Effects of Bacillus subtilis Var. Natto Products on Capillary Blood Flow in Healthy Subjects with Peripheral Coldness: A Double-Blind, Placebo-Controlled, Randomized Parallel Study

Purpose: NKCP®, a natto-derived dietary food supplement whose main component is bacillopeptidase F produced by Bacillus subtilis var. natto, has antithrombotic, fibrinolytic, and pressure-lowering effects, and also is suggested to improve peripheral coldness. However, existing data are based on subjective evaluations with no scientific basis about the effects on peripheral coldness. Therefore, we aimed to investigate the effectiveness of NKCP®for peripheral coldness by measuring changes in blood flow using a laser doppler rheometer and biochemical indices. Patients and Methods: This was a double-blind, randomized, controlled study of individuals aged 30 - 70 years who complained of subjective symptoms of cold hands and feet. They were randomly divided into the NKCP®group and the placebo group to receive NKCP®250 mg once daily and dextrin 250 mg as placebo once daily, respectively. The experiment lasted 8 weeks, with an intervention period of 4 weeks and a washout period of 4 weeks. Results: One-month intake of NKCP®significantly increased blood flow rate for 1 min between 4 and 5 minutes after the end of cold loading compared to that before feeding (p = 0.038). Also, analysis of the 5-minute blood flow rate before and after 4 weeks of feeding showed a significant improvement in the NKCP®group (p = 0.007), although there was no significant difference in the placebo group (p = 0.215). Furthermore, the 5-minute blood flow at 4 weeks after the end of feeding was significantly improved compared to that before feeding in the NKCP®group (p = 0.049). Therefore, the effect continued for at least 1 month after discontinuation of administration. Conclusions: It is possible that NKCP®intake effectively improves blood flow in subjects with peripheral coldness. Therefore, continuous intake of NKCP®is expected to reduce the symptoms of peripheral coldness. In the future, it needs to investigate whether the effect of increasing blood flow after ingestion of NKCP®is effective in improving the symptoms of peripheral coldness.

Dexamethasone prevents vascular damage in earlystage non-freezing cold injury of the sciatic nerve

Non-freezing cold injury is a prevalent cause of peripheral nerve damage, but its pathogenic mechanism is poorly understood, and treatment remains inadequate. Glucocorticoids have anti-inflammatory and lipid peroxidation-inhibiting properties. We therefore examined whether dexamethasone, a synthetic glucocorticoid compound, would alleviate early-stage non-freezing cold injury of the sciatic nerve. We established Wistar rat models of non-freezing cold injury by exposing the left sciatic nerve to cold（3–5°C） for 2 hours, then administered dexamethasone（3 mg/kg intraperitoneally） to half of the models. One day after injury, the concentration of Evans blue tracer in the injured sciatic nerve of rats that received dexamethasone was notably lower than that in the injured sciatic nerve of rats that did not receive dexamethasone; neither Evans blue dye nor capillary stenosis was observed in the endoneurium, but myelinated nerve fibers were markedly degenerated in the injured sciatic nerve of animals that received dexamethasone. After dexamethasone administration, however, endoneurial vasculopathy was markedly improved, although damage to the myelinated nerve fiber was not alleviated. These findings suggest that dexamethasone protects the blood-nerve barrier, but its benefit in non-freezing cold injury is limited to the vascular system.