BioMend® - Clinical Research Data Summary

BIOMend® Lysine-Butyrate Complex

BIOMend® is a clinically studied ingredient used in the following Silver Fern™ Brand product:

Introduction

BIOMend® is a butyrate delivery system composed of a lysine–butyrate complex designed to enhance the stability, tolerability, and bioavailability of butyric acid. Butyrate is a short-chain fatty acid naturally produced by beneficial gut microbes and plays an important role in normal gastrointestinal physiology, immune signaling, and metabolic communication within the body. Research indicates that butyrate levels can vary depending on diet, lifestyle factors, and overall gut microbiome composition. Traditional butyrate salts and triglyceride forms have demonstrated biological activity but can be limited by strong taste, odor, and differences in absorption. BIOMend® was developed to address these challenges by pairing butyrate with lysine, an essential amino acid, to improve palatability and delivery characteristics. Human pharmacokinetic research suggests that lysine butyrate can deliver butyrate into circulation efficiently compared with some conventional forms, supporting its use as a next-generation postbiotic ingredient designed to help support normal butyrate activity in a form suitable for everyday nutritional use.*

These are the studies for BIOMend®. Below, we provided a summary of each key data for each study, along with a link to the complete clinical research.

  1. Summary of Study 1 – Full Study: https://www.nature.com/articles/ncomms10062
  2. Summary of Study 2 – Full Study: https://pubs.rsc.org/en/content/articlelanding/2021/fo/d1fo02116h
  3. Summary of Study 3 – Full Study: https://pubmed.ncbi.nlm.nih.gov/37542852/
  4. Summary of Study 4 – Full Study: https://pubmed.ncbi.nlm.nih.gov/19625695/
  5. Summary of Study 5 – Full Study: https://www.researchgate.net/publication/375885731_Modulation_of_GABA_by_sodium_butyrate_ameliorates_hypothalamic_inflammation_in_experimental_model_of_PCOS
  6. Summary of Study 6 – Full Study: https://pubmed.ncbi.nlm.nih.gov/32476236/
  7. Summary of Study 7 – Full Study: https://pubmed.ncbi.nlm.nih.gov/36469320/
  8. Summary of Study 8 – Full Study: https://pubmed.ncbi.nlm.nih.gov/39003477/
  9. Summary of Study 9 – Full Study: https://www.nature.com/articles/s41598-018-37246-7
  10. Summary of Study 10 – Full Study: https://journalofexerciseandnutrition.com/index.php/JEN/article/view/189
  11. Summary of Study 11 – Full Study: https://pubmed.ncbi.nlm.nih.gov/41422374/
  12. Summary of Study 12 – Full Study: https://pubmed.ncbi.nlm.nih.gov/24343275/
  13. Summary of Study 13 – Full Study: https://pubmed.ncbi.nlm.nih.gov/36014789/
  14. Summary of Study 14 – Full Study: https://pmc.ncbi.nlm.nih.gov/articles/PMC11930386/

Ingredient Manufacturer Link: https://nutrashure.com/ingredients/biomend/



Study 1 Summary

Complete Study Information: https://www.nature.com/articles/ncomms10062

Production of Butyrate from Lysine and the Amadori Product Fructoselysine by a Human Gut Commensal
Nature Communications. 2015;6:10062.

This study investigated a previously unrecognized metabolic pathway through which certain human gut commensal bacteria can convert the amino acid lysine and its glycation product fructoselysine into butyrate. Using a combination of genomic, proteomic, and metabolic analyses, researchers identified specific bacterial enzymes and pathways involved in this conversion. The findings expand scientific understanding of how butyrate can be generated in the gut beyond carbohydrate fermentation alone, demonstrating that dietary amino acids may also serve as substrates for microbial butyrate production within the colon.

Study Design Highlights

  • Study type: Mechanistic microbial metabolism study (in vitro and ex vivo)
  • Subjects: Human gut commensal bacteria (not a human intervention trial)
  • Dosing: Not applicable (cellular/microbial metabolism study)
  • Duration: Metabolic assessments conducted during bacterial growth cycles

Key Findings (What the Study Showed)

Researchers identified a previously uncharacterized pathway through which certain gut microbes convert lysine and related compounds into butyrate. The study demonstrated that lysine and fructoselysine can serve as substrates for microbial butyrate production and that this pathway contributes meaningfully to overall butyrate generation within the microbial ecosystem. These findings expand the current understanding of how butyrate can be produced in the gut beyond the well-known fermentation of dietary fibers.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the study findings, this research demonstrates:
✓ Lysine can act as a precursor in microbial metabolic pathways that contribute to butyrate production in the gut
✓ Butyrate production in the gut may occur through multiple metabolic pathways beyond fiber fermentation
✓ The lysine–butyrate pairing in BIOMend® is grounded in established gut microbial biochemistry

Why This Study Matters

Although this study was not conducted in humans, it provides insight into how different nutrients may contribute to microbial production of short-chain fatty acids. Understanding these pathways helps guide research into nutritional ingredients designed to support normal butyrate metabolism within the gut microbiome, and provides scientific rationale for pairing butyrate with lysine as a delivery strategy.*

Reference Link: https://www.nature.com/articles/ncomms10062



Study 2 Summary

Complete Study Information: https://pubs.rsc.org/en/content/articlelanding/2021/fo/d1fo02116h

A New Paradigm for a New Simple Chemical: Butyrate & Immune Regulation
Dang G, et al. Food & Function. 2021;12(24):12181–12193. doi:10.1039/d1fo02116h.

