Introduction

“Mr. President, A Remarkable Medicine, Has Been Overlooked.” – Jack Dreyfus 

In 1963, Jack Dreyfus (1913-2009), published his writings by that title after discovering phenytoin, a one-hundred-year-old seizure medication, with unexpected mood-elevating and calming effects.

But what led him to this discovery?

With the advent of the Dreyfus Fund, in the 1950s Dreyfus revolutionized the mutual fund industry. Known as the “Lion of Wall Street,” Dreyfus invested in high growth companies rather than the staid dividend paying blue chip stocks, a novel concept at the time.  

But his drive for success led him to experience depression, and so Dreyfus went on a quest for a cure; that’s when he found phenytoin. In short order, his mind cleared, he was able to sleep normally, his depression lifted, and his career path, with an added twist, continued.

Such was his relief from his depression, Dreyfus vowed to “spread the word” to others.  And right on cue, the AMA and the Food and Drug Administration took exception to his writings—after all, it is not like he is a doctor or anything.

Dreyfus dedicated nearly $80 million to studying the uses of phenytoin. Written as a medical mystery, Dreyfus uncovered over 70 symptoms and disorders improved with phenytoin therapy.  The book was Jack’s plea to then President John F. Kennedy to make phenytoin available to the whole world.

Loving a good “Who done it?” and fascinated by medical history, I read Dreyfus’ story shortly after discovering another substance with a broad range of efficacy hidden in plain sight.  By connecting the dots in two of my favorite remedies, Longevinex and Advantage, I felt the same powerful, irresistible urge, a “white hot imperative,” that thing that one has to do to make one’s life meaningful, no matter what, to bring their main ingredient, resveratrol, with more than fifty ways to improve health to my audience’s attention.

The Remarkable Supplement Has Historically Been Overlooked: The Miracle of Resveratrol 

A polyphenol compound found in grapes, berries, peanuts, red wine, and Japanese knotweed, resveratrol is renowned for its anti-inflammatory, antioxidant, and anti-aging activities. ^(5-7)  Resveratrol protects the body against oxidative damage, termed reactive oxidative species (ROS), caused by free radicals while simultaneously reducing the harmful effects of excess androgens, insulin resistance, and chronic degenerative diseases. ⁽⁸⁾ 

 A perusal of a multitude of online supplement companies reveals well over 350 types, brands, and combinations of resveratrol.  What do we make of this array? How do wedecide which ones deserve our attention?  And no, your aunt’s nephew’s third cousin, that twenty-two-year-old brat you hated as a kid who is now in optometry school in Indianapolis, opinion doesn’t count. Instead, and, oh I hate to say it this way.  Here goes. Don’t hate me. ‘‘Trust the science.” (™) 

“The Science”

Two main types of resveratrol exist. The more common “cis” form has its atoms on the same side of a “backbone” double bond, creating a zig-zag or bent shape to its structure. 

The more potent “trans” form is a straighter molecule, positioning its’ atoms on the opposite side of its double bond.  

“Cis”-resveratrol is effective as an anti-inflammatory agent. “Trans”-resveratrol exhibits both anti-inflammatory and antioxidant activity.  Trans-resveratrol is more stable, more readily absorbed, and a more biologically active molecule. ⁽¹⁰⁾  

By eliminating the “cis” resveratrol products, we whittle down our list of three hundred and fifty compounds to less than fifty. Fifty is better than three hundred and fifty, but still too many. 

