ApplePhenon® - Clinical Research Data Summary

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ApplePhenon® Apple Polyphenol Extract

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

Introduction

ApplePhenon® is a clinically studied apple polyphenol extract made from wild, unripe apples and designed to function as a precision prebiotic for the gut microbiome. Unlike traditional fibers that broadly feed many bacteria, ApplePhenon® selectively nourishes beneficial microbes—especially short-chain fatty acid (SCFA)–producing species—helping support a balanced gut microbiome, healthy gut barrier function, and normal metabolic signaling.

These apple polyphenols reach the colon largely intact, where they serve as fuel for beneficial bacteria, helping stimulate the production of short-chain fatty acids such as butyrate. These compounds play an important role in supporting gut integrity, immune balance, and overall metabolic health.

In short, ApplePhenon® isn't bulk fiber—it's targeted microbial nourishment designed to help support a healthy and resilient gut ecosystem.

These are the studies for ApplePhenon®. 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://pubmed.ncbi.nlm.nih.gov/15110105/
  2. Summary of Study 2 – Full Study: https://pubmed.ncbi.nlm.nih.gov/17483009/
  3. Summary of Study 3 – Full Study: https://pubmed.ncbi.nlm.nih.gov/32294883/
  4. Summary of Study 4 – Full Study: https://pubmed.ncbi.nlm.nih.gov/17898508/
  5. Summary of Study 5 – Full Study: https://pubmed.ncbi.nlm.nih.gov/28505543/
  6. Summary of Study 6 – Full Study: https://pubmed.ncbi.nlm.nih.gov/17039666/
  7. Summary of Study 7 – Full Study: https://pubmed.ncbi.nlm.nih.gov/20484838/
  8. Summary of Study 8 – Full Study: https://pubmed.ncbi.nlm.nih.gov/28755406/
  9. Summary of Study 9 – Full Study: https://pubmed.ncbi.nlm.nih.gov/29078780/
  10. Summary of Study 10 – Full Study: https://pubmed.ncbi.nlm.nih.gov/33801641/
  11. Summary of Study 11 – Full Study: https://pubmed.ncbi.nlm.nih.gov/28956697/
  12. Summary of Study 12 – Full Study: https://pubmed.ncbi.nlm.nih.gov/24917557/
  13. Summary of Study 13 – Full Study: https://pubmed.ncbi.nlm.nih.gov/28296588/
  14. Summary of Study 14 – Full Study: https://www.jstage.jst.go.jp/article/jcam/6/2/6_2_69/_article/-char/en

Ingredient Manufacturer Link: https://bggworld.com/applephenon-apple-polyphenols/



Study 1 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/15110105/

The Toxicology and Safety of Apple Polyphenol Extract
Shoji T, Akazome Y, et al. Food and Chemical Toxicology. 2004 Jun;42(6):959–967. doi:10.1016/j.fct.2004.02.008.

This study evaluated the toxicological safety profile of ApplePhenon®, a polyphenol extract derived from unripe apples. While a very high, non-dietary laboratory dose showed slight activity in one preliminary screening test, multiple follow-up genetic safety assays found no evidence of biologically relevant mutagenic effects.

In both short-term and 90-day high-dose animal studies (up to 2,000 mg per kg of body weight), ApplePhenon® was well tolerated and showed no treatment-related adverse effects, including no significant changes in blood markers, organ health, or overall physiological status.

Key Findings (What the Study Showed)

  • No evidence of biologically relevant mutagenic effects in multiple genetic safety assays
  • Well tolerated in short-term and 90-day high-dose animal studies up to 2,000 mg/kg body weight
  • No treatment-related adverse effects observed
  • No significant changes in blood markers, organ health, or overall physiological status

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the study outcomes, ApplePhenon® was shown to:
✓ Demonstrate a favorable safety profile within tested intake ranges
✓ Be well tolerated at high doses in controlled safety studies
✓ Show no treatment-related adverse effects on blood markers or organ health
✓ Produce no evidence of mutagenic activity in follow-up genetic assays

Why This Study Matters

This foundational safety study establishes the tolerability of ApplePhenon® across a wide range of intake levels and provides the toxicological foundation upon which subsequent human clinical trials were built. The absence of adverse effects at doses far exceeding typical dietary intake reinforces the ingredient's safety profile for daily use.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/15110105/



Study 2 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/17483009/

Effects of ApplePhenon® and Ascorbic Acid on Exercise Performance
Nutrition. 2007 May;23(5):419–423.

