Sok Cheon Pak’s research while affiliated with Charles Sturt University and other places

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Publications (173)


A Flow diagram of evidence selection.
The immune restorative effects of rice bran arabinoxylan compound (RBAC). (A) shows some immune functions that are affected by tumour growth resulting in the suppression of antitumor activity. (B) shows the biological response-modifying effects of RBAC restoring immune function in cancer patients.
The anticancer effect of RBAC is achieved through both the intrinsic pathway via the increased susceptibility of CD95 (Fas/APO-1) ligands in the cancerous cells to promote apoptosis and the extrinsic pathway through the downregulation of the antiapoptotic Bcl-2 proteins to lower membrane potentials, leading to the upregulation of the tumour-suppressing P53 gene and the upregulated production of the apoptotic Bax and caspase-3 signalling proteins. Malignant cell proliferation is arrested with evidence of increased hypodiploid cell counts in the SubG1 phase in cell cycle analysis. The antioxidant and cytokine-modulating capacities of RBAC also augment proapoptotic activity.
A summary of the potential benefits of RBAC in cancer treatment.
Forest Plot of survival events of RBAC-treated group compared to those of the control group.

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Rice bran arabinoxylan compound as a natural product for cancer treatment – an evidence-based assessment of the effects and mechanisms
  • Literature Review
  • Full-text available

May 2024

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96 Reads

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1 Citation

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Jeanman Kim

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Sok Cheon Pak

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.

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Rice Bran Arabinoxylan Compound and Quality of Life (RBAC-QoL) of Cancer Patients: An Interim Analysis of the RBAC-QoL Study

January 2024

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60 Reads

Cureus

Background The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design The RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods Participants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates. Results Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.


Rice Bran Arabinoxylan Compound and Quality of Life of Cancer Patients: Statistical Plan and Interim Analysis

October 2023

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27 Reads

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.


Rice Bran Arabinoxylan Compound as a Natural Product for Cancer Treatment – An Evidence-based Assessment of the Effects and Mechanisms

October 2023

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18 Reads

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3 Citations

Natural products, especially biologically active compounds derived from plants, have been and continue to be invaluable in anticancer research and therapeutic discoveries. Rice bran arabinoxylan compound (RBAC) is a heteropolysaccharide extract of defatted rice bran obtained through enzymatic treatment with Lentinus Edodes mycelium. RBAC exhibited antitumour properties by arresting in vivo tumour growth in several murine models. In vitro experiments showed RBAC to promote apoptosis in cancer cells by increasing the susceptibility of CD95 (Fas/APO-1) ligands and downregulating Bcl-2 proteins to trigger the permeabilisation of the mitochondrial membrane. RBAC may restore immune dysfunction in cancer patients, most notably by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses. As such, RBAC acts on the immune system to enhance chemopreventative activity and block tumourigenesis. In treatment, RBAC works synergistically with other natural products and chemotherapeutic agents, such as daunorubicin and paclitaxel, by enhancing drug transport to increase DNA damage in tumours and reduce proliferation. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence, and prolonged survival time. RBAC has been shown to augment the endogenous antioxidant system to prevent oxidative stress and thus protect against the harmful side effects of radiation therapy. RBAC also has chemoprotective effects, with animal and human studies showing reduced toxicity and side effects from chemotherapy, leading to improved health-related quality of life. Meta-analysing the best available evidence indicates that RBAC treatment increases the odds of survival among cancer patients by 4.02 times (95% CI: 1.67, 9.69) in the first year and 2.89 (95% CI: 1.56, 5.35) times in the second year after commencing treatment, compared to those not treated with RBAC. Notwithstanding, additional research is needed to characterise, quantify, and standardise the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to further substantiate the treatment efficacies.


Modified rice bran arabinoxylan as a nutraceutical in health and disease—A scoping review with bibliometric analysis

August 2023

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78 Reads

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2 Citations

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.


Modified Rice Bran Arabinoxylan by Lentinus edodes Mycelial Enzyme as an Immunoceutical for Health and Aging—A Comprehensive Literature Review

August 2023

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36 Reads

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6 Citations

Molecules

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.