We need to dive deeper.  Which of the myriad of benefits noted above that we see from resveratrol are most important?  It comes down to individual circumstances of course, but from my lens over the targets of both medical repair and longevity, here are my top five go-to’s:
 

1. Resveratrol reduces inflammation:

• • Resveratrol reduces oxidative stress, an imbalance between the production of reactive oxygen species (ROS), essentially “wear and tear on the body, and the ability of the body’s natural antioxidant defenses to neutralize them. This imbalance leads to inflammation, cellular damage, and insulin resistance. ⁽¹¹⁾

• • Resveratrol reduces inflammatory cytokines, small proteins essential for cell-to-cell communication in the immune system. Cytokine proteins regulate inflammation, hematopoiesis, and other immune responses. ⁽¹²⁾  RSV reduces inflammatory cytokines TNF-α, IL-1β, IL-6, and IFN-γ while inducing the anti-inflammatory cytokine IL-10.(13)

2. Resveratrol improves HDL (Good) Cholesterol) and Reduces LDL (Bad cholesterol):

• • A study of middle-aged and elderly mice found a significant difference in cholesterol levels if treatments started early. (5-month-old mice are equivalent to ages 39-47 in human years.  7-month-old mice equal ages 56-69). (14)

• • HMG-Co synthase and reductase are the enzymes that control cholesterol synthesis.

• • On average, resveratrol reduces total cholesterol by 7.65 mg/dL (15)

3. Increases Insulin Sensitivity (16)

• • Resveratrol improves insulin utilization by reducing inflammation and cholesterol levels, decreasing vasoconstriction and vascular remodeling to lessen the ischaemic environment for tissues.  

• • Improved blood flow to tissues counteracts the vasoconstriction caused by hyperinsulinemia, resulting in improved glucose utilization. 

• • Resveratrol activates Sirtuins, longevity-inducing proteins that regulate cellular processes, including aging, cell death, and stress resistance.

• • Resveratrol activates NAD-dependent proteins like estradiol (E2). (17)  RSV preferentially binds estrogen receptors (ER), promoting glucose transporter type-4 (GLUT4) translocation and increasing glucose uptake. (18)

• • Resveratrol improves insulin resistance by reducing oxidative stress. (11)

4. Enhances Cardioprotection (19)

• • Resveratrol boosts nitric oxide (NO) levels, enhancing blood flow to the heart and brain, and lowers lactate dehydrogenase levels. It reduces the occurrence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF), while protecting blood vessels, lowering LDL cholesterol, and preventing blood clots. Moderate red wine consumption (1-2 drinks or 150-300 mL/day) is associated with a reduced cardiovascular risk (RR: 0.66, 95% CI 0.57-0.75), unlike white wine. 

5. Has Antineoplastic Effects 

• • RSV activates the Nrf2 gene expression to downgrade cancer-inducing catechol estradiol. (22)

• • Resveratrol suppresses tumor regrowth after therapy with cisplatin. RSV has the potential to prolong disease-free living. (23)

• • Resveratrol’s antioxidant and anti-inflammatory mitigate chemo-radiation toxicity in normal tissue.(24)

• • RSV sensitizes cancer cells to both chemotherapy drugs and radiation. (25)

• • RSV slows the growth of certain types of cancer by reducing inflammation. (26)

• • Preclinical cancer studies with at least a modicum of success in reducing symptoms or prolonging survival
    include: (27)
    
    •  
    • • Skin cancer
    • • Breast cancer
    • • Colorectal Cancer
    • • Prostate Cancer
    • • Liver cancer
    • • Pancreatic cancer
    • • Lung Cancer

Thus we are back to our original question: How do we choose from the fifty or so medically active trans-resveratrol products?

The ‘Source’ and Peripherals are With You

Of all the sources of resveratrol, the most potent, most bioavailable, and most sought-after is that derived from Japanese knotweed. (28) Japanese knotweed grows in dense stands, quickly reaching incredible heights, making it almost impossible for predators to feed on or trample it. Its roots are also incredibly hardy, making a strand of Japanese knotweed a reliable source.  

Longevinex and Longevinex Advantage’s resveratrol is derived solely from Japanese knotweed. In addition to their Japanese knotweed-based resveratrol content, the Peripherals make Longevinex and Longevinex Advantage shine.

Longevinex, the original’s peripherals include quercetin, rice bran IP6, vitamin D3, nucleotides, beta-cyclodextrin, fisetin, beta-glucan, and vitamin B1 as benfotiamine.

