Yes, ashwagandha supplementation significantly reduces stress in adults, as shown by multiple clinical trials and meta-analyses.

Evidence from Clinical Trials and Meta-Analyses

Numerous randomized controlled trials and systematic reviews confirm that ashwagandha (Withania somnifera) supplementation leads to significant reductions in perceived stress compared to placebo. A 2022 meta-analysis of 12 RCTs (1,002 participants) found ashwagandha significantly reduced stress (standardized mean difference: -1.75) and anxiety, with effective doses typically between 300–600 mg/day (Akhgarjand et al., 2022; Arumugam et al., 2024; Salve et al., 2019; Gopukumar et al., 2021; Chandrasekhar et al., 2012). Benefits are observed after 4–12 weeks of supplementation, with improvements measured by validated scales such as the Perceived Stress Scale and reductions in cortisol levels (Arumugam et al., 2024; Salve et al., 2019; Gopukumar et al., 2021; Chandrasekhar et al., 2012).

Mechanisms and Safety

Ashwagandha’s stress-reducing effects are primarily attributed to its modulation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to lower cortisol (the primary stress hormone) and improved neurotransmitter balance (GABA, serotonin) (Speers et al., 2021; Pandit et al., 2024; Arumugam et al., 2024; Lopresti et al., 2019; Haber et al., 2024; Malec, 2024). Most studies report a favorable safety profile, with only mild adverse effects and no serious safety concerns in the short term (Akhgarjand et al., 2022; Arumugam et al., 2024; Salve et al., 2019; Gopukumar et al., 2021). However, the certainty of evidence is rated as low to moderate due to variability in study quality and extract standardization (Akhgarjand et al., 2022; Arumugam et al., 2024; Gopukumar et al., 2021; D’cruz & Andrade, 2022).

Conclusion

Current research strongly supports ashwagandha’s ability to reduce stress and lower cortisol in adults, with a favorable safety profile for short-term use. More high-quality, long-term studies are needed to confirm optimal dosing, safety, and efficacy.

References

Speers, A., Cabey, K., Soumyanath, A., & Wright, K. (2021). Effects of Withania somnifera (Ashwagandha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Current Neuropharmacology, 19, 1468 - 1495. https://doi.org/10.2174/1570159X19666210712151556

Akhgarjand, C., Asoudeh, F., Bagheri, A., Kalantar, Z., Vahabi, Z., Shab-Bidar, S., Rezvani, H., & Djafarian, K. (2022). Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta‐analysis of randomized controlled trials. Phytotherapy Research, 36, 4115 - 4124. https://doi.org/10.1002/ptr.7598

Pandit, S., Srivastav, A., Sur, T., Chaudhuri, S., Wang, Y., & Biswas, T. (2024). Effects of Withania somnifera Extract in Chronically Stressed Adults: A Randomized Controlled Trial. Nutrients, 16. https://doi.org/10.3390/nu16091293

Arumugam, V., Vijayakumar, V., Balakrishnan, A., Bhandari, R., Boopalan, D., Ponnurangam, R., Thirupathy, V., & Kuppusamy, M. (2024). Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis.. Explore, 20 6, 103062. https://doi.org/10.1016/j.explore.2024.103062

Lopresti, A., Smith, S., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract. Medicine, 98. https://doi.org/10.1097/MD.0000000000017186

Salve, J., Pate, S., Debnath, K., & Langade, D. (2019). Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study. Cureus, 11. https://doi.org/10.7759/cureus.6466

Gopukumar, K., Thanawala, S., Somepalli, V., Rao, T., Thamatam, V., & Chauhan, S. (2021). Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Evidence-based Complementary and Alternative Medicine : eCAM, 2021. https://doi.org/10.1155/2021/8254344

Haber, M., Czachor, A., Kula, P., Juśkiewicz, A., Grelewicz, O., Kucy, N., Servaas, E., Kotula, A., & Siemiątkowski, R. (2024). Ashwagandha as an Adaptogen: Its Influence on Sleep Patterns, Stress Response, and Anxiety in Modern Life. Journal of Education, Health and Sport. https://doi.org/10.12775/jehs.2024.68.55327

Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. Indian Journal of Psychological Medicine, 34, 255 - 262. https://doi.org/10.4103/0253-7176.106022

D’cruz, M., & Andrade, C. (2022). Potential clinical applications of Ashwagandha (Withania somnifera) in medicine and neuropsychiatry. Expert Review of Clinical Pharmacology, 15, 1067 - 1080. https://doi.org/10.1080/17512433.2022.2121699

Malec, K. (2024). The impact of ashwagandha on sleep quality, anxiety reduction, and stress lowering: comparative analysis of available studies. Journal of Education, Health and Sport. https://doi.org/10.12775/jehs.2024.52.015

Yes, collagen supplementation can relieve joint pain, especially in people with osteoarthritis or activity-related joint discomfort.

Evidence from Meta-Analyses and Clinical Trials

Multiple systematic reviews and meta-analyses confirm that oral collagen supplementation leads to statistically significant reductions in joint pain and improvements in function for individuals with osteoarthritis (OA) and those experiencing joint discomfort from physical activity (García-Coronado et al., 2018; Liang et al., 2024; Simental-Mendía et al., 2024; Zdzieblik et al., 2017). Collagen derivatives show small-to-moderate but clinically meaningful effects on pain relief and functional improvement, with a strong safety profile (Liang et al., 2024; Simental-Mendía et al., 2024; García-Coronado et al., 2018). These benefits are observed across various forms of collagen, including hydrolyzed and type II collagen, and are supported by randomized controlled trials in both older adults with OA and younger, physically active adults (Zdzieblik et al., 2021; Mohammed & He, 2021; Oesser et al., 2016; Khatri et al., 2021; Clark et al., 2008; Zdzieblik et al., 2017; Schulze et al., 2024).

Effects in Different Populations

• Osteoarthritis Patients: Collagen supplementation consistently reduces pain and stiffness and improves joint function compared to placebo (García-Coronado et al., 2018; Liang et al., 2024; Simental-Mendía et al., 2024; Zdzieblik et al., 2017; T et al., 2017).
• Physically Active Adults/Athletes: Collagen peptides significantly reduce activity-related joint pain and the need for additional therapies, with effects confirmed by both participant and physician assessments (Zdzieblik et al., 2021; Oesser et al., 2016; Khatri et al., 2021; Clark et al., 2008; Zdzieblik et al., 2017; Schulze et al., 2024).
• Healthy, Pain-Free Adults: Some studies in healthy, older adults without diagnosed joint disease found no significant difference between collagen and placebo for knee pain reduction (Bongers et al., 2020).

Conclusion

Collagen supplementation is supported by strong evidence for reducing joint pain and improving function in people with osteoarthritis and those with activity-related joint discomfort. Effects are less clear in healthy, pain-free individuals, but collagen is generally safe and well-tolerated.

