July/August 2019

Pain: The Role of Nutrition
By KC Wright, MS, RDN, LD
Today’s Geriatric Medicine
Vol. 12 No. 4 P. 14

Data from the 2012 National Health Interview Study showed that more than 25 million American adults had pain every day for the preceding three months.1 Chronic pain can be debilitating and have a significant socioeconomic impact.2 Beyond surgery and other interventions, both prescription and nonprescription medications have been standard protocol to help mitigate chronic pain. Long-term use of pharmacologics can have unwanted side effects and a high risk of addiction, especially with opioids. Pain is one of the leading reasons Americans turn to complementary healing modalities such as yoga, massage, meditation, and nutritional supplements that may help attenuate pain.3

Many individuals with chronic pain have elevated levels of proinflammatory cytokines in blood and tissues, a normal biologic process in response to injury, infection, or irritation.4 If the inflammatory process persists, it can develop into a chronic condition associated with chronic pain. Emerging literature suggests certain nutrients may help alleviate chronic pain through management of inflammation via oxidative stress. As many whole foods comprise bioactive compounds with anti-inflammatory effects, diet and nutrition should be integrated in the approach to treating older adults with chronic pain.

Anti-Inflammatory Diet
The United States’ food supply is flooded with empty-calorie processed foods containing unhealthful fats, refined carbohydrates, sugar, and sodium. This Western diet is low in fiber, micronutrients, and antioxidants, and is considered proinflammatory. Studies looking at the influence of diet on inflammatory markers show that consumption of foods high in fiber, healthful oils, fruits, vegetables, and those low in sugars, starchy carbohydrates, and unhealthful fats can reduce inflammation and disease.3 Consumption of fruits and vegetables, which contain many vitamins, minerals, and antioxidants, is inversely associated with inflammation and oxidative stress; the higher the intake of plant foods, the lower the occurrence of oxidative stress.4 Specifically, to reduce proinflammatory cytokines and reactive oxygen species, a minimum daily intake of five servings of fruits and vegetables is recommended.

High–glycemic index foods such as white bread are rapidly digested, cause substantial increases in blood sugar levels after being eaten, and may contribute to oxidative stress and low-grade inflammation, both in acute and chronic pain. Whole grain foods have a low glycemic index and are rich in bioactive compounds (eg, polyphenols, phytic acid, and lignin) with anti-inflammatory properties, including the reduction of free radicals and the activation of antioxidant enzymes. A recent study confirmed that a low–glycemic index diet was more effective in reducing chronic inflammation as measured by lower concentrations of C-reactive protein than was a high–glycemic index diet.4

Extra-virgin olive oil (EVOO) is the main source of fat in the Mediterranean diet. The high concentration of monounsaturated fat and many bioactive compounds such as polyphenols in EVOO characterize its anti-inflammatory and antioxidant properties. (Other seed oils don’t have the same benefit as EVOO.) This could explain why the incidence of cancer and heart diseases is lower in the Mediterranean basin than in other geographic areas. When phenolic phytochemicals were extracted from EVOO and evaluated for their nutraceutical properties, they were found to be effective in treating knee pain in early-stage knee osteoarthritis.4

Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are essential and must be obtained from the diet. Western diets tend to be higher in omega-6 PUFAs than omega-3s (ranging from a 10:1 to 20:1 ratio or higher), with each PUFA having an opposite function along the cyclo-oxygenase pathway—the enzymatic route that converts fatty acids to prostaglandins that mediate inflammation and pain. Omega-6 PUFAs stimulate inflammation, whereas omega-3 PUFAs decrease inflammation. The predominant omega-6 PUFA is linoleic acid, which is found in corn, sunflower, safflower, soybean, and sesame oils, as well as in nuts and seeds. In a randomized controlled trial involving 56 patients, omega-3 fats were increased and omega-6 fats were decreased, resulting in reduced headache pain,3 although there are few other studies that suggest a diet higher in omega-6 PUFAs compared with omega-3 PUFAs increases chronic inflammation.5

The most potent omega-3 PUFAs—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are found mainly in cold water fish, such as salmon, mackerel, tuna, herring, pompano, swordfish, trout, and sardines. Another omega-3 fat, alpha-linolenic acid (ALA), is found in vegetable oils (eg, flaxseed, soybean, canola), nuts (especially walnuts), ground flaxseed and flaxseed oil, leafy vegetables, and some animal fat, especially from grass-fed livestock. The human body generally uses ALA for energy, because it’s inefficient in converting it into EPA and DHA,6 especially in aging.4

The strongest evidence for the dietary benefits of omega-3 fats pertains to their ability to reduce potentially fatal arrhythmias.7 Omega-3 fats also lower blood pressure and heart rate, improve blood vessel function, and—at higher doses than those typically found in the diet—may lower triglycerides and ease inflammation. There’s evidence that omega-6 fats also positively influence cardiovascular risk factors, but, as they are ubiquitous in the diet, it’s only prudent to increase consumption of omega-3 fats. Dietary guidelines recommend eating 8 oz (approximately two servings) of seafood per week, particularly fatty, darker meat fish that are richer in EPA and DHA.

