Dear Osa friends,
Calcium and vitamin D get a lot of airtime when it comes to bone health, but vitamin K, a fat-soluble micronutrient, is also an essential player in this game. While calcium needs to be ingested and vitamin D ensures calcium gets absorbed into the bloodstream, it is vitamin K that directs the calcium into the bones. This also means that vitamin K helps to keep calcium out of artery walls–a win for our vascular health. But how much vitamin K do we need, and how can we get it? Let’s get into it.
Vitamin K exists in two known forms:
- K1 (aka phylloquinone) is the main form stored in the liver, where it is utilized to produce proteins involved in blood clotting. It is also thought to be converted to K2 in the body to a small degree. In the diet, this form of vitamin K is found primarily in green vegetables like collard greens, kale, and broccoli, and also in soybeans.
- K2 (aka menaquinone) is found in tissues apart from the liver, including the pancreas, bones, and blood vessels. It is a cofactor (i.e., necessary ingredient) for an enzyme called gamma glutamyl carboxylase that activates a protein called osteocalcin that is responsible for taking calcium from the blood and incorporating it bone tissue, thereby strengthening the bone and increasing bone density. Through the same enzyme, K2 also activates a protein known as matrix GLA protein, which helps to keep calcium out of the arteries and other soft tissues, where it can otherwise promote stiffness and calcification.1 K2 is largely found in foods of animal origin like butter, cheese, meats (especially organ meats), eggs, and we also get it from fermented foods: natto is the heavy hitter here, but K2 is also found in other fermented soy products like tempeh and miso, and other ferments like sauerkraut, kimchi, yogurt, and kefir.
Evidence-based recommendations
The plot thickens when it comes to trying to understand optimal intake of vitamin K for bone health. Here I’m going to give you topline recommendations, and then we’re going to dive a little deeper into vitamin K2 supplementation.
Vitamin K1
An intake of roughly 250 mcg daily has been observed to significantly decrease the risk of hip fracture in older adults, compared to intakes of less than 100 mcg per day.2 You can meet and exceed with amount by having two servings of green vegetables daily. A serving is typically 1 cup raw or 1/2 cup cooked.
If you want more bang for your green buck, you can go with a heavy hitter such as collards (530 mcg per 1/2 cup cooked), turnip greens (426 mcg per 1/2 cup cooked), or parsley (246 mcg in just 1/4 cup!). Most other greens contain somewhere between 100 and 150 mcg per serving.
Remember that vitamin K is a fat-soluble vitamin and so be sure to consume your greens with a bit of fat, such as olive oil or avocado oil, or seeds such as sunflower or pumpkin seeds, for example.
Vitamin K2
K2 is a star when it comes to bone health because of its role activating osteocalcin. Unfortunately, we don’t have solid data on optimal amounts to consume, nor do we have good information about the amounts found in various foods because vitamin K content is typically reported only as K1.
Vitamin K2 exists in a number of forms that differ by the number of carbon-and-hydrogen groups (called “isoprenyl” groups for the nerds out there) that they have attached. Vitamin K2 also goes by the name “menaquinone,” or MK for short, and a number after the MK indicates the number of those isoprenyl groups it has attached. MK-4 and MK-7 are the most studied in bone health.
With the exception of the form MK-4, all forms of vitamin K2 are synthesized by bacteria. This is why fermented foods are good sources of K2. But also, animals convert some dietary K1 to K2 (as MK-4) in the body, and so we can get K2 by consuming animal products and by eating more K1 ourselves.
For general bone health, two or more servings of fermented foods daily is my recommendation for vitamin K2. This can also help you decrease systemic inflammation and increase your gut microbiome diversity—check out the blog exploring this topic in case you missed it!
Options for fermented foods include: yogurt, kefir, kimchi, sauerkraut, other lacto-fermented vegetables, kombucha (unsweetened or very lightly sweetened), kvass, tempeh, miso, and natto.
(Note: If you are particularly sensitive to histamine, fermented foods may be off the table for you. In this case, you can plan to get K2 from animal foods, listed below.)
Eggs (preferably pastured), liver (organic), meat (preferably grass-fed), and cheese (preferably full fat and aged), are sources of K2 to consume on a weekly basis, provided that they fit your dietary pattern and preferences.
Digging Deeper: K2 Research
I’d like to note that although the research into vitamin K2 supplementation has been conducted in postmenopausal women, this DOES NOT mean that men do not also need to be proactive about their bone health. More women than men develop osteoporosis; however, men are by no means immune to it, and men who do experience fractures have a higher mortality associated with the fractures than do women. 3 That said, the data that we do have is in postmenopausal women, and we’re going to explore that here.
K2 and Postmenopausal Bone Health
A recent meta-analysis that investigated the effect of vitamin K2 on postmenopausal osteoporosis concluded that vitamin K2 supplementation significantly improved lumbar spine BMD, and has the potential to reduce fracture incidence, without adverse reactions.4
Ok, but how much and what form?
Of the 16 studies in this meta-analysis, 12 tested MK-4 and the remaining four tested MK-7.
The studies utilizing MK-7 used doses ranging from 180 ug/day to 375 ug/day and lasted 1-3 years.
]The results of these studies were mixed, with supplementation having at best a slowing effect on postmenopausal bone loss but not substantially improving markers of bone turnover or bone density (as measured by DEXA scan) in any of the studies. One study, which gave 180 ug/day of MK-7 for a 3-year time period, found that MK-7 supplementation favorably affected bone strength in the femoral neck.5 Importantly, bone fracture was not a measured outcome in any of these studies.
The remainder of the clinical trials involved MK-4, which was dosed at 45 mg/day.