Longevinex Advantage mimics its parent, Longevinex, while adding lutein/zeaxanthin for eye protection and pure hyaluronan to thicken hair, smooth the skin, lubricate the joints, and cushion the nerves. (29)

The Main Ingredient-Trans-Resveratrol

Trans-resveratrol (TRV) promotes nitric oxide, enhances endothelial (blood vessel wall) function and blood flow while reducing arterial stiffness, inflammation, oxidative stress, and (bad) LDL cholesterol.  (30)

TRV crosses the blood-brain barrier, reducing neuronal inflammation and oxidative stress. TRV slows the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease. (31)

TRV activates SIRT1, promoting mitochondrial well-being, cellular energy production, and DNA repair mechanisms while slowing senescence and aging.  (32)

The Peripherals

1. 1. Quercetin: Quercetin, a potent antioxidant flavonoid, works synergistically with trans-resveratrol to promote vasodilation, improve circulation, and reduce blood pressure and LDL cholesterol, lowering the risk of blood clots. It protects neurons from oxidative stress, supporting brain health and reducing neurodegenerative risks. Additionally, quercetin activates key cellular pathways like AMPK and autophagy, reducing senescent cells to support longevity.

   2. Vitamin D3 (36): Vitamin D3 is essential for reducing inflammation, supporting immune health, and maintaining strong bones. It regulates blood pressure, aids insulin metabolism, and stabilizes mood. Vitamin D3 also plays a role in cognitive function, reducing neurodegenerative risks, and supports restful sleep. Additionally, it influences hormone production, including testosterone, by aiding in cholesterol conversion, and low levels are linked to mood and cognitive issues like anxiety and cognitive decline.
   3. Cyclodextrin: Obtained from starch and composed of seven glucose units in a ring-like structure, beta-cyclodextrin is used as an inclusion complex to enhance the absorption and bioavailability of other ingredients. (42) By forming complexes with various compounds, beta-cyclodextrin improves resveratrol’s solubility, stability, and bioavailability in Longevinex.  Utilized in the food and fragrance industries, beta-cyclodextrin preserves sensitive flavors and aromas, preventing their degradation due to exposure to light, heat, or oxidation.  On a global scale, beta-cyclodextrins form inclusion complexes with air pollutants and soil contaminants, aiding environmental cleanup efforts. (43)

   4. Rice Bran IP6IP6 (inositol hexaphosphate) from rice bran is a powerful antioxidant that boosts immune health and cellular integrity, promoting healthy cell growth. It helps reduce LDL cholesterol absorption, decreasing cardiac disease risk, and lowers hyperglycemia risk associated with high-fat diets. Additionally, IP6 supports an anti-inflammatory response by modulating cytokines and offers anti-hypertensive benefits, enhancing overall vascular function.  

5. 5. Nucleotides: Nucleotides are essential for cellular repair, DNA synthesis, and ATP energy production, helping combat age-related fatigue and support collagen synthesis for skin health. They play a key role in immune function by aiding in immune cell production, while also regulating cellular processes through cAMP and cGMP signaling.

   6. Beta Glucan: A polysaccharide found in yeast, oats, and mushrooms, beta-glucan modulates the immune system. (56) Beta-glucan activates immune cells, enhancing their ability to defend against pathogens and decreasing chronic inflammation. (57) Beta-glucans boost collagen for a more youthful-looking skin, reduce the appearance of fine lines and wrinkles, improve skin elasticity and firmness, enhance skin hydration and moisture retention, and support a healthy, vibrant complexion. (58)

   7. Fisetin: Fisetin, a powerful flavonoid antioxidant, combats oxidative stress, helping to protect against age-related cognitive decline and neurodegenerative diseases. It supports memory, brain function, focus, concentration, and mood.

   8. Vitamin B1 as Benfotiamine: Offers superior bioavailability, protecting nerve tissue from oxidative stress and AGEs, which are linked to aging and age-related diseases. It enhances cognitive function, supports healthy skin aging, boosts collagen production, and helps reduce wrinkles and age spots. Advantage contains the same ingredients as Longevinex with the added benefits of lutein/zeaxanthin to preserve eye health and hyaluronic acid to lubricate and thicken the skin.

