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Physionic: Daily Summaries Delivered
by Nicolas Verhoeven
I simplify scientific studies for you. If you want a transparent, detailed source of information for your nutrition, health, performance, etc., welcome to Physionic!
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- 3 days ago13 min
FDA approved Arthritis Drug shown to Stop Aggressive Cancer!
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with Biorender0:00 - Introduction0:27 - Genetics and Mitochondria: Married7:50 - Reusing Old Medicine to Fight CancerReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][Study 1115] Un W, Hao C, Wang Z, et al. SWI/SNF subunit SMARCD1 deficiency promotes clear cell renal cell carcinoma progression via mitochondrial reprogramming. Nature Communications. Published online October 8, 2026. doi:10.1038/s41467-026-78285-3.[Study 1116] Bezwada D, Perelli L, Lesner NP, et al. Mitochondrial complex I promotes kidney cancer metastasis. Nature. 2024;633(8031):923–931. doi:10.1038/s41586-024-07812-3.Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 5 days ago7 min
These Two Molecules are Pushing Anti-Aging Science Forward!
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with BiorenderAnti-Aging Series: https://www.youtube.com/playlist?list=PLwiri7XRU2i-HLExt7W-5qp_z2tIP_UvU0:00 - Introduction0:55 - Senolytics: An Advanced Future3:44 - Bone, Kidneys, Liver, and…5:57 - Molecules and ConsiderationsReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][Study 1093] Hickson LJ, Langhi Prata LGP, Bobart SA, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019;47:446–456. doi:10.1016/j.ebiom.2019.08.069.[Study 1094] Farr JN, Atkinson EJ, Achenbach SJ, et al. Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial. Nat Med. 2024;30:2605–2612. doi:10.1038/s41591-024-03096-2.[Study 1095] Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554–563. doi:10.1016/j.ebiom.2018.12.052.[Study 1096] Martyanov V, Whitfield ML, Varga J. Senescence signature in skin biopsies from systemic sclerosis patients treated with senolytic therapy: potential predictor of clinical response? Arthritis Rheumatol. 2019;71(10):1766–1767. doi:10.1002/art.40934.[Study 1097] Hambright WS, Duke VR, Goff AD, et al. Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes. Aging Cell. 2024;23. doi:10.1111/acel.14113.[Study 1098] Gao X, Roder J, Minas LT, et al. Effects of two fisetin dosing regimens on reducing senescence-related genes in peripheral blood mononuclear cells in aged humans. Preprints. Published online July 22, 2026. doi:10.20944/preprints202607.1685.v1.[Study 1099] Koning M, Kovynev A, Fondevila MF, et al. Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial. Nat Metab. 2026. doi:10.1038/s42255-026-01643-4.Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 1 weeks ago14 min
‘An Incredibly Common Food That Melts Clogged Arteries (Most Eat Them Wrong)’
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with Biorender0:00 - Introduction1:08 - Artery Damage: Origin of Plaque?5:20 - Lycopene reduces Oxidation9:12 - A 'Healthy' Fat?9:50 - Cardiovascular Disease Outcomes and Plaque Reversal12:55 - Main PointsReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][1] Constantinides P, Harkey M. Ann N Y Acad Sci. 1990;598:113–124. DOI: 10.1111/j.1749-6632.1990.tb42283.x[2] Faggiotto A, et al. Arteriosclerosis. 1984;4:323–340. DOI: 10.1161/01.ATV.4.4.323[3] Huang L, et al. Nature. 2019;569:565–569. DOI: 10.1038/s41586-019-1140-4[4] Juul K, et al. Circulation. 1996;94:1698–1704. DOI: 10.1161/01.CIR.94.7.1698[5] Chang MY, et al. J Lipid Res. 2001;42:824–833. DOI: 10.1016/S0022-2275(20)31645-X[6] Story EN, et al. Annu Rev Food Sci Technol. 2010;1:189–210. DOI: 10.1146/annurev.food.102308.124120[7] Ghaffari MA, Ghiasvand T. J Food Biochem. 2011;35:228–240. DOI: 10.1111/j.1745-4514.2010.00378.x[8] Romanchik JE, et al. J Nutr Biochem. 