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Simple flow diagram showing different stages of the clinical trial. ǂ Declined to participate when informed that the intervention included unlabeled coded sachets. ¥ Not enrolled to adjust males/females ratio to 1. § The principal investigator was not involved in the randomization or allocation procedure, which was performed by a statistician ignorant of the study. Ø Close monitoring, daily follow-up of subjects, and the relatively short period of the study (3 months) resulted in the absence of any dropouts.
Source publication
Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-agi...
Citations
... These findings are consistent with the numerous pieces of in vivo and in vitro evidence that confirm the capacity of RBAC to enhance NK cell activity in healthy subjects (Ghoneum 1998;Ghoneum and Jewett 2000;Ghoneum and Abedi 2004;Kim et al. 2007;Badr El-Din et al. 2008;Giese et al. 2008;Pérez-Martínez et al. 2015). RBAC has also been shown to enhance the cytotoxic activity of NK cells via inducing the expression of CD107a in geriatric subjects (Elsaid et al. 2018), which led to enhanced innate defense and reduced cases of influenza-like illnesses in an RCT with elderly patients (Elsaid et al. 2021). Overall, the NK cell immunomodulatory effects of RBAC have also been thoroughly reviewed by Ghoneum (2016) bran extracted through other methods, such as acid hydrolysis and bioconversion, also exhibited potent immunomodulatory effects on the non-specific immune responses, including NK cell activity (Ji et al. 2020). ...
Context
Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties.
Objective
This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment.
Methods
This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis.
Results
The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year.
Conclusion
RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.
... Additionally, it activates natural killer (NK) cells [36] and increases human B and T cell mitogen responses. Remarkably, Biobran/MGN-3 supplementation has also been found to reduce the incidence of influenza-like illnesses in elderly subjects [37], act against HIV in vitro [38], and significantly reduce the viral load of patients infected with chronic hepatitis C [39]. Biobran/MGN-3 thus has the capacity to enhance antiviral responses. ...
... Furthermore, Biobran/MGN-3 has been shown to be a potent anticancer agent. Biobran/MGN-3-stimulated DCs were able to prime cytotoxic CD8 cells and increase cancer-killing activity [33,34], and Biobran/MGN-3 has been demonstrated to modulate psychoneuroimmune activity and thereby enhance the health-related quality of life in healthy older adults [40] and in cancer patients [36,37]. ...
... Rat studies showed that Biobran/MGN-3 treatment significantly protects against D-GalN-induced liver injury and hepatitis [57], and Biobran/MGN-3 of low molecular fraction also protects against acute liver injury through the inhibition of JNK/MAPK and NF-кB expression [58]. Further work has also found that Biobran/MGN-3 consumption by elderly subjects reduced their incidence of influenza-like illnesses (ILI) [37]. As previously mentioned, Biobran/MGN-3 has furthermore been found to exert potent antiviral activity against the coronavirus, specifically against SARS-CoV-2, in vitro and in silico [31]. ...
Corona Virus Disease 19 (COVID-19) has been a major pandemic impacting a huge population worldwide, and it continues to present serious health threats, necessitating the development of novel protective nutraceuticals. Biobran/MGN-3, an arabinoxylan rice bran, is a potent immunomodulator for both humans and animals that has recently been demonstrated to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We here investigate Biobran/MGN-3′s potential to enhance an antiviral immune response in humans. Peripheral blood mononuclear cells (PBMCs) derived from eight subjects taking Biobran/MGN-3 (age 55–65 years) and eight age-matched control subjects were stimulated with irradiated SARS-CoV-2 virus and then subjected to immuno-phenotyping and multiplex cytokine/chemokine assays. Results showed that PBMCs from subjects supplemented with Biobran/MGN-3 had significantly increased activation of plasmacytoid dendritic cells (pDCs) coupled with increased IFN-α secretion. We also observed higher baseline expression of HLA-DR (human leukocyte antigen-DR isotype) on dendritic cells (DCs) and increased secretion of chemokines and cytokines, as well as a substantial increase in cytotoxic T cell generation for subjects taking Biobran/MGN-3. Our results suggest that Biobran/MGN-3 primes immunity and therefore may be used for boosting immune responses against SARS-CoV-2 infections and other diseases, particularly in high-risk populations such as the elderly.