9. 9. Lutein/Zeaxanthin: Reduce oxidative stress, enhance visual acuity, protect against age-related macular degeneration (AMD) and cataracts. (66-67) Lutein and Zeaxanthin promote healthy skin by improving hydration while preventing the formation of fine lines and wrinkles. (68)

10. 10. Hyaluronic Acid: (69-70) Naturally found in skin, connective tissues, and joints, boosts skin hydration, elasticity, and firmness for a youthful appearance while also supporting joint lubrication, comfort, and flexibility.

Summary

Resveratrol, one of our top go-to supplements, is known for its over fifty health benefits. With more than 350 varieties available, finding an effective, safe, and affordable option at times feels overwhelming.

Once we discovered that resveratrol has two distinct molecules, we immediately ruled out the weaker “cis” resveratrol, narrowing our options from over 350 to fewer than 50 trans-resveratrol molecules.

“Trans” resveratrol has superior bioavailability and is a more potent biological agent. Unlike its “cis” counterpart, trans-resveratrol remains stable and retains its efficacy when exposed to elements. More importantly, TRV activates SIRT1, a cellular and mitochondrial health and longevity protein. After thoroughly searching for a product that meets our criteria and sports a superior delivery system containing cyclodextrin, we discovered Longevinex Inc.’s Longevinex and Longevinex Advantage.   

Cyclodextrin, a sugar molecule derived from starch, enhances the absorption and bioavailability of the  other ingredients. Combined with trans-resveratrol, cyclodextrin elevates Longevinex to “gold metal” status among resveratrol supplements.

Longevinex and Longevinex Advantage are designed to enhance your anti-aging, anti-inflammatory, and antioxidant regimens. Each component acts synergistically with each other creating a 1+1=5 rather than 2 effect.  The result is a streamlined, comprehensive, (and effective) supplement for enhancement of your l overall well-being.
 

References

1. https://supplements.selfdecode.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/

