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.
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)
- 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)
Omega-3 fatty acids (EPA/DHA)
- 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)
- 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)
- 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)
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- 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
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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
- 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)
- 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
- 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)
- 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)
- 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)
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