Changes in the Human Gut Microbiome during Dietary Supplementation with Modified Rice Bran Arabinoxylan Compound

July 2023

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62 Reads

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5 Citations

Molecules

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Sok Cheon Pak

This study investigated the effects of a modified rice bran arabinoxylan compound (RBAC) as a dietary supplement on the gut microbiota of healthy adults. Ten volunteers supplemented their diet with 1 g of RBAC for six weeks and 3 g of RBAC for another six weeks, with a three-week washout period. Faecal samples were collected every 3 weeks over 21 weeks. Microbiota from faecal samples were profiled using 16S rRNA sequencing. Assessment of alpha and beta microbiota diversity was performed using the QIIME2 platform. The results revealed that alpha and beta diversity were not associated with the experimental phase, interventional period, RBAC dosage, or time. However, the statistical significance of the participant was detected in alpha (p < 0.002) and beta (weighted unifrac, p = 0.001) diversity. Explanatory factors, including diet and lifestyle, were significantly associated with alpha (p < 0.05) and beta (p < 0.01) diversity. The individual beta diversity of six participants significantly changed (p < 0.05) during the interventional period. Seven participants showed statistically significant taxonomic changes (ANCOM W ≥ 5). These results classified four participants as responders to RBAC supplementation, with a further two participants as likely responders. In conclusion, the gut microbiome is highly individualised and modulated by RBAC as a dietary supplement, dependent on lifestyle and dietary intake.


Modified Rice Bran Arabinoxylan by Lentinus Edodes Mycelial Enzyme as an Immunoceutical for Health and Aging – A Comprehensive Literature Review

July 2023

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112 Reads

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1 Citation

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.


Paper60

June 2023

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4 Reads

Journal of Functional Foods

The genoprotective effect of a single ingestion of red grape juice on human DNA was explored. Twenty subjects (10 males and 10 females) were recruited for this study. Subjects were randomly assigned to two groups and each group consisted of five males and five females. Ten were asked to drink 250 mL commercially available grape juice without any addictive while the other ten in the control group consumed water instead. Blood samples were taken immediately before and two hours after ingestion of either grape juice or water. The blood samples were then embedded in agarose and irradiated with ultraviolet-B followed by the comet assay. The slides were stained with Giemsa stain and DNA damage was assessed through the grading of the comet head and tail. Results showed a statistically significant decrease in DNA damage with grape juice consumption compared to the control group. This study illustrated that red grape juice drink was sufficient to protect cellular DNA from oxidative stress at least within two hours.


Fig. 1. Comet images captured from conventional bright microscope by using Giemsa staining. (A) Grade 0, undamaged (B) grade1, mildly damaged (C) grade 2, moderately damaged (D) grade 3, from moderately to severely damaged (E) grade 4, severely damaged DNA.
In vivo genoprotective effect against UV irradiation by red grapes (Vitis vinifera L.) juice

June 2023

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17 Reads

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1 Citation

Journal of Functional Foods

The genoprotective effect of a single ingestion of red grape juice on human DNA was explored. Twenty subjects (10 males and 10 females) were recruited for this study. Subjects were randomly assigned to two groups and each group consisted of five males and five females. Ten were asked to drink 250 mL commercially available grape juice without any addictive while the other ten in the control group consumed water instead. Blood samples were taken immediately before and two hours after ingestion of either grape juice or water. The blood samples were then embedded in agarose and irradiated with ultraviolet-B followed by the comet assay. The slides were stained with Giemsa stain and DNA damage was assessed through the grading of the comet head and tail. Results showed a statistically significant decrease in DNA damage with grape juice consumption compared to the control group. This study illustrated that red grape juice drink was sufficient to protect cellular DNA from oxidative stress at least within two hours.


Citations (61)


... In cancer research, RBAC has exhibited anticancer properties by arresting in vivo tumour growth in murine models and in vitro experiments showed RBAC promoted apoptosis in cancer cells by increasing the responsiveness of CD95 (Fas/APO-1) ligands (Ooi, Micalos, Kim, et al., 2023). RBAC has also been demonstrated to restore immune dysfunction in cancer patients by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses (Ooi, Micalos, Kim, et al., 2023). ...