References

Zdzieblik, D., Brame, J., Oesser, S., Gollhofer, A., & König, D. (2021). The Influence of Specific Bioactive Collagen Peptides on Knee Joint Discomfort in Young Physically Active Adults: A Randomized Controlled Trial. Nutrients, 13. https://doi.org/10.3390/nu13020523

Mohammed, A., & He, S. (2021). A Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy of a Hydrolyzed Chicken Collagen Type II Supplement in Alleviating Joint Discomfort. Nutrients, 13. https://doi.org/10.3390/nu13072454

García-Coronado, J., Martínez-Olvera, L., Elizondo-Omaña, R., Acosta-Olivo, C., Vilchez-Cavazos, F., Simental‐Mendía, L., & Simental-Mendía, M. (2018). Effect of collagen supplementation on osteoarthritis symptoms: a meta-analysis of randomized placebo-controlled trials. International Orthopaedics, 43, 531-538. https://doi.org/10.1007/s00264-018-4211-5

Oesser, S., Schulze, C., Zdzieblik, D., & König, D. (2016). Efficacy of specific bioactive collagen peptides in the treatment of joint pain. Osteoarthritis and Cartilage, 24. https://doi.org/10.1016/J.JOCA.2016.01.370

Khatri, M., Naughton, R., Clifford, T., Harper, L., & Corr, L. (2021). The effects of collagen peptide supplementation on body composition, collagen synthesis, and recovery from joint injury and exercise: a systematic review. Amino Acids, 53, 1493 - 1506. https://doi.org/10.1007/s00726-021-03072-x

Clark, K., Sebastianelli, W., Flechsenhar, K., Aukermann, D., Meza, F., Millard, R., Deitch, J., Sherbondy, P., & Albert, A. (2008). 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinion, 24, 1485 - 1496. https://doi.org/10.1185/030079908X291967

Liang, C., Cheng, H., Lee, Y., Liao, C., & Huang, S. (2024). Efficacy and safety of collagen derivatives for osteoarthritis: a trial sequential meta-analysis.. Osteoarthritis and cartilage. https://doi.org/10.1016/j.joca.2023.12.010

Simental-Mendía, M., Ortega-Mata, D., Acosta-Olivo, C., Simental‐Mendía, L., Peña-Martínez, V., & Vilchez-Cavazos, F. (2024). Effect of collagen supplementation on knee osteoarthritis: an updated systematic review and meta-analysis of randomised controlled trials.. Clinical and experimental rheumatology. https://doi.org/10.55563/clinexprheumatol/kflfr5

Zdzieblik, D., Oesser, S., Gollhofer, A., & König, D. (2017). Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides.. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 42 6, 588-595. https://doi.org/10.1139/apnm-2016-0390

Schulze, C., Schunck, M., Zdzieblik, D., & Oesser, S. (2024). Impact of Specific Bioactive Collagen Peptides on Joint Discomforts in the Lower Extremity during Daily Activities: A Randomized Controlled Trial. International Journal of Environmental Research and Public Health, 21. https://doi.org/10.3390/ijerph21060687

T, W., L, L., N, C., P, C., K, T., & A, G. (2017). Efficacy of Oral Collagen in Joint Pain - Osteoarthritis and Rheumatoid Arthritis. Journal of Arthritis, 6, 1-4. https://doi.org/10.4172/2167-7921.1000233

Bongers, C., Haaf, D., Catoire, M., Kersten, B., Wouters, J., Eijsvogels, T., & Hopman, M. (2020). Effectiveness of collagen supplementation on pain scores in healthy individuals with self-reported knee pain; A randomized controlled trial.. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. https://doi.org/10.1139/apnm-2019-0654

Yes, CoQ10 supplementation can improve certain aspects of cardiometabolic health, especially in people with existing metabolic or cardiovascular conditions, but effects vary by outcome and population.

Effects on Cardiometabolic Markers

• Blood Pressure: CoQ10 supplementation significantly reduces systolic blood pressure (SBP), particularly in patients with diabetes or dyslipidemia, with optimal effects at 100–200 mg/day. The impact on diastolic blood pressure is less consistent (Zhao et al., 2022; Zhang et al., 2017; Patiño-Cardona et al., 2024).
• Glycemic Control: CoQ10 can lower fasting blood glucose and HbA1c, especially in individuals with type 2 diabetes or metabolic syndrome. The benefit is greater in those with higher baseline glucose levels (Patiño-Cardona et al., 2024; Xu et al., 2021; Dludla et al., 2020).
• Lipid Profile: Evidence shows modest reductions in total cholesterol, LDL, and triglycerides, and a slight increase in HDL. However, results are inconsistent and more pronounced in populations with dyslipidemia or coronary artery disease (Zhang et al., 2017; Patiño-Cardona et al., 2024; Jorat et al., 2018; Liu et al., 2022).
• Inflammation and Oxidative Stress: CoQ10 supplementation improves markers of inflammation (e.g., IL-6, CRP) and oxidative stress, which may contribute to its cardiometabolic benefits (Mirhashemi et al., 2016; Dludla et al., 2020; Pan et al., 2024).
• Cardiac Function and Outcomes: In heart failure and post-myocardial infarction patients, CoQ10 improves ejection fraction, reduces mortality, and lowers hospitalizations, with the strongest evidence in heart failure populations (Borges, 2024; Borges, 2024; Alarcón-Vieco et al., 2023; Pan et al., 2024).

Conclusion

CoQ10 supplementation offers moderate benefits for blood pressure, glycemic control, and cardiac function, especially in high-risk groups. Effects on lipid profiles are less consistent. More large, high-quality trials are needed to clarify optimal use and target populations.

References

Zhao, D., Liang, Y., Dai, S., Hou, S., Liu, Z., Liu, M., Dong, X., Zhan, Y., Tian, Z., & Yang, Y. (2022). Dose-response Effect of Coenzyme Q10 Supplementation On Blood Pressure Among Patients With Cardiometabolic Disorders: A GRADE-assessed Systematic Review and Meta-analysis of Randomized Controlled Trials.. Advances in nutrition. https://doi.org/10.1093/advances/nmac100

Zhang, P., Yang, C., Guo, H., Wang, J., Lin, S., Li, H., Yang, Y., & Ling, W. (2017). Treatment of coenzyme Q10 for 24 weeks improves lipid and glycemic profile in dyslipidemic individuals.. Journal of clinical lipidology, 12 2, 417-427.e5. https://doi.org/10.1016/j.jacl.2017.12.006

Patiño-Cardona, S., Garrido-Miguel, M., Pascual-Morena, C., Berlanga-Macías, C., Lucerón-Lucas-Torres, M., Alfaro-González, S., & Martínez-García, I. (2024). Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review. Journal of Cardiovascular Development and Disease, 11. https://doi.org/10.3390/jcdd11120377

Jorat, M., Tabrizi, R., Mirhosseini, N., Lankarani, K., Akbari, M., Heydari, S., Mottaghi, R., & Asemi, Z. (2018). The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Lipids in Health and Disease, 17. https://doi.org/10.1186/s12944-018-0876-4

Xu, Y., Yang, G., Zuo, X., Gao, J., Jia, H., Han, E., Liu, J., Wang, Y., & Yan, H. (2021). A systematic review for the efficacy of coenzyme Q10 in patients with chronic kidney disease. International Urology and Nephrology, 54, 173-184. https://doi.org/10.1007/s11255-021-02838-2

Mirhashemi, S., Najafi, V., Raygan, F., & Asemi, Z. (2016). The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction: A randomized, double-blind, placebo-controlled trial. ARYA Atherosclerosis, 12, 158 - 165.