1997;8:681–688. DOI: 10.1016/S0955-2863(97)00119-8[Study 592] Sesso HD, et al. J Nutr. 2003;133:2336–2341. DOI: 10.1093/jn/133.7.2336[Study 587] Zou ZY, et al. Br J Nutr. 2014;111:474–480. DOI: 10.1017/S0007114513002730[9] Schwab US, et al. J Nutr. 1998;128:1703–1709. DOI: 10.1093/jn/128.10.1703[10] Lichtenstein AH, et al. Arterioscler Thromb. 1994;14:168–175. DOI: 10.1161/01.ATV.14.1.168[11] Kiecolt-Glaser JK, et al. Brain Behav Immun. 2012;26:988–995. DOI: 10.1016/j.bbi.2012.05.011[12] Dong Y, et al. Nutrients. 2022;14:5307. DOI: 10.3390/nu14245307[13] Nestel P, et al. Am J Clin Nutr. 2002;76:326–330. DOI: 10.1093/ajcn/76.2.326[14] Sanders TA, et al. Am J Clin Nutr. 2011;94:973–980. DOI: 10.3945/ajcn.111.018036[15] Chan DC, et al. Nutr Metab Cardiovasc Dis. 2016;26:1140–1145. DOI: 10.1016/j.numecd.2016.07.012[16] Skulas-Ray AC, et al. Am J Clin Nutr. 2011;93:243–252. DOI: 10.3945/ajcn.110.003871[17] Ballantyne CM, et al. Am J Cardiol. 2012;110:984–992. DOI: 10.1016/j.amjcard.2012.05.031[18] Bays HE, et al. Am J Cardiol. 2011;108:682–690. DOI: 10.1016/j.amjcard.2011.04.015[19] Budoff MJ, et al. Eur Heart J. 2020;41:3925–3932. DOI: 10.1093/eurheartj/ehaa652[20] Kita Y, et al. J Am Heart Assoc. 2020;9:e015593. DOI: 10.1161/JAHA.119.015593[21] Albert MA, et al. JAMA. 2001;286:64–70. DOI: 10.1001/jama.286.1.64[22] Ridker PM, et al. N Engl J Med. 2008;359:2195–2207. DOI: 10.1056/NEJMoa0807646[23] Manson JE, et al. N Engl J Med. 2019;380:23–32. DOI: 10.1056/NEJMoa1811403[24] ASCEND Study Collaborative Group, et al. N Engl J Med. 2018;379:1540–1550. DOI: 10.1056/NEJMoa1804989[25] Bhatt DL, et al. N Engl J Med. 2019;380:11–22. DOI: 10.1056/NEJMoa1812792Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 1 weeks ago4 min
Put these in your Ears and Protect your Brain!
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with Biorender0:00 - Introduction1:29 - Long-term consequences4:28 - Social Isolation and More Considerations6:15 - A Disheartening Twist7:40 - Retwisting to a Heartening Twist, or something like that...8:54 - 24% Increased Risk10:04 - Use TheseReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][Study 346] Livingston et al. Dementia prevention and care: 2024 Lancet Commission. Lancet. 2024.[Study 1103] Yeo et al. Hearing devices, cognitive decline, and dementia: meta-analysis. JAMA Neurol. 2023.[Study 1104] Peribáñez García et al. Audiometric hearing loss, cognitive impairment, and dementia: meta-analysis. Am J Otolaryngol. 2026.[Study 1105] Lin et al. Hearing loss and cognitive decline in older adults. JAMA Intern Med. 2013.[Study 1106] Tai et al. Hearing impairment, hearing aids, and cognitive impairment: TLSA. BMC Geriatr. 2021.[Study 1107] Bucholc et al. Hearing aids, MCI-to-dementia conversion, and dementia progression. Alzheimers Dement (N Y). 2021.[Study 1108] Amieva et al. Hearing problems, mortality, depression, disability, and dementia: 25-year study. J Gerontol A. 2018.[Study 1109] Mahmoudi et al. Hearing aids and time to dementia, depression, or falls diagnosis. J Am Geriatr Soc. 2019.[Study 1110] Lin. Hearing loss and cognition in older US adults. J Gerontol A. 2011.[Study 1111] Davies et al. Hearing impairment and incident dementia: ELSA. J Am Geriatr Soc. 2017.[Study 1112] Chang et al. Hearing loss severity and dementia risk in South Korea. Sci Rep. 2020.[Study 1113] Lin et al. Hearing intervention and cognitive decline: ACHIEVE randomized trial. Lancet. 2023.[A] Fig. 3: Global cognition only—top two graphs (primary, secondary, and sensitivity analyses).[Study 1114] Chen et al. Hearing intervention in older adults with MCI: CHOICE randomized trial. JAMA Neurol. 2026.[1] Golub et al. Hearing loss and incident dementia in a multiethnic cohort. J Am Geriatr Soc. 2017.Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 2 weeks ago13 min
Dr. Rhonda Patrick: ‘Scientists discovered a Supplement that Repairs Aging Mitochondria!’
