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Modulatory Effects of Triphala and Manjistha Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
Peterson, CT, Pourang, A, Dhaliwal, S, Kohn, JN, Uchitel, S, Singh, H, Mills, PJ, Peterson, SN, Sivamani, RK
Journal of alternative and complementary medicine (New York, N.Y.). 2020;(11):1015-1024
Abstract
Objectives: Triphala (which contains Emblica officinalis, Terminalia bellerica, and Terminalia chebula) and manjistha (Rubia cordifolia), have received increased clinical attention. The aim of the study was to evaluate the effects of triphala, manjistha, or placebo dietary supplementation on gut microbiota as such studies in humans are lacking. Design: This was a 4-week randomized, double-blind, placebo-controlled pilot trial. Setting: This trial was conducted at the University of California Davis, Department of Dermatology. Subjects: A total of 31 healthy human subjects were randomized to 3 groups. Interventions: The 3 groups were instructed to take 2,000 mg of either triphala, manjistha or placebo daily for 4 weeks. Outcome Measures: The impact of treatment on gut microbiota composition was evaluated following a 4-week dietary intervention by profiling fecal communities with 16S rRNA profiling in triphala (n = 9), manjistha (n = 9), or placebo (n = 11) treated subjects that completed the intervention. Results: An average of 336 phylotypes were detected in each sample (range: 161 to 648). The analysis of gut microbiota in placebo control and herb-supplemented participants indicated that responses were highly personalized, and no taxa were uniformly altered by the medicinal herb supplementation protocol. Subjects in both treatment groups displayed a trend toward decreased Firmicutes to Bacteroidetes ratio and increased relative abundance of Akkermansia muciniphila. Both medicinal herb treatments reduced the relative abundance of Rikenellaceae, primarily reflecting changes in Alistipes spp. Conclusions: Dietary supplementation with medicinal herbs altered fecal microbial communities. Despite the lack of a clear response signature, a group of bacterial taxa were identified that were more commonly altered in herb-supplemented participants compared to placebo controls. Clinicaltrials.gov identifier NCT03477825.
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Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics.
Peterson, CT
Journal of evidence-based integrative medicine. 2020;:2515690X20957225
Abstract
Recent data suggest gut microbiota dysbiosis as a contributing factor in neurodegenerative diseases, such as Parkinson's Disease (PD) and Alzheimer's Disease (AD), and these pathologies may manifest via the microbiota-gut-brain-axis, which comprises bidirectional communication through neuroimmune, neuroendocrine, and direct neural pathways such as the vagus nerve. Preclinical and human clinical trial data reveal exciting potential for novel treatment targets and therapeutic modulation with prebiotics, medicinal herbs, probiotics, and synbiotics in health, aging, and neurodegeneration and are reviewed here. While greater insights and characterization of the microbiota-gut-brain axis have been revealed over the past decade, salient questions related to the pathology, pathogenesis and clinical treatment of the axis in the context of both health and neurodegenerative disease remain and are discussed in this review. Future directions such as additional well-controlled, large scale, longitudinal human clinical trials are urgently needed to further elucidate both mechanism and therapeutic opportunity in health, neurological disease, and disease subpopulations to ensure that the next decade ushers the dawn of targeted therapeutic modulation of the microbiota-gut-brain axis.
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Prebiotic Potential of Herbal Medicines Used in Digestive Health and Disease.
Peterson, CT, Sharma, V, Uchitel, S, Denniston, K, Chopra, D, Mills, PJ, Peterson, SN
Journal of alternative and complementary medicine (New York, N.Y.). 2018;24(7):656-665
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Triphala, licorice and slippery elm are key treatments for gastrointestinal health and disease in traditional systems of medicine. Prebiotics are defined as undigested dietary carbohydrates that alter the gut microbiota and promote human health. They reach the site of action in the colon mostly unmetabolized and are broken down by enzymes. The aim of the study was to find out whether the complex carbohydrates present in herbal medicine may be strong drivers to modulate gut microbiota composition. The study recruited 12 healthy men and women, aged between 30-60 years who had previously followed a vegan or vegetarian diet for more than 1 year, to donate a single stool sample. Results show that both the sugar and protein content of these herbal medicines drive alterations in gut microbiota profiles. Each of these herbal medicines studied, uniquely altered gut bacteria communities. Authors conclude that the health benefits of these herbs are mostly due to their ability to alter the gut microbiota in a manner that is predicted to improve colonic epithelium function, reduce inflammation, and promote protection from bacterial pathogenic infection.
