Tetsuro Shibakusa

Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy A Prospective Randomized Trial

BACKGROUND It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. METHODS Forty-three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single-blind, parallel-group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre- and postoperative interleukin (IL)-6, C-reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. RESULTS Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL-6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre- and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). CONCLUSIONS This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.

Enhancement of postoperative recovery by preoperative oral co-administration of the amino acids, cystine and theanine, in a mouse surgical model.

BACKGROUND & AIMS Glutathione (GSH) is important in the control of immune responses, and its levels decline following trauma. We previously reported that the oral administration of cystine/theanine (CT) increased GSH synthesis and that CT intake inhibited intense exercise-induced inflammation. Based on these results, we hypothesised that CT inhibits surgically induced inflammation and promotes postoperative recovery. Our aim was to confirm this hypothesis using a mouse surgical model. METHODS CT or a vehicle (V) was administered orally to mice once a day for 5 days, until the day of surgery. On the day of surgery, a sham operation or an intestinal manipulation was performed 2 h after the oral administration of CT or V. Levels of IL-6 in the blood and GSH in the intestine were analysed 2 h after surgery. Behavioural analysis was also undertaken after surgery. RESULTS Treatment with CT inhibited the manipulation-induced increase in IL-6 in the blood and decrease in GSH in the intestine. There was a significant negative correlation between IL-6 in the blood and GSH in the intestine. In addition, behavioural analysis revealed that CT administration improved locomotor activity and food intake after surgery. CONCLUSION These results suggest that CT suppresses inflammatory responses by inhibiting the surgically induced decrease in GSH in the small intestine and promotes postoperative recovery.

Cystine improves survival rates in a LPS-induced sepsis mouse model

BACKGROUND & AIMS The control of inflammation is important for suppressing severe sepsis. Oral administration of cystine and theanine have been shown to suppress inflammatory responses due to invasion. Furthermore, the uptake of cystine into monocytes is promoted by exposure to lipopolysaccharide (LPS). In the present study, the effects of cystine were examined in the context of inflammatory responses. METHODS Cystine was orally administered to mice, and the levels of interleukin (IL)-6 in the blood and spleen and the survival rates were calculated after the administration of LPS. The effects of cystine as well as neutralising anti-IL-10 antibodies on the LPS-induced production of IL-6 and IL-10 were examined in a monocyte cell line. RESULTS The oral administration of cystine reduced IL-6 levels in the blood and spleen after LPS stimulation and improved survival rates. The addition of cystine to monocytes suppressed LPS-induced IL-6 production but enhanced IL-10 production. A neutralising anti-IL-10 antibody eliminated the inhibitory effects of cystine on the LPS-induced production of IL-6. CONCLUSIONS The oral administration of cystine suppressed IL-6 production following LPS stimulation and improved survival rates in mice with LPS-induced sepsis. The enhanced production of IL-10 by monocytes may be involved in this anti-inflammatory response.

Insufficient Intake of L-histidine Reduces Brain Histamine and Causes Anxiety-Like Behaviors in Male Mice

L-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. L-histidine is also important as a precursor of histamine. Brain histamine is synthesized from L-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary L-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice.

Cystine and theanine: amino acids as oral immunomodulative nutrients

The decreases in the glutathione (GSH) level in the mouse spleen and liver after immune stimulation are suppressed by the oral administration of cystine and theanine (CT). GSH is considered to be important for the control of immune responses. Antibody production in mice after infection is enhanced by the oral administration of CT. In humans, also, the oral administration of CT has been confirmed to enhance antibody production after vaccination against Flu and also reduce the incidence of cold. However, the GSH level is reduced by intense exercise and surgery. In clinical studies of body-builders and long-distance runners, the intake of CT suppressed excessive inflammatory reactions and a decline in immune functions after intense training. Surgery as well as intense exercise induces excessive inflammatory reactions. In mice, the preoperative administration of CT suppressed excessive inflammatory reactions associated with surgery and promoted the postoperative recovery. Moreover, in clinical studies of gastrectomized patients, CT intake suppressed excessive postoperative inflammatory reactions and induced early recovery. If infection is regarded as invasive stress, CT intake is considered to exhibit an immunomodulatory effect by suppressing the decrease in GSH due to invasive stress. The clarification of their detailed action mechanisms and their application as medical or function foods is anticipated.

PP253-SUN CYSTINE SUPPRESSES INFLAMMATORY REACTION INDUCED BY LPS THROUGH AUGMENTATION OF INTERLEUKIN-10 PRODUCTION

(p = 0.049). No interaction between treatment and exercise was observed (p = 0.519). Higher postprandial concentrations of essential amino acids and leucine are possible mediating factors for the FSR response. Conclusion: Ingestion of a high whey protein, leucineenriched supplement resulted in a higher overall postprandial muscle protein synthesis rate in healthy older subjects compared with a conventional dairy product.