This double-blind, placebo-controlled, three-way crossover human trial evaluated the effects of ApplePhenon® supplementation on physical performance during prolonged exercise. Eighteen healthy adults consumed ApplePhenon® (1,200 mg/day), ascorbic acid (1,000 mg/day), or placebo for 8 days per intervention, then completed a 2-hour cycling protocol designed to induce fatigue. Peak sprint performance (maximum velocity over 10 seconds) was measured early and late in the exercise session to assess changes in performance over time.

Study Design Highlights

  • Study design: Double-blind, placebo-controlled, three-way crossover human trial
  • Participants: 18 healthy adults
  • Duration: 8 days per intervention
  • Dose:
    • ApplePhenon®: 1,200 mg/day
    • Ascorbic Acid (Vitamin C): 1,000 mg/day
    • Placebo

Key Findings (What the Study Showed)

Physical Performance During Prolonged Exercise

ApplePhenon® supplementation helped maintain maximum cycling velocity during the later stages of the exercise protocol compared with placebo. The decline in peak sprint performance from early to late exercise was smaller in the ApplePhenon® group, indicating better maintenance of performance during prolonged exertion. Vitamin C did not demonstrate measurable benefits compared with placebo.

Note: The study reported statistically significant preservation of peak velocity, but did not publish specific percentage improvements. Results were expressed as relative differences in maintained maximum velocity compared with placebo.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, ApplePhenon® was shown to:
✓ Help maintain peak cycling performance during prolonged exercise
✓ Support sustained power output during extended workloads
✓ Produce greater maintenance of performance compared with Vitamin C in this study

Why This Study Matters

This controlled human trial demonstrates that apple polyphenols may support sustained physical performance during extended exercise, potentially through their role in supporting antioxidant defenses during physical stress. The authors suggest the observed effects may be related to ApplePhenon®'s polyphenol profile, which may help support the body's antioxidant defenses during intense exercise, help maintain normal muscle function during prolonged workloads, and support the body's natural response to exercise-induced oxidative stress.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/17483009/



Study 3 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/32294883/

Administration of Apple Polyphenol Supplements for Skin Conditions in Healthy Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Nutrients. 2020 Apr 12;12(4):1071.

This randomized, double-blind, placebo-controlled human clinical trial evaluated several markers of skin appearance following controlled UV exposure in 59 healthy women (ages 20–39) who supplemented with ApplePhenon® for 12 weeks. Researchers evaluated skin redness (erythema), melanin levels (pigmentation), skin lightness (L-value), and skin hydration and barrier markers (water content and TEWL).

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trial
  • Participants: 59 healthy women (ages 20–39)
  • Duration: 12 weeks
  • Dose:
    • ApplePhenon®: 300 mg/day
    • ApplePhenon®: 600 mg/day
    • Placebo

Key Findings (What the Study Showed)

Skin Appearance Following UV Exposure

Participants taking ApplePhenon® showed smaller increases in skin redness and melanin levels following UV exposure compared with placebo. Supplementation was also associated with better maintenance of skin lightness (L-value) during the study period. These effects were observed at both the 300 mg and 600 mg doses, suggesting benefits may occur across moderate intake levels.

What Did Not Change

No significant differences were observed in skin moisture content or trans-epidermal water loss (TEWL), indicating the observed effects were related to skin appearance following UV exposure rather than general moisturization.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, ApplePhenon® was shown to:
✓ Support smaller increases in skin redness following UV exposure
✓ Help maintain healthy skin pigmentation markers during UV exposure
✓ Support better maintenance of skin lightness (L-value)
✓ Demonstrate benefits at both 300 mg and 600 mg daily doses
✓ Be well tolerated with over 95% compliance over 12 weeks

Why This Study Matters

Laboratory analysis identified strong antioxidant activity from procyanidins in apple polyphenols, including the ability to neutralize superoxide radicals. The researchers suggest these compounds may help support the skin's natural antioxidant defenses, help maintain normal skin responses to environmental stressors, and support healthy skin appearance following UV exposure. These findings highlight the potential role of apple polyphenols in supporting skin health through antioxidant mechanisms.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/32294883/



Study 4 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/17898508/

Apple Polyphenols Influence Cholesterol Metabolism in Healthy Subjects with Relatively High Body Mass Index
Journal of Oleo Science. 2007;56(8):417–428.