This review paper summarizes a broad body of scientific research examining the biological roles of butyrate, a short-chain fatty acid produced by the gut microbiota. The authors describe how butyrate participates in several cellular signaling pathways involved in immune communication, metabolic processes, and interactions between the gut microbiome and host tissues. The paper discusses how butyrate enters cells through specific transporters and participates in cellular signaling processes, including histone deacetylase (HDAC) regulation and receptor-mediated pathways such as GPR41, GPR43, and GPR109.

Key Findings (What the Study Showed)

The authors highlight that butyrate participates in cellular signaling pathways involved in immune communication, interacts with receptors such as GPR41, GPR43, and GPR109 that are involved in metabolic and immune signaling, influences gene expression through HDAC-related pathways, and plays an important role in host–microbiome metabolic communication.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the review findings, butyrate was shown to:
✓ Participate in cellular signaling pathways involved in immune communication
✓ Interact with GPR41, GPR43, and GPR109 receptors involved in metabolic and immune signaling
✓ Influence gene expression through HDAC-related pathways
✓ Play an important role in host–microbiome metabolic communication

Why This Study Matters

Although this paper is a scientific review rather than a clinical intervention study, it provides insight into how butyrate participates in biological processes related to gut microbiome activity and immune signaling. Understanding butyrate biology helps guide research into nutritional ingredients designed to support normal microbiome-related metabolic activity.*

Reference Link: https://pubs.rsc.org/en/content/articlelanding/2021/fo/d1fo02116h



Study 3 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/37542852/

The Impact of Microbiota-Derived Short-Chain Fatty Acids on Macrophage Activities in Disease
Biomedicine & Pharmacotherapy. 2023;165:115276. doi:10.1016/j.biopha.2023.115276.

This review examines how microbiota-derived short-chain fatty acids (SCFAs) — including butyrate, propionate, and acetate — participate in immune signaling processes through their interactions with immune cells such as macrophages. The authors summarize evidence from cellular, animal, and translational research describing how SCFAs interact with multiple biological pathways involved in immune communication, including T-cell differentiation, dendritic cell signaling, macrophage activity, and epigenetic regulation through HDAC-related mechanisms.

Key Findings (What the Study Showed)

  • Butyrate influences signaling pathways associated with immune cell activity and participates in biological processes related to regulatory T-cell differentiation
  • Propionate interacts with signaling pathways involved in dendritic cell communication
  • Short-chain fatty acids broadly participate in macrophage signaling pathways and immune cell communication, and interact with receptor-mediated pathways and epigenetic regulatory mechanisms
  • Variations in SCFA production may influence immune-related signaling processes associated with the gut microbiome

Benefits of BIOMend® Demonstrated by This Study

Based directly on the review findings, microbiota-derived SCFAs including butyrate were shown to:
✓ Participate in macrophage signaling pathways and immune cell communication
✓ Influence biological processes related to regulatory T-cell differentiation
✓ Interact with receptor-mediated pathways and epigenetic regulatory mechanisms
✓ Act as important signaling molecules produced by the gut microbiota

Why This Study Matters

Although this paper is a scientific review, it provides insight into how microbiome-derived metabolites such as butyrate participate in biological communication between the digestive system and immune system. Understanding SCFA biology helps guide research into nutritional ingredients designed to support normal microbiome-related metabolic processes.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/37542852/



Study 4 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/19625695/

Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers
J Nutr. 2009 Sep;139(9):1619-25. doi: 10.3945/jn.109.104638. PMID: 19625695; PMCID: PMC2728689.

This study examined cellular mechanisms by which butyrate interacts with intestinal epithelial cells, focusing on tight junction assembly in a human intestinal cell model (Caco-2 monolayers). Researchers evaluated how physiologically relevant concentrations of butyrate influence cellular signaling pathways involved in epithelial barrier structure and organization. The results showed that butyrate activated AMP-activated protein kinase (AMPK), a cellular signaling pathway involved in energy sensing and cellular regulation.

