ASRA News, November 2021

Diet and Dietary Supplements in Chronic Pain

Nov 1, 2021

Evan Z. Cohen, DO, and Tina Doshi, MD, MHS

Cite as: Cohen EZ, Doshi T. Diet and dietary supplements in chronic pain. ASRA News 2021;46. https://doi.org/10.52211/asra110121.070 


Dietary supplements are the most common complementary health approach for U.S. adults with musculoskeletal pain,1 but 80% of Americans report receiving conflicting dietary advice.2 Patients rely on physicians to provide evidence-based dietary recommendations, especially for medical conditions such as chronic pain. Every food possesses a unique combination of macronutrients (ie, fats, carbohydrates, and protein) and micronutrients (eg, vitamins, minerals) that can influence its overall health effects, and understanding those components is critical to evaluating the role of individual foods and overall diets in chronic pain.

 

Macronutrients

Dietary fat intake may modulate pain pathways by altering neuropeptide and hormone synthesis, and influencing serotonin, norepinephrine, and dopamine neurotransmission.3 Saturated fats, as found in butter, cheese, and animal products, are associated with risk for cardiovascular disease, obesity, and metabolic syndrome.4 Unsaturated fats include omega-3 and omega-6 polyunsaturated fatty acids (PUFAs), which are precursors for inflammatory mediator synthesis (e.g., prostaglandins).5 Both omega-3 and omega-6 PUFAs produce pro- and anti-inflammatory compounds, with omega-3 pathways often considered more anti-inflammatory and omega-6 more proinflammatory.6 Foods containing healthy omega fats are often rich in both: omega-3 sources include fish, chia, flax, walnuts, and soybeans, and omega-6 sources include vegetable and seed oils, walnuts, and avocado.

The U.S. Food and Drug Administration, Department of Health and Human Services, American Heart Association, and American College of Cardiology advocate minimizing saturated fat intake and substituting with polyunsaturated fats, particularly omega-3 PUFAs.7,8 A 2007 meta-analysis of inflammatory joint pain studies found that omega-3 supplementation (usually fish oil) was associated with significant reductions in joint pain intensity, minutes of morning stiffness, number of painful or tender joints, and nonsteroidal anti-inflammatory drug use.9 A 2018 cross-sectional study of patients with knee pain found that high ratios of omega-6 to omega-3 PUFAs, as seen in the typical American diet, were associated with increased pain, functional limitations, perception of stress, and experimentally evoked pain sensitivity.10 PUFA supplementation for chronic pain is typically 1–4 g daily, with clinical effects typically noted two to three weeks after initiation.9,11

Carbohydrates are classified as simple or complex. Simple carbohydrates (eg, sugar) are frequently found in processed foods and have a high glycemic index (ie, produce rapid increases in blood glucose). Complex carbohydrates (eg, fiber-rich carbohydrates, resistant starch), found in foods like whole grains, vegetables, and fruit, have a low glycemic index. Rapid spikes in glucose and insulin secretion are associated with release of proinflammatory mediators.12 Results from a 2020 randomized, controlled trial (RCT) demonstrated that a low-carbohydrate diet significantly reduced pain intensity in knee osteoarthritis compared to low-fat or control (usual) diet, with proportional reductions in serum markers of oxidative stress.13

Dietary proteins are not well studied in pain. Some preclinical evidence suggests that soy protein may have antinociceptive properties.14,15 Low-grade clinical evidence suggests that soy protein compared to milk protein could benefit patients with mastodynia16 and osteoarthritis pain,17 but a similar study in fibromyalgia patients found no benefit.18

 

Micronutrients

Vitamins, minerals, and other micronutrients may also have a role in mediating chronic pain. The B vitamins are eight vitamins necessary to normal immune and nervous system function, with limited data suggesting that B vitamin supplementation may be effective for nociceptive and neuropathic pain conditions, including osteoarthritis, low back pain, and peripheral neuropathy.19–21 However, specific B vitamins used, dosing, and comparators vary widely across studies, with most studies lacking long-term follow-up.