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with BiorenderDr. Patrick's Video: https://www.youtube.com/shorts/1Du-MKJOjk80:00 - Introduction1:05 - It Clears out Old Mitochondria!4:30 - It Rejuvenates the Immune System!6:54 - VO2 Boost, Anti-Aging Benefits11:52 - A Huge Caveat!13:22 - Main PointsReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][1] Singh A, D'Amico D, Andreux PA, et al. Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population. Eur J Clin Nutr. 2022;76(2):297-308. doi:10.1038/s41430-021-00950-1 [2] Alpert A, Pickman Y, Leipold M, et al. A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring. Nat Med. 2019;25(3):487-495. doi:10.1038/s41591-019-0381-y [3] Imboden MT, Harber MP, Whaley MH, Finch WH, Bishop DL, Kaminsky LA. Cardiorespiratory fitness and mortality in healthy men and women. J Am Coll Cardiol. 2018;72(19):2283-2292. doi:10.1016/j.jacc.2018.08.2166. [6] Bailey SJ, Winyard P, Vanhatalo A, et al. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009;107(4):1144-1155. doi:10.1152/japplphysiol.00722.2009[7] Lansley KE, Winyard PG, Bailey SJ, et al. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc. 2011;43(6):1125-1131. doi:10.1249/MSS.0b013e31821597b4[8] Cuenca E, Jodra P, Pérez-López A, et al. Effects of Beetroot Juice Supplementation on Performance and Fatigue in a 30-s All-Out Sprint Exercise: A Randomized, Double-Blind Cross-Over Study. Nutrients. 2018;10(9):1222. Published 2018 Sep 4. doi:10.3390/nu10091222[Study 230] D'Amico D, Olmer M, Fouassier AM, et al. Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis. Aging Cell. 2022;21(8):e13662. doi:10.1111/acel.13662[Study 232] Singh A, D'Amico D, Andreux PA, et al. Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med. 2022;3(5):100633. doi:10.1016/j.xcrm.2022.100633[Study 549] Denk D, Singh A, Kasler HG, et al. Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Nat Aging. 2025;5(11):2309-2322. doi:10.1038/s43587-025-00996-xPlease use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 2 weeks ago9 min
Why is Cheese immune to raising Cardiovascular Disease risk?