... A major finding of this study is feeding rice bran to poultry had a strong effect on combating AI prevalence. Rice bran could be useful in treating Influenza like illness (Elsaid et al. 2021). This effect might be due to adding rice bran to poultry diet which can lead an increase of secretory Immunoglobulin (IgA) resulting clearing of mucosa associated HPAI and LPAI. ...
AB S T RA C T Avian Influenza (AI) infection persists in the northeastern part of Bangladesh, Sylhet region. The presence of AI as natural infection in backyard chicken was recently carried out by one of our pilot studies using rapid antigen detection kit from cloacal swab sample. This study aimed at assessing sero-prevalence (antibody positivity) and associated risk factors of avian influenza (AI) infection in three locations of Sylhet region by observational epidemiological and questionnaire-based approach. A total of 282 individual backyard chicken serum raised under free ranging or semi-intensive housing system; pooled to 156 household sample was subjected to serological examinations (ELISA and Hemagglutination inhibition test). Among the Univariate odds ratio of the risk factors and prevalence: feeding rice bran, poultry house location, mud house, bamboo house, Upazilas location and contact with wildlife variables result was significant. To be precise, our data shows a significant association of AI risk for poultry houses in yard rearing system (1.48-11.61% of 95% CI of OR). Also, seroprevalence was higher in backyard chicken encountered with wild birds (1.34-8.21 of 95% CI of OR). Surprisingly, mud Poultry house and feeding rice bran reduced AI seropositivity as a contributing risk factor (1.48-10.68% and 1.48-15.15% of 95% CI of OR, respectively) in backyard chicken. Based on our findings, an overall higher prevalence of 54.84 and 25.83% was observed from samples of Dakshin Surma and South Sunamganj upazila, respectively whereas the lowest prevalence of 25.83% was observed in Kanaighat upazila. Findings from this study merit that bird-level AI infection persists in the study location and associated risk factors or protective factors needs to be further assessed.
... A recent review by Egashira [17] also concurred that RBAC prevented liver damage in hepatitis by inhibiting the NK-κB and JNK/MAPK expression. Other notable beneficial actions of RBAC include antiinflammation [48,90,96,126,[139][140][141][142], antioxidant [85,98,120,[142][143][144][145], radioprotection [116,142,143], chemoprevention [118,121,122], antiallergy [96,98,123,126,146], antibacterial [84,86,94], antifatigue [131,147], antiflu [147][148][149], gastroprotection [129,[147][148][149][150], and antihyperlipidemia [151,152]. ...
... A recent review by Egashira [17] also concurred that RBAC prevented liver damage in hepatitis by inhibiting the NK-κB and JNK/MAPK expression. Other notable beneficial actions of RBAC include antiinflammation [48,90,96,126,[139][140][141][142], antioxidant [85,98,120,[142][143][144][145], radioprotection [116,142,143], chemoprevention [118,121,122], antiallergy [96,98,123,126,146], antibacterial [84,86,94], antifatigue [131,147], antiflu [147][148][149], gastroprotection [129,[147][148][149][150], and antihyperlipidemia [151,152]. ...
... RBAC has also been studied for potential applications in 15 other conditions apart from healthy subjects and cancer patients. These conditions include liver diseases [48,85,[133][134][135][136][137][138][139], HIV [12,[153][154][155], CFS [131,147,156], IBS [157], common cold/flu [148,149], Alzheimer's [144], and diabetes [151,152]. Endo et al. [15] pointed out that many lifestyle-related chronic diseases were caused by oxidative stress leading to chronic inflammation through the "friendly fire" of immune dysregulation. ...
Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English (MEDLINE, ProQuest, CENTRAL, Emcare, CINAHL+, Web of Science), Japanese (CiNii, J-Stage), Korean (KCI, RISS, ScienceON), and Chinese (CNKI, Wanfang) sources while combining bibliometrics and network analyses for data visualisation. Searches were conducted between September and October 2022. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median = 3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). Over 50% of the research was from the USA (29/98, 29.59%) and Japan (22/98, 22.45%). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. As an oral supplement taken as an adjuvant during chemoradiotherapy, cancer patients reported reduced side effects and improved quality of life in human studies, indicating RBAC's impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.