Borges, J. (2024). Translational Cardiology: Practical Insights into the Coenzyme Q10 Role as Potential Therapeutic Agent for Cardiovascular Disease Treatment via Systematic Review and Meta-Analysis of Prospective Cohort Studies. Translational Medicine: Open Access. https://doi.org/10.33140/tmoa.02.01.04

Borges, J. (2024). The Role of Coenzyme Q10 in Cardiovascular Disease Treatment: An Updated 2024 Systematic Review and Meta-Analysis of Prospective Cohort Studies (2000-2023). **. https://doi.org/10.1101/2024.07.03.24309736

Alarcón-Vieco, E., Martínez-García, I., Sequí-Domínguez, I., Rodríguez-Gutiérrez, E., Moreno-Herráiz, N., & Pascual-Morena, C. (2023). Effect of coenzyme Q10 on cardiac function and survival in heart failure: an overview of systematic reviews and meta-analyses.. Food & function. https://doi.org/10.1039/d3fo01255g

Liu, Z., Tian, Z., Zhao, D., Liang, Y., Dai, S., Liu, M., Hou, S., Dong, X., , Z., & Yang, Y. (2022). Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials.. The Journal of clinical endocrinology and metabolism. https://doi.org/10.1210/clinem/dgac585

Dludla, P., Orlando, P., Silvestri, S., Marcheggiani, F., Cirilli, I., Nyambuya, T., Mxinwa, V., Mokgalaboni, K., Nkambule, B., Johnson, R., Mazibuko-Mbeje, S., Muller, C., Louw, J., & Tiano, L. (2020). Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences, 21. https://doi.org/10.3390/ijms21093247

Pan, W., Zhou, G., Hu, M., Li, G., Zhang, M., Yang, H., Li, K., Li, J., Liu, T., Wang, Y., & Jin, J. (2024). Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway. BMC Cardiovascular Disorders, 24. https://doi.org/10.1186/s12872-024-03729-x

Yes, creatine supplementation helps improve muscle strength, especially when combined with resistance training.

Yvidét: Please note that females showed little to no significant improvement in some studies.

Evidence Across Age Groups and Genders

• Adults under 50: Creatine supplementation with resistance training significantly increases both upper- and lower-body muscle strength compared to placebo. The effect is especially pronounced in males, with males showing significant gains and females showing little to no significant improvement in some studies (Wang et al., 2024).
• Older adults: Creatine also augments gains in muscle strength and lean tissue mass when combined with resistance training. The benefits are observed in both men and women, though the effect size may be smaller and more variable, especially for lower-body strength in older females unless the training duration is at least 24 weeks (Forbes et al., 2021; Chilibeck et al., 2017; Santos et al., 2021; Forbes & Candow, 2024).

Mechanisms and Supplementation Strategies

• Creatine increases intramuscular phosphocreatine stores, enhancing ATP resynthesis during high-intensity exercise, which allows for greater training volume and intensity (Wang et al., 2024; Forbes et al., 2021; Chilibeck et al., 2017; Jangada et al., 2025; Kreider & Stout, 2021).
• Both high-dose (loading) and lower daily doses are effective, and supplementation only on training days can still yield strength benefits (Forbes et al., 2021; Chilibeck et al., 2017).
• The effect is consistent across different training protocols, populations, and dosing strategies, indicating broad applicability (Lanhers et al., 2016; Lanhers et al., 2015; Kuźnieców et al., 2025; Janik et al., 2024).

Conclusion

Creatine supplementation is a well-supported, effective strategy for improving muscle strength in both young and older adults, especially when combined with resistance training. The benefits are robust across dosing strategies and training protocols, with the strongest effects seen in males and with longer training durations.

References

Wang, Z., Qiu, B., Li, R., Han, Y., Petersen, C., Liu, S., Zhang, Y., Liu, C., Candow, D., & Del Coso, J. (2024). Effects of Creatine Supplementation and Resistance Training on Muscle Strength Gains in Adults <50 Years of Age: A Systematic Review and Meta-Analysis. Nutrients, 16. https://doi.org/10.3390/nu16213665

Forbes, S., Candow, D., Ostojić, S., Roberts, M., & Chilibeck, P. (2021). Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults. Nutrients, 13. https://doi.org/10.3390/nu13061912

Chilibeck, P., Kaviani, M., Candow, D., & Zello, G. (2017). Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access Journal of Sports Medicine, 8, 213 - 226. https://doi.org/10.2147/OAJSM.S123529

Kuźnieców, T., Karaban, Ł., Paszkowska, M., Mularczyk, K., Borawski, M., Ciuła, A., Jakubiak, A., Miśkiewicz, J., Znamirowska, P., & Kupis, M. (2025). Additional Benefits of Creatine Monohydrate Supplementation on Muscle Strength, Muscle Mass Gain and Training Performance - A Systematic Review. Quality in Sport. https://doi.org/10.12775/qs.2025.41.60300

Santos, E., De Araújo, R., Candow, D., Forbes, S., Guijo, J., De Almeida Santana, C., Prado, W., & Botero, J. (2021). Efficacy of Creatine Supplementation Combined with Resistance Training on Muscle Strength and Muscle Mass in Older Females: A Systematic Review and Meta-Analysis. Nutrients, 13. https://doi.org/10.3390/nu13113757

Jangada, A., Borges, A., Ferreira, M., Santos, Y., Barbosa, M., Rani, R., Fernandes, J., De Medeiros, F., De Lima Paiva, A., & Peters, G. (2025). IMPACTO DA SUPLEMENTAÇÃO COM CREATINA NO DESEMPENHO FÍSICO E NA RECUPERAÇÃO MUSCULAR: UMA REVISÃO NARRATIVA. Revista ft. https://doi.org/10.69849/revistaft/pa10202503301956

Lanhers, C., Pereira, B., Naughton, G., Trousselard, M., Lesage, F., & Dutheil, F. (2016). Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis. Sports Medicine, 47, 163-173. https://doi.org/10.1007/s40279-016-0571-4

Janik, I., Kuśmierska, M., & Kuśmierski, J. (2024). Impact of Creatine Supplementation on Strength Training. Quality in Sport. https://doi.org/10.12775/qs.2024.15.51885

