Vitamin K2 (Menaquinone)
Vitamin K2, also known as menaquinone, is one of the more recently discovered vitamins. While vitamins K1 (phylloquinone) and K3 (menadione) are best known for their roles in blood coagulation (i.e., clotting), vitamin K2 is considered supportive of bone integrity and the circulatory system, and most relevant to MS, the nervous1 and immune2 systems.
Vitamin K2 at a dose of 100 nmol3 appears to protect oligodendrocyte precursors (involved in myelination) and both developed and undeveloped neurons4 from oxidative injury and mitochondria against dysfunction5, and can reduce inflammation2, all processes relevant to MS6). Of note, vitamin K2 was found in significantly higher concentrations in myelinated parts than in non-myelinated parts of the brain in animals7. Because of vitamin K2’s potential role in MS, it may affect clinical progress of the disease.
In an animal model of MS, vitamin K2 at a dose of 62.5 mg/kg provided prior to disease initiation was associated with decreased severity compared to unsupplemented controls, possibly related to reduced inflammatory cellular infiltration into brain cells and the spinal cord. This benefit was not observed when treatment was administered after the disease took hold8, suggesting that maintaining a sound vitamin K2 status may be preventive in high-risk individuals.
A cross-sectional study comparing MS patients (most RRMS) to healthy controls revealed blood levels of vitamin K2 to be more than three-fold higher in healthy controls compared to MS patients (p < 0.001). In addition, there was an age-associated decline in vitamin K2 levels that was more pronounced in MS patients. Increasing numbers of relapses/attacks per year were significantly associated with reduced vitamin K2 levels, and there was a trend toward an association between higher disability and lower levels. Interestingly, higher sun exposure tended to increase levels6.
Vitamin K1 deficiency in pregnant women and newborns can be dangerous, possibly resulting in hemorrhage. Vitamin K is naturally found in human milk. Though maternal vitamin K supplementation is typically not needed to meet the daily recommended adequate dietary intake, maternal with 5 mg daily increases milk vitamin K levels and can improve vitamin K status in breastfed infants, who are at higher risk of potentially fatal vitamin K deficiency bleeding9.
The recommended daily intake for women is 90 mcg/day, and doesn’t change depending on pregnancy or lactation. The safe upper limit is considered to be 1000 mcg/day10. The daily recommendation for vitamin K2 is 10-45 mcg/day11, the latter being the form suggested to address MS. These amounts are consistent with those found to be potentially protective in MS3.
There is not yet a formal recommendation for vitamin K2 intake, but experts researching its benefits suggest 10-45 mcg/day. Food sources include dairy (e.g., butter and cheese) and other animal products (e.g., beef liver, chicken, eel, and egg yolk), as well as fermented foods (e.g., natto and sauerkraut)12.
References
1.Kurosu M, Begari E. Vitamin K2 in electron transport system: are enzymes involved in vitamin K2 biosynthesis promising drug targets? Molecules. Mar 10 2010;15(3):1531-53. doi:10.3390/molecules15031531
2.Pizzorno JE, Murray, M. Text book of natural medicine, 4th Edition. Churchill Livinstone (Elsevier); 2013.
3.Li J, Wang H, Rosenberg PA. Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes. J Neurosci Res. Jul 2009;87(9):1997-2005. doi:10.1002/jnr.22029
4.Li J, Lin JC, Wang H, et al. Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J Neurosci. Jul 2 2003;23(13):5816-26.
5.Josey BJ, Inks ES, Wen X, Chou CJ. Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents. J Med Chem. Feb 14 2013;56(3):1007-22. doi:10.1021/jm301485d
6.Lasemi R, Kundi M, Moghadam NB, Moshammer H, Hainfellner JA. Vitamin K2 in multiple sclerosis patients. Wien Klin Wochenschr. May 2018;130(9-10):307-313. doi:10.1007/s00508-018-1328-x
7.Carrie I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr. Jan 2004;134(1):167-72. doi:10.1093/jn/134.1.167
8.Moriya M, Nakatsuji Y, Okuno T, Hamasaki T, Sawada M, Sakoda S. Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats. J Neuroimmunol. Dec 30 2005;170(1-2):11-20. doi:10.1016/j.jneuroim.2005.08.001
9.Vitamin K. Drugs and Lactation Database (LactMed(R)). 2006.
10.Safe upper intake levels for vitamins and minerals (Ministry of Family and Consumer Affairs) (2006).
11.Akbulut AC, Pavlic A, Petsophonsakul P, et al. Vitamin K2 Needs an RDI Separate from Vitamin K1. Nutrients. Jun 21 2020;12(6)doi:10.3390/nu12061852
12.Elder SJ, Haytowitz DB, Howe J, Peterson JW, Booth SL. Vitamin k contents of meat, dairy, and fast food in the u.s. Diet. J Agric Food Chem. Jan 25 2006;54(2):463-7. doi:10.1021/jf052400h