BERBERINE HCL (600MG)

CLAIM: Supports healthy blood sugar metabolism and appetite control

SOURCES:
1. Guo J, et al. (2021) — Meta-analysis, 46 clinical trials. HbA1c reduction -0.73%, fasting glucose -0.86 mmol/L, BMI -1.07 kg/m2. PubMed ID: 34956436
2. Xiong P, et al. (2020)—Systematic review, 983 participants. BMI reduction -0.29 kg/m2, waist circumference -1.78 cm. Coventry University
3. Yin J, et al. (2008) — RCT vs. Metformin. HbA1c reduced from 9.5% →7.5%, equivalent efficacy. PMC2410097
4. Cao C, et al. (2019) — 80 metabolic syndrome patients. Improved glucose and lipid markers. PMC6434235
5. Liu D, et al. (2025) — Meta-analysis. Triglycerides -0.367 mmol/L, glucose -0.515 mmol/L. Frontiers in Pharmacology

GINGER ROOT (130MG)

CLAIM: Aids digestion and supports glucose response SOURCES: 1. Zhu J, et al. (2018) — Meta-analysis, 10 studies, 490 participants. HbA1c -1.00%, fasting glucose-21.24 mg/dL. PMC5818945 2. Foroutan M, et al. — 98 diabetic patients. Significant HbA1c reduction (P=0.006). Journal of Renal Injury Prevention 3. Paudel KR, et al. (2025) — 6-Gingerol activates AMPK, stimulates GLUT-4. Frontiers in Pharmacology 4. Journal.medtigo.com (2025) — Decrease in TNF-a (P=0.006), IL-6 (P=0.02), CRP (P=0.012) 5. Ebrahimzadeh A, et al. (2022) — Systematic review. Improved glucose, HbA1c, and blood pressure TURMERIC ROOT (200MG) CLAIM: Reduces inflammation & oxidative stress SOURCES: 1. Effects of Curcumin Supplementation on Biomarkers of Inflammation, Oxidative Stress, and Endothelial Function: A Meta-Analysis of Meta-Analyses - Zeynab Kavyani et al, 2024, Prostaglandins Other Lipid Mediat. (Umbrella meta-analysis) — Aggregating 21 meta-analyses (hundreds of patients) found curcumin (turmeric) significantly lowers inflammatory markers — e.g. C-reactive protein (WMD -0.87 mg/L), interleukin-6 (-0.97 pg/mL), TNF-a (-2.72 pg/mL) - and reduces oxidative stress - malondialdehyde (ES-0.81) - while boosting antioxidant enzymes (SOD, catalase, GPX) PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. These results confirm turmeric's potent anti-inflammatory and antioxidative effects in humans. 2. Curcuminoid-Piperine Combination in Metabolic Syndrome: A RCT and Meta-Analysis - Yunes Panahi et al., 2015, Clinical Nutrition (Double-blind RCT) — In 117 patients with metabolic syndrome, 8 weeks of bioavailable curcumin (1 g/day) + piperine led to significant drops in CRP and MDA levels and increased SOD activity versus placebo PUBMED.NCBI.NLM.NIH.GOV indicating markedly improved systemic inflammation and oxidative stress status; a meta-analysis within the study also confirmed curcumin's CRP-lowering effect (~2.2 mg/L overall) PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. 3. Effects of Curcumin on Serum Cytokine Concentrations in Subjects with Metabolic Syndrome - Yunes Panahi et al., 2016, Biomed. Pharmacother. (Post-hoc analysis of RCT) — Curcumin (1 g/day for 8 weeks) in 117 metabolic syndrome patients produced significantly greater reductions in pro-inflammatory cytokines TNF-α, IL-6, MCP-1, and TGF-ẞ compared to placebo (all p<0.001) PUBMED.NCBI.NLM.NIH.GOV PUBMED.NCBI.NLM.NIH.GOV. demonstrating turmeric's strong anti-inflammatory action in a clinical population. 4. Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a RCT- Amir Rahimnia et al, 2015, Drug Research (Randomized trial) — In patients with knee osteoarthritis, curcumin supplementation for 6 weeks significantly lowered circulating oxidative stress markers (e.g. reduced lipid peroxidation) and reduced hs-CRP levels compared to baseline PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV, correlating with reductions in pain and inflammation. (This supports turmeric's antioxidant and anti-inflammatory benefits in chronic inflammatory conditions.) 