One trial found that 45 mg/day of MK-4 was as effective as a synthetic vitamin D analog (alfacalcidol) for improving bone mineral density in a population of Chinese women.6 This study also measured fracture occurrence during the study period and found a lower occurrence of fracture in the MK-4 group compared to the alfacalcidol group (1.9% vs. 3.8%). Of course, instead of choosing one bone nutrient over another, in clinical practice I will optimize vitamin D levels and also consider vitamin K2 supplementation.
A different study tested the effect of MK-4 at 45 mg/day as an adjunctive treatment to alendronate (Fosamax), a pharmaceutical that suppresses bone turnover. This study found that the addition of MK-4 led to a greater increase in femoral neck (i.e., hip) bone mineral density and also decreased the level of un-activated osteocalcin, a risk factor for fracture. 7
Another trial which tested 45 mg/day of MK-4 against a placebo in post-menopausal women without osteoporosis found that MK-4 preserved hip bone strength as measured by bone mineral content and femoral neck width, without significantly affecting bone mineral density.8 These authors also note the limitations of bone mineral density as a stand-alone measure of bone strength–a topic to dig into further another time!
Take Home Messages on Vitamin K2 Supplementation
MK-4 is the primary form of circulating vitamin K in the body, and other forms of vitamin K are converted to MK-4 in tissues. However, MK-4 has a shorter half life (minutes to hours) compared to the longer chain forms like MK-7 (2-3 days), and no data are available on lower supplemental doses of MK-4. 45 mg/day is indeed a pharmacological dose and is given as a prescription for osteoporosis in Japan.
For these reasons, MK-7 (180 ug/day) might be the more logical choice for low-dose, once daily supplementation. However, recall that there is no evidence that this alone will result in marked improvements to bone health. It may be used as a part of a multi-pronged intervention to improve bone health, which would include optimizing dietary pattern, vitamin D, calcium, other minerals, and incorporating resistance and other impact exercise.
On the other hand, MK-4 at 45 mg/day (given in divided doses) has a superior body of evidence supporting its effectiveness in reducing bone fracture in postmenopausal women. This supplement is an option to discuss with your healthcare provider, particularly if you are postmenopausal and have a diagnosis of osteopenia or osteoporosis. Always discuss with your healthcare provider/s before making any changes to your supplements to make sure they are safe and effective for you.*
Let’s Review
My general recommendation for dietary vitamin K: Two servings of green vegetables and two servings of fermented foods daily. Animal foods such as eggs, liver, meats, and cheeses may be incorporated on a weekly basis that fits your dietary pattern.
For vitamin K2 supplementation: MK-7 at 180-375 ug/day, or talk to your doctor about utilizing 45 mg/day of MK-4, in divided doses. It is the 45 mg/day of MK-4 that has shown to be effective in reducing fracture risk in postmenopausal women, and this is the outcome that we care most about.
In health,
References
1.Hariri E, Kassis N, Iskandar J, Schurgers LJ, Saad A, Abdelfattah O, et al. Vitamin K2—a neglected player in cardiovascular health: a narrative review. Open Heart. 2021;8:e001715. https://doi.org/10.1136/openhrt-2021-001715 https://openheart.bmj.com/content/8/2/e001715
2.Booth, S. L., Tucker, K. L., Chen, H., Hannan, M. T., Gagnon, D. R., Cupples, L. A., Wilson, P. W., Ordovas, J., Schaefer, E. J., Dawson-Hughes, B., & Kiel, D. P. (2000). Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. The American journal of clinical nutrition, 71(5), 1201–1208. https://doi.org/10.1093/ajcn/71.5.1201 https://pubmed.ncbi.nlm.nih.gov/10799384/
3.Center, J. R., Nguyen, T. V., Schneider, D., Sambrook, P. N., & Eisman, J. A. (1999). Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet (London, England), 353(9156), 878–882. https://doi.org/10.1016/S0140-6736(98)09075-8 https://pubmed.ncbi.nlm.nih.gov/10093980/
4. Ma, M. L., Ma, Z. J., He, Y. L., Sun, H., Yang, B., Ruan, B. J., Zhan, W. D., Li, S. X., Dong, H., & Wang, Y. X. (2022). Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Frontiers in public health, 10, 979649. https://doi.org/10.3389/fpubh.2022.979649 https://pubmed.ncbi.nlm.nih.gov/36033779/
5. Knapen, M. H., Drummen, N. E., Smit, E., Vermeer, C., & Theuwissen, E. (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 24(9), 2499–2507. https://doi.org/10.1007/s00198-013-2325-6 https://pubmed.ncbi.nlm.nih.gov/23525894/
6. Jiang, Y., Zhang, Z. L., Zhang, Z. L., Zhu, H. M., Wu, Y. Y., Cheng, Q., Wu, F. L., Xing, X. P., Liu, J. L., Yu, W., & Meng, X. W. (2014). Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial. Clinical interventions in aging, 9, 121–127. https://doi.org/10.2147/CIA.S54107 https://pubmed.ncbi.nlm.nih.gov/24426779/
7. Hirao, M., Hashimoto, J., Ando, W., Ono, T., & Yoshikawa, H. (2008). Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. Journal of bone and mineral metabolism, 26(3), 260–264. https://doi.org/10.1007/s00774-007-0823-3 https://pubmed.ncbi.nlm.nih.gov/18470667/
8. Knapen, M. H., Schurgers, L. J., & Vermeer, C. (2007). Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 18(7), 963–972. https://doi.org/10.1007/s00198-007-0337-9 https://pmc.ncbi.nlm.nih.gov/articles/PMC1915640/
*Disclaimer: This does not constitute medical advice and is for general informational purposes only. Please consult with your healthcare provider to determine whether diet, supplement, or lifestyle changes are right for you.
Photo by micheile henderson on Unsplash