Lanhers, C., Pereira, B., Naughton, G., Trousselard, M., Lesage, F., & Dutheil, F. (2015). Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses. Sports Medicine, 45, 1285-1294. https://doi.org/10.1007/s40279-015-0337-4

Forbes, S., & Candow, D. (2024). Creatine and strength training in older adults: an update. Translational Exercise Biomedicine, 1, 212 - 222. https://doi.org/10.1515/teb-2024-0019

Kreider, R., & Stout, J. (2021). Creatine in Health and Disease. Nutrients, 13. https://doi.org/10.3390/nu13020447

Evidence for Evening Primrose Oil in Menopause Symptom Relief Is Mixed—Some Benefit for Psychological and Physical Symptoms, Limited Effect on Hot Flashes

Summary of Research Findings

Hot Flashes and Vasomotor Symptoms

• Most systematic reviews and randomized controlled trials (RCTs) find that evening primrose oil (EPO) does not significantly reduce the frequency or severity of hot flashes or night sweats compared to placebo (Christelle et al., 2020; Chenoy et al., 1994; Thevi et al., 2024; Mehrpooya et al., 2018; Kang et al., 2002; Sharifi et al., 2024).
• Some studies report a small reduction in hot flash severity, but not in frequency or duration, and EPO is generally less effective than black cohosh for these symptoms (Thevi et al., 2024; Mehrpooya et al., 2018).

Psychological and Physical Symptoms

• EPO shows more consistent benefit for psychological symptoms (such as mood swings, irritability, and anxiety) in postmenopausal women, with several RCTs reporting significant improvements compared to placebo (Sharif & Darsareh, 2019; Ghavi et al., 2023; Safdari et al., 2021).
• EPO may also reduce physical symptoms like flushing, sleep disorders, and musculoskeletal discomfort, with some studies showing significant improvements over placebo (Dastenaie et al., 2017; Ghavi et al., 2023).

Hormonal and Combination Effects

• EPO can significantly change hormone levels (FSH, estradiol) and improve psychological symptoms, similar to fennel, but not more effective than fennel (Ghavi et al., 2023).
• Combination products containing EPO and other herbal extracts have shown broader symptom relief, but the specific contribution of EPO is unclear (Rattanatantikul et al., 2020; Yakoot et al., 2011).

Safety

• EPO is generally well tolerated, with mild side effects such as gastric upset or headache reported infrequently (Sharif & Darsareh, 2019; Thevi et al., 2024).

Conclusion

Current research indicates that evening primrose oil is not effective for reducing hot flashes, but may help with psychological and some physical symptoms in menopausal women. The overall quality of evidence is moderate to low, and further large, high-quality studies are needed to clarify its benefits and safety.

References

Christelle, K., Zulkfili, M., Noor, N., & Draman, N. (2020). The Effects of Evening-Primrose Oil on Menopausal Symptoms: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Current Women's Health Reviews, 16, 265-276. https://doi.org/10.2174/1573404816999200702162750

Sharif, S., & Darsareh, F. (2019). Impact of evening primrose oil consumption on psychological symptoms of postmenopausal women: a randomized double-blinded placebo-controlled clinical trial.. Menopause. https://doi.org/10.1097/GME.0000000000001434

Chenoy, R., Hussain, S., Tayob, Y., O'brien, P., Moss, M., & Morse, P. (1994). Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ, 308, 501 - 503. https://doi.org/10.1136/bmj.308.6927.501

Thevi, T., De, S., & Soe, H. (2024). Evening Primrose Oil for Menopause Hot Flashes: Systematic Review and Meta-Analysis. Journal of Menopausal Medicine, 30, 127 - 134. https://doi.org/10.6118/jmm.23038

Ghavi, F., Shakeri, F., Farahnaz, H., & Abdolahian, S. (2023). Comparison of the Effect of Fennel and Evening Primrose Oil on Menopausal Problems and Hormonal Levels: A Randomized Controlled Trial. Iranian Journal of Nursing and Midwifery Research, 28, 430 - 435. https://doi.org/10.4103/ijnmr.ijnmr_149_22

Dastenaie, B., Safdari, F., Raisi, Z., & Karimian, Z. (2017). The Effect of Evening Primrose Plant on Physical Symptoms of Menopause. Journal of Babol University of Medical Sciences, 19, 34-40. https://doi.org/10.22088/JBUMS.19.2.34

Safdari, F., Dastenaei, B., Kheiri, S., & Karimiankakolaki, Z. (2021). Effect of Evening Primrose Oil on Postmenopausal Psychological Symptoms: A Triple-Blind Randomized Clinical Trial. Journal of Menopausal Medicine, 27, 58 - 65. https://doi.org/10.6118/jmm.21010

Rattanatantikul, T., Maiprasert, M., Sugkraroek, P., & Bumrungpert, A. (2020). Efficacy and Safety of Nutraceutical on Menopausal Symptoms in Post-Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journal of Dietary Supplements, 19, 168 - 183. https://doi.org/10.1080/19390211.2020.1853648

Mehrpooya, M., Rabiee, S., Larki-Harchegani, A., Fallahian, A., Moradi, A., Ataei, S., & Javad, M. (2018). A comparative study on the effect of “black cohosh” and “evening primrose oil” on menopausal hot flashes. Journal of Education and Health Promotion, 7. https://doi.org/10.4103/jehp.jehp_81_17

Kang, H., Ansbacher, R., & Hammoud, M. (2002). Use of alternative and complementary medicine in menopause. International Journal of Gynecology & Obstetrics, 79. https://doi.org/10.1016/S0020-7292(02)00297-7

Yakoot, M., Salem, A., & Omar, A. (2011). Effectiveness of a Herbal Formula in Women with Menopausal Syndrome. Complementary Medicine Research, 18, 264 - 268. https://doi.org/10.1159/000333430

Sharifi, M., Nourani, N., Sanaie, S., & Hamedeyazdan, S. (2024). The effect of Oenothera biennis (Evening primrose) oil on inflammatory diseases: a systematic review of clinical trials. BMC Complementary Medicine and Therapies, 24. https://doi.org/10.1186/s12906-024-04378-5

Yes, hyaluronic acid improves signs of skin aging by enhancing skin hydration, elasticity, firmness, and reducing wrinkles.

Evidence from Clinical Trials and Reviews

• Injectable Hyaluronic Acid: Systematic reviews and randomized controlled trials consistently show that injectable hyaluronic acid (HA) significantly reduces wrinkles, increases skin elasticity, improves hydration, and enhances overall skin radiance. These effects are superior to those of anti-aging creams alone, with improvements seen as early as one month after treatment and lasting for several months (Zhou & Yu, 2025; Fanian et al., 2023; Baspeyras et al., 2013; Ghatge & Ghatge, 2023).
• Oral Supplementation: Oral intake of full-spectrum hyaluronan has been shown in double-blind, placebo-controlled trials to improve skin hydration (+10.6%), elasticity, firmness, and reduce wrinkle depth and volume within 28 days, with good safety and patient satisfaction (Michelotti et al., 2021).
• Topical Application: Topical HA, especially low-molecular-weight formulations, significantly improves skin hydration, elasticity, and reduces wrinkle depth, with better penetration and efficacy for lower molecular weights (Pavicic et al., 2011; Waggett et al., 2024).