5. Curcumin and Multiple Health Outcomes: An Umbrella Review - Mario Giacosa et al., 2020, British Journal of Nutrition (Umbrella review) — Concludes that curcumin/turmeric has clinically relevant anti-inflammatory and antioxidant effects: across numerous RCTs it consistently lowers inflammation (CRP, cytokines) and oxidative damage markers, with one analysis noting curcumin's effects on inflammatory mediators are comparable to some pharmaceuticals but with a strong safety profile SCIENCEDIRECT.COMPUBMED.NCBI.NLM.NIH.GOV. This evidence underpins turmeric root's role in reducing chronic inflammation and oxidative stress in humans. CEYLON CINNAMON (400MG) CLAIM: Helps with insulin sensitivity & antioxidant support SOURCES: 1. Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes - Alam Khan et al., 2003, Diabetes Care (RCT) — In 60 type 2 diabetics, 40 days of cinnamon (1, 3 or 6 g/day) yielded 18– 29% lower fasting blood glucose levels (vs. no change on placebo) along with significant reductions in triglycerides, LDL, and total cholesterol PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV, demonstrating improved insulin sensitivity and metabolic control. 2. Cinnamon Supplementation on Glycemic Control in Type 2 Diabetes and PCOS: An Umbrella Meta-Analysis - Meysam Zarezadeh et al, 2023, Diabetol. Metab. Syndr. (Meta-analysis of meta- analyses) — Pooled evidence from 11 meta-analyses showed cinnamon supplementation significantly lowers fasting plasma glucose (~11 mg/dL), fasting insulin, HOMA-IR (insulin resistance index), and HbA1c in patients with type 2 diabetes or PCOS, confirming cinnamon's benefit to insulin sensitivity and glycemic control DMSJOURNAL.BIOMEDCENTRAL.COM. 3. Impact of Cinnamon Supplementation on Inflammation and Oxidative Stress Biomarkers: A Systematic Review and Meta-Analysis - Changyou Zhu et al, 2020, Compl. Therapies Med. (Meta- analysis of 12 RCTs) — Cinnamon (1.5-4 g/day) significantly reduced circulating C-reactive protein (-2.22 mg/L) and malondialdehyde (-0.79 μmol/L), a lipid peroxidation marker, while increasing total antioxidant capacity, indicating that cinnamon supplementation can reduce inflammation and oxidative stress in humans PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. 4. Antioxidant Effects of a Cinnamon Extract in People With Impaired Fasting Glucose-Anne-Marie Roussel et al., 2009, J. Am. Coll. Nutr. (Double-blind RCT) — Overweight pre-diabetic adults who took 500 mg/day of aqueous Ceylon cinnamon extract for 12 weeks showed increased plasma antioxidant status (higher FRAP and thiol levels) and decreased plasma MDA (oxidative stress marker) relative to placebo PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV supporting cinnamon's antioxidant benefits. 5. Ceylon Cinnamon: A Versatile Ingredient for Diabetes - Review - Junaid Ghaffor et al, 2022, Food Sci. & Nutrition (Review) — Ceylon cinnamon (Cinnamomum zeylanicum) has demonstrated anti- diabetic potential in human studies: e.g. an ethanolic cinnamon extract trial in type 2 diabetics showed a 69% fasting blood glucose reduction by week 4 (versus baseline) PUBMED.NCBI.NLM.NIH.GOVSCIENCEDIRECT.COM, and cinnamon's polyphenols are noted to improve insulin receptor function and have robust antioxidant activity, aiding glucose control and reducing oxidative damage in diabetes. (Evidence synthesis from multiple studies. PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV APPLE CIDER VINEGAR POWDER (65MG) CLAIM: Aids fat metabolism and appetite control SOURCES: 1. Abou-Khalil R, et al. (2024) — 120 participants, 12 weeks. 