Study Design Highlights

  • Study type: In vitro mechanistic study using human intestinal epithelial cells (Caco-2 model)
  • Dosing: Butyrate concentrations of approximately 2–5 mM, representing levels observed within the intestinal environment
  • Duration: Short-term cellular exposure (hours to days)
  • Outcomes measured: Transepithelial electrical resistance (TEER), tight junction protein localization, and activation of AMPK signaling pathways

Key Findings (What the Study Showed)

In this epithelial cell model, butyrate exposure was associated with:

  • Increased transepithelial electrical resistance (TEER), a laboratory measure of epithelial barrier characteristics
  • Changes in the organization of tight junction proteins
  • Activation of AMPK signaling pathways involved in cellular energy regulation

When AMPK activity was inhibited experimentally, these cellular effects were reduced, suggesting that AMPK signaling plays a role in the observed cellular responses.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the study findings, butyrate was shown to:
✓ Participate in cellular signaling pathways within intestinal epithelial cells
✓ Influence TEER measurements associated with epithelial barrier characteristics
✓ Activate AMPK signaling pathways involved in cellular energy regulation
✓ Support changes in tight junction protein organization in intestinal cell models

Why This Study Matters

Although this research was conducted in a laboratory cell model, it contributes to scientific understanding of how microbiome-derived metabolites such as butyrate interact with intestinal epithelial cells. Mechanistic studies help guide research into nutritional ingredients that support normal gastrointestinal physiology.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/19625695/



Study 5 Summary

Complete Study Information: https://www.researchgate.net/publication/375885731_Modulation_of_GABA_by_sodium_butyrate_ameliorates_hypothalamic_inflammation_in_experimental_model_of_PCOS

Modulation of GABA by Sodium Butyrate Ameliorates Hypothalamic Inflammation in an Experimental Model of PCOS
BMC Neuroscience. 2023;24(1):62. doi:10.1186/s12868-023-00834-z.

This preclinical study evaluated how sodium butyrate influenced neurochemical and immune-related signaling pathways in a letrozole-induced rat model used to study polycystic ovary syndrome (PCOS). Researchers examined markers associated with neuroimmune activity in the hypothalamus, including inflammatory signaling molecules, microglial activation, and GABA-related neurotransmitter pathways.

Study Design Highlights

  • Study type: Preclinical animal study (rat model)
  • Dosing: Oral sodium butyrate at approximately 300 mg/kg body weight per day
  • Duration: Approximately 6 weeks following induction of the experimental model
  • Outcomes measured: Cytokine expression levels, microglial activation markers, indicators of GABA-related neurotransmitter activity

Key Findings (What the Study Showed)

The study observed that sodium butyrate exposure was associated with:

  • Changes in cytokines involved in immune signaling
  • Changes in markers associated with microglial activation
  • Changes in biological indicators related to GABA-associated signaling pathways

These observations were linked to cellular mechanisms involving histone deacetylase (HDAC)–related signaling pathways.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the preclinical findings, sodium butyrate was shown to:
✓ Influence cytokines involved in neuroimmune signaling
✓ Interact with markers associated with microglial activation
✓ Interact with GABA-associated signaling pathways through HDAC-related mechanisms
✓ Demonstrate interactions between gut-derived metabolites and neuroimmune pathways

Why This Study Matters

Although this research was conducted in an animal model, it contributes to scientific understanding of how microbiome-derived metabolites such as butyrate interact with signaling pathways associated with communication between the digestive system and nervous system. Mechanistic studies help guide research into nutritional ingredients designed to support microbiome-related metabolic activity.*

Reference Link: https://www.researchgate.net/publication/375885731_Modulation_of_GABA_by_sodium_butyrate_ameliorates_hypothalamic_inflammation_in_experimental_model_of_PCOS



Study 6 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/32476236/

Microbiota Changes Induced by Microencapsulated Sodium Butyrate in Patients with Inflammatory Bowel Disease
Neurogastroenterology & Motility. 2020;32(10):e13914. doi:10.1111/nmo.13914.

This clinical study evaluated how oral microencapsulated sodium butyrate influenced gut microbiota composition in individuals diagnosed with inflammatory bowel disease (IBD). Because butyrate is rapidly absorbed in the upper digestive tract, researchers used a microencapsulated formulation designed to improve delivery to the colon. The study examined changes in microbiota composition and patient-reported wellness indicators during the supplementation period.

Study Design Highlights

  • Study type: Human clinical intervention study
  • Population: Adults diagnosed with inflammatory bowel disease
  • Dose: 1,800 mg/day microencapsulated sodium butyrate
  • Duration: 60 days of continuous supplementation
  • Outcomes measured: Changes in gut microbiota composition, relative abundance of specific bacterial genera, patient-reported quality-of-life indicators

Key Findings (What the Study Showed)

During the study period, sodium butyrate supplementation was associated with:

  • Changes in gut microbiota composition
  • Increased relative abundance of certain butyrate-producing bacterial taxa, including members of the Butyricoccus genus and the Lachnospiraceae family
  • Improvements in patient-reported wellness measures

The intervention was reported to be well tolerated.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical findings, microencapsulated sodium butyrate was shown to:
✓ Influence gut microbiota composition during supplementation
✓ Support increased relative abundance of butyrate-producing bacterial taxa
✓ Be associated with improvements in patient-reported wellness measures
✓ Be well tolerated over the 60-day intervention period

Why This Study Matters

This study provides insight into how butyrate supplementation may interact with the gut microbiome. Microbiota composition may shift during supplementation with microbial metabolites, and research on delivery systems such as microencapsulation helps guide development of nutritional ingredients designed to interact with the gut microbiome.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/32476236/



Study 7 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/36469320/

Therapeutic Effects of Butyrate on Pediatric Obesity: A Randomized Clinical Trial
JAMA Network Open. 2022;5(12):e2244912. doi:10.1001/jamanetworkopen.2022.44912.

