Protocol development in integrative medicine is not typically a simple process. Individuals require individualized care, and what works for one patient may not work for another.

To establish these protocols, we first developed a Rating Scale that could be used to discern the rigor of evidence supporting a specific nutrient’s therapeutic effect.

The following protocols were developed using only A through C-quality evidence.

Qualifying studies
Minimum requirements
Systematic review or meta-analysis of human trials
RDBPC human trials
2+ studies and/or 1 study with 50 + subjects
RDBPC human trials
1 study

The biomarkers of oxidative stress have been strongly linked to aging. (26)(29) Oxidative stress biomarkers, such as lipoprotein phospholipase A2 (Lp-PLA2), isoprostanes, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-Oxo-dG), derivatives of reactive oxygen metabolites, oxidized glutathione/glutathione, 4-hydroxy-2, 3-nonenal (4-HNE), and protein carbonylation, have all been linked with increased risk of frailty and pre-frailty. (29) In addition, cardiovascular mortality has been associated with increased serum markers of oxidative stress, such as derivatives of reactive oxygen metabolites (D-ROM) and total thiol levels (TTL). (26)

Antioxidants may help to mitigate the potential negative effects of prolonged oxidative stress. Additionally, ingredients with antioxidant function have shown potential for reducing oxidative damage caused by exercise when taken by healthy individuals. 

The protocol below is intended to support healthy aging through ingredients focused on attenuating damage caused by oxidative stress.

Coenzyme Q10 (CoQ10)

200 mg, once per day, minimum 2 weeks (25)

  • Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased, and malondialdehyde (MDA) and diene levels were decreased after CoQ10 supplementation (12)(15)(33)
  • CoQ10 supplementation has been shown to decrease the level of age-related cardiovascular fibrosis through its antioxidant and anti-inflammatory actions (7)(8)
  • Systematic review and meta-analysis of 19 studies found CoQ10 supplementation to improve markers for oxidative stress demonstrated by and increase in total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), and decrease in malondialdehyde (MDA) (23)
  • Two systematic reviews have shown improvements in antioxidant systems as demonstrated by increases in SOD, CAT, and TAC activity, and decreases in MDA and diene levels (1)(12)
  • When given 200 mg of ubiquinol before strenuous exercise, healthy adults were found to have decreased oxidative stress and increased antioxidant status as demonstrated by improved levels of isoprostanes, 8-OHdG, oxidized LDL, hydroperoxides and CAT activity (25)
Coenzyme Q10 in the Fullscript catalog


600-2000 mg, once per day, minimum 12 weeks (24)

  • Curcumin (in a Longvida® proprietary preparation) supplementation has been shown to increase vascular nitric oxide bioavailability, reduce oxidative stress, and, therefore, improve artery endothelial resistance (24)
  • Meta-analysis of 8 clinical studies found curcumin supplementation improved oxidative stress demonstrated by decreases in MDA when given curcuminoids at a dose of 600 mg per day; additionally, when piperine was used in combination, the effect was greater  (20)
  • Systematic review of 11 articles found curcumin effective in decreasing inflammation, oxidative stress, pain, and muscle damage while improving muscle performance and recovery (30)
  • Meta-analysis of 8 clinical studies found curcumin supplementation improved oxidative stress demonstrated by a decrease in MDA and increase in SOD when supplemented for four weeks; effects improved when combined with peperine (20)
  • Systematic review and meta-analysis of 15 randomized controlled found curcumin improved inflammation and antioxidant status as demonstrated by decreases in interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and MDA (31)
Curcumin in the Fullscript catalog


300-745 mg, once per day, minimum 5 weeks (10)(22

  • Polyphenol supplementation in normal dose (299 mg/d) or high dose (745 mg/d)  decreased 8-hydroxy-2′-deoxyguanosine (8-Oxo-dG), 8-iso-prostaglandin F2α (8-iso-PGF2α), erythrocyte catalase, and glutathione reductase (GR) activity in obese and overweight non-smoking adults; additionally, waist circumference, BMI, and leptin were decreased (22)
  • In different age groups, resveratrol provided protection against protein carbonylation and lipid peroxidation, and cellular levels of glutathione (GSH) and sulfhydryl (-SH) were restored during oxidative injury in erythrocytes; additionally, resveratrol has been shown to up-regulate plasma membrane redox system (PMRS) and ascorbate free radical reductase activity (19)
  • Systematic review and meta-analysis of 14 studies found improved antioxidant status and subsequent performance improvements as demonstrated by a 1.9% increase in exercise performance in athletes when supplemented for a minimum of 7 days (28)
Polyphenols in the Fullscript catalog


