Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial

LC-Plasma is a unique LAB which activates plasmacytoid dendritic cells (pDC) in healthy subjects. However, efficacy during consecutive HIE have not been evaluated. We conducted human study and researched the effects of LC-Plasma in athletes. The results indicated that LC-Plasma supplementation for 13 days would able to increase maturation marker of pDC (CD86) and decrease cumulative days of URTI symptom. Furthermore, we observed that LC-Plasma ingestion could decrease cumulative days of fatigue. These findings indicated that intake of LC-Plasma would prevent URTI infection via pDC activation and improve fatigue accumulation, suggesting that our hypothesis was acceptable.

There were no significantly differences between the groups in the training records during intervention (Table 1). It was reported that exercise for more than 11 h a week is reported to be high intensity and increasing URTI morbidity [29]. Although we did not strictly control exercise, both groups exercised for more than 11 h a week. Therefore, we thought that high intensity exercise was loaded to both groups as the physical condition of subjects became decrease. In addition, CPK and LDH as markers of muscle damage, and adrenaline and cortisol as stress hormones were also no different at day 14 (Table 2). These results suggested that exercise stress load between the placebo and LC-Plasma group was comparable in this study.

CPK, LDH and adrenaline were significantly increased at day 14 compared to day 1. Our data showed that exercise during the intervention period was high enough to affect markers of muscle damage and stress hormone. CPK and adrenaline reported to increase after HIE and to be involved in immunity and fatigue [3032]. We found that maturation markers (CD86 and HLA-DR) on DCs were decreased in the placebo group (Fig. 2). These results indicated that DCs are also involved in immuno-reduction under high stress condition such as consecutive HIE.

We showed that CD86 on pDC increased in the LC-Plasma group compared to the placebo group after consecutive HIE. This suggests that LC-Plasma increases pDC maturation in athletes under HIE as in general healthy subjects as reported previously [23].

Cumulative incidence days of URTI and symptom like sneeze or running nose decreased in the LC-Plasma group. Since pDC were reported to play antiviral functions [10] and that 70% of the causes of URTI were viral infections [12], we can conclude that LC-Plasma supplementation relieves URTI morbidity during HIE via pDC activation. In previous reports, LC-Plasma supplementation for more than 4 weeks was effective in general healthy subjects [23, 24, 28]. We found that LC-Plasma was effective even in a short intervention period of 13 days. Because this study was conducted under high stress conditions, the effect of LC-Plasma supplementation could be confirmed earlier and clearly.

We found that fatigue accumulation was lower in the LC-Plasma group compared to the placebo group. There are no reports regarding probiotics improving fatigue in athletes. Therefore, here we showed for the first time that LAB material such as LC-Plasma supplementation was effective for improving fatigue during consecutive HIE. For people under physically stressful conditions such as athletes, fatigue accumulation is a serious problem [3335], therefore our finding is valuable for athletes.

Since there was no significant difference in markers of muscle damage and stress in LC-Plasma group compared to Placebo, LC-Plasma might not directly affect recovery through these markers. Although detailed mechanism for fatigue reduction by LC-Plasma is not fully understood, one possibility is autonomic nerves, affected by HIE and related to fatigue [36]. Athletes who develop chronic fatigue or depression due to excessive HIE were reported to have abnormal autonomic nerves [37]. It was also reported that TLR9 knock out mice exhibited changes of autonomic nerve functions (heart rate and pulse interval) and behavior with responsiveness to stress [38]. Considering that LC-Plasma is a ligand of TLR9 [22], LC-Plasma might affect autonomic nerves and accordingly improve fatigue state via TLR9. Further research is necessary in order to confirm the precise mechanism of LC-Plasma regarding fatigue.

There were some limitations regarding the analysis, which may affect the results of this study. The study subjects were composed of only male and university students. Furthermore, even though the exercise load was not different between groups, the training regime was not strictly controlled. Since this study was conducted in 13 days of ingestion which is thought to be relatively short period, the efficacy of LC-Plasma for athletes during long-term ingestion was unknown. More extensive studies with a wide range of subjects or homogeneous exercise load like ergometer exercise or long and high intensive exercise are required to confirm our findings.