This randomized, double-blind, placebo-controlled human clinical trial evaluated markers related to lipid metabolism and body composition in 71 healthy adults (men and women) with BMI 23–30 who supplemented with apple polyphenols for 12 weeks.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trial
  • Participants: 71 healthy adults (men and women) with BMI 23–30
  • Duration: 12 weeks
  • Dose:
    • Apple polyphenols: 600 mg/day (primarily procyanidins)
    • Hop bract polyphenols
    • Placebo
  • Measured outcomes:
    • Total cholesterol and LDL cholesterol
    • Abdominal fat via CT scan (visceral, subcutaneous, and total fat area)
    • Adiponectin levels
    • Safety and tolerability

Key Findings (What the Study Showed)

1. Lipid Metabolism Markers

Participants consuming apple polyphenols showed changes in markers related to cholesterol metabolism, including lower total and LDL cholesterol measurements compared with placebo. These changes became more apparent during the later weeks of the intervention and were greater than those observed in the hop polyphenol comparison group.

2. Abdominal Fat and Metabolic Markers

Visceral fat area decreased in the apple polyphenol group while it increased in the placebo group over the course of the study. Adiponectin levels were maintained or modestly increased in participants consuming apple polyphenols, whereas levels declined in the placebo group. Adiponectin is a hormone involved in metabolic regulation and normal insulin signaling.

3. Body Weight and Lifestyle Factors

Participants taking apple polyphenols experienced modest downward trends in body weight and BMI during the study period. Importantly, no significant changes were reported in calorie intake, macronutrient intake, or physical activity levels, suggesting the observed changes occurred independently of major lifestyle modifications during the study.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support healthy lipid metabolism including total and LDL cholesterol
✓ Help reduce visceral fat area compared with placebo
✓ Support healthy adiponectin levels and insulin signaling
✓ Support modest improvements in body weight and BMI trends
✓ Be well tolerated with no clinically relevant adverse effects

Why This Study Matters

The authors propose several potential mechanisms through which apple polyphenols may support lipid metabolism, including supporting normal digestion and handling of dietary fats, influencing bile acid metabolism, supporting healthy fat oxidation pathways, and supporting normal adipose tissue signaling through adiponectin. These mechanisms are consistent with the biological activity of procyanidin-rich apple polyphenols and help explain the broad metabolic effects observed across multiple studies.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/17898508/



Study 5 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/28505543/

Chronic Administration of Apple Polyphenols Ameliorates Hyperglycaemia in High-Normal and Borderline Subjects: A Randomized, Placebo-Controlled Trial
Diabetes Research and Clinical Practice. 2017 Jul;129:43–51.

In a 12-week randomized, placebo-controlled trial, adults with higher-range but still normal fasting glucose levels consumed 600 mg/day of apple polyphenols or placebo. Researchers evaluated how supplementation influenced the body's response to a standard oral glucose tolerance test (OGTT), which measures changes in blood glucose following carbohydrate intake.

Key Findings (What the Study Showed)

Participants taking apple polyphenols showed a smaller rise in post-meal glucose levels during the OGTT compared with those taking placebo. These findings suggest apple polyphenols may help support a healthier post-meal glucose response and normal glucose metabolism.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support a healthier post-meal glucose response during a controlled glucose challenge
✓ Help maintain normal glucose metabolism in adults with high-normal fasting glucose
✓ Demonstrate benefits at a practical daily dose of 600 mg over 12 weeks

Why This Study Matters

Daily supplementation with apple polyphenols was associated with improved post-meal glucose handling during a controlled glucose challenge, supporting the role of apple polyphenols in maintaining healthy glucose metabolism. This is particularly relevant for individuals with high-normal glucose levels seeking nutritional support for metabolic balance.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/28505543/



Study 6 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/17039666/

Clinical Effects of Apple Polyphenols on Persistent Allergic Rhinitis: A Randomized Double-Blind Placebo-Controlled Parallel Arm Study
Journal of Investigational Allergology and Clinical Immunology. 2006;16(5):283–289.