10-30 mg, once or twice per day, for 8-24 weeks (6)(14)(16)(17)(34)

  • Improved endothelial function was correlated with improvements in antioxidative enzymatic activity and in the oxidative and inflammatory profile (14)
  • 5 mg and 15 mg doses of lycopene decreased oxidative stress as shown by decreased lymphocyte DNA comet tail lengths and increased SOD activity; 15 mg doses additionally decreased hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 and increased β-carotene, LDL-particle size, and reactive hyperemia peripheral arterial tonometry (RH-PAT) (14)
  • Lycopene supplementation at a dose of 30 mg per day decreased oxidative damage to DNA and urinary 8-hydroxy deoxoguanosine (8-OHdG) in healthy volunteers (6)
  • Postmenopausal women experienced a decrease in endogenous DNA damage when given 12 mg of single carotenoid (beta-carotene, lutein, or lycopene) of 4 mg of mixed carotenoids (34)
Lycopene in the Fullscript catalog

NAC (N-Acetyl-Cysteine) 

600-1800 mg per day for minimum of 1-3 months to adults and older adults (2)(3)(9)(11)

  • Older individuals have lower glutathione levels, lower glutathione synthesis, higher oxidative stress and F(2)-isoprostanes but can be improved with supplementation of glutathione precursors including NAC and glycine (27)
  • Increased blood catalase, GSH, GSH/GSSG, glutathione peroxidase, neutrophil capacity, and total thiol groups (TTG), and reduced GSSG, oxidized homocysteine (Hcy) and free Hcy:oxidized Hcy ratio, superoxide anions, MDA, NO, VCAM-1, improving antioxidant status and possibly slowing progression of vascular damage (3)(5)(9)(18)(21)(32)
  • Reduced total peroxide and oxidative stress indices, malondialdehyde (MDA), sperm DNA damage and increased total antioxidant capacity (2)(11)
  • Reduced oxidative stress indices, malondialdehyde (MDA), sperm DNA fragmentation and increased total antioxidant capacity in infertile men with asthenoteratozoospermia (11)
  • Reduced protein carbonyl groups, serum lead content, and increased glutamate dehydrogenase activity indicating improved oxidative stress in workers with lead exposure (13)
NAC in the Fullscript catalog