A randomized, quadruple-blind, placebo-controlled clinical trial published in JAMA Network Open evaluated the effects of oral sodium butyrate supplementation in children and adolescents with obesity when used alongside standard lifestyle interventions. Over a 6-month period, researchers assessed weight-related measures, metabolic biomarkers, inflammatory markers, and appetite-related hormones. The study reported that butyrate supplementation was associated with greater likelihood of achieving clinically meaningful reductions in BMI and changes in several metabolic and inflammatory biomarkers compared with placebo.

Study Design Highlights

  • Study design: Randomized, quadruple-blind, placebo-controlled clinical trial
  • Population: Children and adolescents with obesity participating in a weight management program
  • Dose: 20 mg per kg body weight per day (up to approximately 800 mg/day)
  • Duration: 6 months alongside standard lifestyle-based care
  • Primary outcome: Proportion of participants achieving at least a 0.25 reduction in BMI standard deviation (SD) score

Key Findings (What the Study Showed)

1. Primary Outcome — BMI-Related Measure

  • Butyrate group achieving BMI SD reduction: 96%
  • Placebo group achieving BMI SD reduction: 56%
  • Difference was statistically significant

2. Secondary Outcomes Observed

  • Waist circumference: −5.07 cm (butyrate vs. placebo)
  • Fasting insulin: −5.41 μU/mL
  • HOMA-IR: −1.14
  • Ghrelin: −47.89 μg/mL
  • IL-6: −4.81 pg/mL
  • microRNA-221: −2.17

All differences reported reached statistical significance (P < 0.05).

3. Microbiome Insights

Researchers reported that participants with higher levels of butyrate-producing bacteria at baseline appeared more likely to experience the BMI-related outcome defined in the study, suggesting individual microbiome composition may influence physiological responses to microbial metabolites such as butyrate.

4. Safety & Tolerability

  • Mild nausea or headache reported in two participants during the first month — symptoms were transient and resolved without discontinuation
  • No serious adverse events related to the intervention were reported

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical outcomes, oral butyrate supplementation was shown to:
✓ Support a significantly higher proportion of participants achieving BMI SD reductions
✓ Support favorable changes in waist circumference, fasting insulin, and HOMA-IR
✓ Support changes in ghrelin, an appetite-related hormone
✓ Support changes in IL-6 and microRNA-221, markers of metabolic and immune signaling
✓ Be generally well tolerated over a 6-month period

Why This Study Matters

Although conducted in a pediatric clinical population, this research contributes to the broader scientific understanding of how short-chain fatty acids produced by the gut microbiome participate in physiological signaling pathways related to metabolism, appetite regulation, and immune communication. These findings help inform ongoing research exploring nutritional strategies that support the body's natural microbiome-derived metabolic processes.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/36469320/



Study 8 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/39003477/

Effects of Short-Chain Fatty Acid-Butyrate Supplementation on Expression of Circadian-Clock Genes, Sleep Quality, and Inflammation in Patients with Active Ulcerative Colitis
Lipids in Health and Disease. 2024;23(1):216. doi:10.1186/s12944-024-02203-z.

This randomized, double-blind, placebo-controlled clinical trial evaluated how oral sodium butyrate supplementation influenced inflammatory biomarkers, circadian-clock gene expression, and sleep-related outcomes in 36 adults diagnosed with active ulcerative colitis over a 12-week intervention period.

Study Design Highlights

  • Study design: Double-blind, randomized, placebo-controlled clinical trial
  • Population: 36 adults diagnosed with active ulcerative colitis
  • Dose: 600 mg/kg body weight per day sodium butyrate
  • Duration: 12 weeks
  • Comparator: Placebo

Key Findings (What the Study Showed)

1. Inflammatory Biomarkers

  • Faecal calprotectin: Butyrate group −133.8 ± 155.6 µg/g vs. placebo group +51.6 ± 95.6 µg/g (p < 0.001)
  • hs-CRP: Butyrate group −0.36 mg/L vs. placebo group +0.48 mg/L (p < 0.001)

