by William Clearfield, D.O. for Longevinex

“Doc,” Teddy said, “I looked up this ‘revers-it-all’ stuff you gave me.”

“Resveratrol,” I replied.

“Right, reverse-it-all, Teddy replied. “There’s like at least fifty ways it helps.”

“Sounds like a song,” I replied.

“Paul Simon,” Teddy said. “50 Ways to Leave Your Lover.”

“Except there are only five ways mentioned in the song,” I replied. “Can you
name them?”

“Umm,” Teddy said.

“Now I pull a Judge Judy on you,” I said. “Um, is not an answer.”

I looked up at the ceiling momentarily, then ticked off the ways.
“1. Slip out the back, Jack,
2. Make a new plan, Stan,
3. No need to be coy, Roy,
4. Hop on the bus, Gus and
5. Drop off the key, Lee.

They never mentioned the other forty-five,” I said.

Teddy looked at me wide-eyed. “Doc! Unbelievable.”

“Hey, “I said. “I’m from the Sixties. So what can, err, “reverse-it-all” do?”

Holding up one finger at a time, first on my left hand, then my right, with the help of a little cheat sheet I keep in my desk drawer.

The Resveratrol (RSV) 50 (2-5)

“1. It reduces inflammation.
2. Improves cholesterol
3. Increases insulin sensitivity
4. Protects the heart
5. Is an anti-cancer agent
6. Enhances memory and cognition
7. Improves bone strength
8. Increase your wind and endurance
9. Helps you lose weight
10. Improves your skin.”

Teddy was speechless. “Keep going,” he said. “You’ve already topped the song.”

“The problem is all inside your head,” I said. (6)
“The first line,” Teddy said.
“Right,” I said. “Ok, I’m on a roll.”

11. Protects against ultraviolet radiation
12. Protects against macular degeneration
13. Improves liver function
14. Lowers cholesterol., you know this.
15. Protects against hardening of the arteries, atherosclerosis
16. Protects the brain and decreases the chance of stroke
17. Decreases the incidence of “sugar” diabetes
18. Enhances the immune system
19 Protects against infections
20. Improves breathing your respiratory function
21. Reduces reactive oxidative stress, the accumulation of toxins in the body from wear and tear and daily life, and the ability of the body’s natural antioxidant defenses to neutralize them.
22. Improves sleep
23. Helps alleviate anxiety
24. Helps alleviate depression
25. Reduces joint pain. Halfway through.
26. Improves muscle strength
27. Aids in relieving erectile dysfunction
28. Protects the brain from neurodegenerative diseases, Alzheimer’s Disease, and Parkinson’s Disease
29. You will live longer
30. Protects the gut
31. Protects against foodborne illnesses
32. Reduces asthma
33. Lessens autoimmune disease symptoms
34. Protects the liver
35. Protects the kidney
36. Lessens menopause symptoms
37. Improves fertility
38. Strengthens your teeth and gums
39. Is an anti-viral agent
40. Reduces arthritis-Just ten to go.
41. Improves ADHD symptoms
42. Improves your lung function
43. Protects your skin against cancer
44. Improves insulin resistance
45. Reduces the risk of heart disease
46. Reduces the risk of dementia
47. Reduces the risk of obesity
48. Balances estrogen
49. Reduces chronic fatigue syndrome

And lastly, drum roll,

50. Reduces the risk of and improves the outcomes of migraine headaches.”

“Ta, da,” I exclaimed, taking a bow. “50 ways….With, as you call it, reverse-it-all.”

“Wow wow, doc,” Teddy replied. “How…No one…”

I pulled out my cheat sheet. “This helps,” I said.

It truly is reverse-it-all,” Teddy said, “How can it do all of that?”

I shot Teddy a glance.

“The answer is easy if you think logically,” I said. (7)

“The second line,” Teddy said.

“It is. You left yourself open for that one.” I looked, then tapped at my watch.

“So, how does it work?” Teddy asked.

“I have other things to do today,” I said.

“Now you are Judge Judy,” Teddy said.

“Right. Let’s look at the first five, at least. We can pick up the rest next time.”