Vitamin D, found in oily fish and milk, maintains calcium homeostasis and modulates gene expression for cell growth, neuromuscular function, and immune function.22 A 2017 systematic review and meta-analysis found that vitamin D supplementation decreased chronic widespread pain, although it uncovered no correlation between change in pain scores and change in serum vitamin D levels.23

Magnesium has many physiologic functions, but its particular relevance to pain is its antagonism of the N-methyl-D-aspartate receptor, which serves a key role in central sensitization.24 In 2012, the American Academy of Neurology and American Headache Society provided a level B recommendation (ie, probably effective, should be considered) for magnesium to prevent migraine, with a typical dose of 600 mg daily.25 However, a 2020 systematic review of nine RCTs found mixed or no evidence of benefit for magnesium in most chronic pain conditions, concluding that the overall evidence was equivocal.26

Curcumin (the primary compound in turmeric), a polyphenol, is not an essential dietary component but possesses antioxidant and anti-inflammatory properties and may promote analgesia via COX inhibition, anti-TNF, and free radical scavenging.27 A 2015 systematic review of eight RCTs concluded that curcuminoids significantly reduced pain across a heterogeneous group of acute and chronic pain conditions.11

Almost all studies of micronutrients in chronic pain are limited by short-term follow-up, heterogeneous pain indications, and small sample sizes, making it difficult to gauge true efficacy. Nevertheless, over 97% of Americans consume less than the recommended amount of vitamin D, and 48% consume inadequate magnesium,28 so micronutrient supplementation may be indicated regardless of potential analgesic benefits. In addition, the above supplements are generally safe and well-tolerated, with few serious adverse events reported.

 

Dietary Programs and Pain

Some research has evaluated complete diets for chronic pain. Designed for testing in rodents, the Total Western Diet (TWD) mimics the average American diet, comprised of large quantities of red meat, dairy products, and processed and artificially sweetened foods, with little to no fruits, vegetables, fish, or whole grains.29 The TWD is high in saturated fats and simple carbohydrates, with fewer polyunsaturated fats, complex carbohydrates, essential vitamins, and minerals than recommended. Compared to mice fed a standard diet, those fed a TWD have increased mechanical and thermal pain sensitivity, increased weight gain, and elevated proinflammatory cytokine levels.30

Unlike the TWD, the Mediterranean diet is rich in fruits, vegetables, whole grains, and legumes, with a high ratio of monounsaturated to saturated fats. This diet can lower serum markers of inflammation and oxidative stress, with significant reductions in some (but not all) measures of pain and disability in inflammatory and non-inflammatory arthritis.31,32 A 2021 meta-analysis of 43 studies comparing various diets for chronic pain reported that although no single diet stands out, whole-food diets like the Mediterranean diet have an overall positive effect on pain reduction.33

Finally, intermittent fasting (IF) has recently gained popularity. IF is a straightforward method of caloric restriction, an intervention that can be challenging to implement but has robust evidence of health benefits.34 Limiting food consumption to 6–10 hours per day (or 500–1000 calories for one to two days per week) precipitates metabolic switching to ketogenesis, which in turn may reduce free radical production, improve glucose regulation, and decrease inflammation.34 Preclinical studies have demonstrated potential benefits of IF, some with direct relevance to chronic pain, including weight loss, reduced insulin resistance, enhanced cognitive function and delayed neurodegeneration, and amelioration of inflammatory and autoimmune states.34 There are currently no published RCTs evaluating IF in pain. Moreover, potential adverse effects of IF include irritability, reduced concentration, and hypoglycemia, so it may not be appropriate for all patients.35

Although physicians and patients have many dietary choices and supplements to consider, multimodal pain management can include counseling on patient-oriented nutritional interventions that optimize overall health and address important pain-related comorbidities, such as obesity, metabolic syndrome, and inflammation. Increasing consumption of whole foods, supplementing vitamin and mineral deficiencies, and regulating caloric intake are low-risk interventions that can provide modest benefits in chronic pain.