2. Circadian Gene Expression (Fold-Change vs. Baseline)

  • CRY1: Butyrate 2.22 ± 1.59 vs. placebo 0.63 ± 0.49
  • CRY2: Butyrate 2.15 ± 1.26 vs. placebo 0.93 ± 0.80
  • PER1: Butyrate 1.86 ± 1.77 vs. placebo 0.65 ± 0.48
  • BMAL1: Butyrate 1.85 ± 0.97 vs. placebo 0.86 ± 0.63

3. Sleep Quality (PSQI)

  • Butyrate group: −2.94 ± 3.50 vs. placebo group +1.16 ± 3.61 (p < 0.001)

4. Quality-of-Life Indicator (IBDQ-9)

  • Butyrate group: +17.00 ± 11.36 vs. placebo group −3.50 ± 6.87 (p < 0.001)

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical outcomes, sodium butyrate supplementation was shown to:
✓ Support significant reductions in faecal calprotectin and hs-CRP compared with placebo
✓ Support greater changes in circadian-clock gene expression including CRY1, CRY2, PER1, and BMAL1
✓ Support improvements in sleep quality scores (PSQI)
✓ Support improvements in quality-of-life indicators (IBDQ-9)
✓ Be generally well tolerated during the 12-week study period

Why This Study Matters

Although conducted in a clinical population, this study adds to the growing body of literature exploring how short-chain fatty acids produced by the gut microbiome participate in physiological signaling pathways that influence immune communication, circadian biology, and sleep-related processes.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/39003477/



Study 9 Summary

Complete Study Information: https://www.nature.com/articles/s41598-018-37246-7

Effects of Oral Butyrate Supplementation on the Inflammatory Potential of Circulating Peripheral Blood Mononuclear Cells in Healthy and Obese Males
Cleophas MCP, et al. Scientific Reports. 2019;9:775.

This human intervention study evaluated how oral sodium butyrate supplementation influenced immune cell signaling responses in circulating peripheral blood mononuclear cells (PBMCs) in 9 lean healthy adult males and 10 adult males diagnosed with metabolic syndrome. Unlike many butyrate studies that focus on gastrointestinal outcomes, this study examined systemic immune signaling responses in circulating monocytes.

Study Design Highlights

  • Study design: Pre–post human intervention study (no placebo control)
  • Population: 9 lean healthy adult males; 10 adult males with metabolic syndrome
  • Dose: 4 grams per day (oral) sodium butyrate
  • Duration: 4 weeks
  • Outcomes measured: Cytokine production (IL-6, TNF-α, IL-10) and trained immunity responses following stimulation with oxLDL, β-glucan, and BCG

Key Findings (What the Study Showed)

The study reported statistically significant changes in trained immunity responses in participants with metabolic syndrome following the supplementation period:

  • Lower IL-6 responses following LPS stimulation
  • Lower TNF-α responses following Pam3CSK4 stimulation
  • Changes in β-glucan–induced trained immunity responses, including IL-10 signaling

Minimal changes in cytokine responses were observed in lean healthy participants. The intervention did not broadly suppress baseline immune responses, suggesting the observed effects were specific to trained immunity signaling pathways rather than general immune inhibition.

Benefits of BIOMend® Demonstrated by This Study

Based directly on the study findings, oral sodium butyrate supplementation was shown to:
✓ Influence trained innate immune responses in circulating monocytes in individuals with metabolic syndrome
✓ Support changes in IL-6 and TNF-α trained immunity responses
✓ Demonstrate effects specific to trained immunity pathways rather than general immune suppression
✓ Provide human evidence that oral butyrate can influence immune cell signaling outside the gastrointestinal tract

Why This Study Matters

This study provides human evidence that oral butyrate supplementation can influence immune cell signaling responses outside the gastrointestinal tract. The findings add to the broader scientific understanding of how microbiome-derived metabolites participate in systemic immune communication and metabolic signaling processes. The study is best interpreted as a mechanistic investigation of immune biology due to its small sample size, male-only population, and lack of a placebo control.*

Reference Link: https://www.nature.com/articles/s41598-018-37246-7



Study 10 Summary

Complete Study Information: https://journalofexerciseandnutrition.com/index.php/JEN/article/view/189

Pharmacokinetics of Different Butyrate Formulations: A Randomized Crossover Trial
Journal of Exercise and Nutrition. 2023;6(2):189.

This randomized crossover pharmacokinetic study evaluated how different oral butyrate formulations influence circulating butyrate levels in 10 healthy adult men. Researchers compared serum butyrate responses following ingestion of lysine butyrate, sodium butyrate, and tributyrin, each providing an equivalent amount of butyric acid (786 mg). Blood samples were collected over 210 minutes after ingestion to assess pharmacokinetic parameters.