6-8 kg weight loss, BMI -2.7 to -3. BMJ Nutrition 2. Khezri SS, et al. (2018) — Weight, BMI, and hip circumference reduction with diet support 3. Cobb KM, et al. (2021) — Activates AMPK, enhances fatty acid oxidation. PMC8136602 4. Kondo T, et al. (2009) — 175 participants, weight loss 2-4 lbs, reduced triglycerides. PubMed: 19661687 5. Multiple animal studies — Appetite suppression via GLP-1 and PYY satiety hormones GOLDENSEAL ROOT POWDER (6.5MG) CLAIM: Natural berberine source with synergistic alkaloids SOURCES: 1. Ettefagh KA, et al. (2010) — LC-MS analysis: berberine 6.12%, hydrastine 0.60%. PMC3100400 2. Same study-Synergistic antibacterial activity, efflux pump inhibitors 3. Predny ML, et al. (2005) — USDA standards: >2% hydrastine, >2.5% berberine. Forest Service Research 4. NBK350390- Clinical uses, anti-inflammatory properties 5. MSD Manuals (2023) — Goldenseal berberine lowers fasting glucose and HbA1c BIOPERINE® BLACK PEPPER EXTRACT (3MG) CLAIM: Maximizes ingredient absorption SOURCES: 1. Guo J, et al. (2021) — Mechanism: increased microvilli, membrane modification. PMC7353321 2. Shoba G, et al. (1998) — Curcumin + BioPerine: 2000% higher bioavailability. BioPerine.com 3. Vladimir B, et al. (1999) — Beta-carotene: ~2x increase. Nutrition Research 4. Tripathi AK, et al. (2022) — Silybin +146-181%, raloxifene +2x. PMC8796742 5. US Patent 5536506A (1995) — Suppression of mixed oxidases, enhanced bioavailability * These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.

Each ingredient in Calm Mode is transparently supported by up to five peer-reviewed studies. Ashwagandha Extract (Withania somnifera, 100 mg) Claim: Helps the body adapt to stress and maintain steady energy Chandrasekhar K et al. (2012) – 300 mg KSM-66 daily reduced cortisol by 27.9% vs 7.9% placebo; improved stress scores (P<0.0001). PMC3573577 Lopresti AL et al. (2019) – Systematic review: standardized ashwagandha extracts reduced stress and anxiety across 5 RCTs. Hum Psychopharmacol. 34(3):e2694 Dongre S et al. (2021) – 600 mg daily improved Perceived Stress Scale by 32% at 8 weeks. J Diet Suppl. 18(4):446-458 Kulkarni SK & Dhir A (2008) – Ashwagandha exhibited adaptogenic and anxiolytic effects in animal models. Pharmacol Biochem Behav. 90(2): 239-247 NIH ODS (2025) – Fact sheet confirms safety profile and stress-reduction effects in humans.ods.od.nih.gov L-Theanine (50 mg) Claim: Supports mental clarity and relaxation without drowsiness Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial – Shinsuke Hidese et al., 2019, Nutrients (Double-blind crossover RCT) — Found that 200 mg/day of L-theanine for 4 weeks significantly reduced anxiety and improved sleep quality and executive function in healthy adults without causing sedation pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov. Safety and Efficacy of AlphaWave® L-Theanine Supplementation for 28 Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial – Marc Moulin et al., 2024, Neurology and Therapy (RCT) — After 28 days, 400 mg/day L-theanine led to lower stress and better sleep: perceived stress scores decreased and sleep quality and cognitive attention improved