... Such findings were also confirmed by Elsaid et al. [74] in a study with randomly selected geriatric volunteers (age ≥ 56) from a larger placebo-RCT (n = 80). Twelve participants who took 500 mg/day of Biobran MGN-3 or placebo (6 in each group) were tested for NKC CD107a expression before treatment and after study completion at 3 months. ...
... Hence, Elsaid et al. [108] concluded that a low dose of Biobran MGN-3 (250 mg/day) over 3 months could improve the QoL of older adults. Another RCT by Elsaid et al. [74] focused on the effects of Biobran MGN-3 on strengthening the innate immunity of older adults by assessing the incidents of influenza-like illnesses (ILI). Immunosenescence is known to amplify susceptibility to viral infections, such as influenza, even with vaccination. ...
... Eighty generally healthy older adults (≥56 years old, male-to-female ratio: 1 to 1) enrolled in the study by Elsaid et al. [74]. Participants were randomly allocated to take either 500 mg/day of Biobran MGN-3 or placebo powder for 3 months, with the incidence of ILI infection monitored during the trial. ...
Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran enzymatically treated with Lentinus edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n = 37) primary research articles fulfilled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote innate defence by upregulating macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC has been shown to be a safe and effective nutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as a nutraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.
... Most of the RCTs entered the current study was conducted in healthy adults [38], healthy geriatrics [23,39], and HIV-positive patients [40]. According to Elsaid et al., 2018 [23], RBAC supplementation for one month decreased ALT and AST, which was significant for serum AST at a dose of 500 mg/day in healthy geriatrics. ...
Summary
Background & aims
Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Methods
In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied.
Results
Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value=0.001, I2 (%)= 46.9; P heterogeneity=0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value=0.001, I2 (%)= 29.9; P heterogeneity=0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value=0.001, I2 (%)= 46.9; P heterogeneity=0.170).
Conclusions
In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results.
Registry number for systematic reviews or meta-analyzes
CRD42022361002, registration time: 29/09/2022.
... Biobran/MGN-3, a rice bran arabinoxylan, is a polysaccharide containing beta-1,4 xylopyronase hemicellulose [9] that has been proven to be an efective antioxidant that prevents free radical formation and enhances the antioxidant defense system [10]. We have also recently reported Biobran's benefcial efects on aging [11,12] and neurodegenerative diseases [10], and recent studies have furthermore reported the antidiabetic efect of Biobran in streptozotocininduced diabetic rats [13]. Te current study investigates Biobran's efect against diabetes-induced cognitive impairment and hippocampal synaptotoxicity via oxidative stress and the IR/Akt/NF-κB signaling pathway in rats. ...
Type 2 diabetes mellitus (T2DM) is a common metabolic disease accompanied by cognitive impairment, hippocampal malfunctioning, and inflammation. Biobran/MGN-3, an arabinoxylan rice bran, has been shown to have an antidiabetic effect in streptozotocin-induced diabetic rats. The present study investigates Biobran’s effect against diabetes-induced cognitive impairment and synaptotoxicity in the hippocampus via oxidative stress and the IR/A/NF-κB signaling pathway in rats. Diabetes was induced via i.p. injection of streptozotocin (STZ) (40 mg/kg BW); STZ-treated rats were then administered Biobran (100 mg/kg BW) for 4 wks. Biobran supplementation improved motor coordination and muscular strength, as assessed by Kondziella’s inverted screen test. Biobran also improved concentration levels of glutathione (GSH), antioxidant enzymes, acetylcholine (ACh), dopamine, serotonin, insulin receptor (IR), and alpha serine-threonine protein kinase (Akt); it protected against elevated levels of glucose, total cholesterol, triglycerides, oxidative stress markers, TBARS, NO, AChE, and MAO; and it significantly decreased inflammatory cytokines levels of IL-1β, NF-κB, TNF-α, and amyloid β1-42. Moreover, Biobran ameliorated hippocampal histological alterations. Immunohistochemical observations showed that Biobran reduced overexpression of hippocampal synaptophysin and Ki67 relative to untreated diabetic rats. Biobran may ameliorate hippocampal alterations in diabetic rats via its antidiabetic, antiproliferative, anti-inflammatory, antiapoptotic, and antioxidant effects.
