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.

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

Inflammation can have both positive and negative health effects. Acute inflammation works with the immune system to address infectious and non-infectious cellular damage. (1) However, when inflammation becomes chronic, it can seriously impact health. For example, studies have shown a correlation between chronic inflammation and all-cause, cancer, cardiovascular, and cerebrovascular mortality. (10)(12)

Curcumin (Curcuma longa)

600–1,000 mg, total per day, minimum 8–10 weeks (4)(13)

  • Curcumin decreased C-reactive protein (CRP) (-0.58 mg/l), tumor necrosis factor-alpha (TNF-α) (-3.48 pg/ml), interleukin 6 (IL-6) (-1.31 pg/ml), and malondialdehyde (MDA) (-0.33 umol/l), and increased superoxide dismutase (SOD) activity (20.51 u/l) and total antioxidant capacity (TAC) (0.21 mmol/l). (3)
  • In patients with various chronic diseases, curcumin decreased CRP (-3.67 mg/l) and hs-CRP concentrations. (4
  • Compared to placebo, curcumin decreased IL-6 by ~49%, TNF-α by ~63%, and MDA by ~38% in patients with diabetes mellitus. (13)
Curcumin in the Fullscript catalog

Omega-3 fatty acids (EPA/DHA)

2.5 g, total per day, minimum 12 weeks (7)(15

  • In patients with various health conditions, omega-3s moderately decreased serum CRP, as well as IL-6 and TNF-α with a smaller effect. (5)
  • Compared to placebo, omega-3 supplementation decreased total serum cortisol by 19% and IL-6 levels by 33% during a stressful event, and CRP by ~30%, IL-6 by ~22%, and TNF-α by ~16% in patients with chronic kidney disease undergoing hemodialysis. (7)(15)
Omega-3 fatty acids in the Fullscript catalog

Probiotics

1.6 × 109 CFU, total per day, minimum 8 weeks (8)(11)

  • Prebiotics and probiotics modulate the intestinal microbiome and decrease oxidative stress and inflammation by increasing intestinal anaerobes and maintaining the integrity of the intestinal barrier. (6
  • Compared to placebo, a multistrain synbiotic reduced TNF-α by ~6% and hs-CRP by ~10% in postmenopausal females with obesity and a history of hormone-receptor-positive breast cancer. (11
  • Compared to placebo, Lactobacillus rhamnosus GG reduced IL1-Beta and lipopolysaccharide concentrations by ~ 35% and ~30%, respectively, in patients with CAD. (8)
Probiotics in the Fullscript catalog

Quercetin

≥ 500 mg, total per day, minimum of 8 weeks (2)(9)(14)

  • In individuals with chronic diseases, quercetin had a large effect on decreasing IL-6 and a smaller effect on decreasing serum CRP. (9
  • Quercetin decreased TNF-α and IL-6 in females with polycystic ovarian syndrome. (14)
  • Compared to placebo, quercetin increased serum TAC by ~20% in post-myocardial infarction patients. (2)
Quercetin in the Fullscript catalog