significantly compared to placebo link.springer.comlink.springer.com. Effects of L-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study – Yoshitake Baba et al., 2021, J. Medicinal Food (RCT) — Daily 100.6 mg L-theanine for 12 weeks in adults (age 50–69) enhanced attention and working memory, indicating improved cognitive function (mental clarity) with no adverse drowsiness reported naturalhealthresearch.orgnaturalhealthresearch.org. L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients With Schizophrenia and Schizoaffective Disorder: An 8-Week… Placebo-Controlled Study – Michael S. Ritsner et al., 2011, J. Clin. Psychiatry (RCT) — Adjunctive L-theanine (400 mg/day) for 8 weeks significantly reduced anxiety and activation symptoms in schizophrenia patients versus placebo, with authors noting it was well-tolerated and did not cause sedation psychiatrist.compsychiatrist.com. The effects of L-theanine supplementation on the outcomes of patients with mental disorders: a systematic review – Kasra Assadian et al., 2024, BMC Psychiatry (Systematic review of RCTs) — This review of 11 trials found L-theanine consistently reduced stress and anxiety symptoms more effectively than control conditions in populations including generalized anxiety and ADHD, supporting its relaxation benefits without sedative side-effects pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov. Golden Root Extract (Rhodiola rosea, 100 mg) Claim: Supports focus, mood, and resilience under stress Darbinyan V et al. (2000) – 170 mg daily for 14 days improved fatigue index and mental performance in physicians. Phytomedicine. 7(2):85-89 Edwards D et al. (2012) – 400 mg daily for 6 weeks reduced stress symptoms and improved work performance. Phytother Res. 26(3):444-450 Panossian A & Wikman G (2010) – Review: Rhodiola extracts exhibit adaptogenic effects, reducing cortisol and improving cognition. Phytomedicine. 17(7):481-493 EMA Assessment (2011) – Traditional use approval for temporary relief of stress-related symptoms. EMA/HMPC/577346/2009 Olsson EMG et al. (2009) – 288 mg R. rosea improved mental performance during stress. Hum Psychopharmacol. 24(3): 23-34 Bacopa Extract (Bacopa monnieri, 100 mg) Claim: Promotes memory, focus, and cognitive performance Stough C et al. (2001) – 300 mg Bacopa daily for 12 weeks improved memory recall and retention in healthy adults. Psychopharmacology. 156(4):481-484 Roodenrys S et al. (2002) – 150 mg daily enhanced speed of visual information processing and reduced anxiety. Neuropsychopharmacology. 27(2):279-281 Pase MP et al. (2012) – Systematic review: Bacopa improves cognition in RCTs with standardized extracts. J Altern Complement Med. 18(7):647-652 Calabrese C et al. (2008) – 450 mg daily reduced anxiety and improved cognitive function in elderly. Hum Psychopharmacol. 23(6): 463-469 Lemon Balm Extract (Melissa officinalis, 100 mg) Claim: Promotes relaxation Kennedy D et al. (2004) – Single dose (1.6 g) improved calmness and alertness in healthy volunteers. Nutr Neurosci. 7(3):181-185 Shakeri A et al. (2016) – Review of traditional and clinical data supports lemon balm’s GABA-transaminase inhibition. J Funct Foods. 21: 5-15 Passion Flower Extract (Passiflora incarnata, 100 mg) Claim: Helps calm the mind and support emotional balance Miyasaka LS et al. (2007) – Passion flower extract reduced anxiety comparably to benzodiazepine without sedation. Phytother Res. 21(2):187-189 Akhondzadeh S et al. (2001) – Improved generalized anxiety symptoms vs placebo (P<0.05). J Clin Pharm Ther. 26(5):363-367 Ngan A & Conduit R (2011) – Tea extract improved subjective sleep quality in healthy adults. Phytother Res. 25(8):1153-1159 Santos RF et al. (2022) – Systematic review: safety and efficacy for anxiety and sleep disturbances. Braz J Psychiatry. 