Reference:

Rice Bran Arabinoxylan Compound and Quality of Life of Cancer Patients: Statistical Plan and Interim Analysis
Rice bran arabinoxylan compound as a natural product for cancer treatment – an evidence-based assessment of the effects and mechanisms

... The following sections synthesize the evidence on how RBAC exerts synergistic effects to prevent cancer development or support cancer treatment and the potential mechanisms. A preprint of this work has been deposited in an online platform for open access (Ooi et al. 2023a). ...

Rice Bran Arabinoxylan Compound as a Natural Product for Cancer Treatment – An Evidence-based Assessment of the Effects and Mechanisms

... This study is a secondary analysis of the evidence gathered from a previous scoping review that systematically identified all preclinical and clinical studies for RBAC published until the end of 2022. The characteristics of all included studies (n = 98) with bibliographic and network analyses were reported in an earlier manuscript (Ooi et al. 2023b). Two recent RBAC studies published after the scoping study completion were also considered in this review (Hajtó et al. 2022;Ghoneum et al. 2023). ...

Modified rice bran arabinoxylan as a nutraceutical in health and disease—A scoping review with bibliometric analysis

... BioBran containing rice kefiran was selected as it activates the body's NK cells, T cells, B cells, and macrophages through [1] direct blood circulation and [2] stimulation of Peyer's patches in the ileum, and it also regulates immunity. It is thought to have activating, antiinflammatory, anti-allergic, anti-oxidant properties, etc. [11][12][13][14], and is highly likely to be useful in improving aging. ...

Modified Rice Bran Arabinoxylan by Lentinus edodes Mycelial Enzyme as an Immunoceutical for Health and Aging—A Comprehensive Literature Review

Molecules

... However, the extent of RBAC's bioavailability remained unclear with the lack of any pharmacokinetic study [103]. A recent preliminary investigation by Schupfer et al. [104] found that RBAC consumption as a dietary supplement could potentially modulate the gut microbiome of some healthy individuals. Hence, it is likely for RBAC to be only partially absorbed in the digestive tract, with the unabsorbed portion serving as prebiotics to the gut microbiota. ...

Changes in the Human Gut Microbiome during Dietary Supplementation with Modified Rice Bran Arabinoxylan Compound

... In addition to wheat-derived arabinoxylan, rice bran arabinoxylan compound (RBAC) is a widely used dietary supplement whose effect on the gut microbiota has not been exploited. Schupfer et al 39 investigated the effect of RBAC on healthy adults' microbiota by examining the changes in the microbiota composition during the supplementation of RBAC. Research has demonstrated that its impact is strongly influenced by an individual's lifestyle, age, and diet. ...

Changes in the Human Gut Microbiome during Dietary Supplementation with Modified Rice Bran Arabinoxylan Compound

Molecules

... Finally, the slide was dried and kept at room temperature before scoring under light microscope at 100X (Primostar 3, Zeiss, Baden-Württemberg, German). Scoring of comet cells was described in the previous study (Chan et al., 2023). ...

In vivo genoprotective effect against UV irradiation by red grapes (Vitis vinifera L.) juice

Journal of Functional Foods

... The present review was conducted on the heels of a scoping study that systematically searched, screened, assessed, extracted, and synthesised the available evidence sources from preclinical to clinical studies to map out the translational research of RBAC from inception until the end of 2022 [18]. The scoping study included all scholarly articles reporting results from primary research (basic, in vitro, animal, and human) on the effects of RBAC on any biological activities related to human health or disease conditions. ...

Modified Rice Bran Arabinoxylan as a Nutraceutical in Health and Disease – A Scoping Review with Bibliometric Analysis

... Traditional Chinese Medicine (TCM) exhibits a unique "multicomponent, multitarget" effect, leveraging its advantage in holistic treatment and holds promise as an effective approach for treating AD (Kim et al., 2023). Danggui Shaoyao San (DSS), a classic TCM prescription, is known for its liver-nourishing, blood-tonifying, and spleen-invigorating properties (Fu et al., 2016). ...

Effectiveness and Safety of Pattern Identification-Based Herbal Medicine for Alzheimer's Disease: A Systematic Review and Meta-Analysis
  • Citing Article
  • March 2023

Journal of Integrative and Complementary Medicine