 


 

Dr. Evan Cohen
Evan Z. Cohen, DO, is a resident, postgraduate year 3, in the department of Physical Medicine and Rehabilitation at Johns Hopkins School of Medicine in Baltimore, MD.

 

Dr. Tina Doshi

Tina Doshi, MD, MHS, is an assistant professor of anesthesiology and critical care medicine in the Division of Pain Medicine at Johns Hopkins School of Medicine in Baltimore, MD.

References

  1. Clarke TC, Black LI, Stussman BJ, et al.. Trends in the use of complementary health approaches among adults: United States, 2002–2012. Natl Health Stat Report 2015;(79):1. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4573565
  2. International Food Information Council. 2017 food and health survey: food confusion. Published 2017. Accessed July 29, 2021. https://foodinsight.org/wp-content/uploads/2017/04/2017_Food_and_Health_Survey_-_Final_Report-rev.pdf
  3. Yehuda S, Rabinovitz S, Carasso RL, et al. Fatty acids and brain peptides. Peptides 1998;19(2):407–19. https://doi.org/10.1016/S0196-9781(97)00295-7
  4. Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity. Circulation 2016;133(2):187–225. https://doi.org/10.1161/CIRCULATIONAHA.115.018585
  5. Neitzel JJ. Fatty acid molecules: a role in cell signaling. Nat Educ 2010;3(9):57. https://www.nature.com/scitable/topicpage/fatty-acid-molecules-a-role-in-cell-14231940
  6. Bagga D, Wang L, Farias-Eisner R, et al. Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A 2003;100(4):1751–6. https://doi.org/10.1073/pnas.0334211100
  7. Van Horn L, Carson JAS, Appel LJ, et al. Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC) guidelines: a scientific statement from the American Heart Association. Circulation 2016;134(22):e505–29. https://doi.org/10.1161/CIR.0000000000000462
  8. U.S. Department of Agriculture, U.S. Department of Health and Human Services. Dietary guidelines for americans, 2020–2025. Published 2020. Accessed July 29, 2021. https://www.dietaryguidelines.gov/resources/2020-2025-dietary-guidelines-online-materials
  9. Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 2007;129(1-2):210–23. https://doi.org/10.1016/j.pain.2007.01.020
  10. Sibille KT, King C, Garrett TJ, et al. Omega-6:omega-3 PUFA ratio, pain, functioning, and distress in adults with knee pain. Clin J Pain 2018;34(2):182–9. https://doi.org/10.1097/AJP.0000000000000517
  11. Prego-Domínguez J, Hadrya F, et al. Polyunsaturated fatty acids and chronic pain: a systematic review and meta-analysis. Pain Physician 2016;19(8):521–35. https://doi.org/10.36076/ppj/2016.19.521
  12. Levitan EB, Cook NR, Stampfer MJ, et al. Dietary glycemic index, dietary glycemic load, blood lipids, and C-reactive protein. Metabolism 2008;57(3):437–43. https://doi.org/10.1016/j.metabol.2007.11.002
  13. Strath LJ, Jones CD, George AP, et al. The effect of low-carbohydrate and low-fat diets on pain in individuals with knee osteoarthritis. Pain Med (United States) 2020;21(1):150–60. https://doi.org/10.1093/pm/pnz022
  14. Totsch SK, Waite ME, Sorge RE. Dietary influence on pain via the immune system. Prog Mol Biol Transl Sci 2015;131:435–69. https://doi.org/10.1016/bs.pmbts.2014.11.013
  15. Tall JM, Raja SN. Dietary constituents as novel therapies for pain. Clin J Pain 2004;20(1):19–26. https://doi.org/10.1097/00002508-200401000-00005
  16. McFadyen IJ, Chetty U, Setchell KDR, et al. A randomized double blind cross-over trial of soya protein for the treatment of cyclical breast pain. Breast 2000;9(5):271–6. https://doi.org/10.1054/brst.1999.0149
  17. Arjmandi BH, Khalil DA, Lucas EA, et al. Soy protein may alleviate osteoarthritis symptoms. Phytomedicine 2004;11(7–8):567–75. https://doi.org/10.1016/j.phymed.2003.11.001