This randomized, double-blind, placebo-controlled human clinical trial evaluated several nasal and upper respiratory markers during a 4-week intervention in 33 adults experiencing persistent seasonal nasal discomfort.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trial
  • Participants: 33 adults experiencing persistent seasonal nasal discomfort
  • Duration: 4 weeks
  • Dose:
    • Low dose: 50 mg/day apple polyphenols
    • High dose: 200 mg/day apple polyphenols
    • Placebo control

Key Findings (What the Study Showed)

Sneezing Frequency

In the high-dose group, fewer participants reported higher levels of sneezing by the end of the study period compared with baseline.

Nasal Comfort Measures

Participants taking apple polyphenols showed improvements in measures related to nasal discharge and nasal tissue appearance compared with placebo. Investigators also reported improvements in clinical assessments of nasal tissue appearance in participants receiving apple polyphenols.

Medication Use

Participants in the apple polyphenol groups showed trends toward lower medication scores during the study period, indicating reduced reliance on additional symptom-management medications, although this difference was not statistically significant.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support improvements in nasal comfort measures compared with placebo
✓ Help support healthy upper respiratory immune responses
✓ Show trends toward reduced medication reliance during the study period
✓ Be well tolerated with no clinically meaningful adverse effects

Why This Study Matters

Supplementation with apple polyphenols for four weeks was associated with improvements in several nasal comfort measures compared with placebo. These findings suggest apple polyphenols may support healthy upper respiratory immune responses, adding to the evidence base for apple polyphenols as biologically active compounds across multiple physiological systems.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/17039666/



Study 7 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/20484838/

Evaluation of Safety of Excessive Intake and Efficacy of Long-Term Intake of Beverages Containing Apple Polyphenols
Journal of Oleo Science. 2010;59(6):321–338. doi:10.5650/jos.59.321

This set of randomized, double-blind, placebo-controlled human clinical trials evaluated safety markers and changes in abdominal fat distribution in adults supplementing with apple polyphenols. The long-term intake trial included 94 adults ranging from moderately underweight to moderately obese; the excessive intake safety trial included 30 adults.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trials
  • Participants:
    • Long-term intake trial: 94 adults ranging from moderately underweight to moderately obese
    • Excessive intake safety trial: 30 adults
  • Dose:
    • Standard intake: 600 mg/day apple polyphenols for 12 weeks
    • Excessive intake safety study: approximately three times the standard daily intake for 4 weeks

Key Findings (What the Study Showed)

Abdominal Fat Distribution

Participants consuming apple polyphenols showed changes in visceral fat area and markers related to body composition during the study period:

  • Significant decreases observed at 8 weeks (p < 0.05)
  • Greater reductions observed at 12 weeks (p < 0.01)
  • Reductions in visceral fat area were greater in the apple polyphenol group compared with placebo
  • Participants who began the study with higher visceral fat measurements showed the most noticeable changes
  • Participants with lower baseline visceral fat measurements did not experience significant changes

Safety and Tolerability

Across both trials, apple polyphenol consumption was well tolerated. Researchers reported no clinically meaningful changes in blood chemistry markers, physical examination findings, liver function markers, or kidney function markers. In the excessive-intake study, participants consumed approximately three times the standard intake for four weeks without reported safety concerns.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support healthy body composition and abdominal fat distribution
✓ Produce progressive improvements in visceral fat area over 12 weeks
✓ Show the greatest benefits in participants with higher baseline visceral fat
✓ Be well tolerated at standard and excessive intake levels
✓ Demonstrate no adverse changes in blood chemistry, liver, or kidney markers

Why This Study Matters

This study demonstrates that apple polyphenol intake may support healthy body composition as part of a balanced lifestyle, with progressive improvements in visceral fat area over time. The excessive-intake safety data further reinforces the favorable tolerability profile of ApplePhenon® across a wide range of intake levels.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/20484838/



Study 8 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/28755406/

Effect of Apple Polyphenols on Vascular Oxidative Stress and Endothelium Function: Translational Study
Molecular Nutrition & Food Research. 2017.

This translational study combined laboratory experiments with a randomized, double-blind, placebo-controlled human clinical trial to examine how apple polyphenols influence vascular function and markers related to metabolic health. Sixty-two adults consumed 300 mg/day of apple polyphenols for 8 weeks. Researchers evaluated markers related to vascular responsiveness, oxidative stress pathways, and metabolic signaling.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trial with laboratory component
  • Participants: 62 adults
  • Dose: 300 mg/day apple polyphenols
  • Duration: 8 weeks

Key Findings (What the Study Showed)

Mechanistic Findings (Laboratory Research)

Laboratory experiments showed that apple polyphenols interacted with oxidative stress pathways associated with vascular function. In these experiments, polyphenols influenced the activity of enzymes involved in reactive oxygen species generation, suggesting a potential mechanism through which apple polyphenols may support antioxidant defenses within vascular tissues.

