# Effect of Vitamin K Supplementation on Testosterone Production in a Rat Model of Late-Onset Hypogonadism

## TL;DR

This study explores whether vitamin K, specifically MK-4, can help increase testosterone levels in rats with a condition similar to low testosterone in older men.

## Contribution

The study is the first to show that MK-4, but not VK1, can improve testosterone production in a rat model of low testosterone.

## Key findings

- MK-4 supplementation significantly increased serum testosterone levels in low-Ts rats.
- MK-4 activated the protein kinase A pathway, which is important for testosterone production.
- VK1 supplementation had no significant effect on testosterone levels or testicular structure.

## Abstract

Late-onset hypogonadism (LOH) is an age-related condition characterized by a decline in testosterone (Ts) levels and associated symptoms that impair quality of life in older men. Although Ts replacement therapy is available, its clinical use is limited by adverse effects. Vitamin K (VK) is a fat-soluble vitamin that functions as a cofactor for γ-glutamylcarboxylase and plays important roles in blood coagulation and bone homeostasis. Menaquinone-4 (MK-4), a VK homolog predominantly found in animal-derived foods, has been shown to enhance Ts production in healthy male rats. However, whether this effect occurs under low-Ts conditions remains unclear. In this study, we investigated the effects of VK on LOH using a leuprorelin acetate (LA)-induced low-Ts rat model. Male Sprague–Dawley rats were administered sustained-release LA and fed a control diet or diets supplemented with VK1 or MK-4 (75 mg/kg) for 4 weeks. Compared with the control group, MK-4 supplementation significantly ameliorated the reduction in serum Ts levels and seminiferous tubule diameter, whereas VK1 supplementation showed no significant effects. Furthermore, MK-4 supplementation activated the protein kinase A signaling pathway, which is directly involved in testicular Ts production. These findings suggest that MK-4 supplementation may represent a novel nutritional strategy for the management of LOH.