The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

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  1. Akbari, A., Mobini, G. R., Agah, S., Morvaridzadeh, M., Omidi, A., Potter, E., Fazelian, S., Ardehali, S. H., Daneshzad, E., & Dehghani, S. (2020). Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials. European Journal of Clinical Pharmacology, 76(11), 1483–1499. (A)
  2. Ciftci, H., Verit, A., Savas, M., Yeni, E., & Erel, O. (2009). Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology, 74(1), 73–76. (C)
  3. Coles, L. D., Tuite, P. J., Öz, G., Mishra, U. R., Kartha, R. V., Sullivan, K. M., Cloyd, J. C., & Terpstra, M. (2018). Repeated-Dose Oral N-Acetylcysteine in Parkinson’s Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress. Journal of Clinical Pharmacology, 58(2), 158–167. (C)
  4. Conus, P., Seidman, L. J., Fournier, M., Xin, L., Cleusix, M., Baumann, P. S., Ferrari, C., Cousins, A., Alameda, L., Gholam-Rezaee, M., Golay, P., Jenni, R., Woo, T.-U. W., Keshavan, M. S., Eap, C. B., Wojcik, J., Cuenod, M., Buclin, T., Gruetter, R., & Do, K. Q. (2018). N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis. Schizophrenia Bulletin, 44(2), 317–327. (B)
  5. De Mattia, G., Bravi, M. C., Laurenti, O., Cassone-Faldetta, M., Proietti, A., De Luca, O., Armiento, A., & Ferri, C. (1998). Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes. Diabetologia, 41(11), 1392–1396. (C)
  6. Devaraj, S., Mathur, S., Basu, A., Aung, H. H., Vasu, V. T., Meyers, S., & Jialal, I. (2008). A dose-response study on the effects of purified lycopene supplementation on biomarkers of oxidative stress. Journal of the American College of Nutrition, 27(2), 267–273. (B)
  7. Hamilton, S. J., Chew, G. T., & Watts, G. F. (2009). Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care, 32(5), 810–812. (C)
  8. Hargreaves, I. P., & Mantle, D. (2019). Coenzyme Q10 Supplementation in Fibrosis and Aging. Advances in Experimental Medicine and Biology, 1178, 103–112. (C)
  9. Hashemi, G., Mirjalili, M., Basiri, Z., Tahamoli-Roudsari, A., Kheiripour, N., Shahdoust, M., Ranjbar, A., Mehrpooya, M., & Ataei, S. (2019). A Pilot Study to Evaluate the Effects of Oral N-Acetyl Cysteine on Inflammatory and Oxidative Stress Biomarkers in Rheumatoid Arthritis. Current Rheumatology Reviews, 15(3), 246–253. (C)
  10. Janiques, A. G. de P. R., Leal, V. de O., Stockler-Pinto, M. B., Moreira, N. X., & Mafra, D. (2014). Effects of grape powder supplementation on inflammatory and antioxidant markers in hemodialysis patients: a randomized double-blind study. Jornal Brasileiro de Nefrologia: ’Orgao Oficial de Sociedades Brasileira E Latino-Americana de Nefrologia, 36(4), 496–501. (C)
  11. Jannatifar, R., Parivar, K., Roodbari, N. H., & Nasr-Esfahani, M. H. (2019). Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men. Reproductive Biology and Endocrinology: RB&E, 17(1), 24. (C)
  12. Jorat, M. V., Tabrizi, R., Kolahdooz, F., Akbari, M., Salami, M., Heydari, S. T., & Asemi, Z. (2019). The effects of coenzyme Q10 supplementation on biomarkers of inflammation and oxidative stress in among coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Inflammopharmacology, 27(2), 233–248. (A)
  13. Kasperczyk, S., Dobrakowski, M., Kasperczyk, A., Romuk, E., Rykaczewska-Czerwińska, M., Pawlas, N., & Birkner, E. (2016). Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers. Toxicology and Industrial Health, 32(9), 1607–1618. (C)
  14. Kim, J. Y., Paik, J. K., Kim, O. Y., Park, H. W., Lee, J. H., Jang, Y., & Lee, J. H. (2011). Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men. Atherosclerosis, 215(1), 189–195. (C)
  15. Lee, B.-J., Huang, Y.-C., Chen, S.-J., & Lin, P.-T. (2012). Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease. Nutrition , 28(3), 250–255. (C)
  16. Mackinnon, E. S., Rao, A. V., Josse, R. G., & Rao, L. G. (2011). Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women. Osteoporosis International: A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 22(4), 1091–1101. (C)
  17. Misra, R., Mangi, S., Joshi, S., Mittal, S., Gupta, S. K., & Pandey, R. M. (2006). LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial. The Journal of Obstetrics and Gynaecology Research, 32(3), 299–304. (C)