Human Clinical Findings

After eight weeks of supplementation, participants consuming apple polyphenols showed changes in several markers associated with vascular and metabolic function compared with baseline measurements:

  • Changes in markers related to fasting glucose metabolism
  • Changes in uric acid levels
  • Improvements in endothelial responsiveness, a commonly used measure of vascular function
  • No significant changes were observed in unrelated blood chemistry markers, suggesting the effects were specific to pathways examined in the study

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support healthy vascular responsiveness and endothelial function
✓ Interact with oxidative stress pathways associated with vascular health
✓ Support markers related to fasting glucose metabolism
✓ Demonstrate targeted effects specific to the pathways examined

Why This Study Matters

The findings suggest that apple polyphenols may interact with biological pathways involved in vascular responsiveness and oxidative stress signaling. These interactions may help support healthy vascular function and metabolic processes. The translational design — combining lab and human data — provides a more complete picture of how apple polyphenols work at a mechanistic level.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/28755406/



Study 9 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/29078780/

The Effect of an Apple Polyphenol Extract Rich in Epicatechin and Flavan-3-ol Oligomers on Brachial Artery Flow-Mediated Vasodilatory Function
Nutrition Journal. 2017;16:73.

This randomized, double-blind, placebo-controlled crossover human trial evaluated the effects of apple polyphenols on flow-mediated dilation (FMD) of the brachial artery, a commonly used measure of endothelial function and vascular responsiveness. Sixty adults ages 40–65 consumed an apple polyphenol extract providing 100 mg epicatechin per day during two 4-week intervention periods separated by a washout period.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled crossover human trial
  • Participants: 60 adults ages 40–65
  • Dose: Apple polyphenol extract providing 100 mg epicatechin per day
  • Duration: Two 4-week intervention periods separated by a washout period

Key Findings (What the Study Showed)

Short-Term Vascular Response

Apple polyphenol intake produced a statistically significant short-term increase in flow-mediated dilation within approximately 1.5 hours after consumption, compared with baseline measurements. The improvement in FMD (~1.2–1.4%) indicates a measurable vascular response following intake of the polyphenol extract.

Longer-Term Findings

After the 4-week supplementation period, there were no statistically significant differences between the apple polyphenol and placebo groups in flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), blood pressure measurements, or vascular inflammation markers. The placebo group also showed modest changes in FMD, which reduced between-group differences.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the study outcomes, apple polyphenols were shown to:
✓ Produce measurable short-term changes in vascular responsiveness following intake
✓ Demonstrate biological activity on endothelial function within 1.5 hours of consumption
✓ Be well tolerated with no clinically relevant adverse effects
✓ Maintain normal laboratory values throughout the study period

Why This Study Matters

This study demonstrates that apple polyphenols can produce measurable short-term effects on vascular responsiveness following intake. The lack of clear long-term differences in this study may reflect the relatively healthy baseline vascular function of participants and individual variability in polyphenol metabolism. The confirmed short-term vascular activity supports the biological relevance of apple polyphenols for vascular health.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/29078780/



Study 10 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/33801641/

A Polyphenol-Enriched Variety of Apple Alters Circulating Immune Cell Gene Expression and Faecal Microbiota Composition in Healthy Adults
Nutrients. 2021;13(4):1092.

This randomized, placebo-controlled crossover human trial evaluated potential effects on gut microbiota composition and immune-related gene expression in 25 healthy adults. Participants consumed either one polyphenol-rich red-fleshed apple daily or a control white-fleshed apple during two 2-week intervention periods with a washout phase.

Study Design Highlights

  • Study design: Randomized, placebo-controlled crossover human trial
  • Participants: 25 healthy adults
  • Intervention: One polyphenol-rich red-fleshed apple daily vs. control white-fleshed apple
  • Duration: Two 2-week intervention periods with a washout phase

Key Findings (What the Study Showed)

Immune-Related Gene Expression

Researchers identified 18 genes with differential expression between the polyphenol-rich apple and the control apple. Most of these genes were associated with immunoglobulin production and B-cell activity, suggesting that apple polyphenols may interact with pathways involved in immune system signaling.