Conclusion

Robust clinical evidence demonstrates that hyaluronic acid—whether injected, taken orally, or applied topically—effectively improves multiple signs of skin aging, including hydration, elasticity, firmness, and wrinkle reduction. Injectable and oral forms show particularly strong and rapid results.

References

Zhou, R., & Yu, M. (2025). The Effect of Local Hyaluronic Acid Injection on Skin Aging: A Systematic Review and Meta‐Analysis. Journal of Cosmetic Dermatology, 24. https://doi.org/10.1111/jocd.16760

Fanian, F., Deutsch, J., Bousquet, M., Boisnic, S., André, P., Catoni, I., Beilin, G., Lemmel, C., Taieb, M., Gomel-Toledano, M., Issa, H., & Garcia, P. (2023). A hyaluronic acid-based micro-filler improves superficial wrinkles and skin quality: a randomized prospective controlled multicenter study. Journal of Dermatological Treatment, 34. https://doi.org/10.1080/09546634.2023.2216323

Michelotti, A., Cestone, E., De Ponti, I., Pisati, M., Spartà, E., & Tursi, F. (2021). Oral intake of a new full-spectrum hyaluronan improves skin profilometry and ageing: a randomized, double-blind, placebo-controlled clinical trial. European Journal of Dermatology, 31, 798 - 805. https://doi.org/10.1684/ejd.2021.4176

Baspeyras, M., Rouvrais, C., Liégard, L., Delalleau, A., Letellier, S., Bacle, I., Courrech, L., Murat, P., Mengeaud, V., & Schmitt, A. (2013). Clinical and biometrological efficacy of a hyaluronic acid-based mesotherapy product: a randomised controlled study. Archives of Dermatological Research, 305, 673 - 682. https://doi.org/10.1007/s00403-013-1360-7

Ghatge, A., & Ghatge, S. (2023). The Effectiveness of Injectable Hyaluronic Acid in the Improvement of the Facial Skin Quality: A Systematic Review. Clinical, Cosmetic and Investigational Dermatology, 16, 891 - 899. https://doi.org/10.2147/CCID.S404248

Waggett, S., Lyles, E., & Schlesinger, T. (2024). Update on Low-Molecular Weight Hyaluronic Acid in Dermatology: A Scoping Review. EMJ Dermatology. https://doi.org/10.33590/emjdermatol/cchb4701

Pavicic, T., Gauglitz, G., Lersch, P., Schwach-Abdellaoui, K., Malle, B., Korting, H., & Farwick, M. (2011). Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment.. Journal of drugs in dermatology : JDD, 10 9, 990-1000.

Lion’s Mane supplementation may support cognitive function, especially in older adults and those with mild cognitive impairment, but evidence in healthy young adults is limited.

Evidence in Older Adults and Cognitive Impairment

• Multiple systematic reviews and clinical trials report that Lion’s Mane (Hericium erinaceus) supplementation can improve cognitive test scores (such as MMSE and HDS-R) in older adults and those with mild cognitive impairment (MCI) (Komoń et al., 2024; Lewis et al., 2021; Hersant et al., 2023).
• Benefits are most pronounced with doses of 3–3.2 g/day over 12–16 weeks (Lewis et al., 2021).
• Improvements include memory, attention, and daily functioning, with effects often reversing after stopping supplementation (Lewis et al., 2021).
• Lion’s Mane may also increase brain-derived neurotrophic factor (BDNF), supporting neuroprotection (Komoń et al., 2024).

Evidence in Healthy Adults

• Studies in healthy young adults show little to no significant cognitive benefit from Lion’s Mane supplementation, even at higher doses (up to 10 g/day) (Cha et al., 2024; Lewis et al., 2021).
• Some reviews note possible improvements in mood or stress, but robust cognitive enhancement is not consistently observed in this group (Cha et al., 2024; Lewis et al., 2021; Nieman et al., 2023).

Safety and Mechanisms

• Lion’s Mane is generally well-tolerated, with rare mild gastrointestinal side effects (Komoń et al., 2024; Lewis et al., 2021).
• Proposed mechanisms include antioxidant, anti-inflammatory, and neurotrophic effects, possibly mediated through the gut-brain axis (Komoń et al., 2024; Contato & Conte‐Junior, 2025).

Conclusion

Lion’s Mane supplementation is promising for cognitive support in older adults and those with MCI, but there is little evidence for cognitive benefits in healthy young adults. More large-scale, long-term studies are needed to confirm these effects and determine optimal dosing.

References

Komoń, A., Romańczuk, K., Kamińska-Omasta, K., Wójtowicz, J., Ujazda, D., Bodziony, K., Tyniec, M., & Morshed, K. (2024). Neuroprotective and Cognitive Benefits of Hericium erinaceus: A Comprehensive Review of Recent Clinical Studies. Biuletyn Głównej Biblioteki Lekarskiej, 57, 279 - 290. https://doi.org/10.2478/bgbl-2024-0038

Cha, S., Bell, L., Shukitt-Hale, B., & Williams, C. (2024). A review of the effects of mushrooms on mood and neurocognitive health across the lifespan. Neuroscience & Biobehavioral Reviews, 158. https://doi.org/10.1016/j.neubiorev.2024.105548

Lewis, J., Poles, J., Shaw, D., Karhu, E., Khan, S., Lyons, A., Sacco, S., & McDaniel, H. (2021). The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review. Journal of Clinical and Translational Research, 7, 575 - 620. https://doi.org/10.18053/jctres.07.202104.014

Hersant, H., He, S., Maliha, P., & Grossberg, G. (2023). Over the Counter Supplements for Memory: A Review of Available Evidence. CNS Drugs, 37, 797-817. https://doi.org/10.1007/s40263-023-01031-6

Contato, A., & Conte‐Junior, C. (2025). Lion’s Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential—A Narrative Review. Nutrients, 17. https://doi.org/10.3390/nu17081307

Nieman, K., Zhu, Y., Tucker, M., & Koecher, K. (2023). The Role of Dietary Ingredients in Mental Energy - A Scoping Review of Randomized Controlled Trials.. Journal of the American Nutrition Association, 1-16. https://doi.org/10.1080/27697061.2023.2244031

Yes, L-theanine supplementation can modestly improve sleep quality and related outcomes, especially in people with sleep disturbances.

Evidence from Systematic Reviews and Meta-Analyses

Multiple recent systematic reviews and meta-analyses of randomized controlled trials show that L-theanine supplementation significantly improves subjective sleep onset latency (how quickly one falls asleep), daytime dysfunction, and overall subjective sleep quality in both healthy individuals and those with sleep problems (Bulman et al., 2025; Bulman et al., 2023). Effective doses typically range from 50–655 mg per day, with higher doses not providing additional benefit and possibly being detrimental (Bulman et al., 2023). Improvements have been observed in sleep onset, total sleep time, sleep efficiency, and reduced early awakenings (Bulman et al., 2023; Imafuku et al., 2023).