2. Salehi, B., Mishra, A. P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P. V. T., Martins, N., & Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 6(3), 91. https://doi.org/10.3390/biomedicines6030091
3. Ramírez-Garza, S. L., Laveriano-Santos, E. P., Marhuenda-Muñoz, M., Storniolo, C. E., Tresserra-Rimbau, A., Vallverdú-Queralt, A., & Lamuela-Raventós, R. M. (2018). Health Effects of Resveratrol: Results from Human Intervention Trials. Nutrients, 10(12), 1892. https://doi.org/10.3390/nu10121892
4. Lolita Kuršvietienė, Inga Stanevičienė, Aušra Mongirdienė, Jurga Bernatonienė, Multiplicity of effects and health benefits of resveratrol, Medicina, Volume 52, Issue 3, 2016, Pages 148-155,ISSN 1010-660X
5. Koushki, M., Amiri-Dashatan, N., Ahmadi, N., Abbaszadeh, H. A., & Rezaei-Tavirani, M. (2018). Resveratrol: A miraculous natural compound for disease treatment. Food science & nutrition, 6(8), 2473–2490. https://doi.org/10.1002/fsn3.855
6. Koushki, M., Amiri-Dashatan, N., Ahmadi, N., Abbaszadeh, H. A., & Rezaei-Tavirani, M. (2018). Resveratrol: A miraculous natural compound for disease treatment. Food science & nutrition, 6(8), 2473–2490. https://doi.org/10.1002/fsn3.855
7. Salehi, B., Mishra, A. P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P. V. T., Martins, N., & Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 6(3), 91. https://doi.org/10.3390/biomedicines6030091
8. https://supplements.selfdecode.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/
9. https://www.amazon.com/s?k=resveratrol+supplements&crid=5U6HU0AD4NSP&sprefix=resveratrol+supplements%2Caps%2C771&ref=nb_sb_noss_1
10. Meng T, Xiao D, Muhammed A, Dengresveratrol’s Chen L, He J. Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules. 2021 Jan 5;26(1):229. doi: 10.3390/molecules26010229. PMID: 33466247; PMCID: PMC7796143.
11. Zhang, T., Chi, Y., Ren, Y., Du, C., Shi, Y., & Li, Y. (2019). Resveratrol Reduces Oxidative Stress and Apoptosis in Podocytes via Sir2-Related Enzymes, Sirtuin 1 (SIRT1)/Peroxisome Proliferator-Activated Receptor γ Co-Activator 1α (PGC-1α) Axis. Medical science monitor : international medical journal of experimental and clinical research, 25, 1220–1231. https://doi.org/10.12659/MSM.911714
12. Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37. https://doi.org/10.1097/AIA.0b013e318034194e
13. Meng, T., Xiao, D., Muhammed, A., Deng, J., Chen, L., & He, J. (2021). Anti-Inflammatory Action and Mechanisms of Resveratrol. Molecules (Basel, Switzerland), 26(1), 229. https://doi.org/10.3390/molecules26010229
14.  Sánchez-Melgar, A., Izquierdo-Ramírez, P. J., Griñán-Ferré, C., Pallàs, M., Martín,  M., & Albasanz, J. L. (2022). Neuroprotective Effects of Resveratrol by Modifying Cholesterol Metabolism and Aβ Processing in SAMP8 Mice. International journal of molecular sciences, 23(14), 7580. https://doi.org/10.3390/ijms23147580  
15. Akbari, M., Tamtaji, O. R., Lankarani, K. B., Tabrizi, R., Dadgostar, E., Haghighat, N., Kolahdooz, F., Ghaderi, A., Mansournia, M. A., & Asemi, Z. (2020). The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Lipids in health and disease, 19(1), 25. https://doi.org/10.1186/s12944-020-1198-x
16. Wong, R. H. X., & Howe, P. R. C. (2018). Resveratrol Counteracts Insulin Resistance-Potential Role of the Circulation. Nutrients, 10(9), 1160. https://doi.org/10.3390/nu10091160
17. Cantó, C., & Auwerx, J. (2012). Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?. Pharmacological reviews, 64(1), 166–187. https://doi.org/10.1124/pr.110.003905
18.  Penumathsa, S. V., Thirunavukkarasu, M., Zhan, L., Maulik, G., Menon, V. P., Bagchi, D., & Maulik, N. (2008). Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. Journal of cellular and molecular medicine, 12(6A), 2350–2361. https://doi.org/10.1111/j.1582-4934.2008.00251.x