44(1):120-130 Charles T et al. (2010) – Animal study: anxiolytic effects via GABAergic modulation. J Ethnopharmacol. 127(1): 188-196 Hops Extract (Humulus lupulus, 50 mg) Claim: Naturally supports relaxation and healthy sleep patterns Evidence: A randomized, double-blind, placebo-controlled study of a fixed valerian–hops extract combination (Ze 91019) in non-organic insomnia – U. Koetter et al., 2007, Phytotherapy Research (RCT) — A nightly herbal combination containing valerian and hops (120 mg) for 4 weeks significantly shortened sleep latency compared to placebo, demonstrating that adding hops extract produced greater improvements in falling asleep pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov. The Sedative Effect of Non-Alcoholic Beer in Healthy Female Nurses – Lourdes Franco et al., 2012, PLoS ONE (Clinical trial) — In 17 nurses working night shifts, consuming one bottle of hops-rich non-alcoholic beer with dinner for 14 days improved sleep parameters: time to fall asleep decreased and nighttime restlessness reduced, and self-reported anxiety also declined despite the beer containing no alcohol (effect attributed to hops) pubmed.ncbi.nlm.nih.govpsychologytoday.com. Effect of Non‐Alcoholic Beer on Subjective Sleep Quality in a University Stressed Population – Lourdes Franco et al., 2014, Acta Physiol. Hung. (Intervention study) — Among 30 healthy students with high stress, two weeks of nightly hops-enhanced non-alcoholic beer led to significantly better sleep quality scores and shorter sleep latency than a control period, indicating hops intake can promote relaxation and healthier sleep patterns restorativemedicine.org. Effects of a Hops (Humulus lupulus L.) Dry Extract Supplement on Self-Reported Depression, Anxiety and Stress Levels in Healthy Young Adults: A RCT – Ioannis Kyrou et al., 2017, Hormones (Athens) (Double-blind crossover RCT) — Four weeks of daily hops extract (~400 mg) produced significant reductions in anxiety, depression, and stress ratings compared to placebo in moderately stressed young adults, without causing daytime drowsiness pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov. Hops (Humulus lupulus) Monograph – Clinical Overview (Various authors, 2021, summary of human studies) – Restorative Medicine Journal (Review) — Multiple human trials indicate hops exerts mild sedative and anxiolytic effects: for example, nighttime consumption of hops (e.g. in non-alcoholic beer) significantly improved sleep quality and reduced anxiety in healthy subjects restorativemedicine.orgrestorativemedicine.org, and a month-long hops supplement trial in adults showed reduced stress and anxiety scores versus placebo restorativemedicine.org. (Summary of evidence from clinical trials.) * These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. GABA CLAIM: Supports calm, focused mood EVIDENCE: 1. Systematic review (2020) — 14 human studies: oral GABA shows acute relaxation/stress and some sleep benefits, but overall evidence is limited; more rigorous RCTs needed. Use to set expectation language. PMC+1 2. Acute EEG + stress (2006 RCT/crossover) — 100 mg GABA- increased alpha waves, decreased beta vs water/L-theanine; small human stress task also