There are many nutritional supplements that offer omega-3 fats, but the source, dosage, and interactions with medications all should be considered. Various research has found that subjects used fewer NSAIDs when they were treated with omega-3 fats for rheumatoid arthritis, and an analgesic effect has been shown with supplementation for inflammatory joint pain.3 Omega-3 supplement doses used in many studies range from 3,000 to 4,000 mg of combined EPA and DHA, which usually can be found in 6,000 to 8,000 mg of fish oil. In most good-quality microdistilled fish oil preparations, EPA and DHA combined will be about one-half the amount of the dosage. For example, a 1,000-mg capsule may have 230 mg of EPA and 270 mg of DHA for a total of 500 mg of the omega-3 PUFAs.

High red meat consumption is associated with elevated plasma concentrations of inflammatory biomarkers. An eight-week intervention in which two groups of subjects were given either meat or legumes for protein showed a significant difference in the inflammatory marker for high sensitivity C-reactive protein from -1.3 (meat) to 1.7 (legume, p=0.019).4 Legumes and other plant foods high in water-insoluble fiber are also beneficial for any patients with chronic pain who may suffer from opioid-induced constipation. Red wine is rich in numerous molecules that fight inflammation and oxidation, in particular flavonoids.3 Moderate consumption—a 5-oz glass daily for women (<2 for men)—merits consideration in the absence of opioid use.

Turmeric and ginger are related tubers that have been studied extensively for their anti-inflammatory properties. A systematic review of ginger concluded that it’s a powerful anti-inflammatory that’s useful in treating pain because it disrupts the cyclooxygenase-2 pathway that promotes inflammation.3

Although curcumin, the active component of turmeric, has been found to have effects similar to those of ibuprofen for osteoarthritis of the knee and to be useful for postoperative pain,3 several well-controlled clinical studies have failed to show clinical benefits with curcumin.8 The bioavailability of curcumin may explain differing research outcomes. Formulations of bioavailability-enhanced curcumin have been shown to overcome absorption issues and are now the most commonly used types of curcumin supplements.9 The turmeric root or rhizome made into a powder or extract appears to be the active form (compared with the leaf and flower) with a suggested dose of 1,000 mg. The optimal dose of curcumin hasn’t yet been established.

Nutritional Supplements
Glucosamine and chondroitin are naturally occurring substances in the body and are the major structural components of cartilage, the tough, elastic connective tissue found in joints. Although consumers commonly used them as nutritional supplements for knee pain, research is mixed on the effectiveness of glucosamine and/or chondroitin for reducing pain, perhaps due to the variation that exists among different trial protocols. A 16-week double-blinded, randomized, placebo-controlled trial of 34 males found that a combination of glucosamine hydrochloride (1,500 mg/day) and chondroitin sulfate (1,200 mg/day) relieved symptoms of degenerative joint disease of the knee and lower back.10 The visual analog scale for pain recorded at clinic visits decreased by 26.6%. Similarly, a systematic meta-analysis showed that glucosamine and chondroitin was efficacious for treatment of osteoarthritis.11

However, another randomized controlled trial of 205 subjects with knee osteoarthritis indicated that glucosamine was no more effective than placebo.12 In addition, a multicenter, double-blind, placebo-controlled trial evaluated 1,583 randomly assigned patients with symptomatic knee osteoarthritis, but neither glucosamine nor chondroitin sulfate reduced pain effectively overall in the group of patients with knee osteoarthritis.13

Another similar multicenter trial randomly assigned 605 patients with chronic knee pain to four groups taking glucosamine, chondroitin, both, or a placebo.14 All four groups demonstrated a reduction in knee pain, with the glucosamine and chondroitin combination group demonstrating significant reduction in joint space narrowing at the two-year follow-up visit. Overall, a critical review of the use of these nutritional supplements summarized that treatment produced conflicting evidence.2 Taken in appropriate amounts, glucosamine and chondroitin generally are considered safe for healthy people not taking any other medications. In some individuals, glucosamine can cause gastrointestinal discomfort, drowsiness, skin reactions, and headache, while chondroitin occasionally can cause stomach upset.13