19. Li-Man Hung, Jan-Kan Chen, Shiang-Suo Huang, Ren-Shen Lee, Ming-Jai Su, Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes, Cardiovascular Research, Volume 47, Issue 3, August 2000, Pages 549–555, https://doi.org/10.1016/S0008-6363(00)00102-4
20. https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/red-wine/art-20048281#:~:text=Resveratrol%20might%20help%20prevent%20damage,cholesterol)%20and%20prevent%20blood%20clots.   
21. Brown, L., Kroon, P. A., Das, D. K., Das, S., Tosaki, A., Chan, V., Singer, M. V., & Feick, P. (2009). The biological responses to resveratrol and other polyphenols from alcoholic beverages. Alcoholism, clinical and experimental research, 33(9), 1513–1523. https://doi.org/10.1111/j.1530-0277.2009.00989.x
22.  Alavi, M., Farkhondeh, T., Aschner, M. et al. Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation. Cancer Cell Int 21, 579 (2021). https://doi.org/10.1186/s12935-021-02280-5
23.  Tan L, Wang W, He G, Kuick RD, Gossner G, Kueck AS, Wahl H, Opipari AW, Liu JR. Resveratrol inhibits ovarian tumor growth in an in vivo mouse model. Cancer. 2016 Mar 1;122(5):722-9. doi: 10.1002/cncr.29793. Epub 2015 Nov 30. PMID: 26619367.          
24. Mortezaee K, Najafi M, Farhood B, Ahmadi A, Shabeeb D, Musa AE. Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization. Curr Cancer Drug Targets. 2020;20(2):130-145. doi: 10.2174/1568009619666191019143539. PMID: 31738153.
25. Ko, J. H., Sethi, G., Um, J. Y., Shanmugam, M. K., Arfuso, F., Kumar, A. P., Bishayee, A., & Ahn, K. S. (2017). The Role of Resveratrol in Cancer Therapy. International journal of molecular sciences, 18(12), 2589. https://doi.org/10.3390/ijms18122589
26. Athar, M., Back, J. H., Tang, X., Kim, K. H., Kopelovich, L., Bickers, D. R., & Kim, A. L. (2007). Resveratrol: a review of preclinical studies for human cancer prevention. Toxicology and applied pharmacology, 224(3), 274–283. https://doi.org/10.1016/j.taap.2006.12.025
27. Cucu AA, Baci GM, Dezsi Ş, Nap ME, Beteg FI, Bonta V, Bobiş O, Caprio E, Dezmirean DS. New Approaches on Japanese Knotweed (Fallopia japonica) Bioactive Compounds and Their Potential of Pharmacological and Beekeeping Activities: Challenges and Future Directions. Plants (Basel). 2021 Nov 29;10(12):2621. doi: 10.3390/plants10122621. PMID: 34961091; PMCID: PMC8705504.
28.  https://longevinex.com/product/advantage-dietary-supplements/
29. Li H, Xia N, Hasselwander S, Daiber A. Resveratrol and Vascular Function. Int J Mol Sci. 2019 Apr 30;20(9):2155. doi: 10.3390/ijms20092155. PMID: 31052341; PMCID: PMC6539341.
30. Yadav E, Yadav P, Khan MMU, Singh H, Verma A. Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction. Front Pharmacol. 2022 Sep 16;13:922232. doi: 10.3389/fphar.2022.922232. PMID: 36188541; PMCID: PMC9523540.
31. Fang Y, Wang X, Yang D, Lu Y, Wei G, Yu W, Liu X, Zheng Q, Ying J, Hua F. Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node. Front Aging Neurosci. 2021 Sep 20;13:738686. doi: 10.3389/fnagi.2021.738686. PMID: 34616289; PMCID: PMC8489683.
32. A. Victor Ana David, Arulmoli, R., and Parasuraman, S., “Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid”, Pharmacognosy Reviews, vol. 10, no. 20, pp. 84-89, 2016.
33. Chiang MC, Tsai TY, Wang CJ. The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms. Int J Mol Sci. 2023 Mar 28;24(7):6328. doi: 10.3390/ijms24076328. PMID: 37047299; PMCID: PMC10094159.
34. Antero Salminen, Kai Kaarniranta, AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network, Ageing Research Reviews, Volume 11, Issue 2, 2012, Pages 230-241, ISSN 1568-1637, https://doi.org/10.1016/j.arr.2011.12.005.
35. Wang H, Chen W, Li D, Yin X, Zhang X, Olsen N, Zheng SG. Vitamin D and Chronic Diseases. Aging Dis. 2017 May 2;8(3):346-353. doi: 10.14336/AD.2016.1021. PMID: 28580189; PMCID: PMC5440113.