showed immune changes. Use for "promotes relaxation within 1 hour." PUBMED+1 3. Insomnia RCT (2018, 4 weeks) — Rice-germ GABA improved subjective sleep quality and objective sleep efficiency without serious AEs. Supports sleep quality → next-day calm/focus angle. PUBMED+1 4. Cao C, et al. (2019) — 80 metabolic syndrome patients. Improved glucose and lipid markers. PMC6434235 5. Low-dose GABA RCT (2022, double-blind) — 75 mg/day reduced sleep latency increased N3 sleep, lowered arousal index vs placebo. Great for "low-dose efficacy" support.THEJCN.COM+2PMC+2 PASSION FLOWER (PASSIFLORA INCARNATA) CLAIM: Traditionally used to ease nervous tension EVIDENCE: 1. Miyasaka LS, et al. (2007) - Randomized, double-blind trial: Passion flower extract reduced anxiety as effectively as oxazepam. (Phytother Res. 2007;21(2):187-9. PMID: 17177576) 2. Akhondzadeh S, et al. (2001) - Passion flower improved generalized anxiety disorder symptoms comparable to prescription medication. (J Clin Pharm Ther. 2001;26(5):363-7. PMID: 11575780) 3. Ngan A, Conduit R. (2011) – Passion flower tea improved subjective sleep quality in a double- blind trial. (Phytother Res. 2011;25(8):1153-9. PMID: 21480475) 4. Santos RF, et al. (2022) – Systematic review: Passiflora incarnata safe and effective for mild anxiety and sleep disorders. (Braz J Psychiatry. 2022;44(1):120-130. PMID: 33524400) 5. Aguirre-Hernández E, et al. (2007) – Animal studies: Passion flower exhibited anxiolytic and sleep-promoting effects. (J Ethnopharmacol. 2007;109(2):264-70. PMID: 17391854) SAFFRON (CROCUS SATIVUS) CLAIM: Supports calm mindset and reduces stress-related cravings EVIDENCE: 1. Lopresti AL, et al. (2019) – Meta-analysis: Saffron supplementation reduces depression and anxiety symptoms. (Hum Psychopharmacol 2019;34(3):e2694. PMID: 31006920) 2. Papakostas Gl, et al. (2021) - Saffron as effective as standard antidepressants for mild-to- moderate depression in multiple trials. (J Affect Disord. 2021;293:242-250. PMID: 34242882) 3. Kell G, et al. (2017) - Saffron extract significantly reduced snacking and food cravings in healthy adults. (Nutrients. 2017;9(6):636. PMCID: PMC5490645) 4. Hausenblas HA, et al. (2015) - Saffron extract reduced emotional eating, promoted greater satiety in randomized trial. (J Integr Med. 2015;13(2):89-93. PMID: 26118849) 5. Shafiee M, et al. (2018) – Systematic review and meta-analysis show Saffron effective in reducing anxiety symptoms. (Phytother Res. 2018;32(11):1956-1964. PMID: 30144250) ST. JOHN'S WORT (HYPERICUM PERFORATUM) CLAIM: Helps maintain emotional balance EVIDENCE: 1. Ng QX, et al. (2017) – Meta-analysis: St. John's wort as effective as SSRIs for mild to moderate depression; well tolerated. (J Affect Disord. 2017;210:211-221. PMID: 28088338) 2. Apaydin EA, et al. (2016) – Comprehensive review: Consistent evidence for efficacy and safety in mild/moderate depression. (Systematic Reviews. 2016;5:67. PMID: 27188912) 3. Linde K, et al. (2008) - Cochrane review: Hypericum more effective than placebo and similarly effective as antidepressants. (Cochrane Database Syst Rev. 2008;4:CD000448. PMID: 18843608) 4. Gastpar M, et al. (2006) – Double-blind trial: St. John's Wort improved mood without sedative side-effects. (BMJ. 2006;332:1059-65. PMID: 16513656) 5. Fava M, et al. (2005) - St. John's Wort demonstrates safety and sustained mood support during extended use. (J Clin Psychopharmacol. 2005;25(5):441-7. PMID: 16160622) * These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.