The Resveratrol (RSV) 50 (1-5)

  1. Resveratrol reduces inflammation
    a. Resveratrol reduces oxidative stress, an imbalance between the
    production of reactive oxygen species (ROS) and the ability of the
    body's natural antioxidant defenses to neutralize them. This
    imbalance leads to inflammation, cellular damage, and insulin
    resistance. (8)
    b. Resveratrol reduces the inflammatory cytokines, small proteins
    essential for cell-to-cell communication in the immune system.
    Cytokines are key in regulating inflammation, hematopoiesis, and
    other immune responses. (9) RSV reduces inflammatory cytokines
    TNF-α, IL-1β, IL-6, and IFN-γ while reducing the anti-inflammatory
    cytokine IL-10. (10)
  2. Resveratrol improves HDL (Good) Cholesterol) and
    Reduces LDL (Bad cholesterol)
    a. A study of middle-aged and elderly mice found a significant
    difference in cholesterol levels if treatment started early. (5-month-old mice are equivalent to ages 39-47 in human years. 7-month-old mice equal ages 56-69). (11)

b. HMG-Co synthase and reductase are the enzymes that control cholesterol synthesis.
c. On average, resveratrol reduces total cholesterol by 7.65 mg/dL (12)

Increasing Insulin Sensitivity (13)

  1. Resveratrol improves insulin utilization by reducing inflammation and cholesterol levels, decreasing vasoconstriction and vascular remodeling to lessen the ischaemic environment for tissues.
  2. Improved blood flow to tissues counteracts the vasoconstriction caused by hyperinsulinemia resulting in improved glucose utilization.
  3. Resveratrol activates sirtuins, longevity-inducing proteins that regulate cellular processes, including aging, the death of cells, and their stress resistance.
  4. Resveratrol activates NAD-dependent proteins in a manner similar to estradiol (E2). (14) RSV preferentially binds estrogen receptors (ER), promoting glucose transporter type-4 (GLUT4) translocation and increases glucose uptake. (15)
  5. Resveratrol improves insulin resistance by reducing oxidative stress. (8)

Cardioprotection (16)

  1. Resveratrol increases nitric oxide (NO) and decreases lactate dehydrogenase levels, increasing blood flow to the heart and brain. RSV reduces the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF).
  2. Resveratrol prevents damage to blood vessels, reduces low-density lipoprotein (LDL) cholesterol (the “bad” cholesterol), and prevents blood clots. (17)
  3. RSV reduces relative cardiovascular risk (RR) dose-dependently with red but not white wine consumption. A significant risk reduction (RR: 0.66, 95% CI 0.57-0.75) was associated with moderate (1-2 drinks or 150-300 mL/d) versus no wine consumption. (18)

Antineoplastic Effects of Resveratrol

  1. RSV activates the Nrf2 gene expression to downgrade cancer-inducing catechol estradiol. (19)
  2. Resveratrol suppresses tumor regrowth after therapy with cisplatin. RSV has the potential to prolong disease-free living. (20)
  3. Resveratrol’s antioxidant and anti-inflammatory indicate it can mitigate chemo-radiation toxicity in normal tissue. (21)
  4. RSV sensitizes a variety of cancer cells to both chemotherapy drugs and radiation. (22)
  5. RSV slows the growth of certain types of cancer by reducing inflammation. (23)
  6. Preclinical cancer studies with at least a modicum of success in reducing symptoms or prolonging survival include: (24)
    Skin cancer
    Breast cancer
    Colorectal Cancer
    Prostate Cancer
    Liver cancer
    Pancreatic cancer
    Lung Cancer

Side Effects of Resveratrol

Resveratrol in low doses, 1.0 gm. per day, does not appear to have any side effects. At 2.5 g or more, reported complications include nausea, vomiting, diarrhea, and liver dysfunction in patients with non-alcoholic fatty liver disease. (25) In our practice and the literature we reviewed, no reported major side effects in long-term clinical trials were noted. (26) RSV is safe and well-tolerated at up to 5 g/day, either as a single dose or as a fraction of a multiple dosing per day schedule. (27)

The Source of Resveratrol is Key to its Efficacy

“One last thing, Doc, “ Teddy said. “There are more than 350 different reverse-it-alls out there. How do I know which one to take?”

“Great question,” I replied. “There are two major forms of ‘reverse-it-all.’ Darn,..

Now you have me saying it. There’s a cis and a trans-resveratrol.” (28).

“A cis and a trans,” Teddy said. “I’m from Wilkes Barre, Pa. “The only ‘sis’ I know is my sister Audrey.”

“Cis, c-i-s,” I said spelling it out. “Not your sister. The cis-resveratrol compound, found in grapes and red wine, is only 5-10% potent. It is chemically different than the more biologically active ‘trans’-resveratrol form. Trans-resveratrol is derived from Polygonum cuspidatum, Japanese knotweed, is 99% pure and approximately 20 times stronger and cheaper to extract than cis-resveratrol.” (29)


“How do you know all this?” Teddy asked. “In your head, no less!”

I showed him my “cheat sheet” once more.

