Why You Need to Combine MK4 and D3

Many nutrients complement each other and work synergistically. When taken together, they have more health benefits than either one alone. Vitamin K2 (as MK4) and Vitamin D3 are great examples. This article reviews the science and clinical trials, showing how they work together to improve bone density, maintain strong bones, and promote cardiovascular and immune health. 

“Strong Bones.” Guaranteed.

Strong bones require healthy amounts of minerals, especially calcium, and collagen. The minerals give bone its hardness, while collagen gives bone its ultimate strength. Two primary cells, osteoblasts and osteoclasts, maintain healthy bone. Osteoblasts build new bone, while osteoclasts break down and recycle old bone.

As I write in my book, Fracture-Proof Your Bones, bone loss happens when these two cells are out of balance; when osteoclasts break down bone faster than osteoblasts create new, healthy bone. Fortunately, taking MK4 and vitamin D3 can tip the balance back in your favor, promote healthy bone density, and maintain strong bones. 

In 2007, I created the first bone health product that combined the clinical trial dose of MK4 (45 mg/day) with vitamin D3. The research on the nutrients and the results customers have shared are so compelling that all of our MK4+D3 products are backed by NBI’s “Strong Bones” Guarantee.

Here are some of the studies published in peer-reviewed medical journals. 

Puts Calcium Into Bones

Vitamin D enhances calcium absorption, and MK4 directs the calcium into bone. Without vitamin D, only 10 to 15% of dietary calcium is absorbed. On the other hand, getting enough vitamin D enhances calcium absorption by 30-40%.¹  

Bone is the largest reservoir of calcium in the body. Once calcium is in your blood, it must be directed into the bone. Otherwise, it can accumulate to dangerous levels in the blood. Based on published clinical trials and basic studies, researchers concluded that MK4 enhances vitamin D’s ability to add minerals to bone.²

Promotes Healthy Bone Density

Clinical trials show that taking MK4 (45 mg/day) improves bone density and maintains bone strength. A two-year clinical trial with 172 women (average age 53 years old) divided the volunteers into four groups. They took MK4 (45 mg/day) alone, vitamin D3 alone, or MK4 plus vitamin D3. The fourth group served as a control and received only dietary counseling. All women had low bone mineral density at the beginning of the study.  

Bone mineral density increased significantly more in the MK4+D3 group than in the other groups, and this improvement was evident after just six months of taking the nutrients. After two years, 67.8% of volunteers taking MK4+D3 had a 2% or greater increase in bone density, while 45.2% had a 5% or greater increase.³  

Another two-year randomized clinical trial divided 92 women (mean age about 64) into four groups. The women took MK4 (45 mg/day) alone, vitamin D3 alone, MK4 (45 mg/day) plus vitamin D3, or only calcium. 

After two years, bone density decreased by 0.79% in women who took only calcium. Bone density in women who took only vitamin D3 decreased by 0.44% in the first year but increased by 0.38% by the end of the second year. The best results were noted in the volunteers who took MK4 plus D3. In this group, bone density increased 1.49% during the first year and 1.35% after two years.⁴ 

In a third clinical trial lasting six months, 78 women (ages 61 to 74) took MK4 (45 mg/day) plus vitamin D3 and calcium, or only vitamin D3 and calcium. Bone density increased in those taking MK4, but decreased in women who took only vitamin D3 and calcium.⁵

Muscle Strength and Balance

While MK4 promotes calcium deposition in bone, vitamin D provides the added benefit of promoting healthy balance and muscle strength and reducing fall risk. That’s an important benefit since most fractures happen because someone falls.  

Vitamin D is associated not only with larger, stronger muscles, but also with fewer falls and fractures at higher levels. In a review of five clinical trials with 1237 people, when vitamin D levels were low (< 5 ng/mL) and then increased to > 40 ng/mL with vitamin D, the risk of falling decreased by 22% compared with placebo.⁶  

Vitamin D also supports bone strength at higher levels, as shown by fewer fractures. Researchers concluded that maintaining blood vitamin D levels between 30 and 44 ng/mL (75-110 nmol/L) is associated with reducing falls and fractures. Vitamin D levels above 30 ng/mL are associated with a 20% decrease in nonvertebral fractures and an 18% decrease in hip fractures. Similarly, the greatest decrease in fall risk occurs when vitamin D is about 30 ng/mL, and all-cause mortality decreased when blood levels were 40-48 ng/mL (100-120 nmoL/L).⁷

Maintains Strong Bones

MK4 (45 mg/day in divided doses) maintains bone strength, as clinical trials indicate. One meta-analysis of clinical trials concluded that MK4 (45 mg daily) maintains strong bones. The volunteers who took the nutrient had bones that were 70% stronger than those who didn’t take MK4.⁸ Another review of data from 19 randomized, controlled clinical trials involving 6,759 volunteers reached the same conclusion–MK4 (45 mg/day in divided doses) maintains strong bones.⁹ 

A more recent systematic review and meta-analysis published in 2022 confirmed these findings. This study pooled data from 10 randomized, controlled clinical trials with 5,413 women ages 45-81. The data showed that volunteers taking MK4 had 62% stronger bones than those who did not.¹⁰ Another review of the research published in 2022 evaluated data from 20 randomized, controlled clinical trials with 3,950 volunteers. The clinical trials lasted 6 to 36 months. The authors concluded that taking MK4 (45 mg/day) maintained strong bones, with 68% stronger bones in the people taking MK4.¹¹

Genetic Effects

Your body constantly turns genes on and off, depending on nutrients in your cells and other factors. Both MK4 and Vitamin D enter cells and activate healthy genetic expression. They turn on genes that promote osteoblast production by binding to the steroid and xenobiotic receptor (SXR)/pregnancy X receptor (PXR).^12,13 This matters because osteoblasts create new, healthy bone. 

MK4 also activates genes involved in bone collagen accumulation. These include growth differentiation factor 15 (GDF15), Stanniocalcin, Tenascin-c and bone morphogenic protein-2 (BMP-2).^14-16 Helping to magnify the benefits of MK4, cells exposed to vitamin D had a 2.5-5 times increase in bone collagen (Type I collagen) production.¹⁷ 

Inflammation

Nuclear factor kappa beta (NF-kB) helps regulate inflammation. Elevated levels of NF-kB are associated with increased inflammation, which stimulates osteoclast production. It also helps osteoclasts stay alive longer, giving them more time to destroy bone. This is problematic because osteoclasts destroy bone. Chronic inflammation destroys bones. It reduces the amount of minerals in bones and damages bone collagen, an important structural component of bones. Promoting healthy inflammation balance is important for maintaining strong bones. MK4 and Vitamin D have been shown to inhibit NF-kB.^15,18,19 

Inflammation is created by pro-inflammatory chemicals such as interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and others. Your body produces chemicals to counteract these pro-inflammatory molecules and balance the inflammation. These include IL-4 and IL-10. In animal studies, vitamin D has been shown to promote healthy inflammation balance by decreasing the pro-inflammatory chemicals and increasing those that counteract and calm the inflammation.²⁰ This activity has also been confirmed in humans.^17,21 

RANKL

RANKL is a cellular receptor that’s involved in bone health. Increased RANKL activity damages bone. MK4 and vitamin D reduce RANKL activity, associated with improved bone health.²²

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