Study Design Highlights

  • Study design: Randomized, three-arm crossover clinical trial
  • Population: 10 healthy adult men
  • Intervention: Single oral dose of three butyrate formulations, each delivering 786 mg butyric acid
  • Monitoring window: 0 to 210 minutes post-ingestion

Key Findings (What the Study Showed)

Systemic Exposure (AUC₀–₂₁₀)

  • Lysine butyrate: ~189 µg·min/mL
  • Sodium butyrate: ~144 µg·min/mL
  • Tributyrin: ~108 µg·min/mL

Peak Plasma Concentration (Cmax)

  • Lysine butyrate: ~4.53 µg/mL
  • Sodium butyrate: ~2.51 µg/mL
  • Tributyrin: ~0.91 µg/mL

Time to Peak Concentration (Tmax)

  • Lysine butyrate: ~20 minutes
  • Sodium butyrate: ~22.5 minutes
  • Tributyrin: ~51.5 minutes

Benefits of BIOMend® Demonstrated by This Study

Based directly on the pharmacokinetic outcomes, lysine butyrate was shown to:
✓ Produce the highest observed peak circulating butyrate concentration among all three formulations
✓ Deliver the greatest total systemic butyrate exposure (AUC) among formulations tested
✓ Reach peak circulating levels rapidly (~20 minutes)
✓ Demonstrate superior absorption characteristics compared with tributyrin
✓ Be generally well tolerated following single-dose administration

Why This Study Matters

This study contributes to the understanding of how different supplemental forms of butyrate influence systemic availability following ingestion. Lysine butyrate demonstrated the highest observed peak plasma concentration and greatest total exposure among the formulations tested, providing pharmacokinetic rationale for BIOMend®'s lysine–butyrate delivery approach.*

Reference Link: https://journalofexerciseandnutrition.com/index.php/JEN/article/view/189



Study 11 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/41422374/

Efficacy of Microencapsulated Sodium Butyrate as Add-On Therapy in Inducing Remission in Patients with Mild-to-Moderate Ulcerative Colitis: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study
Medical Science Monitor. 2024;30:e945684. doi:10.12659/MSM.945684.

This multicenter, double-blind, randomized, placebo-controlled clinical study evaluated the effects of microencapsulated sodium butyrate (MSB) in adults diagnosed with mild-to-moderate ulcerative colitis. Participants received 300 mg of MSB twice daily (600 mg/day total) or placebo in addition to their existing therapy for eight weeks.

Study Design Highlights

  • Study design: Multicenter, double-blind, randomized, placebo-controlled clinical trial
  • Population: Adults diagnosed with active mild-to-moderate ulcerative colitis
  • Dose: 600 mg/day microencapsulated sodium butyrate (300 mg twice daily)
  • Duration: 8 weeks alongside existing standard therapy

Key Findings (What the Study Showed)

Clinical Score Changes

  • Proportion achieving ≥3-point reduction in Total Mayo Score: MSB 51% vs. placebo 21.3% (p = 0.005)
  • Proportion reaching predefined study threshold (TMS ≤2, no rectal bleeding, normal stool frequency): MSB 31.4% vs. placebo 6.4% (p = 0.004)

Endoscopic and Biomarker Outcomes

  • Proportion with ≥1-point reduction in endoscopic score: MSB 25.5% vs. placebo 4.6% (p = 0.006)
  • Proportion with fecal calprotectin ≤250 µg/g: MSB 41.2% vs. placebo 17.0% (p = 0.009)
  • Increases in fecal butyric acid levels were associated with changes in study outcomes during the intervention period

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical outcomes, microencapsulated sodium butyrate was shown to:
✓ Support significantly higher rates of improvement in Total Mayo Score compared with placebo
✓ Support significantly higher rates of endoscopic score improvement
✓ Support significantly higher proportions of participants achieving favorable fecal calprotectin levels
✓ Demonstrate associations between fecal butyric acid levels and study outcomes
✓ Be generally well tolerated with no significant safety concerns

Why This Study Matters

This study contributes to the broader body of research examining how microbiome-derived metabolites such as butyrate interact with intestinal and immune signaling pathways, and helps expand scientific understanding of how targeted delivery of microbial metabolites may influence biological markers commonly measured in gastrointestinal research.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/41422374/



Study 12 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/24343275/

Microencapsulated Sodium Butyrate Administered to Patients with Diverticulosis Decreases Incidence of Diverticulitis — A Prospective Randomized Study
Int J Colorectal Dis. 2014;29(3):387-393. doi:10.1007/s00384-013-1807-5.

This prospective, randomized, placebo-controlled clinical study evaluated the effects of microencapsulated sodium butyrate (MSB) supplementation in 73 adults diagnosed with diverticulosis over a 12-month intervention period. Researchers monitored clinically diagnosed diverticulitis episodes, imaging-confirmed findings, and patient-reported symptom and quality-of-life measures.

