3 Ways Nutrition Can Help with Acute Pain and Inflammation

3 Ways Nutrition Can Help with Acute Pain and Inflammation

I know it’s been awhile since I’ve posted here. One reason is I’ve been busy with the launch of FunctionalMedicineCE.com a few months ago. We are hosting our second virtual symposium in a few weeks on February 29th. Dr. Frank Bodnar, DC is one of our speakers and he wrote this great post about ways we can use nutrition in inflammation and addressing pain. I hope this is beneficial to both pharmacists and patients out there as we journey on to healing together.

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Pharmacists play a crucial role in treating acute pain and inflammation. If patients don’t head to the emergency room or urgent care center, their local pharmacy is certainly the next destination. The advantage as a pharmacist is that managing acute conditions doesn’t have to require a lengthy consultation or a complex workup. While providing clarity on the best over-the-counter analgesic to help manage acute symptoms is crucial, the value pharmacists can provide extends well beyond the normal transaction. You observe not only the grimaces, body language and postures of different pain issues but can offer an effective nutraceutical solution that targets the same biochemical pathway as traditional pharmaceuticals that a patient would otherwise never hear about.   

It’s fair to say that most pharmacists want the best for their patients’ health and are a highly trusted player on the patient’s health care team. Offering nutritional recommendations to a patient’s self-care acute pain strategy doesn’t have to be complicated. The most common traditional treatments of acute pain and inflammation reinforce blocking inflammation as the primary strategy. Nutraceuticals also have literature that show NFkB, PLA2, 5-LOX, COX-2 and COX-1 pathway modulation and clinical efficacy with a variety of inflammatory conditions.^1-5

No clinician would disagree that controlling inflammation, reducing pain and improving a patient’s function as quickly as possible are good, ethical strategies. A patient-centered pharmacist understands not only the side effects and nutrient depletions but the best long-term healing mechanisms that should be considered as well. The value is more complete healing, less future pain and a satisfied patient that will let others know about their experience and your expertise.

Acute pain and inflammation can last anywhere from 1-3 days, with cardinal signs of heat, redness, swelling, pain and loss of function lingering a bit longer. Acute inflammation is driven by the body’s immune system responding to tissue injury and plays a key role in stimulating the pain signaling from the peripheral tissue. Local chemokines and pain hormones signal the initiation of vasodilation, white blood cell infiltration and clotting factors and immunoglobulins, soon followed by tissue regenerating cells such as fibroblasts. Biochemically we see acute-phase proteins such as C-reactive protein (CRP), cytokines, growth factors, eicosanoids, adhesion molecules and matrix metalloproteinases elevated.⁶If inflammation and free radical damage continues tissue injury and fibrosis can occur.⁷

The body does a great job of stopping the damage, cleaning the injured area and quickly beginning the repair process, and we want to support these processes as much as possible rather than just focusing on their inhibition. Emerging studies are showing that blocking the inflammatory response may result in delayed healing in bone in the short-term and possibly other connective tissues over the long run, possibly resulting in tissue that is at risk for future irritation and injury.^8,9 Diet and supplementation have been shown to support healing and inflammatory mechanisms¹⁰ and offer a key strategy beyond resting, icing, compressing and elevating (RICE) an injury. 

During acute pain and inflammation there are three primary nutritional recommendations that can be incorporated to enhance your patient’s outcomes.

