Why You Need to Combine MK4 and D3

By Dr. John Neustadt

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 studies on the nutrients, and customers’ results, have been so impressive that NBI offers a “Strong Bones” Guarantee. When you take one of our MK4+D3 products, we guarantee your bone density will improve within six months.

But more importantly, we guarantee that you’ll have strong bones. Therefore, if someone breaks a bone, we’ll refund the money for all qualifying purchases between their bone density tests. You don’t have to take my word for it. 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

Improves 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 a combination of MK4 plus vitamin D3. The fourth group acted as a control and only received some dietary counseling. All women had low bone mineral density at the beginning of the study.  

Not only did bone mineral density significantly increase more in the MK4+D3 group compared to the other groups, but this improvement was already evident after just six months of taking the nutrients. After two years, 67.8% of the volunteers taking MK4+D3 had their bone density increase by 2% or more, while 45.2% had a 5% or greater increase in bone density.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, the combination of MK4 (45 mg/day) plus vitamin D3, or only calcium. 

After two years, bone decreased 0.79% in the women who only took calcium. The bone density in women who only took vitamin D3 decreased in the first year by 0.44% but then 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 that lasted six months, 78 women (ages 61 to 74) took the combination of MK4 (45 mg/day), vitamin D3, and calcium or only vitamin D3 and calcium. Bone density increased in those taking the MK4 but decreased in the 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.  

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

Vitamin D also maintains strong bones at higher levels, as indicated 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 greater than 30 ng/mL is associated with a 20% decrease in nonvertebral fractures and an 18% decrease in hip fractures. Similarly, the greatest decrease in the risk of falling is seen when someone’s vitamin D is about 30 ng/mL, and dying from any cause was reduced when the blood level was 40-48 ng/mL (100-120 nmoL/L).⁷

Maintains Strong Bones

MK4 (45 mg/day in divided doses) maintains bone strength, as fewer fractures in clinical trials indicate.  

One meta-analysis of clinical trials concluded that MK4 (45 mg daily) maintains strong bones, as indicated by 70% fewer fractures in volunteers.⁸ 

Another review of the data that evaluated 19 randomized, controlled clinical trials involving 6,759 volunteers reached the same conclusion–MK4 (45 mg/day in divided doses) maintains strong bones as indicated by reducing fractures in clinical trials.⁹ 

A more recent systematic review and meta-analysis published in 2022 confirmed the earlier research. This study pooled data from 10 randomized, controlled clinical trials with 5,413 women ages 45-81. The data showed that MK4 maintains strong bones, as indicated by 62% fewer fractures in volunteers.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, as indicated by 68% fewer fractures.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 the creation of osteoblasts by binding to the steroid and xenobiotic receptor (SXR)/pregnancy X receptor (PXR).^12,13 This is important 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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