Clinical Trials and Special Populations

L-theanine has been shown to improve sleep efficiency and quality in children with ADHD, with no significant adverse effects at 400 mg/day (Lyon et al., 2011; Shahab et al., 2025; Innocenti et al., 2023). In adults, L-theanine (alone or in combination with other bioactives) has been associated with better sleep quality, though some studies using combinations did not find significant benefits over placebo (Gutiérrez-Romero et al., 2024; Stevens et al., 2017). In cancer patients with insomnia, L-theanine improved sleep more than placebo, but less than melatonin (Kurdi et al., 2024).

Conclusion

L-theanine supplementation is supported by moderate-to-strong evidence for improving subjective sleep quality, sleep onset, and daytime function, especially at moderate doses. It is generally safe, but more research is needed to determine optimal dosing and long-term effects.

References

Bulman, A., Cunha, N., Marx, W., Turner, M., McKune, A., & Naumovski, N. (2025). The effects of L-theanine consumption on sleep outcomes: A systematic review and meta-analysis.. Sleep medicine reviews, 81, 102076. https://doi.org/10.1016/j.smrv.2025.102076

Bulman, A., D'Cunha, N., Marx, W., Turner, M., Mckune, A., & Naumovski, N. (2023). The Effects of L-Theanine Supplementation on Quality of Sleep: A Systematic Review. The 14th European Nutrition Conference FENS 2023. https://doi.org/10.3390/proceedings2023091032

Gutiérrez-Romero, S., Torres-Narváez, E., Zamora-Gómez, A., Castillo-Castillo, S., Latorre-Velásquez, A., Betancourt-Villamizar, C., & Mendivil, C. (2024). Effect of a nutraceutical combination on sleep quality among people with impaired sleep: a randomised, placebo-controlled trial. Scientific Reports, 14. https://doi.org/10.1038/s41598-024-58661-z

Imafuku, F., Yamamoto, K., Tanaka, E., Aoki, R., & Nishino, S. (2023). Analysis of the Effects of Known Sleep-Support Supplements in Relation to Life Habits, Sleep Conditions, and Sleep Problems. Nutrients, 15. https://doi.org/10.3390/nu15102377

Lyon, M., Kapoor, M., & Juneja, L. (2011). The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial.. Alternative medicine review : a journal of clinical therapeutic, 16 4, 348-54.

Kurdi, M., As, A., Ladhad, D., Mitragotri, M., & Baiju, A. (2024). Comparison Between Efficacy of Oral Melatonin and Oral L-theanine in Improving Sleep in Cancer Patients Suffering From Insomnia: A Randomised Double-blinded Placebo-controlled Study. Indian Journal of Palliative Care, 30, 176 - 181. https://doi.org/10.25259/IJPC_89_2023

Stevens, N., Dorsett, J., DaBell, A., Eggett, D., Han, X., & Parker, T. (2017). Subjective assessment of the effects of an herbal supplement containing lavender essential oil on sleep quality: A randomized, double-blind, placebo-controlled crossover study. Cogent Medicine, 4. https://doi.org/10.1080/2331205X.2017.1380871

Shahab, S., Balushi, R., Qambar, A., Abdulla, R., Qader, M., Abdulla, S., & Jahrami, H. (2025). Efficiency of Different Supplements in Alleviating Symptoms of ADHD with or Without the Use of Stimulants: A Systematic Review. Nutrients, 17. https://doi.org/10.3390/nu17091482

Innocenti, A., Lentini, G., Rapacchietta, S., Cinnirella, P., Elia, M., Ferri, R., & Bruni, O. (2023). The Role of Supplements and Over-the-Counter Products to Improve Sleep in Children: A Systematic Review. International Journal of Molecular Sciences, 24. https://doi.org/10.3390/ijms24097821

The evidence for magnesium supplementation improving sleep is mixed, with some studies showing modest benefits and others finding little to no effect, especially in well-designed clinical trials.

Summary of Research Findings

Clinical Trial and Meta-Analysis Evidence

• Several randomized controlled trials (RCTs) and meta-analyses report small improvements in sleep onset latency (time to fall asleep) and subjective sleep quality with magnesium supplementation, particularly in older adults and those with insomnia symptoms. For example, one meta-analysis found a reduction in sleep onset latency by about 17 minutes, but the overall quality of evidence was low to very low, and improvements in total sleep time were not statistically significant (Mah & Pitre, 2021; Liaqat et al., 2023; Saba et al., 2022).
• Some recent RCTs in healthy adults and those with self-reported sleep problems found significant improvements in sleep quality, deep/REM sleep, and reduced stress with magnesium supplementation compared to placebo (Briskey et al., 2024; Breus et al., 2024; Hausenblas et al., 2024). However, these studies often have small sample sizes and short durations.

Observational and Mechanistic Studies

• Observational studies consistently show an association between higher magnesium intake/status and better sleep quality or longer sleep duration (Arab et al., 2022; Zhang et al., 2021). However, these studies cannot prove causation.
• Magnesium may influence sleep by modulating stress hormones (cortisol), melatonin, and neurotransmitters involved in sleep regulation (Khalid et al., 2024; Liaqat et al., 2023; Saba et al., 2022).

Limitations and Inconsistencies

• Results are inconsistent: Some RCTs show no significant benefit over placebo, and improvements may be limited to those with low magnesium status or specific populations (e.g., elderly, people with insomnia, or certain medical conditions) (Arab et al., 2022; Mah & Pitre, 2021; Zhao et al., 2025; Nielsen et al., 2010; Gallagher et al., 2024).
• The quality of evidence is often low, with small sample sizes, short follow-up, and risk of bias (Mah & Pitre, 2021; Rawji et al., 2024).

Conclusion

Magnesium supplementation may offer modest improvements in sleep quality or onset for some individuals, especially those with low magnesium or insomnia, but the overall evidence is inconsistent and of low quality. Larger, well-designed trials are needed to clarify its effectiveness for sleep in the general population.

