Vitamin K2 MK-4 vs MK-7: Why I Changed My Mind About Which Form to Recommend

I'll admit it—for years, I dismissed the whole MK-4 versus MK-7 debate as supplement industry hype. "Vitamin K is vitamin K," I'd tell patients. "Just eat your greens." Then I started seeing something odd in my clinic: patients on the same K2 supplements reporting wildly different outcomes. One 62-year-old woman with osteoporosis saw her bone density improve dramatically on MK-7, while another with similar markers showed minimal change. Meanwhile, a 55-year-old male patient with arterial calcification saw better results with MK-4. So I actually dug into the research—and here's what changed my mind completely.

Quick Facts Box

What Research Actually Shows (Not What Supplement Companies Claim)

Here's what drives me crazy—so many brands market MK-4 as "the natural form" because it's found in animal foods. But that's misleading. Yes, grass-fed butter has MK-4. But you'd need to eat pounds of it daily to get therapeutic doses. The MK-4 in supplements is almost always synthetic (menatetrenone). That's not necessarily bad—just be honest about it.

The real difference comes down to pharmacokinetics. A 2022 randomized crossover study (PMID: 35456723) gave 42 healthy adults either 420 mcg of MK-4 or 180 mcg of MK-7. They measured blood levels every few hours. MK-7 peaked later (6-8 hours vs 2-4 hours for MK-4) and—here's the key—stayed elevated for days. After 24 hours, MK-7 levels were still 8 times higher than baseline, while MK-4 had returned to near baseline. That longer circulation time matters because vitamin K2 works by activating proteins that need sustained exposure.

But—and this is important—longer blood circulation doesn't automatically mean better tissue distribution. Dr. Cees Vermeer's team in the Netherlands (they're the K2 research leaders) published a 2020 review in Nutrients (doi: 10.3390/nu12051245) analyzing tissue studies. MK-7 gets preferentially taken up by bone and liver. MK-4 shows up in places MK-7 barely reaches: pancreas, salivary glands, and—interestingly—the brain. Animal studies (I know, not human, but suggestive) show MK-4 crosses the blood-brain barrier while MK-7 doesn't.

Which brings me to osteocalcin activation—that's the protein that puts calcium into bone. A 2021 Japanese study in Osteoporosis International (n=244 postmenopausal women over 12 months) compared 45 mg of MK-4 (yes, milligrams—that's 45,000 mcg) to 180 mcg of MK-7. Both improved bone mineral density, but the MK-7 group needed 250 times less to achieve similar results. The MK-4 dose was pharmaceutical-grade (it's a prescription drug for osteoporosis in Japan), not something you'd get in a typical supplement.

Dosing & Recommendations: Stop Wasting Your Money

Okay, let's get practical. Most over-the-counter MK-4 supplements contain 100-500 mcg. Based on the research I just mentioned, that's probably too low to significantly activate osteocalcin. The effective dose for MK-4 seems to be in the milligram range. Meanwhile, 100-200 mcg of MK-7 appears sufficient for most people.

Here's my clinical approach:

For general bone/cardiovascular support: 100-200 mcg MK-7 daily. Take it with a fat-containing meal—vitamin K is fat-soluble. I've had good results with Thorne's product because they use the all-trans isomer (the active form) and third-party test. Some cheaper brands use cis-isomers that aren't as effective.

If you're taking blood thinners (warfarin/Coumadin): Don't change your K2 supplementation without talking to your doctor and dietitian. Consistent vitamin K intake matters more than avoiding it completely. I work with cardiology patients to find their "sweet spot" dose that doesn't interfere with INR.

When I might consider MK-4: Honestly, fewer cases than I used to think. Maybe in neurological conditions where brain uptake matters—but the evidence there is preliminary. Some functional medicine practitioners recommend MK-4 for dental health (it concentrates in salivary glands), but we need better human studies.

One more thing—timing. I used to say "any time of day." Now I recommend taking K2 with your largest meal that contains fat. A small 2019 study (n=36) in the European Journal of Nutrition found absorption increased by 37% when taken with 20+ grams of fat versus a low-fat meal.

Who Should Be Cautious or Avoid

Look, no supplement is for everyone. Here's where I pump the brakes:

On warfarin: I already mentioned this, but it's worth repeating. Vitamin K directly counteracts warfarin. If you're on it, work with your healthcare team to find consistent dosing. Don't start or stop K2 supplements on your own.

Kidney disease patients: Vitamin K2 helps prevent vascular calcification, which is common in CKD. But—and this is important—a 2023 study in Clinical Journal of the American Society of Nephrology (n=517, 48-week trial) found high-dose MK-7 (400 mcg) didn't improve arterial stiffness in dialysis patients. The researchers speculated that by stage 5 CKD, the calcification process might be too advanced. Earlier stages might benefit, but we need more research.

Pregnancy: The safety data just isn't there for high-dose supplementation. Vitamin K1 (for baby's blood clotting) is standard, but K2 isn't routinely recommended. Food sources are fine—natto, cheese, egg yolks.

People with rare fat malabsorption issues: If you have pancreatic insufficiency, Crohn's affecting your ileum, or biliary obstruction, you might not absorb fat-soluble vitamins well regardless of form. Sometimes we use water-soluble forms or adjust timing with enzyme supplements.

FAQs

Can I get enough K2 from food alone? Possibly, but it depends on your diet. Natto (fermented soybeans) has massive amounts of MK-7—one serving provides about 1,000 mcg. Hard cheeses have MK-4 but in smaller amounts. Most people don't eat natto regularly (the smell...), so supplementation makes sense for targeted benefits.

Should I take K2 with vitamin D3? Yes, they work synergistically. Vitamin D helps absorb calcium, K2 directs where it goes. I usually recommend taking them together with a meal containing fat. Many quality supplements combine them—Life Extension's D+K product is one I trust.

What about K1 vs K2? Different jobs. K1 (phylloquinone) is for blood clotting—it activates clotting factors in your liver. K2 activates proteins that manage calcium deposition. You need both, but they're not interchangeable.

Any side effects? In proper doses, rarely. A few patients report mild digestive upset with MK-7, usually when starting. Taking it with food helps. Extremely high doses (thousands of mcg) might theoretically interfere with vitamin E absorption, but that's not a concern at recommended levels.

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