Gut Microbiota Composition

Consumption of the polyphenol-rich apple resulted in modest shifts in certain bacterial populations, including:

  • Increases in:
    • Lactobacillus
    • Butyricicoccus
    • Sutterella
  • Decreases in:
    • Streptococcus
    • Ruminococcus
    • Blautia
    • Roseburia

Overall microbial diversity remained stable, indicating targeted changes rather than broad disruption of the microbiome.

Metabolic Markers

No significant changes were observed in cholesterol, triglycerides, C-reactive protein, or body weight. The study primarily examined microbiome and immune-related signaling responses rather than metabolic outcomes.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the study outcomes, apple polyphenols were shown to:
✓ Influence immune-related gene expression pathways in healthy adults
✓ Support targeted shifts in gut microbial composition
✓ Increase beneficial bacteria including Lactobacillus and Butyricicoccus
✓ Maintain overall microbial diversity while producing selective microbiome changes

Why This Study Matters

The results suggest that polyphenol-rich apples can influence both gut microbial composition and immune-related cellular signaling pathways in healthy adults. These findings support the role of apple polyphenols as biologically active dietary compounds that interact with the gut-immune axis, providing important mechanistic context for their broader health effects.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/33801641/



Study 11 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/28956697/

Annurca Apple Nutraceutical Formulation Enhances Keratin Expression in a Human Model of Skin and Promotes Hair Growth and Tropism in a Randomized Clinical Trial
Journal of Medicinal Food. 2018.

This study combined in vitro laboratory studies using human keratinocytes with a randomized, double-blind, placebo-controlled human clinical trial in 250 adults (ages 30–83). Participants supplemented with an Annurca apple polyphenol extract (rich in procyanidin B2), or the same extract combined with biotin, zinc, and selenium, for 8 weeks. Researchers evaluated markers related to keratin production and hair characteristics.

Study Design Highlights

  • Study design: In vitro laboratory studies + randomized, double-blind, placebo-controlled human clinical trial
  • Participants: 250 adults (ages 30–83)
  • Intervention: Annurca apple polyphenol extract rich in procyanidin B2; also tested combined with biotin, zinc, and selenium
  • Duration: 8 weeks

Key Findings (What the Study Showed)

Keratin Production (Laboratory Studies)

Apple polyphenol extract increased keratin expression in cultured human keratinocytes in a dose- and time-dependent manner. No negative effects on cell viability were observed during testing.

Human Study Findings

After 8 weeks of supplementation, participants consuming the apple polyphenol formulation showed measurable changes in several hair-related markers compared with baseline measurements, including:

  • Increased hair count per square centimeter
  • Increased hair fiber weight
  • Increased keratin content within hair fibers

Improvements were observed within the first month of the study and continued throughout the intervention period.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, apple polyphenols were shown to:
✓ Support keratin production in laboratory models of human skin cells
✓ Support increased hair count per square centimeter
✓ Support increased hair fiber weight and keratin content
✓ Demonstrate progressive improvements over the 8-week study period
✓ Be well tolerated across a wide age range with no adverse effects

Why This Study Matters

The combined laboratory and clinical findings suggest that polyphenol-rich apple extracts may support keratin production and hair characteristics associated with healthy hair growth. The combination of in vitro mechanistic data and human clinical evidence provides a robust foundation for understanding how apple polyphenols interact with keratin biology.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/28956697/



Study 12 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/24917557/

Acute Effects of an Unripe Apple Preparation Containing Phlorizin in Healthy Volunteers
Journal of the Science of Food and Agriculture. 2015.

This randomized, placebo-controlled acute human intervention study evaluated 6 healthy adults who consumed a single dose of a powder derived from unripe apple pomace containing fiber and polyphenols, including phlorizin. Researchers evaluated participants' responses during a standard oral glucose tolerance test (OGTT).

Key Findings (What the Study Showed)

Participants consuming the apple-derived preparation showed a smaller early rise in blood glucose levels following the glucose challenge compared with the control condition. The study also observed increases in urinary glucose excretion following intake of the apple preparation.

Mechanistic Insights

Phlorizin, a naturally occurring apple polyphenol, has been shown to interact with glucose transport processes involved in carbohydrate absorption and handling. The preparation also contained soluble fiber components that may influence the rate of carbohydrate absorption.