  18. Wahner-Roedler DL, Thompson JM, Luedtke CA, et al. Dietary soy supplement on fibromyalgia symptoms: a randomized, double-blind, placebo-controlled, early phase trial. Evid Based Complement Altern Med 2011;2011:350697. https://doi.org/10.1093/ecam/nen069
  19. Magaña-Villa MC, Rocha-González HI, Fernández del Valle-Laisequilla C, et al. B-vitamin mixture improves the analgesic effect of diclofenac in patients with osteoarthritis: a double blind study. Drug Res (Stuttg) 2013;63(6):289–92. https://doi.org/10.1055/s-0033-1334963
  20. Mibielli MA, Geller M, Cohen JC, et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Curr Med Res Opin 2009;25(11):2589–99. https://doi.org/10.3111/13696990903246911
  21. Ang CD, Alviar MJM, Dans AL, et al. Vitamin B for treating peripheral neuropathy. Cochrane Database Syst Rev 2008;3. https://doi.org/10.1002/14651858.CD004573.pub3
  22. National Institute of Health. Vitamin D health professional fact sheet. Published 2021. Accessed July 29, 2021. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional
  23. Yong WC, Sanguankeo A, Upala S. Effect of vitamin D supplementation in chronic widespread pain: a systematic review and meta-analysis. Clin Rheumatol 2017;36(12):2825–33. https://doi.org/10.1007/s10067-017-3754-y
  24. Shin H-J, Na H-S, Do S-H. Magnesium and pain. Nutrients 2020;12(8):1–13. https://doi.org/10.3390/NU12082184
  25. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache 2012;52(6):930–45. https://doi.org/10.1111/j.1526-4610.2012.02185.x
  26. Park R, Ho AMH, Pickering G, et al.. Efficacy and safety of magnesium for the management of chronic pain in adults: a systematic review. Anesth Analg 2020;131(3):764–75. https://doi.org/10.1213/ANE.0000000000004673
  27. Sun J, Chen F, Braun C, et al. Role of curcumin in the management of pathological pain. Phytomedicine 2018;48:129–40. https://doi.org/10.1016/J.PHYMED.2018.04.045
  28. U.S. Department of Agriculture Agricultural Research Service. Usual nutrient intake from food and beverages, by gender and age, what we eat in America, NHANES 2013–2016. Published 2019. Accessed July 29, 2021. http://www.ars.usda.gov/nea/bhnrc/fsrg
  29. Hintze KJ, Benninghoff AD, Ward RE. Formulation of the Total Western Diet (TWD) as a basal diet for rodent cancer studies. J Agric Food Chem 2012;60(27):6736–42. https://doi.org/10.1021/jf204509a
  30. Totsch SK, Waite ME, Tomkovich A, et al. Total Western Diet alters mechanical and thermal sensitivity and prolongs hypersensitivity following complete Freund’s adjuvant in mice. J Pain 2016;17(1):119–25. https://doi.org/10.1016/j.jpain.2015.10.006
  31. Veronese N, Stubbs B, Noale M, et al. Adherence to a Mediterranean diet is associated with lower prevalence of osteoarthritis: data from the osteoarthritis initiative. Clin Nutr 2017;36(6):1609–14. https://doi.org.10.1016/j.clnu.2016.09.035
  32. Hagen KB, Byfuglien MG, Falzon L, et al. Dietary interventions for rheumatoid arthritis. Cochrane Database Syst Rev 2009;1. https://doi.org/10.1002/14651858.CD006400.pub2
  33. Field R, Pourkazemi F, Turton J, et al. Dietary Interventions are beneficial for patients with chronic pain: a systematic review with meta-analysis. Pain Med 2021;22(3):694-714. https://doi.org/10.1093/pm/pnaa378
  34. de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med 2019;381(26):2541–51. https://doi.org/10.1056/nejmra1905136
  35. Lamos EM, Malek R, Munir KM. Effects of intermittent fasting on health, aging, and disease. Reply. N Engl J Med 2020;382(18):1771–4. https://doi.org/10.1056/NEJMc2001176
Close Nav