“Don’t waste your time watching nonsense on YouTube,” I said. “Don’t watch idiot politicians on cable news shows all day long. I don’t even have a television. Pick out an interest, make it your “white hot imperative,” that thing you have to do, no matter what is going on in the world, and become the expert.”

“I’m old, doc,” Teddy said. “I’m 73. It’s too late for me.”

“Teddy,” I said. “Teddy. My favorite mentor, Dr. Jim Naccarato, told me long ago:”

“Don’t let the old man in. When you stop learning, stop contributing, and stop being passionate, then you are old. Only 1% of the world’s inventions and innovations were created by those under 40. 35% of all the great works of the universe were developed by 60-70-year-olds, 23% by 70-80-year-olds, and 8% by those over 80. You can do it too if you want.” (30)

“Wow,” Teddy said. “I never knew.”

“You’re in your prime,” I said. “Don’t be a schlemiel. Go for the gold. You’re lucky you came to my office after you ran your car through your kitchen wall. (See May 15, 2023 article for details). Would you ever have known about this incredible ‘reverse-it-all,’ as you call it?

“Not likely,” Teddy said.

“You’ve heard fifty ways modern science proves resveratrol supports health. Five of them in depth.”

“You promise to tell me about the other 45,” Teddy said.

I held out my hand, pinky finger, side up to Teddy. He hooked his left to my right. “Pinky swear, “ I said. “We will cover them in our next visit.”

“Pinky swear,” Teddy said. “Do it once more.” “Do what?” I asked.

“The list,” he said. “All fifty. It’s poetry. I ain’t never seen anything like it.” “The list,” I said. “You want me to recite the list? Again.”

“Again, Teddy said.

I took a deep breath, closed my eyes briefly, and pictured The ‘List’ in my head. “Here goes,” I said.


  1. sveratrol-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.
  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.
  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. 50 Ways to Leave Your Lover, by Paul Simon and Phl Ramone, from the albumin “Still Crazy after all These Years, Colombia Records, December 19
  6. Ibid.
  7. 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, Sirtuins1 (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.
  8. Zhang, J. M., & An, J. (2007). Cytokines, inflammation, and pain. International anesthesiology clinics, 45(2), 27–37.
  9. 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.
  10. 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.
  11. 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.
  12. Wong, R. H. X., & Howe, P. R. C. (2018). Resveratrol Counteracts Insulin Resistance-Potential Role of the Circulation. Nutrients, 10(9), 1160.
  13. Cantó, C., & Auwerx, J. (2012). Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?. Pharmacological reviews, 64(1), 166–187.
  14. 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.
  15. 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,
  16. e/art-20048281#:~:text=Resveratrol%20might%20help%20prevent%20damage,c holesterol)%20and%20prevent%20blood%20clots.
  17. Brown, L., Kroon, P. A., Das, D. K., Das, S., Tosaki, A., Chan, V., Singer, M. V., & Feick, (2009). The biological responses to resveratrol and other polyphenols from alcoholic beverages. Alcoholism, clinical and experimental research, 33(9), 1513–1523.
  18. 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).
  19. 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.
  20. 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.
  21. Ibid
  22. 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.
  23. 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.
  24. Brown V.A., Patel K.R., Viskaduraki M., Crowell J.A., Perloff M., Booth T.D., Vasilinin G., Sen A., Schinas A.M., Piccirilli G., et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics and effect on the insulin-like growth factor axis. Cancer Res. 2010;70:9003–9011. doi: 10.1158/0008-5472.CAN-10-2364.
  25. Tomé-Carneiro J., Gonzálvez M., Larrosa M., Yáñez-Gascón M.J., García-Almagro F.J., Ruiz-Ros J.A., Tomás-Barberán F.A., García-Conesa M.T., Espín J.C. Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: A triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc. Drugs Ther. 2013;27:37–48. doi: 10.1007/s10557-012-6427-8.
  26. Patel K.R., Scott E., Brown V.A., Gescher A.J., Steward W.P., Brown K. Clinical trials of resveratrol. Ann. N. Y. Acad. Sci. 2011;1215:161–169. doi: 10.1111/j.1749-6632.2010.05853.x.
  27. Anisimova, N.Y., Kiselevsky, M.V., Sosnov, A.V. et al. Trans-, cis-, and dihydro-resveratrol: a comparative study. Chemistry Central Journal 5, 88 (2011).
  28. Soleas, George & Diamandis, Eleftherios & Goldberg, David. (2001). The World of Resveratrol. 10.1007/978-1-4615-1283-7_13.
  29. Jones, B, Age and Great Invention, WORKING PAPER 11359, DOI 10.3386/w11359, ISSUE DATE May 2005,


Related Posts