More vitamin K2, more testosterone

The list of supplements that boost testosterone production has just got a little longer. Nutritionists at Tohoku University in Japan say that male rats synthesise more testosterone if given food that contains high amounts of vitamin K2.


Vitamin K
There are two forms of vitamin K: plant-based vitamin K1 [phylloquinone] found in green vegetables such as peas, broccoli and spinach, and the animal-based K2 [menaquinone]. The difference between the two forms is in the ‘tail’ of prenyl units: K2 has one and K1 doesn’t. The tails vary too: meat and eggs have a tail with four extra prenyl units [MK-4], cheese and quark contain various versions of vitamin K2 with seven, eight and nine prenyl units [MK-7, MK-8 and MK-9]. Fermented products like natto contain a K2 vitamin with seven prenyl units.

We need K2 to enable vital enzymes to function. These include enzymes that synthesise coagulant factors and others that fix calcium in the bones – but vitamin K probably has many more functions. The Japanese research was set up to learn more about these unknown functions of vitamin K2.

The researchers gave one group of lab animals food containing low amounts of vitamin MK-4 – 0.75 mg per kg – and the other group got food containing high amounts of vitamin MK-4 – 75 mg per kg. The experiment lasted for five weeks. In the group that got a high amount of MK-4, the animals’ testosterone levels and their testicular testosterone concentration increased as the experiment progressed. The vitamin had no effect on the level of LH, the pituitary hormone that stimulates testosterone production in the testes.


The food with a high vitamin K content caused an increase in the activity of the enzymes PKA and CREB in the testes. This in turn probably caused the enzyme CYP11A to become more active. This enzyme is responsible for the synthesis of testosterone.

When the researchers repeated their experiment with vitamin K1 they observed hardly any testosterone-boosting effect.

A diet with high levels of vitamin MK-4 “may contribute to the reduced risk of age-related diseases by promoting increased testosterone production in the testis”, the researchers write.

Maybe we’ll hear more about this. The Japanese reveal that they have also done experiments with geranylgeraniol, “a side chain structure of MK-4”. This compound and its analogues have been shown to boost testosterone production in cell studies.

Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells.


Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis.

Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet), one of the predominant K? vitamins present in the testis, for 5 weeks. In vivo testosterone levels of the rats’ plasma and testes were measured by enzyme-linked immunosorbent assay, and in vitro testosterone levels of testis-derived tumor cells (I-10 cells) maintained in Ham’s F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 ?M) at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis.

Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K?, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA) and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of ?-glutamylcarboxylation.

MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders.

PMID: 21914161 [PubMed – indexed for MEDLINE] PMCID: PMC3180407