Each ingredient in Calm Mode is transparently supported by up to five peer-reviewed studies. ASHWAGANDHA EXTRACT (WITHANIA SOMNIFERA, 100 MG) CLAIM: Helps the body adapt to stress and maintain steady energy 1. Chandrasekhar K et al. (2012) – 300 mg KSM-66 daily reduced cortisol by 27.9% vs 7.9% placebo; improved stress scores (P<0.0001). PMC3573577 2. Lopresti AL et al. (2019) - Systematic review: standardized ashwagandha extracts reduced stress and anxiety across 5 RCTs. Hum Psychopharmacol. 34(3):e2694 3. Dongre S et al. (2021) - 600 mg daily improved Perceived Stress Scale by 32% at 8 weeks. J Diet Suppl. 18(4):446-458 4. Kulkarni SK & Dhir A (2008) - Ashwagandha exhibited adaptogenic and anxiolytic effects in animal models. Pharmacol Biochem Behav. 90(2): 239-247 5. NIH ODS (2025) - Fact sheet confirms safety profile and stress-reduction effects in humans.ODS.OD.NIH.GOV L-THEANINE (50 MG) CLAIM: Supports mental clarity and relaxation without drowsiness 1. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial - Shinsuke Hidese et al., 2019, Nutrients (Double- blind crossover RCT) — Found that 200 mg/day of L-theanine for 4 weeks significantly reduced anxiety and improved sleep quality and executive function in healthy adults without causing sedation PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. 2. Safety and Efficacy of Alpha WaveR L-Theanine Supplementation for 28 Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial - Marc Moulin et al., 2024, Neurology and Therapy (RCT) — After 28 days, 400 mg/day L-theanine led to lower stress and better sleep: perceived stress scores decreased and sleep quality and cognitive attention improved significantly compared to placebo link.springer.comlink.springer.com. 3. Effects of L-Theanine on Cognitive Function in Middle-Aged and Older Subjects: A Randomized Placebo-Controlled Study - Yoshitake Baba et al., 2021, J. Medicinal Food (RCT) — Daily 100.6 mg L-theanine for 12 weeks in adults (age 50-69) enhanced attention and working memory, indicating improved cognitive function (mental clarity) with no adverse drowsiness reported NATURALHEALTHRESEARCH.ORGNATURALHEALTHRESEARCH.ORG. 4. L-Theanine Relieves Positive, Activation, and Anxiety Symptoms in Patients With Schizophrenia and Schizoaffective Disorder: An 8-Week... Placebo-Controlled Study - Michael S. Ritsner et al., 2011, J. Clin. Psychiatry (RCT) — Adjunctive L-theanine (400 mg/day) for 8 weeks significantly reduced anxiety and activation symptoms in schizophrenia patients versus placebo, with authors noting it was well-tolerated and did not cause sedation PSYCHIATRIST.COMPSYCHIATRIST.COM. 5. The effects of L-theanine supplementation on the outcomes of patients with mental disorders: a systematic review - Kasra Assadian et al., 2024, BMC Psychiatry (Systematic review of RCTs) — This review of 11 trials found L-theanine consistently reduced stress and anxiety symptoms more effectively than control conditions in populations including generalized anxiety and ADHD, supporting its relaxation benefits without sedative side-effects PMC.NCBI.NLM.NIH.GOVPMC.NCBI.NLM.NIH.GOV. GOLDEN ROOT EXTRACT (RHODIOLA ROSEA, 100 MG) CLAIM: Supports focus, mood, and resilience under stress 1. Darbinyan V et al. (2000) - 170 mg daily for 14 days improved fatigue index and mental performance in physicians. Phytomedicine. 7(2):85-89 2. Edwards D et al. (2012) - 400 mg daily for 6 weeks reduced stress symptoms and improved work performance. Phytother Res. 26(3):444-450 3. Panossian A & Wikman G (2010) - Review: Rhodiola extracts exhibit adaptogenic effects, reducing cortisol and improving cognition. Phytomedicine. 17(7):481-493 4. EMA Assessment (2011) - Traditional use approval for temporary relief of stress-related symptoms. EMA/HMPC/577346/2009 5. Olsson EMG et al. (2009) - 288 mg R. rosea improved mental performance during stress. Hum Psychopharmacol. 24(3): 23-34 BACOPA EXTRACT (BACOPA MONNIERI, 100 MG) CLAIM: Promotes memory, focus, and cognitive performance 1. Stough C et al. (2001)-300 mg Bacopa daily for 12 weeks improved memory recall and retention in healthy adults. Psychopharmacology. 