 
Synergies
Vitamin K2 works synergistically with many ingredients, according to Mr. Anderson, but its core strength is its role in helping the body properly utilize calcium. Vitamin K2 as MK-7 does this by activating K-dependent proteins already in the body. Osteocalcin bind calcium to the bone mineral matrix; Matrix Gla Protein (MGP) inhibits calcium from depositing in arteries, blood vessels, and soft tissues.
 
“To that end, vitamin D is also an important synergistic ingredient. Vitamin D helps to synthesize these K-dependent proteins, so experts like Dr. Mercola suggest that when one increases their D intake, they balance that with vitamin K2.”
 
In addition, while omega-3's mechanism of action is linked to supporting healthy inflammation, triglycerides, blood pressure, and promotion of arterial health, it is not recognized for impacting vascular calcification, which is what makes vitamin K2 a perfect complement.
 
NattoPharma has obtained a patent covering pharmaceutical and nutraceutical products providing vitamin K2 in combination with one or more polyunsaturated fatty acids, including fish and/or krill oil, for benefits related to bone, cartilage, and the cardiovascular system.
 
Mr. Murray said there is a “bone health triangle” consisting of calcium, vitamin D and vitamin K. “The vitamin D mobilizes the calcium into the blood stream. From there, vitamin K plays the crucial role of redepositing the calcium into the bones. Without vitamin K2, calcium will find its way to the arteries and over time a gradual buildup calcifies the arteries for serious coronary problems. Consumers generally know they need calcium for healthy bones and the awareness for vitamin D has grown significantly. Vitamin K2 is now on this same upward path and we are just scratching the surface as we move toward the Mass Market channel.”
 
Quality Control
“Manufacturing pure, stable, efficacious vitamin K2 as MK-7 is a detailed, multi-step process, and it is essential that it be done correctly or the result is an ineffective—and sometimes dangerous—raw material,” Mr. Anderson said.
 
"NattoPharma’s leadership in the vitamin K2 category is also attributed to the company developing these processes and technological breakthroughs that allows us to offer pure, all-trans MK-7. This dedication has led the research community to use MenaQ7 Vitamin K2 as MK-7 as the source material in the substantial body of research confirming vitamin K2’s health benefits.”
 
This focus on quality also creates a material that comes at a higher price, he added. “We are seeing a lot of ‘me too’ in the vitamin K2 category. Companies are ‘borrowing’ NattoPharma’s science to say that their material offers health benefits, while offering sub-par material at a heavily discounted price. Yet, in truth, there is no evidence showing that this cheaper material is effective at all. As an industry, we cannot focus on price as the deciding factor. You truly get what you pay for, and by choosing an unproven raw material that is not clinically validated and patented, you put your brand at risk.”
 
Mr. Murray advised brand owners that, in terms of quality of vitamin K2, it’s important to have an “all trans” product form. “As with many nutrients, there is a ‘cis’ and ‘trans’ formation, much like a right-hand and left-hand glove. Just as we can’t use two left-hand gloves, our bodies only recognize the ‘trans’ form for metabolism so the presence of ‘cis’ isomers is considered an impurity and an indication of a poor-quality vitamin K2 product. Using an HPLC assay, we hope to see a very distinct peak of trans K2 MK7 rather than a ‘head-and-shoulder’ pattern indicating cis isomers and other impurities.”
 
Dr. Bucci noted that the Ritual brand is centered around transparency and traceability, explaining the source and manufacturer of each ingredient, including vitamin K2. “We take transparency so literally we have clear bottles and capsules. For too long, what is actually in many dietary supplements and where they come from has been hidden. Our CEO Katerina Schneider started Ritual partly because she could not know or find out exactly what she was taking and why. We proudly show on our website where each of our ingredients come from and why we chose them. In this world of too much misinformation we chose to be matter of fact.”