Vitamins, Minerals, and Water
Deficiencies of vitamin D have been consistent among populations within the Northern Hemisphere and appear to be more common in the elderly.15,16 Those with chronic pain have more significant deficiencies.17,18 Data from literature have explained the link between vitamin D and chronic pain, demonstrating that low levels of vitamin D are associated with increased central hypersensitivity, such as increased sensitivity to mechanical pain and severity of somatic symptoms in chronic pain patients.4 An improvement in pain has been shown with mere supplementation of vitamin D.19 The Recommended Dietary Allowances (RDAs) for both men and women aged 70 and older increase from the recommendation for those under age 70 of 600 IU to 800 IU per day, with the Tolerable Upper Intake Level set at 4,000 IU per day.20

Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis.21 Deficiencies of vitamin B12 are well known to contribute to neurologic dysfunction and chronic pain.3 Recent human studies have shown that the intramuscular injection of vitamin B12 is significantly important for the treatment of localized pain in the spine.4

In food, vitamin B12 is bound to protein but is released during digestion by the activity of hydrochloric acid and gastric protease in the stomach. It then combines with intrinsic factor, a glycoprotein secreted by the stomach’s parietal cells, for absorption. Older people are at an increased risk for vitamin B12 deficiency for several reasons. Atrophic gastritis affects 10% to 30% of older adults and decreases secretion of hydrochloric acid in the stomach, resulting in decreased absorption of vitamin B12. Pernicious anemia, a condition that affects 1% to 2% of older adults, is characterized by a lack of intrinsic factor; thus, individuals cannot properly absorb B12 in the gastrointestinal tract. Pernicious anemia typically is treated with intramuscular vitamin B12. However, approximately 1% of oral vitamin B12 can be absorbed passively in the absence of intrinsic factor, suggesting that high oral doses also may be an effective treatment.

Older individuals with gastrointestinal disorders, such as celiac or Crohn’s disease, or those who have had gastrointestinal surgery, may also be at risk of vitamin B12 deficiency. The Institute of Medicine recommends that adults older than 50 obtain most of their vitamin B12 from vitamin supplements or fortified foods, though some elderly patients with atrophic gastritis require doses much higher than the RDA to avoid subclinical deficiency. Vitamin B12 injections in patients with pain who weren’t B12 deficient resulted in reduced pain scores and less analgesic use in both active treatment arms of a double-blind, placebo-controlled crossover trial.3

Magnesium is an abundant mineral in the body and naturally present in many foods, but older adults have lower intakes, and magnesium absorption from the gut decreases while renal magnesium increases with age. In addition, some medications (including bisphosphonates, antibiotics, diuretics, and protein pump inhibitors) can alter magnesium status, which can further decrease risk of magnesium depletion.22

Magnesium deficiency is related to factors that promote migraine headaches, including neurotransmitter release and vasoconstriction. Although research on the use of magnesium supplements to prevent or reduce symptoms of migraines is limited, the American Academy of Neurology and the American Headache Society concluded that magnesium therapy is “probably effective” for migraine prevention.23 Magnesium also is being studied for its role in neuropathic pain.3

In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids.4 Nuts, legumes, spinach, and cereals are all good sources of magnesium in the diet that help meet the RDA for older adults; men need 420 mg per day, and women need 320 mg per day.

Water is an essential nutrient and indispensable as a universal solvent for all physiological processes and biochemical reactions. The aging process alters important physiological control systems associated with thirst and satiety, as sensitivity of thirst receptors declines with age. Thus, dehydration is a common problem for older adults. Hydration status is significantly correlated with pain, although it’s unclear whether the mechanism of action involves a cerebrovascular response or an increase in blood cortisol concentration.24 Regardless, adequate water intake for the elderly is particularly important in the presence of chronic pain.

The Management of Chronic Pain: A Food Pyramid
Given the anti-inflammatory properties of many food constituents and the fact that lower markers of inflammation and oxidative stress correspond with lower chronic pain, a recent research review evaluated existing evidence to determine whether there was an optimal diet therapy for the management of chronic pain.4 Results from an analysis of 172 scientific papers led study authors to design a hypothetical nutritional pyramid to serve as an integrative tool in the treatment of chronic pain as well as to help other researchers focus on the often-ignored possible connections between nutrition and chronic pain. The eating pattern described in this pyramid recommended for chronic pain is very similar to the Mediterranean diet. The base of the pyramid recommends 1.5 to 2 L of water daily. From there, foods are recommended in descending order of priority and inclusion: vegetables and fruits, nutrient-dense carbohydrates and whole grains, EVOO, red wine, yogurt, spices, seeds and nuts, legumes, fish, eggs, fresh cheese, poultry, red or processed meat, and sweets, along with daily nutritional supplements of vitamins B12 and D and omega-3.