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the study outcomes, unripe apple polyphenol preparations were shown to:
✓ Help support a smaller post-meal rise in blood glucose during a glucose challenge
✓ Influence carbohydrate handling through phlorizin-related glucose transport interactions
✓ Provide preliminary mechanistic evidence for glucose metabolism support

Why This Study Matters

This small, short-term preliminary study was intended to explore potential mechanisms related to glucose metabolism and provides early mechanistic evidence for how unripe apple polyphenols may influence post-meal glucose responses and carbohydrate handling in the body.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/24917557/



Study 13 Summary

Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/28296588/

A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial
Journal of Medicinal Food. 2017.

This randomized, double-blind, placebo-controlled human clinical trial evaluated changes in markers related to blood lipid metabolism in 250 adults supplementing with Annurca apple polyphenol extract (AppleMetS®) at 800 mg/day for 8 weeks.

Study Design Highlights

  • Study design: Randomized, double-blind, placebo-controlled human clinical trial
  • Participants: 250 adults
  • Intervention: Annurca apple polyphenol extract (AppleMetS®)
  • Dose: 800 mg/day
  • Duration: 8 weeks

Key Findings (What the Study Showed)

Participants consuming the Annurca apple polyphenol extract showed changes in several lipid markers during the study period compared with baseline measurements, including:

  • Reductions in LDL cholesterol
  • Reductions in total cholesterol
  • Increases in HDL cholesterol

Benefits of ApplePhenon® Demonstrated by This Study

Based directly on the clinical outcomes, Annurca apple polyphenols were shown to:
✓ Support healthy LDL cholesterol levels
✓ Help maintain healthy total cholesterol levels
✓ Support favorable HDL cholesterol levels
✓ Be well tolerated with liver and kidney function markers remaining within normal ranges

Why This Study Matters

Supplementation with an Annurca apple polyphenol extract was associated with changes in several markers of lipid metabolism, suggesting apple polyphenols may support healthy cholesterol balance as part of normal metabolic function. This study adds to the convergent evidence across multiple trials showing lipid metabolism support from apple polyphenol extracts.*

Reference Link: https://pubmed.ncbi.nlm.nih.gov/28296588/



Study 14 Summary

Complete Study Information: https://www.jstage.jst.go.jp/article/jcam/6/2/6_2_69/_article/-char/en

Effectiveness of the Apple Polyphenol "Applephenon®" on Lifestyle-Related Disease
Journal of Complementary and Alternative Medicine. 2009.

This scientific review summarizes findings from animal studies, human clinical trials, and safety research examining the biological activity and tolerability of Applephenon®, a polyphenol extract derived from unripe apples and rich in procyanidins. The paper reviews evidence related to lipid metabolism, body composition markers, cholesterol metabolism, physical performance during fatigue, and safety and tolerability.

Key Research Themes

Lipid Metabolism and Body Composition

Across multiple studies, apple polyphenols were associated with changes in markers related to fat metabolism and body composition. Research discussed in the review suggests that apple polyphenols may influence processes involved in digestion and handling of dietary fats, fat metabolism pathways, and adipose tissue signaling.

Cholesterol Metabolism

The review summarizes clinical and experimental findings showing that apple polyphenols may influence markers associated with cholesterol metabolism. These effects are attributed primarily to oligomeric procyanidins, which are major bioactive compounds found in Applephenon®.

Exercise Performance and Fatigue

Several studies referenced in the review report that apple polyphenols may help support physical performance during prolonged exercise. These findings are linked to the antioxidant properties of apple polyphenols and their role in supporting the body's response to exercise-induced oxidative stress.

Safety Profile

A key focus of the review is the safety and tolerability of apple polyphenol extracts. Evidence supporting safety includes repeated-dose toxicology studies, genetic safety assessments, and human clinical trials. Across these studies, apple polyphenols were reported to be well tolerated within the tested intake ranges. Applephenon® has also been recognized as Generally Recognized As Safe (GRAS) for use in food applications.