36. Aranow C. (2011). Vitamin D and the immune system. Journal of investigative medicine: the official publication of the American Federation for Clinical Research, 59(6), 881–886. https://doi.org/10.2310/JIM.0b013e31821b8755
37. Maggio, M., Lauretani, F., De Vita, F., Basaria, S., Lippi, G., Butto, V., Luci, M., Cattabiani, C., Ceresini, G., Verzicco, I., Ferrucci, L., & Ceda, G. P. (2014). Multiple hormonal dysregulation as determinant of low physical performance and mobility in older persons. Current pharmaceutical design, 20(19), 3119–3148. https://doi.org/10.2174/13816128113196660062
38. Abboud M. (2022). Vitamin D Supplementation and Sleep: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients, 14(5), 1076. https://doi.org/10.3390/nu14051076
39. Anjum, I., Jaffery, S. S., Fayyaz, M., Samoo, Z., & Anjum, S. (2018). The Role of Vitamin D in Brain Health: A Mini Literature Review. Cureus, 10(7), e2960. https://doi.org/10.7759/cureus.2960
40. Bikle DD. Vitamin D: Production, Metabolism, and Mechanisms of Action. [Updated 2021 Dec 31]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278935/
41. Wüpper, S., Lüersen, K., & Rimbach, G. (2021). Cyclodextrins, Natural Compounds, and Plant Bioactives-A Nutritional Perspective. Biomolecules, 11(3), 401. https://doi.org/10.3390/biom11030401
42. Giastas P, Yannakopoulou K, Mavridis IM. Molecular structures of the inclusion complexes beta-cyclodextrin-1,2-bis(4-aminophenyl)ethane and beta-cyclodextrin-4,4′-diaminobiphenyl; packing of dimeric beta-cyclodextrin inclusion complexes. Acta Crystallogr B. 2003 Apr;59(Pt 2):287-99. doi: 10.1107/s010876810300257x. Epub 2003 Mar 26. PMID: 12657820.
43. Kapral, M., Wawszczyk, J., Sośnicki, S., & Węglarz, L. (2013). Differential influence of inositol hexaphosphate on the expression of genes encoding TGF-β isoforms and their receptors in intestinal epithelial cells stimulated with proinflammatory agents. Mediators of inflammation, 2013, 436894. https://doi.org/10.1155/2013/436894
44.  Jolfaie NR, Rouhani MH, Surkan PJ, Siassi F, Azadbakht L. Rice Bran Oil Decreases Total and LDL Cholesterol in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Horm Metab Res. 2016;48(7):417-426. doi:10.1055/s-0042-105748
45. Soo Mi Kim, Catherine W. Rico, Sang Chul Lee, Mi Young Kang, Modulatory Effect of Rice Bran and Phytic Acid on Glucose Metabolism in High Fat-Fed C57BL/6N Mice, Journal of Clinical Biochemistry and Nutrition, 2010, Volume 47, Issue 1, Pages 12-17
46. Su, Weifa, et al. “Co-fermented defatted rice bran alters gut microbiota and improves growth performance, antioxidant capacity, immune status and intestinal permeability of finishing pigs.” Animal nutrition (Zhongguo xu mu shou yi xue hui) vol. 11 413-424. 7 Aug. 2022, doi:10.1016/j.aninu.2022.07.008
47. Sapwarobol, Suwimol, et al. “Biological Functions and Activities of Rice Bran as a Functional Ingredient: A Review.” Nutrition and metabolic insights vol. 14 11786388211058559. 5 Dec. 2021, doi:10.1177/11786388211058559
48. Dhansak, Naphatsanan, et al. “The Effect of Rice Bran Extract on Arterial Blood Pressure, Hepatic Steatosis, and Inflammation in Mice Fed with a High-Fat Diet.” Journal of Nutrition and Metabolism vol. 2020 8374287. 26 Jun. 2020, doi:10.1155/2020/837428
49. Zala, D., Schlattner, U., Desvignes, T., Bobe, J., Roux, A., Chavrier, P., & Boissan, M. (2017). The advantage of channeling nucleotides for very processive functions. F1000Research, 6, 724. https://doi.org/10.12688/f1000research.11561.2
50. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. DNA Replication Mechanisms. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26850/
51. Tardy, A. L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A. (2020). Vitamins and Minerals for Energy, Fatigue, and Cognition: A Narrative Review of the Biochemical and Clinical Evidence. Nutrients, 12(1), 228. https://doi.org/10.3390/nu12010228