References

Arab, A., Rafie, N., Amani, R., & Shirani, F. (2022). The Role of Magnesium in Sleep Health: a Systematic Review of Available Literature. Biological Trace Element Research, 201, 121-128. https://doi.org/10.1007/s12011-022-03162-1

Mah, J., & Pitre, T. (2021). Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis. BMC Complementary Medicine and Therapies, 21. https://doi.org/10.1186/s12906-021-03297-z

Khalid, S., Bashir, S., Mehboob, R., Anwar, T., Ali, M., Hashim, M., Waseem, H., & Basharat, S. (2024). Effects of magnesium and potassium supplementation on insomnia and sleep hormones in patients with diabetes mellitus. Frontiers in Endocrinology, 15. https://doi.org/10.3389/fendo.2024.1370733

Briskey, D., Erickson, J., Smith, C., & Rao, A. (2024). Wild Nutrition’s Food-Grown® Magnesium Supplementation Increases Sleep Quality and Sleep Duration and Reduces Stress in a Healthy Adult Population: A Double-Blind, Randomised, Placebo-Controlled Study. Food and Nutrition Sciences. https://doi.org/10.4236/fns.2024.157034

Breus, M., Hooper, S., Lynch, T., & Hausenblas, H. (2024). Effectiveness of Magnesium Supplementation on Sleep Quality and Mood for Adults with Poor Sleep Quality: A Randomized Double-Blind Placebo-Controlled Crossover Pilot Trial. Medical Research Archives. https://doi.org/10.18103/mra.v12i7.5410

Zhang, Y., Chen, C., Lu, L., Knutson, K., Carnethon, M., Fly, A., Luo, J., Haas, D., Shikany, J., & Kahe, K. (2021). Association of magnesium intake with sleep duration and sleep quality: findings from the CARDIA study.. Sleep. https://doi.org/10.1093/CDN/NZAB053_102

Hausenblas, H., Lynch, T., Hooper, S., Shrestha, A., Rosendale, D., & Gu, J. (2024). Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial. Sleep Medicine: X, 8. https://doi.org/10.1016/j.sleepx.2024.100121

Liaqat, A., Rizwan, B., Amjad, A., & Rasool, Z. (2023). Therapeutic Effect of Magnesium Supplementation in Improving Quality of Life among Elderly Insomniac Participants. Pakistan Journal of Health Sciences. https://doi.org/10.54393/pjhs.v4i09.995

Zhao, S., Hu, J., Yue, C., Tian, J., Zhou, S., & Zhu, Q. (2025). Dietary Magnesium Intake Is Associated With Self‐Reported Short Sleep Duration but Not Self‐Reported Sleep Disorder. Brain and Behavior, 15. https://doi.org/10.1002/brb3.70251

Nielsen, F., Johnson, L., & Zeng, H. (2010). Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep.. Magnesium research, 23 4, 158-68. https://doi.org/10.1684/mrh.2010.0220

Rawji, A., Peltier, M., Mourtzanakis, K., Awan, S., Rana, J., Pothen, N., & Afzal, S. (2024). Examining the Effects of Supplemental Magnesium on Self-Reported Anxiety and Sleep Quality: A Systematic Review. Cureus, 16. https://doi.org/10.7759/cureus.59317

Gallagher, C., Austin, V., Dunlop, K., Dally, J., Taylor, K., Pullinger, S., & Edwards, B. (2024). Effects of Supplementing Zinc Magnesium Aspartate on Sleep Quality and Submaximal Weightlifting Performance, following Two Consecutive Nights of Partial Sleep Deprivation. Nutrients, 16. https://doi.org/10.3390/nu16020251

Saba, S., Faizi, F., Sepandi, M., & Nehrir, B. (2022). Effect of short-term magnesium supplementation on anxiety, depression and sleep quality in patients after open-heart surgery. Magnesium research, 35 2, 62-70. https://doi.org/10.1684/mrh.2022.0503

Yes, NAD+ precursor supplementation can enhance cellular energy metabolism, especially in conditions of NAD+ deficiency or metabolic stress, but effects in healthy humans are modest.

Evidence from Clinical and Preclinical Studies

• Mechanistic Role: NAD+ is a critical cofactor for mitochondrial energy production, redox reactions, and cellular metabolism. Supplementation with NAD+ precursors (such as nicotinamide riboside, nicotinamide mononucleotide, and nicotinic acid) reliably increases NAD+ levels in blood and tissues, supporting cellular energy pathways (Dellinger et al., 2017; Huang, 2022).
• Preclinical and Disease Models: Animal and cell studies consistently show that NAD+ precursor supplementation improves mitochondrial function, ATP production, and reduces oxidative stress, especially in models of aging, neurodegeneration, and metabolic disease (Qader et al., 2025; Huang, 2022).
• Human Clinical Trials: In humans, NAD+ precursor supplementation increases NAD+ concentrations and can improve some metabolic markers, such as lipid profiles and glucose metabolism, particularly in individuals with metabolic disorders or older adults (Sohouli et al., 2024; Zhong et al., 2022; Kuerec et al., 2024; Huang, 2022). However, the direct impact on energy metabolism in healthy individuals is limited or inconsistent (Nkrumah-Elie et al., 2021; Zhong et al., 2022; Barker et al., 2022).

Meta-Analyses and Systematic Reviews

• Glucose and Lipid Metabolism: Meta-analyses show that NAD+ precursors can improve lipid profiles and, in some cases, glucose metabolism, but may also slightly increase blood glucose in some populations (Sohouli et al., 2024; Zhong et al., 2022). The most pronounced benefits are seen in those with cardiovascular disease, dyslipidemia, or metabolic syndrome, rather than in healthy people (Zhong et al., 2022; Oliveira-Cruz et al., 2023).
• Physical Performance: Evidence for improved exercise performance or muscle energy in healthy humans is limited, though some studies report increased walking distance or improved subjective well-being in older adults (Nkrumah-Elie et al., 2021; Kuerec et al., 2024; Huang, 2022).

Conclusion

NAD+ precursor supplementation enhances cellular energy metabolism in preclinical and disease models, and can improve metabolic health in at-risk human populations. However, the effect in healthy individuals is modest, with the greatest benefits observed in those with NAD+ depletion or metabolic dysfunction.

References

Sohouli, M., Tavakoli, S., Reis, M., Hekmatdoost, A., & Guimarães, N. (2024). Changes in glucose metabolism, C-reactive protein, and liver enzymes following intake of NAD + precursor supplementation: a systematic review and meta‐regression analysis. Nutrition & Metabolism, 21. https://doi.org/10.1186/s12986-024-00812-0

Nkrumah-Elie, Y., Ishtiaq, Y., Idoine, R., Erickson, A., Rosene, M., & Shao, A. (2021). Dietary Supplementation with NAD+ Precursors to Support Exercise: An Evaluation of the Clinical Evidence. The FASEB Journal, 35. https://doi.org/10.1096/FASEBJ.2021.35.S1.05282

Zhong, O., Wang, J., Tan, Y., Lei, X., & Tang, Z. (2022). Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis. Nutrition & Metabolism, 19. https://doi.org/10.1186/s12986-022-00653-9

Kuerec, A., Wang, W., Yi, L., Tao, R., Lin, Z., Vaidya, A., Pendse, S., Thasma, S., Andhalkar, N., Avhad, G., Kumbhar, V., & Maier, A. (2024). Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration. Mechanisms of Ageing and Development, 218. https://doi.org/10.1016/j.mad.2024.111917