Benefits of ApplePhenon® Demonstrated by This Review

Based directly on the reviewed body of research, apple polyphenols were shown to:
✓ Support healthy lipid metabolism and cholesterol balance
✓ Support healthy body composition and fat distribution markers
✓ Help maintain physical performance during prolonged exercise
✓ Demonstrate a favorable safety profile across toxicology, genetic safety, and human clinical studies
✓ Qualify as Generally Recognized As Safe (GRAS) for food applications

Why This Study Matters

This review summarizes a broad body of research indicating that apple polyphenols are biologically active dietary compounds with a favorable safety profile. The mechanistic insights highlighted — including activity of procyanidin compounds, interaction with lipid digestion and absorption pathways, influence on oxidative stress pathways, and interactions with the gut microbiome — help explain the convergent benefits observed across multiple clinical trials. Together, the reviewed findings support apple polyphenols as versatile nutritional compounds for metabolic function, lipid metabolism, and physical performance.*

Reference Link: https://www.jstage.jst.go.jp/article/jcam/6/2/6_2_69/_article/-char/en

Big-Picture Integration with Other Studies

  • Study 1: ApplePhenon® demonstrated a favorable safety profile and was well tolerated in toxicology and safety studies.
  • Study 2: Supplementation with 1,200 mg/day ApplePhenon® helped support sustained physical performance during prolonged exercise.
  • Study 3: Daily supplementation with ApplePhenon® for 12 weeks supported healthy skin appearance following UV exposure, including improvements in markers related to skin redness and pigmentation.
  • Study 4: In a 12-week clinical study, 600 mg/day of apple polyphenols supported healthy cholesterol metabolism and markers related to body composition.
  • Study 5: Supplementation with 600 mg/day of apple polyphenols for 12 weeks supported healthy glucose metabolism and post-meal glucose handling.
  • Study 6: In a 4-week human study, apple polyphenols supported nasal comfort measures and upper respiratory immune responses.
  • Study 7: Daily intake of 600 mg apple polyphenols for 12 weeks was associated with changes in abdominal fat distribution and body composition markers.
  • Study 8: In a clinical study involving overweight adults, apple polyphenols supported vascular function and markers related to metabolic health.
  • Study 9: Apple polyphenol extracts rich in epicatechin demonstrated measurable short-term effects on vascular responsiveness following intake.
  • Study 10: Consumption of a polyphenol-rich apple for two weeks influenced immune-related gene expression and gut microbiota composition in healthy adults.
  • Study 11: Supplementation with apple polyphenols supported keratin production and hair characteristics associated with healthy hair growth.
  • Study 12: A preliminary study found that a phlorizin-rich unripe apple preparation influenced post-meal glucose responses in healthy adults.
  • Study 13: An 8-week clinical trial found that Annurca apple polyphenol extract supported healthy cholesterol balance.
  • Study 14: A scientific review of animal and human research concluded that apple polyphenols may support lipid metabolism, cholesterol metabolism, and physical performance during exercise.

ApplePhenon® Ingredient Summary & Real-World Relevance

ApplePhenon® is a concentrated apple polyphenol extract made from wild, unripe apples. These young apples naturally contain higher levels of beneficial plant compounds than mature fruit. Through a food-grade extraction process, these compounds are concentrated into a powerful polyphenol profile rich in oligomeric procyanidins, the primary bioactive compounds in ApplePhenon®.

Along with procyanidins, ApplePhenon® contains other naturally occurring polyphenols such as catechin, epicatechin, phenolic acids, and supporting flavonoids. Together, these compounds create a diverse spectrum of plant nutrients that have been studied for their ability to interact with multiple systems in the body.

Polyphenols are biologically active plant compounds that interact with many physiological pathways. Research suggests the polyphenols found in ApplePhenon® support several key systems involved in everyday health — including antioxidant defenses, metabolic signaling pathways related to glucose and lipid metabolism, gut microbiome interactions, and vascular responsiveness and immune system signaling.

ApplePhenon® has been evaluated in multiple safety studies as well as human clinical research. Across these studies, apple polyphenol extracts have demonstrated a favorable safety profile and good tolerability within tested intake ranges, including at approximately 300 mg/day for metabolic and vascular markers, 600 mg/day for lipid metabolism and body composition markers, and up to 1,200 mg/day in short-term studies evaluating physical performance during exertion.

Research suggests apple polyphenols may help support healthy metabolic balance, vascular function, gut microbiome signaling, and physical performance during periods of exertion. ApplePhenon® provides a concentrated source of apple polyphenols with a diverse range of biological activities and a strong safety profile — a versatile nutritional ingredient for individuals seeking to support overall physiological balance and everyday wellness.*

Ingredient Manufacturer Link: https://bggworld.com/applephenon-apple-polyphenols/

ApplePhenon® 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.