156(4):481-484 2. Roodenrys S et al. (2002) - 150 mg daily enhanced speed of visual information processing and reduced anxiety. Neuropsychopharmacology. 27(2):279-281 3. Pase MP et al. (2012) - Systematic review: Bacopa improves cognition in RCTs with standardized extracts. J Altern Complement Med. 18(7):647-652 4. Calabrese C et al. (2008) - 450 mg daily reduced anxiety and improved cognitive function in elderly. Hum Psychopharmacol. 23(6): 463-469 LEMON BALM EXTRACT (MELISSA OFFICINALIS, 100 MG) CLAIM: Promotes relaxation 1. Kennedy D et al. (2004) - Single dose (1.6 g) improved calmness and alertness in healthy volunteers. Nutr Neurosci. 7(3):181-185 2. Shakeri A et al. (2016) - Review of traditional and clinical data supports lemon balm's GABA- transaminase inhibition. J Funct Foods. 21: 5-15 PASSION FLOWER EXTRACT (PASSIFLORA INCARNATA, 100 MG) CLAIM: Helps calm the mind and support emotional balance 1. Miyasaka LS et al. (2007) - Passion flower extract reduced anxiety comparably to benzodiazepine without sedation. Phytother Res. 21(2):187-189 2. Akhondzadeh S et al. (2001) - Improved generalized anxiety symptoms vs placebo (P<0.05). J Clin Pharm Ther. 26(5):363-367 3. Ngan A & Conduit R (2011) - Tea extract improved subjective sleep quality in healthy adults. Phytother Res. 25(8):1153-1159 4. Santos RF et al (2022) - Systematic review: safety and efficacy for anxiety and sleep disturbances. Braz J Psychiatry. 44(1):120-130 5. Charles T et al. (2010) - Animal study: anxiolytic effects via GABAergic modulation. J Ethnopharmacol. 127(1): 188-196 HOPS EXTRACT (HUMULUS LUPULUS, 50 MG) CLAIM: Naturally supports relaxation and healthy sleep patterns EVIDENCE: 1. A randomized, double-blind, placebo-controlled study of a fixed valerian-hops extract combination (Ze 91019) in non-organic insomnia - U. Koetter et al., 2007, Phytotherapy Research (RCT) — A nightly herbal combination containing valerian and hops (120 mg) for 4 weeks significantly shortened sleep latency compared to placebo, demonstrating that adding hops extract produced greater improvements in falling asleep PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. 2. The Sedative Effect of Non-Alcoholic Beer in Healthy Female Nurses - Lourdes Franco et al, 2012, PLOS ONE (Clinical trial) — In 17 nurses working night shifts, consuming one bottle of hops-rich non-alcoholic beer with dinner for 14 days improved sleep parameters: time to fall asleep decreased and nighttime restlessness reduced, and self-reported anxiety also declined despite the beer containing no alcohol (effect attributed to hops) PUBMED.NCBI.NLM.NIH.GOVPSYCHOLOGYTODAY.COM. 3. Effect of Non-Alcoholic Beer on Subjective Sleep Quality in a University Stressed Population - Lourdes Franco et al., 2014, Acta Physiol. Hung. (Intervention study) — Among 30 healthy students with high stress, two weeks of nightly hops-enhanced non-alcoholic beer led to significantly better sleep quality scores and shorter sleep latency than a control period, indicating hops intake can promote relaxation and healthier sleep patterns RESTORATIVEMEDICINE.ORG. 4. Effects of a Hops (Humulus lupulus L) Dry Extract Supplement on Self-Reported Depression, Anxiety and Stress Levels in Healthy Young Adults: A RCT-loannis Kyrou et al, 2017, Hormones (Athens) (Double-blind crossover RCT) — Four weeks of daily hops extract (~400 mg) produced significant reductions in anxiety, depression, and stress ratings compared to placebo in moderately stressed young adults, without causing daytime drowsiness PUBMED.NCBI.NLM.NIH.GOVPUBMED.NCBI.NLM.NIH.GOV. 5. Hops (Humulus lupulus) Monograph - Clinical Overview (Various authors, 2021, summary of human studies) - Restorative Medicine Journal (Review) — Multiple human trials indicate hops exerts mild sedative and anxiolytic effects: for example, nighttime consumption of hops (e.g. in non-alcoholic beer) significantly improved sleep quality and reduced anxiety in healthy subjects RESTORATIVEMEDICINE.ORGRESTORATIVEMEDICINE.ORG and a month-long hops supplement trial in adults showed reduced stress and anxiety scores versus placebo RESTORATIVEMEDICINE.ORG. (Summary of evidence from clinical trials.) * These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.