1. 14-Day Anti-Inflammatory Diet: even with trauma, infection and surgery implementing a diet that focuses on fresh fruits, vegetables, nuts, seeds, anti-inflammatory fats and high-quality sources of protein can enhance the acute healing process and help reduce the potential for pain and inflammation to be further perpetuated. Omega-3 fatty acids, monounsaturated fatty acids, phytonutrients that are packed with antioxidants and natural anti-inflammatory compounds and lean proteins all play pivotal roles in reducing the inflammatory response and aiding in the healing process. The Anti-Inflammatory diet template and should include high amounts of nutrient dense foods:
   1. Protein: Fish, lean meat (beef, chicken), omega-3 eggs, high-quality rice and pea protein powders
   1. Green leafy and cruciferous vegetables: kale, collard greens, spinach, red cabbage, beets, watercress, romaine lettuce, cauliflower, broccoli, artichokes and brussels sprouts
   1. Healthy fats: avocado, olive oil, coconut oil and see list of nuts and seeds
   1. Fruits (high in antioxidants and fiber): strawberries, blueberries, blackberries, raspberries, cranberries, red or purple grapes, kiwi, pineapple, grapefruit, apples, pomegranate, mango, oranges, apples, papaya and cherries
   1. Tubers and others: sweet potatoes, carrots, acorn squash and butternut squash, zucchini, beans, olives, tomatoes, peppers, onions and garlic
   1. Nuts and seeds: almonds, pistachios, walnuts, cashews, pecans, macadamia, brazil nuts, and hazelnuts 

• Whole Turmeric Matrix Supplementation: 500 – 1,000 mg/day for 14 days

The phytochemical analysis of turmeric has revealed that there are 200-plus bioactive molecules present in the natural matrix of turmeric that contribute to its health benefits. The main constituents are the curcuminoids, which include curcumin, demethoxy curcumin and bis-demethoxy curcumin. In addition to this, the non-curcuminoid components like turmerin, turmerones, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone^11-14all showing the ability to reduce pain and inflammation separate from curcumin.^15,16,19-23The broad-spectrum of bioactives mechanistically go above and beyond the primary targets traditional therapies (COX-2, 5-LOX and TNF-α). Whole turmeric root modulates NFkB and pretty much every downstream cytokine and growth factor resulting in less COX-2 activation, MAPK p38 pathway modulation and iNOS expression,^12,13which for a patient means less pain, less inflammation and less swelling. Recently, scientists have discovered that the microbiome metabolizes these bioactives and they enhance the anti-inflammatory signaling capacity of turmeric’s bioactives. Studies show turmeric’s bioactives increase microbiome diversity, inhibit and protect the body from LPS-induced inflammation,¹⁷fortifying enterocyte tight junctions and increasing afferent vagus nerve signaling.¹⁸These broad mechanisms provide a range of benefits that truly match the mechanistic needs of arthritic joints beyond a wear and tear, and local inflammatory approach. 

Multiple double-blind, placebo-controlled clinical trials of osteoarthritis and rheumatoid arthritis patients have shown not only a decrease in pain, increase in joint function, and improved inflammatory and autoimmune biomarkers, but have also outperformed NSAIDs in head-to-head trials.^15,19-23

• Flavonoid and Bromelain Supplementation Recommendation: Bromelain 240 mg (576 GDU)/day, Quercetin Dihydrate 240 mg/day, and Rutin 50 mg/day for 14 days. 

Bromelain is a mixture of enzymes found in the stem of the pineapple (Ananas comosus) that exhibit proteolytic characteristics. Bromelain also supports the chondrocyte’s normal cell cycle via the p53, NFkB and Bcl-2 pathways, and balances IL-1B, IL-6, INF-y, TNF-α cytokines via PGE-2 and COX-2 activity during normal local immune responses. Locally bromelain modulates plasma kinins and fibrin/fibrinogen proteins via MMP, VEGF, bFGF, and EGF activity which all contribute to normal vascular and blood supply to connective tissue and prevent excess fibrosis.²⁴

• A randomized, double-blinded, placebo-controlled study done on performed on 176 boxers found that bromelain supported exercise recovery with notable improvements in bruising on the face and orbits, lips, ears, chest and arms in as little as four days compared to placebo.²²
• A 2017 randomized clinical study published in Rheumatology and Orthopedic Medicine, compared standard medical therapies to proteolytic enzyme therapy in 74 patients with acute joint pain. Patients were evaluated with joint outcome measures, VAS score, hs-CRP, ESR, and liver (ALT, AST) and kidney (creatinine) markers. The results showed that bromelain lowered hs-CRP, ESR improved joint function scores and while keeping normal liver and kidney function and showing no damage the gastric mucosa.²³