Abstract
INTRODUCTION The prebiotic potential of herbal medicines has been scarcely studied. METHODS The authors therefore used anaerobic human fecal cultivation to investigate whether three herbal medicines commonly used in gastrointestinal health and disease in Ayurveda alter the growth and abundance of specific bacterial species. RESULTS Profiling of cultures supplemented with Glycyrrhiza glabra, Ulmus rubra, or triphala formulation by 16S rDNA sequencing revealed profound changes in diverse taxa in human gut microbiota. Principal coordinate analysis highlights that each herbal medicine drives the formation of unique microbial communities. The relative abundance of approximately one-third of the 299 species profiled was altered by all 3 medicines, whereas additional species displayed herb-specific alterations. Herb supplementation increased the abundance of many bacteria known to promote human health, including Bifidobacterium spp., Lactobacillus spp., and Bacteroides spp. Herb supplementation resulted in the reduced relative abundance of many species, including potential pathogens such as Citrobacter freundii and Klebsiella pneumoniae. Herbal medicines induced blooms of butyrate- and propionate-producing species. U. rubra and triphala significantly increased the relative abundance of butyrate-producing bacteria, whereas G. glabra induced the largest increase in propionate-producing species. To achieve greater insight into the mechanisms through which herbal medicines alter microbial communities, the authors assessed the shifts in abundance of glycosyl hydrolase families induced by each herbal medicine. Herb supplementation, particularly G. glabra, significantly increased the representation and potential expression of several glycosyl hydrolase families. DISCUSSION These studies are novel in highlighting the significant prebiotic potential of medicinal herbs and suggest that the health benefits of these herbs are due, at least in part, to their ability to modulate the gut microbiota in a manner predicted to improve colonic epithelium function, reduce inflammation, and protect from opportunistic infection. Forthcoming studies in human clinical trials will test the concordance of the results generated in vitro and the predictions made by genome analyses.
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Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
Peterson, CT, Vaughn, AR, Sharma, V, Chopra, D, Mills, PJ, Peterson, SN, Sivamani, RK
Journal of evidence-based integrative medicine. 2018;:2515690X18790725
Abstract
BACKGROUND Curcuma longa (common name: turmeric) and one of its biologically active constituents, curcumin, have received increased clinical attention. Insufficient data exist on the effects of curcumin and turmeric on the gut microbiota and such studies in humans are lacking. METHODS Turmeric tablets with extract of piperine (Bioperine) (n = 6), curcumin with Bioperine tablets (n = 5), or placebo tablets (n = 3) were provided to healthy human subjects and subsequent changes in the gut microbiota were determined by 16S rDNA sequencing. RESULTS The number of taxa detected ranged from 172 to 325 bacterial species. The placebo group displayed an overall reduction in species by 15%, whereas turmeric-treated subjects displayed a modest 7% increase in observed species posttreatment. Subjects taking curcumin displayed an average increase of 69% in detected species. The gut microbiota response to treatment was highly personalized, thus leading to responders and nonresponders displaying response concordance. These "responsive" subjects defined a signature involving uniform increases in most Clostridium spp., Bacteroides spp., Citrobacter spp., Cronobacter spp., Enterobacter spp., Enterococcus spp., Klebsiella spp., Parabacteroides spp., and Pseudomonas spp. Common to these subjects was the reduced relative abundance of several Blautia spp. and most Ruminococcus spp. CONCLUSIONS All participants' microbiota displayed significant variation over time and individualized response to treatment. Among the responsive participants, both turmeric and curcumin altered the gut microbiota in a highly similar manner, suggesting that curcumin may drive the majority of observed changes observed in turmeric-treated subjects.