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with BiorenderMain Analysis: https://www.youtube.com/watch?v=9i121BcPYlk&t=231s0:00 - Introduction1:03 - Assumptions make an Ass out of You and Me4:33 - The Matrix: Not the Movie6:57 - Keep this in mind...References [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][Study 1100] Feeney EL, Barron R, Dible V, et al. Dairy matrix effects: response to consumption of dairy fat differs when eaten within the cheese matrix—a randomized controlled trial. American Journal of Clinical Nutrition. 2018;108(4):667–674. doi:10.1093/ajcn/nqy146[Study 1101] Soerensen KV, Thorning TK, Astrup A, Kristensen M, Lorenzen JK. Effect of dairy calcium from cheese and milk on fecal fat excretion, blood lipids, and appetite in young men. American Journal of Clinical Nutrition. 2014;99(5):984–991. doi:10.3945/ajcn.113.077735[Study 1102] Rosqvist F, Smedman A, Lindmark-Månsson H, et al. Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study. American Journal of Clinical Nutrition. 2015;102(1):20–30. doi:10.3945/ajcn.115.107045Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 2 weeks ago9 min
TUDCA: A New Way of Addressing Insulin Resistance
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with Biorender0:00 - Introduction1:50 - TUDCA2:59 - Mechanisms of Intrigue4:18 - TUDCA Results7:50 - Dosing & ConsiderationsReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][1] She J, Tuerhongjiang G, Guo M, et al. Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner. Cell Metab. 2024;36(2):408–421.e5. doi:10.1016/j.cmet.2023.12.027.[2] Crosignani A, Battezzati PM, Cestari C, et al. Tauroursodeoxycholic acid for the treatment of chronic hepatitis: a multicentre dose-response study. Hepatol Res. 1998;13:10–19.[3] Ma H, Zeng M, Han Y, et al. A multicenter, randomized, double-blind trial comparing the efficacy and safety of TUDCA and UDCA in Chinese patients with primary biliary cholangitis. Medicine (Baltimore). 2016;95(47). doi:10.1097/MD.0000000000005391.[4] Pan XL, Zhao L, Li L, et al. Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: a double-blind randomized controlled trial. J Huazhong Univ Sci Technolog Med Sci. 2013;33(2):189–194. doi:10.1007/s11596-013-1095-x.[5] Poupon RE, Poupon R, Balkau B; UDCA-PBC Study Group. Ursodiol for the long-term treatment of primary biliary cirrhosis. N Engl J Med. 1994;330(19):1342–1347.[Study 1078] Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010;59(8):1899–1905. doi:10.2337/db10-0308.[Study 1079] Walsh LK, Restaino RM, Neuringer M, Manrique C, Padilla J. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load. Clin Sci (Lond). 2016;130(21):1881–1888. doi:10.1042/CS20160501.[Study 1080] Panzhinskiy E, Hua Y, Culver B, Ren J, Nair S. Endoplasmic reticulum stress upregulates protein tyrosine phosphatase 1B and impairs glucose uptake in cultured myotubes. Diabetologia. 2013;56(3):598–607. doi:10.1007/s00125-012-2782-z.Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
- 3 weeks ago9 min
The ‘Berberine Signature’: A New Heart Disease Protection Uncovered!
*JOIN THE PHYSIONIC INSIDERS [PREMIUM CONTENT]*Join the Physionic Insiders: https://bit.ly/PhysionicInsiders2 *HEALTH AUTONOMY [COURSE]*Learn to Analyze & Apply Studies for Yourself: https://bit.ly/healthautonomy*JOIN THE COMMUNITY*Join my Community [It’s Free!]: https://bit.ly/PhysionicCommunity2*EMAIL LIST*1-2 Weekly Email of Value [It’s Free!]: http://bit.ly/2AXIzK6*HIRE ME FOR CONSULTING:* Consulting: https://bit.ly/3dmUl2H Created with Biorender0:00 - IntroductionYou talkin’ to me, ApoB?A Berberine Story: Genes, Associations, and TrialsReferences [Funding/Conflicts are provided in the free article (found in the email list and Physionic Community Article Library)][1] Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008;57(5):712–717. doi:10.1016/j.metabol.2008.01.013[Study 1076] Zhao JV, Sarsani V, Chen B, Yun H, Hu J, Liang L. Berberine signature and cardiometabolic diseases using randomized controlled trial, cohort study and Mendelian randomization. npj Cardiovasc Health. 2026;3(1):15. doi:10.1038/s44325-026-00113-w[Study 1077] Zhao JV, Chen B, Chan YH, et al. Sex-specific lipid, apolipoprotein B, and lipoprotein(a) responses to berberine based on 2 randomized placebo-controlled trials. JACC Asia. Published online July 11, 2026. doi:10.1016/j.jacasi.2026.06.011Please use the following link to submit your critique: https://bit.ly/PhysionicCritiqueDisclaimer: None of the information provided by this brand is a replacement for your physician's advice. This brand is information for the sake of knowledge and the options of choice it provides, not in any way a personalized prescription. Please consult your physician before making any health related changes.
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