Study Design Highlights

  • Study design: Prospective randomized clinical trial
  • Participants: 73 randomized; 52 completed (30 MSB, 22 placebo)
  • Dose: 300 mg/day microencapsulated sodium butyrate
  • Duration: 12 months

Key Findings (What the Study Showed)

Diverticulitis Episodes

  • MSB group: 2 events (6.7% incidence)
  • Placebo group: 7 events (31.8% incidence)
  • Difference statistically significant (p = 0.0425)

Ultrasound-Confirmed Findings

  • MSB group: 1 confirmed case
  • Placebo group: 5 confirmed cases
  • Difference statistically significant (p = 0.0229)

Patient-Reported Symptom Changes

  • MSB group reporting improvement: 55.7%
  • Placebo group reporting improvement: 22.7%
  • Difference statistically significant (p = 0.0143)

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical outcomes, microencapsulated sodium butyrate was shown to:
✓ Be associated with significantly fewer diverticulitis events over 12 months
✓ Support significantly fewer ultrasound-confirmed diverticulitis cases
✓ Support significantly higher rates of patient-reported symptom improvement
✓ Be well tolerated with no adverse effects reported over 12 months

Why This Study Matters

This study adds to the broader body of research investigating the physiological roles of short-chain fatty acids such as butyrate in the gastrointestinal tract. Targeted delivery systems such as microencapsulation may help researchers better evaluate how microbial metabolites interact with biological markers and clinical outcomes in gastrointestinal research.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/24343275/



Study 13 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/36014789/

Oral Butyrate Supplementation Does Not Improve Disease Activity in Children with Newly Diagnosed Inflammatory Bowel Disease: A Multicenter Randomized Placebo-Controlled Trial
Nutrients. 2022;14(16):3283. doi:10.3390/nu14163283.

Researchers conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of oral sodium butyrate supplementation in children with newly diagnosed Crohn's disease or ulcerative colitis. Participants received sodium butyrate or placebo in addition to their standard induction therapy over a 12-week intervention period.

Study Design Highlights

  • Study design: Multicenter, randomized, double-blind, placebo-controlled clinical trial
  • Population: Children with newly diagnosed inflammatory bowel disease
  • Dose: 300 mg/day oral sodium butyrate
  • Duration: 12 weeks alongside standard induction treatment

Key Findings (What the Study Showed)

  • No statistically significant difference between the butyrate and placebo groups in disease activity scores (PCDAI or PUCAI)
  • Fecal calprotectin decreased in both groups — no significant difference between groups
  • CRP and ESR showed changes during the study period with no significant differences between groups
  • No measurable increase in fecal butyrate levels or significant change in butyrate-producing microbial taxa

Why This Study Matters

This study contributes to the broader scientific literature examining microbiome-derived metabolites such as butyrate and their interactions with gastrointestinal physiology. The findings highlight factors such as formulation characteristics, delivery to the colon, dosing, intervention duration, and concurrent therapies as potential variables influencing study outcomes. Differences in delivery systems and study populations may influence outcomes across clinical investigations, and continued research is ongoing to better understand these variables.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/36014789/



Study 14 Summary

Complete Study Information: https://pmc.ncbi.nlm.nih.gov/articles/PMC11930386/

Effects of Short Chain Fatty Acid-Butyrate Supplementation on the Disease Severity, Inflammation, and Psychological Factors in Patients With Active Ulcerative Colitis: A Double-Blind Randomized Controlled Trial
J Nutr Metab. 2025 Mar 16;2025:3165876. doi: 10.1155/jnme/3165876. PMID: 40123849; PMCID: PMC11930386.

Researchers conducted a randomized, placebo-controlled clinical trial to examine the effects of oral sodium butyrate supplementation (600 mg/kg/day) over 12 weeks in adults with active ulcerative colitis. The study evaluated changes in disease activity scores, inflammatory biomarkers and ratios, and validated psychological questionnaires.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled clinical trial
  • Population: Adults diagnosed with ulcerative colitis
  • Dose: 600 mg/kg/day oral sodium butyrate
  • Duration: 12 weeks
  • Comparator: Placebo
  • Background therapy: Stable background medications permitted during the study

Key Findings (What the Study Showed)

1. Disease Activity Measures

  • Total Mayo Score: ~41% reduction from baseline in butyrate group; no statistically significant change in placebo group
  • Between-group difference was statistically significant

2. Inflammatory Biomarkers

  • hs-CRP: ~38% reduction in butyrate group; no meaningful change in placebo group
  • Neutrophil-to-Lymphocyte Ratio (NLR): ~29% reduction in butyrate group
  • Platelet-to-Lymphocyte Ratio (PLR): ~26% reduction in butyrate group

3. Psychological Measures

  • Depression scores: ~34% reduction in butyrate group
  • Anxiety scores: ~32% reduction in butyrate group
  • Perceived stress: ~30% reduction in butyrate group
  • No statistically significant improvements in these parameters in the placebo group

Benefits of BIOMend® Demonstrated by This Study

Based directly on the clinical outcomes, oral sodium butyrate supplementation was shown to:
✓ Support significant reductions in Total Mayo Score disease activity markers
✓ Support reductions in hs-CRP, NLR, and PLR inflammatory markers
✓ Support improvements in validated depression, anxiety, and perceived stress scores
✓ Demonstrate interactions between gut-derived metabolites, inflammatory pathways, and psychological well-being
✓ Be generally well tolerated over the 12-week study period