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Therapeutic Uses of Triphala in Ayurvedic Medicine.
Peterson, CT, Denniston, K, Chopra, D
Journal of alternative and complementary medicine (New York, N.Y.). 2017;(8):607-614
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AIM: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. METHODS A search of the PubMed database was conducted. RESULTS In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. CONCLUSIONS This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.
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Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).
Peterson, CT, Lucas, J, John-Williams, LS, Thompson, JW, Moseley, MA, Patel, S, Peterson, SN, Porter, V, Schadt, EE, Mills, PJ, et al
Scientific reports. 2016;:32609
Abstract
The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p < 0.01) post-intervention in the experimental (n = 65) compared to control group (n = 54) after Bonferroni correction for multiple testing; within these compounds, the phosphatidylcholine with the greatest decrease in abundance was PC ae C36:4 (delta = -0.34). Application of a 10% FDR revealed an additional 57 metabolites that were differentially abundant between groups. Pathway analysis suggests that the intervention results in changes in metabolites across many pathways such as phospholipid biosynthesis, choline metabolism, and lipoprotein metabolism. The observed plasma metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being.
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The Self-Directed Biological Transformation Initiative and Well-Being.
Mills, PJ, Wilson, KL, Pung, MA, Weiss, L, Patel, S, Doraiswamy, PM, Peterson, CT, Porter, V, Schadt, E, Chopra, D, et al
Journal of alternative and complementary medicine (New York, N.Y.). 2016;(8):627-34
Abstract
OBJECTIVE To examine the effects of a comprehensive residential mind-body program on well-being. DESIGN The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location. SETTING Retreat setting. PARTICIPANTS 69 healthy women (n = 58) and men (n = 11) (mean age ± standard deviation, 53.6 ± 12 years). INTERVENTION The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling. OUTCOME MEASURES A battery of standardized questionnaires. RESULTS Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05). CONCLUSIONS Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.
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Soy Isoflavones for Reducing Bone Loss Study: effects of a 3-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women.
Alekel, DL, Genschel, U, Koehler, KJ, Hofmann, H, Van Loan, MD, Beer, BS, Hanson, LN, Peterson, CT, Kurzer, MS
Menopause (New York, N.Y.). 2015;(2):185-97
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OBJECTIVE This study aims to assess the overall safety and potential endometrium-stimulating effects of soy isoflavone tablets consumed (3 y) by postmenopausal women and to determine endometrial thickness response to treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. METHODS We randomized healthy postmenopausal women (aged 45.8-65.0 y) to placebo control or two doses (80 or 120 mg/d) of soy isoflavones at two sites. We used intent-to-treat analysis (N = 224) and compliant analysis (>95%; N = 208) to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). RESULTS Median values for endometrial thickness (mm) declined from baseline through 36 months. Nonparametric analysis of variance for treatment differences among groups showed no differences in absolute (or percentage of change) endometrial thickness (χ(2) P ranged from 0.12 to 0.69) or in circulating hormones at any time point. A greater number of adverse events in the genitourinary system (P = 0.005) were noted in the 80 mg/day group compared with the 120 mg/day group, whereas other systems showed no treatment effects. The model predicting endometrial thickness response (using natural logarithm) to treatment among compliant women across time points was significant (P ≤ 0.0001), indicating that estrogen exposure (P = 0.0013), plasma 17β-estradiol (P = 0.0086), and alcohol intake (P = 0.023) contributed significantly to the response. Neither the 80 mg/day dose (P = 0.57) nor the 120 mg/day dose (P = 0.43) exerted an effect on endometrial thickness across time. CONCLUSIONS Our randomized controlled trial verifies the long-term overall safety of soy isoflavone tablet intake by postmenopausal women who display excellent compliance. We find no evidence of treatment effects on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, across a 3-year period.
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The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women.
