This was the first randomized, double-blind, placebo-controlled, parallel-group study investigating the immune-modulatory effects of RBEP in healthy adults. This group study revealed that RBEP supplementation significantly increased IFN-γ levels compared with a placebo group, but RBEP supplementation did not appear to enhance NK cell activity as compared to placebo group. Importantly, RBEP supplementation did not cause any significant adverse effects in the present study.
In contrast to these results, previous studies have reported that an enzymatically modified version of rice bran increases NK cell activity; this finding is potentially important because NK cells play important roles in the immune system, including defending against cancer
[2, 9, 10, 13, 15]. Furthermore, RBEP supplementation in mice has been shown to exhibit anticancer effects by enhancing NK cell activity
. Arabinoxylan, mainly xylose polymer from rice bran, have also been reported to increase NK cell activity in patients with various cancers
[9, 13] and in mice bearing Ehrlich ascites
 and renal carcinoma
. The most likely reason for these discrepancies is that the present study examined healthy subjects, whereas the previous studies all examined the effects of RBEP in the context of cancer. McDermott et al.
 concluded that arabinoxylan supplementation was not effective for treating chronic fatigue syndrome, an assessment thought to indirectly measure NK cell activity. Cancer patients have been suggested to have reduced NK cell activity compared with healthy individuals
[18, 19]; thus, significant effects on NK cell activity in healthy individuals may be difficult to observe. In the present study, NK cell activity was significantly increased within the RBEP group after supplementation compared with the same group before supplementation; however, this effect was no longer significant when the RBEP group was compared with the placebo group. Only one previous study in healthy adults reported that supplementation of an arabinoxylan obtained from rice bran increased NK cell activity, although this study did not include a placebo control
In agreement with the results obtained in the present study, previous studies have reported that an arabinoxylan isolated from rice bran significantly increased IFN-γ levels in patients with multiple myeloma
, in mice bearing Ehrlich ascites
, and in in vitro studies
[11, 12, 20]. Furthermore, polysaccharides from Angelica sinensis and from the root of Sanguisorba officinalis have been shown to increase IFN-γ production in spleen cells
 and tumor-bearing mice
, respectively. This immune-enhancing action of arabinoxylan has been proposed to be related to the increased IFN-γ secretion accompanying NK cell activation
. However, IFN-γ is produced not only by NK cells, but also by T and B cells
Previous studies have also reported that RBEP supplementation activates macrophages, both in vivo and in vitro[5, 8]. An arabinoxylan obtained from rice bran, the green leaves of Litsea glutinosa, and wheat bran have been shown to increase macrophage activity, either in vitro[24, 25] or in tumor-bearing mice
. In addition, an arabinoxylan isolated from rice bran increased CD4+ T cell function in human monocyte-derived dendritic cells
, and increased T and B cell proliferation in both humans with and without cancer
[13, 27]. Previous studies have consistently reported that polysaccharides from evening primrose, Curcuma xanthorrhiza, and Angelica sinensis increase macrophage activity and/or T cell proliferation, either in vivo or in vitro[21, 28, 29]. These data, in combination with the data presented in this study, suggest that the increased production of IFN-γ resulting from RBEP supplementation may be mediated by either macrophages, B cells, or T cells, and it is probably not mediated by NK cells.
Kim et al. showed that RBEP supplementation did not exhibit hematopoietic toxicity in a mouse model of solid tumors, thereby providing important evidence that RBEP is safe and could potentially be used to both prevent and treat cancer
. Increased WBC counts have been observed in patients with inflammation
, and have been shown to be associated with high cancer mortality
. In the present study, REBP supplementation led to a negligible decrease in WBC count; however, participant WBC counts remained within the normal range, and thus this finding is clinically non-significant.