Why This Study Matters

This study adds to existing research examining relationships between gut-derived metabolites and systemic inflammatory markers, interactions between gastrointestinal physiology and psychological well-being, and the broader gut–brain axis framework in human health research. Further research is ongoing to better understand these mechanisms and their potential implications.*

Reference Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC11930386/

Big-Picture Integration with Other Studies

  • Study 1: This study demonstrated that certain human gut bacteria can metabolize lysine and fructoselysine into butyrate, identifying an amino acid–driven pathway that may contribute to endogenous butyrate production within the gut microbiome.
  • Study 2: This review summarizes how butyrate influences cellular signaling pathways involved in immune regulation, metabolic activity, and neurological function through mechanisms including HDAC inhibition, NF-κB signaling modulation, and G-protein–coupled receptor activation.
  • Study 3: This review highlights how microbiota-derived short-chain fatty acids such as butyrate influence macrophage activity, immune signaling pathways, and inflammatory balance in a variety of experimental and translational research models.
  • Study 4: This mechanistic study demonstrated that butyrate can support intestinal barrier function in intestinal epithelial cell models by activating AMPK signaling and promoting tight-junction assembly.
  • Study 5: In a preclinical animal model, sodium butyrate supplementation was associated with changes in hypothalamic inflammatory signaling and markers related to GABAergic neurotransmission, suggesting interactions between gut-derived metabolites and neuroimmune pathways.
  • Study 6: In a clinical investigation involving individuals with inflammatory bowel conditions, microencapsulated sodium butyrate supplementation was associated with changes in gut microbiota composition, including increases in butyrate-producing bacterial populations, along with reported improvements in quality-of-life measures.
  • Study 7: In a six-month randomized clinical trial in children and adolescents with obesity, weight-adjusted oral butyrate supplementation was associated with changes in BMI measures and several metabolic and inflammatory markers compared with standard care alone.
  • Study 8: In a 12-week randomized, placebo-controlled trial, oral sodium butyrate supplementation was associated with changes in inflammatory biomarkers, circadian-clock gene expression, sleep quality, and quality-of-life measures in adults with ulcerative colitis.
  • Study 9: In a four-week human intervention study, high-dose oral sodium butyrate supplementation was associated with reductions in trained immunity responses in circulating monocytes from individuals with metabolic syndrome, while minimal changes were observed in lean participants.
  • Study 10: In a randomized crossover pharmacokinetic trial, lysine butyrate demonstrated faster absorption and higher peak circulating butyrate levels than tributyrin, with comparable or greater systemic exposure than sodium butyrate following a single oral dose.
  • Study 11: In an eight-week randomized, placebo-controlled trial involving adults with ulcerative colitis receiving standard therapy, microencapsulated sodium butyrate supplementation was associated with higher rates of improvement in several clinical research measures compared with placebo.
  • Study 12: In a 12-month randomized, placebo-controlled study in individuals with diverticulosis, daily microencapsulated sodium butyrate supplementation was associated with fewer reported diverticulitis episodes and improvements in patient-reported symptom measures compared with placebo.
  • Study 13: In a multicenter randomized clinical trial involving children with newly diagnosed inflammatory bowel disease, oral sodium butyrate supplementation did not demonstrate additional changes in disease activity or inflammatory markers beyond those observed with standard induction therapy.
  • Study 14: In a randomized, placebo-controlled clinical trial, high-dose oral sodium butyrate supplementation over 12 weeks was associated with changes in inflammatory markers, disease activity scores, and validated psychological questionnaire measures in adults with ulcerative colitis.

BIOMend® Ingredient Summary & Real-World Relevance

BIOMend® is designed to translate the well-established biology of butyrate into a practical and well-tolerated supplementation format. Butyrate is a short-chain fatty acid naturally produced by beneficial gut microbes and widely studied for its role in intestinal physiology, immune signaling, metabolic regulation, and host–microbiome communication. A large body of mechanistic, preclinical, and human research has explored how butyrate interacts with cellular pathways involved in epithelial barrier function, inflammatory signaling, metabolic activity, and gut-brain communication.

BIOMend® utilizes a lysine–butyrate complex designed to improve palatability and delivery characteristics compared with traditional butyrate salts. By supporting the availability of this key microbiome-derived metabolite, BIOMend® is intended to complement dietary strategies that support gut health, including fiber intake, probiotics, and prebiotics. Together, these approaches help support the complex biological systems influenced by microbial metabolites, including digestive physiology, immune balance, and communication between the gut and other organs throughout the body.*

Ingredient Manufacturer Link: https://nutrashure.com/ingredients/biomend/

BIOMend® is a clinically studied ingredient used in the following Silver Fern™ Brand product:

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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