Long-Term Inflammation Support Supplement Protocol
Mark Hyman, M.D.’s
Long-Term Inflammation Support
Protocol overview
Last updated: May 13, 2025
8 Nutrients
Omega-3 fatty acids
600mg
Omega-3 fatty acids, particularly EPA and DHA, help support a healthy inflammatory response and influence inflammatory signaling, including cytokine-related pathways. They support healthy cells and immune balance, which can support overall wellness. [1]
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Download the appVitamin D3
125mcg
Vitamin D helps support normal immune function and, in some research settings, has been associated with favorable shifts in inflammatory markers such as C-reactive protein (CRP). Its role as a negative acute-phase reactant suggests involvement in regulating inflammatory responses and supporting overall immune balance. [2]
N-Acetylcysteine
600mg
N-acetylcysteine (NAC) supports glutathione levels, an important antioxidant involved in the body’s natural defenses and healthy inflammatory balance. NAC may help support a healthy inflammatory response and immune function, in part by influencing inflammatory signaling pathways such as NF-κB. [3]
Turmeric Curcumin
500mg
Turmeric (curcumin) may help support a healthy inflammatory response, and research has observed favorable shifts in some inflammatory markers, such as C-reactive protein (CRP), in certain populations. [4]
Quercetin
500mg
Quercetin may help support a healthy inflammatory response by influencing the production of certain inflammatory signaling molecules. Its antioxidant properties support the reduction of oxidative stress, potentially contributing to a balanced immune response and decreased inflammation. [5]
Luteolin
100mg
Luteolin may help support a healthy inflammatory response by influencing inflammatory signaling pathways, including cytokine-related pathways such as TNF-α and IL-6. [6]
Rutin
100mg
Rutin may help support a healthy inflammatory response, in part by influencing inflammatory signaling pathways such as NF-κB and MAPK. It has antioxidant activity and may help support healthy inflammatory signaling. [7]
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Warnings
Avoid taking these supplements with medications such as blood thinners or specific antibiotics, as they may interact and increase risks like bleeding or reduced effectiveness. Avoid if you have allergies to their sources (e.g., citrus, dairy, soy) or conditions like kidney disease, gallstones, or hypercalcemia. Pregnant or breastfeeding individuals, or those with bleeding disorders should consult a healthcare provider before use.
Lifestyle Improvements
Long-term inflammation is associated with many health conditions and aging-related changes, and lifestyle steps can help support a healthy inflammatory balance and overall well-being. Here are practical lifestyle changes to incorporate into your daily routine:
Prioritize a Whole-Food Diet
Focus on nutrient-dense, unprocessed foods to minimize hidden sources of inflammation. Avoid sugar, refined starches, trans fats, and industrial seed oils, as these are key drivers of chronic inflammation. Instead, emphasize:
- Colorful fruits and vegetables rich in phytochemicals to combat oxidative stress.
- Healthy fats like extra virgin olive oil, avocados, and omega-3s from wild-caught fish.
- High-fiber foods to support gut health and reduce endotoxins that can trigger inflammation.
Move Daily
Incorporate exercise into your routine, such as cardio, resistance training, or yoga. Regular physical activity supports your immune system, balances blood sugar, and helps reduce stress, all of which lower inflammation.
Manage Stress
Chronic stress fuels inflammation, so finding ways to calm your nervous system is key. Try meditation, breathwork, or yoga. Incorporate activities like sauna therapy, cold immersion, or even a daily walk in nature to restore balance and promote relaxation.
Address Environmental Toxins
Minimize exposure to environmental toxins like pesticides, heavy metals, and synthetic chemicals in food, household products, and skincare. Simple swaps can significantly reduce your toxic burden.
Support Gut Health
Your gut health plays a critical role in regulating inflammation. Diets high in processed foods and low in fiber can be associated with unfavorable shifts in the gut microbiome and markers linked to inflammation. Support a balanced microbiome by consuming fermented foods, high-fiber vegetables, and targeted gut supplements. Consider addressing food sensitivities like gluten or dairy through an elimination diet to identify and avoid triggers.
Optimize Sleep
High-quality sleep is essential for cellular repair and reducing inflammation. Aim for restorative sleep each night and establish a consistent bedtime routine to support your circadian rhythm. Poor sleep disrupts hormonal balance and increases inflammatory markers like C-reactive protein.
By supporting a healthy inflammatory balance through these foundational steps, you can support long-term health and overall well-being.
Disclaimer
These statements have not been evaluated by the Food and Drug Administration. Any products and informational content displayed on this page are not intended to diagnose, treat, cure, or prevent any disease.
While this Protocol has been created by health experts, it is educational in nature and not a substitute for personalized medical advice. Always consult with your healthcare provider before starting any new supplement regimen, especially if you have underlying health conditions or take medications.
- Poggioli, R., Hirani, K., Jogani, V. G., & Ricordi, C. (2023). Modulation of inflammation and immunity by omega-3 fatty acids: A possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders. European Review for Medical and Pharmacological Sciences, 27(15), 7380–7400. https://doi.org/10.26355/eurrev_202308_33310
- Antonelli, M. J., Kushner, I., & Epstein, M. (2023). The constellation of vitamin D, the acute-phase response, and inflammation. Cleveland Clinic Journal of Medicine, 90(2), 85–89. https://doi.org/10.3949/ccjm.90a.22048
- Santus, P., Signorello, J. C., Danzo, F., Lazzaroni, G., Saad, M., & Radovanovic, D. (2024). Anti-inflammatory and anti-oxidant properties of N-acetylcysteine: A fresh perspective. Journal of Clinical Medicine, 13(14), 4127. https://doi.org/10.3390/jcm13144127
- Rapti, E., Adamantidi, T., Efthymiopoulos, P., Kyzas, G. Z., & Tsoupras, A. (2024). Potential applications of the anti-inflammatory, antithrombotic, and antioxidant health-promoting properties of curcumin: A critical review. Nutraceuticals, 4(4), 562–595. https://doi.org/10.3390/nutraceuticals4040031
- Javadi, F., Ahmadzadeh, A., Eghtesadi, S., Aryaeian, N., Zabihiyeganeh, M., & Rahimi Foroushani, A. (2016). The effect of quercetin on inflammatory factors and clinical symptoms in women with rheumatoid arthritis: A double-blind, randomized controlled trial. Journal of the American College of Nutrition, 35(1), 9–15. https://doi.org/10.1080/07315724.2016.1140093
- Conti, P., Caraffa, A., Gallenga, C. E., Ross, R., Kritas, S. K., Frydas, I., Younes, A., Di Emidio, P., Ronconi, G., & Pandolfi, F. (2021). Powerful anti-inflammatory action of luteolin: Potential increase with IL-38. Biofactors, 47(4), 451–459. https://doi.org/10.1002/biof.1718
- Ganeshpurkar, A., & Saluja, A. K. (2017). The pharmacological potential of rutin. Saudi Pharmaceutical Journal, 25(2), 149–164. https://doi.org/10.1016/j.jsps.2016.04.025
- Lorzadeh, E., Ramezani-Jolfaie, N., Mohammadi, M., Khoshbakht, Y., & Salehi-Abargouei, A. (2019). The effect of hesperidin supplementation on inflammatory markers in human adults: A systematic review and meta-analysis of randomized controlled clinical trials. Chemico-Biological Interactions, 307, 8–15. https://doi.org/10.1016/j.cbi.2019.04.016