... Such findings were also confirmed by Elsaid et al. [68] in a study with randomly selected geriatric volunteers (age ≥56) from a larger placebo-RCT (n=80). Twelve participants who took 500 mg/day of Biobran MGN-3 or placebo (6 in each group) were tested for NKC CD107a expression before treatment and after study completion at 3 months. ...
... Another randomised RCT by Elsaid et al. [68] focused on the effects of Biobran MGN-3 on strengthening the innate immunity of older adults by assessing the incidents of influenza-like illnesses (ILI). Immunosenescence is known to amplify susceptibility to viral infections, such as influenza, even with vaccination. ...
... Hence, Biobran MGN-3, as an antioxidant and immunomodulator, could reduce the risk of contracting ILI while lowering the symptom severity in those infected. Eighty generally healthy older adults (≥56 years old, male-to-female ratio: 1 to 1) enrolled in the study by Elsaid et al. [68]. Participants were randomly allocated to take either 500 mg/day of Biobran MGN-3 or placebo powder for 3 months, with the incidence of ILI infection monitored during the trial. ...
Rice bran arabinoxylan compound (RBAC) is derived from rice bran enzymatically treated with Lentinus Edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n=37) primary research articles fulfiled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote the innate defence by upregulating the macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC is shown to be a safe and effective neutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as an nuetraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.
... Biobran's effect against a range of coronaviruses was also indicated by our previous study in which we reported that Biobran supplementation significantly reduces the incidence of influenza-like illnesses (ILI) in elderly subjects [26]. That study showed that Biobran significantly upregulated the expression levels of retinoic-acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5), as well as downstream ISG15 and MX1 in the human pulmonary epithelial BEAS-2B cell lines. ...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), poses a serious global public health threat for which there is currently no satisfactory treatment. This study examines the efficacy of Biobran/MGN-3 against SARS-CoV-2. Biobran is an arabinoxylan rice bran that has been shown to significantly inhibit the related influenza virus in geriatric subjects. Here, Biobran’s anti-SARS-CoV-2 activity was assessed using MTT and plaque reduction assays, RT-PCR, ELISA techniques, and measurements of SARS-CoV-2-related gene expression and protein levels. For Vero E6 cells infected with SARS-CoV-2, Biobran reduced the viral load by 91.9% at a dose of 100 μg/mL, it reduced viral counts (PFU/mL) by 90.6% at 50 μg/mL, and it exhibited a significant selectivity index (EC50/IC50) of 22.5. In addition, Biobran at 10 μg/mL inhibited papain-like proteinase (PLpro) by 87% and ACE2 SARS-CoV-2 S-protein RBD by 90.5%, and it significantly suppressed SARS-CoV-2 gene expression, down-regulating E-gene and RdRp gene expression by 93% each at a dose of 50 μg/mL and inhibiting the E-protein by 91.3%. An in silico docking study was also performed to examine the protein–protein interaction (PPI) between SARS-CoV-2 RBD and DC-SIGN as well as between serine carboxypeptidase and papain-like protease PLpro. Serine carboxypeptidase, an active ingredient in Biobran, was found to interfere with the binding of SARS-CoV-2 to its receptor DC-SIGN on Vero cells, thus preventing the cell entry of SARS-CoV-2. In addition, it impairs the viral replication cycle by binding to PLpro. We conclude that Biobran possesses potent antiviral activity against SARS-CoV-2 in vitro and suggest that Biobran may be able to prevent SARS-CoV-2 infection. This warrants further investigation in clinical trials.
... In another study by Elsaid et al. (2021), dietary supplementation with RBAC on the incidence of influenza-like illness was investigated in elderly participants. The research design was a double-blind, placebo-controlled clinical trial with 80 healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or RBAC (500 mg/day) for 3 months. ...
This book presents the major therapeutic applications of modified rice bran arabinoxylan compound (RBAC) in cancer as well as other chronic inflammatory diseases. Written by active researchers and clinicians in the field of RBAC, the chapters cover the basic science that defines the unique function of RBAC as well as the clinical evidence derived through human studies. Particular focus is on recent findings from research over the past decades. This book is both practical and evidence based. It will be a core resource for researchers, students, and practitioners of nutrition and natural medicine, as well as be of value to all healthcare professionals with interest in integrative medicine.