Drug–Nutrient Interactions and the Microbiome
NSAIDs may contribute to nutritional deficiencies from intestinal malabsorption and disruption of the microbiome, the masses of microorganisms that inhabit the body and outnumber an individual’s human cells by 10:1.3 The balance of microorganisms may influence health or disease by affecting the absorption of nutrients, causing or preventing excessive gut permeability, affecting the function of the immune system, and stimulating unhealthy fermentation within the gut. They also may be responsible for some forms of abdominal pain. The microbiome is also adversely affected by processed foods and many other drugs commonly used in physical medicine and rheumatology practices, such as protein pump inhibitors, antibiotics, steroids, and hormones. Consuming yogurt daily can help prevent the alteration of the microbiota by opioid therapy as well as counteract the inflammatory state that characterizes chronic pain patients.4

Diet and Nutrition in Patient Evaluation
Nutrition is an important element of health in the older population and can affect the aging process. Older adults often have reduced appetite and energy expenditure, which, coupled with a decline in biological and physiological functions such as reduced lean body mass, changes in cytokine and hormonal levels, and changes in fluid electrolyte regulations, delay gastric emptying and diminish senses of smell and taste.25 Across the health continuum, a Mediterranean-type diet—deemed the 2019 diet of the year by U.S. News & World Report—appears to have the most benefits.26 Thus, implementing the Mediterranean diet as medical nutrition therapy in the management of chronic pain in older adults can be only beneficial. In addition, a good-quality daily multivitamin and one or a few other individual nutritional supplements may be indicated.

— KC Wright, MS, RDN, LD, is a research dietitian at Dartmouth-Hitchcock Medical Center and maintains a nutrition communications practice. She advocates for good food and sustainable food systems at www.wildberrycommunications.com.

References
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2. Lin YC, Wan L, Jamison RN. Using integrative medicine in pain management: an evaluation of current evidence. Anesth Analg. 2017;125(6):2081-2093.

3. Tick H. Nutrition and pain. Phys Med Rehabil Clin N Am. 2015;26:309-320.

4. Rondanelli M, Faliva MA, Miccono A, et al. Food pyramid for subjects with chronic pain: foods and dietary constituents as anti-inflammatory and antioxidant agents. Nutr Res Rev. 2018;31(1):131-151.

5. Health and nutrition letter. Tufts University website. https://www.nutritionletter.tufts.edu/issues/14_7/ask-experts/Q-Is-it-true-that-Americans-eat-excessive-omega-6-fatty-acids_2419-1.html. Updated July 2018. Accessed April 9, 2019.

6. Omega-3 fatty acids: an essential contribution. The Nutrition Source, Harvard School of Public Health website. https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/. Accessed April 9, 2019.

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8. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem. 2017;60(5):1620-1637.

9. Turmeric and curcumin supplements and spices review. ConsumberLab.com website. https://www.consumerlab.com/reviews/turmeric-curcumin-supplements-spice-review/turmeric/#whatitdoes. Updated April 20, 2019. Accessed April 9, 2019.

10. Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Mil Med. 1999;164(2):85-91.

11. McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283(11):1469-1475.

12. McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med. 2004;117(9):643-649.

13. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795-808.

14. Fransen M, Agaliotis M, Nairn L, et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015;74(5):851-858.

15. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281.

16. Melamed ML, Michos ED, Post W, et al. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629-1637.

17. Macfarlane GJ, Palmer B, Roy D, et al. An excess of widespread pain among South Asians: are low levels of vitamin D implicated? Ann Rheum Dis. 2005;64(8):1217-1219.

18. Al Faraj S, Al Mutairi K. Vitamin deficiency and chronic low back pain in Saudi Arabia. Spine. 2003;28(2):177-179.

19. de Torrente de la Jara G, Pecoud A, Favrat B. Musculoskeletal pain in female asylum seekers and hypovitaminosis D3. BMJ. 2004;329(7458):156-157.

20.Vitamin D: fact sheet for health professionals. National Institutes of Health website. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#h2. Updated November 9, 2018. Accessed April 9, 2019.

21. Vitamin B12: fact sheet for health professionals. National Institutes of Health website. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. Updated November 29, 2018. Accessed April 9, 2019.

22. Magnesium: fact sheet for health professionals. National Institutes of Health website. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/. Updated September 26, 2018. Accessed April 9, 2019.

23. Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1346-1353.

24. Kenney WL, Chiu P. Influence of age on thirst and fluid intake. Med Sci Sports Exerc. 2001;33(9):1524-1532.

25. Ahmed T, Haboubi N. Assessment and management of nutrition in older people and its importance to health. Clin Interv Aging. 2010;5:207-216.

26. Best diets 2019. U.S. News & World Report website. https://health.usnews.com/best-diet. Accessed February 11, 2019.