Quercetin is a powerful antioxidant flavonoid in plants including oak trees, onions and tea. Cell studies show quercetin inhibits COXs and LOX enzymes which produce prostaglandins and leukotrienes; reduces inflammatory pain by inhibiting oxidative stress and cytokine production; LPS-induced TNF-a, IL-8, IL-1a release; prevents mast cell release of histamine and inhibits adhesion molecules such as VCAM-1.²⁵Similar to turmeric quercetin has also been shown to support barrier function in the intestines,^26,27modulate NFkB, MAP kinases and inhibit hyaluronidases and MMPs, which are degradatory connective tissue enzymes.²⁵

• A 2019 meta-analysis combined the data of six randomized controlled trials consistent improvements in the acute-phase biomarker, hs-CRP, and while other cytokines such as IL-6 and TNF-a were found to be decreased in individual studies a statistical significance wasn’t reached in the combined data. Overall the authors concluded that quercetin supplementation for pain and inflammation is a promising therapeutic.²⁸

Rutin is a flavonol found abundantly in plants such as apples, tea, buckwheat and passionflower. Rutin supports connective tissue health by inhibiting the enzymes hyaluronidase, collagenase, LOX and COXs, which all contribute to the degradation of connective tissue, and exhibits neuroprotective, analgesic, antiarthritic, broad-spectrum anti-inflammatory support and speeds wound healing in vitro.²⁹

• A meta-analysis of six randomized controlled trials published in the Journal of Pain Research, compared 270 knee patients who received a combination of rutin and bromelain (OEC) to 266 standard patients who received standard medical therapy. The authors found OEC to be comparable for efficacy while tolerable and safe.³⁰

References:

1. Al-Okbi, S. (2012). Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health, 30(8), 738-749. 
2. Sevda Inan (2019). The Potential Role of Nutraceuticals in Inflammation and Oxidative Stress, Nutraceuticals – Past, Present and Future, María Chávarri Hueda, IntechOpen, DOI: 10.5772/intechopen.83797.
3. Gupta, S., Prasad, S., & Aggarwal, B. (2016). Anti-inflammatory Nutraceuticals and Chronic Diseases(1st ed., pp. 1-25). Cham: Springer International Publishing.
4. Al-Okbi, S. (2012). Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis. Toxicology and Industrial Health, 30(8), 738-749.
5. Ravalli S, Szychlinska MA, Leonardi RM, Musumeci G. Recently highlighted nutraceuticals for preventive management of osteoarthritis. World J Orthop 2018; 9(11): 255-261
6. Jain, S., Gautam, V., & Naseem, S. (2011). Acute-phase proteins: As diagnostic tool. Journal of pharmacy & bioallied sciences, 3(1), 118–127. doi:10.4103/0975-7406.76489
7. Edwards, S. (2020). Pathophysiology of Inflammation – Pharmacology – Manual. Retrieved 10 Jan. 2020, from https://www.merckvetmanual.com/pharmacology/anti-inflammatory-agents/pathophysiology-of-inflammation
8. Su, B., & O’Connor, J. (2013). NSAID therapy effects on healing of bone, tendon, and the enthesis. Journal of Applied Physiology, 115(6), 892-899. doi: 10.1152/japplphysiol.00053.2013 
9. Serra, M., et al. (2017). From Inflammation to Current and Alternative Therapies Involved in Wound Healing. International Journal of Inflammation, 2017, 1-17. doi: 10.1155/2017/3406215
10. Seaman, D. (2017). An Anti-inflammatory Diet for Pain Patients. Retrieved 10 February 2020, from https://www.practicalpainmanagement.com/treatments/complementary/anti-inflammatory-diet-pain-patients
11. Suzuki, M and T Nakamura. “Elucidation of Anti-Allergic Activities of Curcumin-Related Compounds with a Special Reference to their .” Biol. Pharm(2005): 1438-1443 
12. Panahi, Y., Darvishi, B., Ghanei, M., Jowzi, N., Beiraghdar, F., & Varnamkhasti, B. (2016). Molecular mechanisms of curcumins suppressing effects on tumorigenesis, angiogenesis and metastasis, focusing on NF-κB pathway. Cytokine & Growth Factor Reviews, 28, 21-29. 
13. Camacho-Barquero, L., Villegas, I., Sánchez-Calvo, J., Talero, E., Sánchez-Fidalgo, S., Motilva, V., & Alarcón de la Lastra, C. (2007). Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. International Immunopharmacology, 7(3), 333-342. 
14. Kumar S, Ahuja V, Sankar MJ, Kumar A, Moss AC. Curcumin for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev(2012 Oct 17;10:CD008424.
15. Daily, J and Mini, Park, S Yang. “Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trial. Journal of Medicine Food(2016): 717-729
16. Amalraj, A, K Varma and Joby Jacob. “A Randomized, Double Blind, Placebo-Controlled, Two Dose, Three Arm, and Parallel-Group Study.” Journal of Medicinal Food(2017): 1022-1030
17. Peterson, C., Vaughn, A., Sharma, V., Chopra, D., Mills, P., Peterson, S., & Sivamani, R. (2018). Effects of Turmeric and Curcumin Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study. Journal of Evidence-Based Integrative Medicine, 23, 2515690X1879072. doi: 10.1177/2515690×18790725
18. Wang, J., Ghosh, S., & Ghosh, S. (2017). Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions. American Journal of Physiology-Cell Physiology, 312(4), C438-C445. 
19. ZHAO, F., GONG, Y., HU, Y., LU, M., WANG, J., & DONG, J. et al. (2014). Curcumin and its major metabolites inhibit the inflammatory response induced by lipopolysaccharide: Translocation of nuclear factor-κB as potential target. Molecular Medicine Reports, 11(4), 3087-3093. doi: 10.3892/mmr.2014.3079
20. Rathnavelu, V., Alitheen, N., Sohila, S., Kanagesan, S., & Ramesh, R. (2016). Potential role of bromelain in clinical and therapeutic applications. Biomedical Reports, 5(3), 283-288. 
21. Pavan, R., Jain, S., Shraddha, & Kumar, A. (2012). Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, 2012, 1-6. 
22. Blonstein JL, Practitioner, Control of swelling in boxing injuries. 01 Aug 1969, 203(214):206].
23. LS, M., M, et al. (2017). Efficacy of a combination of fixed doses of serratiopeptidases, bromelain and methylsulfonylmethane in inflammatory joint diseases. Rheumatology And Orthopedic Medicine, 2(3).
24. Pavan, R., Jain, S., Shraddha, & Kumar, A. (2012). Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International, 2012, 1-6.
25. Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M., & Wang, S. et al. (2016). Quercetin, Inflammation and Immunity. Nutrients,8(3), 167.
26. Lee, B., Moon, K., & Kim, C. (2018). Tight Junction in the Intestinal Epithelium: Its Association with Diseases and Regulation by Phytochemicals. Journal of Immunology Research, 2018, 1-11.
27. Amasheh M, et al. Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells. J Nutr2008 Jun;138(6):1067-73.
28. Ou, Q., Zheng, Z., Zhao, Y., & Lin, W. (2019). Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials. International Journal Of Food Sciences And Nutrition, 1-12.
29. Ganeshpurkar, A., & Saluja, A. (2017). The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal, 25(2), 149-164.
30. Ueberall, M., Mueller-Schwefe, G., Wigand, R., & Essner, U. (2016). Efficacy, tolerability, and safety of an oral enzyme combination vs diclofenac in osteoarthritis of the knee: results of an individual patient-level pooled reanalysis of data from six randomized controlled trials. Journal Of Pain Research, (9), 941-961.