52. Rinnerthaler, M., Bischof, J., Streubel, M. K., Trost, A., & Richter, K. (2015). Oxidative stress in aging human skin. Biomolecules, 5(2), 545–589. https://doi.org/10.3390/biom5020545
53. Chen, C. Z., Schaffert, S., Fragoso, R., & Loh, C. (2013). Regulation of immune responses and tolerance: the microRNA perspective. Immunological Reviews, 253(1), 112–128. https://doi.org/10.1111/imr.12060
54. Cheepala, S., Hulot, J. S., Morgan, J. A., Sassi, Y., Zhang, W., Naren, A. P., & Schuetz, J. D. (2013). Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters. Annual review of pharmacology and toxicology, 53, 231–253. https://doi.org/10.1146/annurev-pharmtox-010611-134609
55. Murphy, E. J., Rezoagli, E., Major, I., Rowan, N. J., & Laffey, J. G. (2020). β-Glucan Metabolic and Immunomodulatory Properties and Potential for Clinical Application. Journal of fungi (Basel, Switzerland), 6(4), 356. https://doi.org/10.3390/jof6040356
56. Goodridge, H. S., Wolf, A. J., & Underhill, D. M. (2009). Beta-glucan recognition by the innate immune system. Immunological Reviews, 230(1), 38–50. https://doi.org/10.1111/j.1600-065X.2009.00793.x
57. https://www.provenskincare.com/skincare-ingredients/beta-glucan-v2/
58. Kubina, R., Krzykawski, K., Kabała-Dzik, A., Wojtyczka, R. D., Chodurek, E., & Dziedzic, A. (2022). Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review. Nutrients, 14(13), 2604. https://doi.org/10.3390/nu14132604
59. Hassan, S. S. U., Samanta, S., Dash, R., Karpiński, T. M., Habibi, E., Sadiq, A., Ahmadi, A., & Bunagu, S. (2022). The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress. Frontiers in pharmacology, 13, 1015835. https://doi.org/10.3389/fphar.2022.1015835
60. Currais A, Prior M, Dargusch R, et al. 2014. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging Cell 13: 379–390.
61. Sambon, M., Wins, P., & Bettendorff, L. (2021). Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine. International journal of molecular sciences, 22(11), 5418. https://doi.org/10.3390/ijms22115418
62. Luevano-Contreras, C., & Chapman-Novakofski, K. (2010). Dietary advanced glycation end products and aging. Nutrients, 2(12), 1247–1265. https://doi.org/10.3390/nu2121247
63. Sambon M, Wins P, Bettendorff L. Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine. International Journal of Molecular Sciences. 2021; 22(11):5418. https://doi.org/10.3390/ijms22115418
64. Zhang, S., & Duan, E. (2018). Fighting against Skin Aging: The Way from Bench to Bedside. Cell transplantation, 27(5), 729–738. https://doi.org/10.1177/0963689717725755
65. Mrowicka, M., Mrowicki, J., Kucharska, E., & Majsterek, I. (2022). Lutein and Zeaxanthin and Their Roles in Age-Related Macular Degeneration-Neurodegenerative Disease. Nutrients, 14(4), 827. https://doi.org/10.3390/nu14040827
66. Mares J. (2016). Lutein and Zeaxanthin Isomers in Eye Health and Disease. Annual review of nutrition, 36, 571–602. https://doi.org/10.1146/annurev-nutr-071715-051110
67. Schwartz S, Frank E, Gierhart D, Simpson P, Frumento R. Zeaxanthin-based dietary supplement and topical serum improve hydration and reduce wrinkle count in female subjects. J Cosmet Dermatol. 2016 Dec;15(4):e13-e20. doi: 10.1111/jocd.12226. Epub 2016 Jun 17. PMID: 27312122.
68. Juncan, A. M., Moisă, D. G., Santini, A., Morgovan, C., Rus, L. L., Vonica-Țincu, A. L., & Loghin, F. (2021). Advantages of Hyaluronic Acid and Its Combination with Other Bioactive Ingredients in Cosmeceuticals. Molecules (Basel, Switzerland), 26(15), 4429. https://doi.org/10.3390/molecules26154429
69. Swann DA, Radin EL, Nazimiec M, Weisser PA, Curran N, Lewinnek G. Role of hyaluronic acid in joint lubrication. Ann Rheum Dis. 1974 Jul;33(4):318-26. doi: 10.1136/ard.33.4.318. PMID: 4415649; PMCID: PMC1006265.