Disclaimer

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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References
  1. Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204–7218. https://doi.org/10.18632/oncotarget.23208 
  2. Dehghani, F., Sezavar Seyedi Jandaghi, S. H., Janani, L., Sarebanhassanabadi, M., Emamat, H., & Vafa, M. (2021). Effects of quercetin supplementation on inflammatory factors and quality of life in post-myocardial infarction patients: A double blind, placebo-controlled, randomized clinical trial. Phytotherapy Research, 35(4), 2085–2098. https://doi.org/10.1002/ptr.6955 (B)
  3. Dehzad, M. J., Ghalandari, H., Nouri, M., & Askarpour, M. (2023). Antioxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Cytokine, 164, 156144. https://doi.org/10.1016/j.cyto.2023.156144 (A)
  4. Gorabi, A. M., Abbasifard, M., Imani, D., Aslani, S., Razi, B., Alizadeh, S., Bagheri-Hosseinabadi, Z., Sathyapalan, T., & Sahebkar, A. (2022). Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials. Phytotherapy Research, 36(1), 85–97. https://doi.org/10.1002/ptr.7284 (A)
  5. Kavyani, Z., Musazadeh, V., Fathi, S., Hossein Faghfouri, A., Dehghan, P., & Sarmadi, B. (2022). Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis. International Immunopharmacology, 111, 109104. https://doi.org/10.1016/j.intimp.2022.109104 (A) 
  6. Lopes, R. de C. S. O., Balbino, K. P., Jorge, M. D. P., Ribeiro, A. Q., Martino, H. S. D., & Alfenas, R. D. C. G. (2018). Modulation of intestinal microbiota, control of nitrogen products and inflammation by pre/probiotics in chronic kidney disease: A systematic review. Nutricion Hospitalaria, 35(3), 722–730. https://doi.org/10.20960/nh.1642 (A)
  7. Madison, A. A., Belury, M. A., Andridge, R., Renna, M. E., Rosie Shrout, M., Malarkey, W. B., Lin, J., Epel, E. S., & Kiecolt-Glaser, J. K. (2021). Omega-3 supplementation and stress reactivity of cellular aging biomarkers: An ancillary substudy of a randomized, controlled trial in midlife adults. Molecular Psychiatry, 26(7), 3034–3042. https://doi.org/10.1038/s41380-021-01077-2 (B)
  8. Moludi, J., Kafil, H. S., Qaisar, S. A., Gholizadeh, P., Alizadeh, M., & Vayghyan, H. J. (2021). Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: A double blind placebo controlled randomized clinical trial. Nutrition Journal, 20(1), 47. https://doi.org/10.1186/s12937-021-00703-7 (C)
  9. Ou, Q., Zheng, Z., Zhao, Y., & Lin, W. (2020). Impact of quercetin on systemic levels of inflammation: A meta-analysis of randomised controlled human trials. International Journal of Food Sciences and Nutrition, 71(2), 152–163. https://doi.org/10.1080/09637486.2019.1627515 (A)
  10. Proctor, M. J., McMillan, D. C., Horgan, P. G., Fletcher, C. D., Talwar, D., & Morrison, D. S. (2015). Systemic inflammation predicts all-cause mortality: A glasgow inflammation outcome study. PloS One, 10(3), e0116206. https://doi.org/10.1371/journal.pone.0116206
  11. Raji Lahiji, M., Zarrati, M., Najafi, S., Yazdani, B., Cheshmazar, E., Razmpoosh, E., Janani, L., Raji Lahiji, M., & Shidfar, F. (2021). Effects of synbiotic supplementation on serum adiponectin and inflammation status of overweight and obese breast cancer survivors: A randomized, triple-blind, placebo-controlled trial. Supportive Care in Cancer, 29(7), 4147–4157. https://doi.org/10.1007/s00520-020-05926-8 (B)
  12. Sharif, S., Van der Graaf, Y., Cramer, M. J., Kapelle, L. J., de Borst, G. J., Visseren, F. L. J., Westerink, J., & SMART study group. (2021). Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes. Cardiovascular Diabetology, 20(1), 220. https://doi.org/10.1186/s12933-021-01409-0
  13. Usharani, P., Mateen, A. A., Naidu, M. U. R., Raju, Y. S. N., & Chandra, N. (2008). Effect of NCB-02, atorvastatin and placebo on endothelial function, oxidative stress and inflammatory markers in patients with type 2 diabetes mellitus: A randomized, parallel-group, placebo-controlled, 8-week study. Drugs in R&D, 9(4), 243–250. https://doi.org/10.2165/00126839-200809040-00004 (B)
  14. Vaez, S., Parivr, K., Amidi, F., Rudbari, N. H., Moini, A., & Amini, N. (2023). Quercetin and polycystic ovary syndrome; inflammation, hormonal parameters and pregnancy outcome: A randomized clinical trial. American Journal of Reproductive Immunology , 89(3), e13644. https://doi.org/10.1111/aji.13644 (B)
  15. Valle Flores, J. A., Fariño Cortéz, J. E., Mayner Tresol, G. A., Perozo Romero, J., Blasco Carlos, M., & Nestares, T. (2020). Oral supplementation with omega-3 fatty acids and inflammation markers in patients with chronic kidney disease in hemodialysis. Applied Physiology, Nutrition, and Metabolism, 45(8), 805–811. https://doi.org/10.1139/apnm-2019-0729 (B)