  18. Nyberg, M., Blackwell, J. R., Damsgaard, R., Jones, A. M., Hellsten, Y., & Mortensen, S. P. (2012). Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans. The Journal of Physiology, 590(21), 5361–5370. (C)
  19. Pandey, K. B., & Rizvi, S. I. (2013). Resveratrol up-regulates the erythrocyte plasma membrane redox system and mitigates oxidation-induced alterations in erythrocytes during aging in humans. Rejuvenation Research, 16(3), 232–240. (C)
  20. Qin, S., Huang, L., Gong, J., Shen, S., Huang, J., Tang, Y., Ren, H., & Hu, H. (2018). Meta-analysis of randomized controlled trials of 4 weeks or longer suggest that curcumin may afford some protection against oxidative stress. Nutrition Research , 60, 1–12. (A)
  21. Raijmakers, M. T. M., Schilders, G. W., Roes, E. M., van Tits, L. J. H., Hak-Lemmers, H. L. M., Steegers, E. A. P., & Peters, W. H. M. (2003). N-Acetylcysteine improves the disturbed thiol redox balance after methionine loading. Clinical Science , 105(2), 173–180. (C)
  22. Rangel-Huerta, O. D., Aguilera, C. M., Martin, M. V., Soto, M. J., Rico, M. C., Vallejo, F., Tomas-Barberan, F., Perez-de-la-Cruz, A. J., Gil, A., & Mesa, M. D. (2015). Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults. The Journal of Nutrition, 145(8), 1808–1816. (B)
  23. Sangsefidi, Z. S., Yaghoubi, F., Hajiahmadi, S., & Hosseinzadeh, M. (2020). The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials. Food Science & Nutrition, 8(4), 1766–1776. (A)
  24. Santos-Parker, J. R., Strahler, T. R., Bassett, C. J., Bispham, N. Z., Chonchol, M. B., & Seals, D. R. (2017). Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress. Aging, 9(1), 187–208. (C)
  25. Sarmiento, A., Diaz-Castro, J., Pulido-Moran, M., Moreno-Fernandez, J., Kajarabille, N., Chirosa, I., Guisado, I. M., Javier Chirosa, L., Guisado, R., & Ochoa, J. J. (2016). Short-term ubiquinol supplementation reduces oxidative stress associated with strenuous exercise in healthy adults: A randomized trial. BioFactors , 42(6), 612–622. (C)
  26. Schöttker, B., Brenner, H., Jansen, E. H. J. M., Gardiner, J., Peasey, A., Kubínová, R., Pająk, A., Topor-Madry, R., Tamosiunas, A., Saum, K.-U., Holleczek, B., Pikhart, H., & Bobak, M. (2015). Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data. BMC Medicine, 13, 300. (A)
  27. Sekhar, R. V., Patel, S. G., Guthikonda, A. P., Reid, M., Balasubramanyam, A., Taffet, G. E., & Jahoor, F. (2011). Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition, 94(3), 847–853. (C)
  28. Somerville, V., Bringans, C., & Braakhuis, A. (2017). Polyphenols and Performance: A Systematic Review and Meta-Analysis. Sports Medicine , 47(8), 1589–1599. (A)
  29. Soysal, P., Isik, A. T., Carvalho, A. F., Fernandes, B. S., Solmi, M., Schofield, P., Veronese, N., & Stubbs, B. (2017). Oxidative stress and frailty: A systematic review and synthesis of the best evidence. Maturitas, 99, 66–72. (A)
  30. Suhett, L. G., de Miranda Monteiro Santos, R., Silveira, B. K. S., Leal, A. C. G., de Brito, A. D. M., de Novaes, J. F., & Lucia, C. M. D. (2021). Effects of curcumin supplementation on sport and physical exercise: a systematic review. Critical Reviews in Food Science and Nutrition, 61(6), 946–958. (A)
  31. Tabrizi, R., Vakili, S., Akbari, M., Mirhosseini, N., Lankarani, K. B., Rahimi, M., Mobini, M., Jafarnejad, S., Vahedpoor, Z., & Asemi, Z. (2019). The effects of curcumin-containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Phytotherapy Research: PTR, 33(2), 253–262. (A)
  32. Urban, T., Akerlund, B., Jarstrand, C., & Lindeke, B. (1997). Neutrophil function and glutathione-peroxidase (GSH-px) activity in healthy individuals after treatment with N-acetyl-L-cysteine. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 51(9), 388–390. (C)
  33. Yen, C.-H., Chu, Y.-J., Lee, B.-J., Lin, Y.-C., & Lin, P.-T. (2018). Effect of liquid ubiquinol supplementation on glucose, lipids and antioxidant capacity in type 2 diabetes patients: a double-blind, randomised, placebo-controlled trial. The British Journal of Nutrition, 120(1), 57–63. (B)
  34. Zhao, X., Aldini, G., Johnson, E. J., Rasmussen, H., Kraemer, K., Woolf, H., Musaeus, N., Krinsky, N. I., Russell, R. M., & Yeum, K.-J. (2006). Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women. The American Journal of Clinical Nutrition, 83(1), 163–169. (C)