Alekel, DL, Van Loan, MD, Koehler, KJ, Hanson, LN, Stewart, JW, Hanson, KB, Kurzer, MS, Peterson, CT
The American journal of clinical nutrition. 2010;(1):218-30
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BACKGROUND Our previous study indicated that soy protein with isoflavones lessened lumbar spine bone loss in midlife women. OBJECTIVE We examined the efficacy of isoflavones (extracted from soy protein) on bone mineral density (BMD) in nonosteoporotic postmenopausal women. We hypothesized that isoflavone tablets would spare BMD, with biological (age, body weight, serum 25-hydroxyvitamin D) and lifestyle (physical activity, dietary intake) factors modulating BMD loss. DESIGN Our double-blind, randomized controlled trial (36 mo) included healthy postmenopausal women (aged 45.8-65.0 y) with intent-to-treat (n = 224) and compliant (n = 208) analyses. Treatment groups consisted of a placebo control group and 2 soy isoflavone groups (80 compared with 120 mg/d); women received 500 mg calcium and 600 IU vitamin D(3). Outcomes included lumbar spine, total proximal femur, femoral neck, and whole-body BMD. RESULTS Analysis of variance for intent-to-treat and compliant (> or =80%) models, respectively, showed no treatment effect for spine (P = 0.46, P = 0.21), femur (P = 0.86, P = 0.46), neck (P = 0.17, P = 0.14), or whole-body (P = 0.86, P = 0.78) BMD. From baseline to 36 mo, BMD declined regardless of treatment. In intent-to-treat and compliant models, respectively, BMD decreases were as follows: spine (-2.08%, -1.99%), femur (-1.43%, -1.38%), neck (-2.56%, -2.51%), and whole body (-1.66%, -1.62%). Regression analysis (compliant model) indicated that age, whole-body fat mass, and bone resorption were common predictors of BMD change. After adjustment for these factors, 120 mg (compared with placebo) was protective (P = 0.024) for neck BMD. We observed no treatment effect on adverse events, endometrial thickness, or bone markers. CONCLUSION Our results do not show a bone-sparing effect of extracted soy isoflavones, except for a modest effect at the femoral neck. This trial was registered at clinicaltrials.gov as NCT00043745.
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Isoflavone-rich soy protein prevents loss of hip lean mass but does not prevent the shift in regional fat distribution in perimenopausal women.
Moeller, LE, Peterson, CT, Hanson, KB, Dent, SB, Lewis, DS, King, DS, Alekel, DL
Menopause (New York, N.Y.). 2003;(4):322-31
Abstract
OBJECTIVE Menopause-induced estrogen deficiency increases the risk of cardiovascular disease, which is related to a shift in regional fat distribution. We tested the hypothesis that estrogen-like isoflavones in soy protein isolate (SPI+) would lessen both regional fat gain and lean loss compared with isoflavone-poor soy (SPI-). DESIGN Perimenopausal participants (N = 69) were randomly assigned (double-blind) to 24 weeks of treatment (40 g soy or whey protein per day): SPI+ (n = 24), SPI- (n = 24), or whey control (n = 21); each participant had blood drawn in the fasted (12 hours) state, had physical activity assessed, and kept a 5-day food diary. Dual-energy x-ray absorptiometry was used to examine the effects of SPI+ on regional fat and lean tissue distribution changes in the waist, hip, and thigh regions. RESULTS Mean body mass increased (P < 0.01) in each group, but treatment had no effect on gain in overall body mass, fat mass, or lean mass using analysis of variance. In all treatment groups combined, lean mass increased in each region; fat mass increased only in the waist region. Treatment had an effect (P = 0.039) on hip lean mass and a marginal effect (P = 0.077) on thigh fat. Regression analyses revealed that SPI+ diminished the increase in thigh fat (P = 0.018) and heightened the increase in hip lean (P = 0.035) mass. Carbohydrate intake (P = 0.006) and cohort (reflective of season; P = 0.011) contributed to the gain in thigh fat. Total protein intake (P = 0.0012), plasma insulin (P = 0.0034), and physical activity (P = 0.047) contributed to the gain in hip lean mass. CONCLUSIONS Gain in hip lean mass was greater (P = 0.014) in SPI+ than other groups, but SPI+ did not reduce the disease-promoting menopausal shift in regional fat mass.