Oliveira-Cruz, A., Macedo-Silva, A., Silva-Lima, D., Sanchez-Almeida, J., Cruz-Coutinho, L., Tavares, M., & Majerowicz, D. (2023). Effects of Supplementation with NAD  +   Precursors on Metabolic Syndrome Parameters: A Systematic Review and Meta-Analysis. Hormone and Metabolic Research. https://doi.org/10.1055/a-2382-6829

Dellinger, R., Santos, S., Morris, M., Evans, M., Alminana, D., Guarente, L., & Marcotulli, E. (2017). Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging and Mechanisms of Disease, 3. https://doi.org/10.1038/s41514-017-0016-9

Qader, M., Hosseini, L., Abolhasanpour, N., Oghbaei, F., Maghsoumi-Norouzabad, L., Salehi-Pourmehr, H., Fattahi, F., & Sadeh, R. (2025). A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models. BMC Neuroscience, 26. https://doi.org/10.1186/s12868-025-00937-9

Barker, F., Hart, A., Sayer, A., & Witham, M. (2022). Effects of nicotinamide adenine dinucleotide precursors on measures of physical performance and physical frailty: A systematic review. JCSM Clinical Reports, 7, 106 - 93. https://doi.org/10.1002/crt2.56

Huang, H. (2022). A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Frontiers in Aging, 3. https://doi.org/10.3389/fragi.2022.851698

Yes, NAD+ precursor supplementation shows promise for supporting brain health, especially in preclinical studies, but human evidence is still emerging.

Evidence from Preclinical and Animal Studies

Extensive research in rodent models demonstrates that NAD+ precursors—such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide (NAM)—can improve learning, memory, and cognitive function in conditions like aging, Alzheimer’s disease, diabetes, traumatic brain injury, and vascular dementia. These benefits are linked to reduced inflammation, oxidative stress, and apoptosis, as well as enhanced mitochondrial function and DNA repair in the brain (Qader et al., 2025; Hosseini et al., 2021). NAD+ precursors also activate sirtuins, which help protect neurons and support synaptic plasticity, both critical for cognitive health (Qader et al., 2025).

Human Studies and Clinical Insights

Human trials are more limited but show that NAD+ precursors (especially NR) can safely and sustainably increase NAD+ levels in older adults, which is associated with improved cellular metabolism and DNA repair—processes important for brain health (Dellinger et al., 2017). Some small clinical studies in Alzheimer’s disease report improvements in biomarkers and cognitive measures after NR supplementation, but larger and longer-term trials are needed to confirm these effects (Alghamdi & Braidy, 2024). In other conditions, such as chronic fatigue syndrome, NADH supplementation has reduced cognitive fatigue and improved quality of life, suggesting potential neuroprotective effects (Castro-Marrero et al., 2021).

Conclusion

NAD+ precursor supplementation is strongly neuroprotective in animal models and increases NAD+ in humans, but definitive proof of cognitive benefits in healthy people or those at risk for decline is still lacking. More large-scale, long-term human studies are needed.

References

Qader, M., Hosseini, L., Abolhasanpour, N., Oghbaei, F., Maghsoumi-Norouzabad, L., Salehi-Pourmehr, H., Fattahi, F., & Sadeh, R. (2025). A systematic review of the therapeutic potential of nicotinamide adenine dinucleotide precursors for cognitive diseases in preclinical rodent models. BMC Neuroscience, 26. https://doi.org/10.1186/s12868-025-00937-9

Hosseini, L., Mahmoudi, J., Pashazadeh, F., Salehi-Pourmehr, H., & Sadigh-Eteghad, S. (2021). Protective Effects of Nicotinamide Adenine Dinucleotide and Related Precursors in Alzheimer’s Disease: A Systematic Review of Preclinical Studies. Journal of Molecular Neuroscience, 71, 1425 - 1435. https://doi.org/10.1007/s12031-021-01842-6

Alghamdi, M., & Braidy, N. (2024). Supplementation with NAD+ Precursors for Treating Alzheimer’s Disease: A Metabolic Approach. Journal of Alzheimer's Disease, 101, S467 - S477. https://doi.org/10.3233/JAD-231277

Castro-Marrero, J., Segundo, M., Lacasa, M., Martínez-Martínez, A., Sentañes, R., & Alegre-Martín, J. (2021). Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 13. https://doi.org/10.3390/nu13082658

Dellinger, R., Santos, S., Morris, M., Evans, M., Alminana, D., Guarente, L., & Marcotulli, E. (2017). Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging and Mechanisms of Disease, 3. https://doi.org/10.1038/s41514-017-0016-9

Yes, taking probiotics can boost the immune system, but the effects are generally modest, strain-specific, and more pronounced in certain populations.

Yvidét: Although the overall research shows evidence, please note that the effects were modest in healthy adults.

Immune-Boosting Effects and Mechanisms

Probiotics enhance immune function through several mechanisms, including strengthening the intestinal barrier, modulating gut microbiota, and directly interacting with immune cells. They can increase the production of immunoglobulins (such as IgA), stimulate regulatory T cells, and modulate cytokine responses, leading to improved immune regulation and reduced inflammation (Javanshir et al., 2021; Lehtoranta et al., 2020; Tegegne & Kebede, 2022; Pishkar et al., 2023; Morshedi et al., 2019; Pyo et al., 2024). Probiotics also promote the activity of natural killer (NK) cells and phagocytes, which are important for innate immunity (Kazemi et al., 2020; Miller et al., 2019; Finamore et al., 2019; Nisaa et al., 2025).

Evidence from Clinical Studies and Meta-Analyses

• Meta-analyses and systematic reviews show that probiotics can lead to small but significant increases in certain immune cell counts (e.g., T cells, NK cells, monocytes) and activity, especially in elderly or immunocompromised individuals (Kazemi et al., 2020; Miller et al., 2019; Finamore et al., 2019; Nisaa et al., 2025).
• Randomised controlled trials in healthy adults report limited but sometimes significant effects on immune and inflammatory markers, with some studies showing increased antibody production and improved responses to vaccines (Mohr et al., 2020; Yeh et al., 2018; Chen et al., 2022; Khalesi et al., 2018).
• Strain-specific effects: The immune benefits depend on the probiotic strains used, dosage, and individual host factors. Not all probiotics have the same impact (Lehtoranta et al., 2020; Kazemi et al., 2020; Tegegne & Kebede, 2022; Yeh et al., 2018; Picó-Monllor et al., 2021).

Conclusion

Probiotics can modestly boost immune function, particularly by enhancing gut and mucosal immunity, but the effects are variable and depend on the specific strains and populations studied. More research is needed to determine optimal strains and dosing for consistent immune benefits.

References

Javanshir, N., Hosseini, G., Sadeghi, M., Esmaeili, R., Satarikia, F., Ahmadian, G., & Allahyari, N. (2021). Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. Biological Procedures Online, 23. https://doi.org/10.1186/s12575-021-00160-w

Lehtoranta, L., Latvala, S., & Lehtinen, M. (2020). Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review. Nutrients, 12. https://doi.org/10.3390/nu12103163

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