EPA, DHA and other ingredients offer support for chronic inflammation

Exercise, especially intense exercise, results in inflammation. This response is not all bad, as acute inflammation plays a role in repairing damage. When unresolved, inflammation becomes chronic and can have a negative effect on muscles, joints and other tissues in the body. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), pro-resolving mediators, curcumin, boswellia serrata, tart cherry juice and other natural ingredients target out-of-control inflammation.

Let Acute Inflammation Run its Course

Inflammation is the immune system’s initial response to an injury. The immune system brings in the cleanup crew, clears out damage and sets the stage for building new tissue. Soon after an injury, blood flow increases, bringing chemical mediators and defense cells to the injured area. Chemical mediators have a multifaceted role in healing. They increase circulation, enhance permeability of cell membranes, bring white blood cells to the area and remove debris while reducing excess edema.¹

To rapidly decrease inflammation, particularly the swelling, redness and heat that comes along with inflammation, some people pop anti-inflammatory medications and supplements. Yet this may do more harm than good. Research showed taking nonsteroidal anti-inflammatory drugs (NSAIDs) soon after an injury can squash the beneficial actions of chemical mediators and delay soft tissue healing.¹ Plus, NSAIDs are only mildly effective at symptom relief.,^2,3 NSAIDs aren’t the only factor that can shortcut the beneficial actions of the immune system. Antioxidant supplements can also blunt the immune system’s response after an injury.

“Skeletal muscle that is highly metabolically active produces reactive oxygen species (ROS), which is generally believed to be related to skeletal muscle inflammation and injury,” stated Sarah McKinley-Barnard, Ph.D., CISSN, assistant professor of the exercise science department of health, kinesiology, and sport, University of South Alabama. “Production of ROS can cause irreversible damage to the cell by disrupting its homeostasis (‘normal’ environment), including the structural component of the cell. When a muscle cell becomes damaged, inflammatory cells migrate to the site of injury to begin methods to repair the damage. Essentially, there are several steps that occur that actually cause ‘chaos’ in the cell before regeneration and repair mechanisms can take place; however, this ‘chaos’ is a necessary precursor to the repair process.”

ROS are essential for muscle functioning but, in excess, they can impair muscle contraction and contribute to weakness, fatigue and dysfunction.^4,5 Therefore, it is important to have some free radicals without letting them take over and run amok. In high doses, both vitamins C and E have been shown to interfere with cell signaling after resistance training, impair increases in muscle strength from participation in a regular strength-training program, and interfere with adaptations to endurance training.^6,7,8

Curbing Chronic Inflammation

While acute inflammation is better left alone, chronic inflammation can keep an active adult on the sidelines for an extended period. Yet there are many solutions to attenuating unresolved inflammation and some functional ingredients on the horizon.

EPA and DHA

The omega-3 fatty acids EPA and DHA are incorporated into cell membranes, where they make membranes more elastic, flexible and resistant to damage.⁹ Both EPA and DHA also attenuate inflammatory pathways in the body.¹⁰ In untrained individuals, EPA and DHA decreased muscle soreness and perceived pain while improving range of motion after a damaging bout of eccentric exercise.^11,12,13  It appears those who do not regularly eat fish will benefit the most.¹⁴ At this time it, is not clear if EPA and DHA can help reduce inflammation and pain in trained athletes, particularly those who regularly consume fish.

“Fish oil has been proposed to attenuate the inflammatory responses associated with exercise-induced muscle damage and delayed onset muscle soreness; however, the research on this supplement is inconsistent,” McKinley-Barnard said. “This may be due to individual variability of the extent of muscle damage, as well as factors including exercise type, age, training status, etc.” EPA and DHA may have added benefits for immune functioning and stimulation of muscle tissue remodeling when protein intake is insufficient.¹⁵ Suggested doses range from 2 to 3 g/d of EPA and DHA.

Specialized Proresolving Mediators

Specialized proresolving mediators (SPMs) include resolvins, protectins, lipoxins and maresins. SPMs are produced from EPA and DHA and allow acute inflammation to run its course while terminating chronic inflammation and promoting tissue repair and regeneration.¹⁶ These molecules show promise, yet no studies to date examine their potential for mitigating chronic inflammation in active adults or athletes.

Boswellia Serrata

“Boswellia serrata enriched with 30% 3-O-acetyl-11-keto-beta (AKBA)-boswellic acid exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme, a key enzyme involved in the biosynthesis of pro-inflammatory compounds called leukotrienes,” said Shawn Wells, R.D., , food and supplement formulator. “Research shows supplementation with 250 mg of boswellia serrata AKBA (as 5-LOXIN from PTL Health Solutions 125 mg taken twice daily) reduces joint pain and improves physical function in as little as 7 days of treatment.¹⁷ In addition to reducing pro-inflammatory mediators, 5-LOXIN also reduces the activity of joint-degrading enzymes,” Wells said. Doses range from 100 to250 mg/d. 

Collagen

Collagen is on fire lately thanks to research showing it can help improve ligament strength and tendon health when combined with a source of vitamin C and taken an hour before physical therapy or training.¹⁸ “Collagen isn’t really anti-inflammatory, but works alongside anti-inflammatory ingredients to help build healthy joint cartilage,” said Juliana Erickson, senior marketing manager, Consumer Health & Nutrition, Lonza.

“Dietary collagen provides a very unique amino acid profile, particularly rich in typically under-consumed amino acids glycine, proline and hydroxyproline,” Wells said. There is no other food that comes close to the same amino acid makeup as collagen.

“These are the very same raw-material building blocks that our bodies need to make our own collagen-containing connective tissues, such as our skin, cartilage, bones, intestinal lining, tendons and more,” Wells said. “Interestingly, there’s evidence that collagen protein is particularly attracted to the areas in your body where you need it most, and research shows that supplementation with collagen peptides, which stimulate the body’s own production of collagen, can support healthy skin¹⁹, joint²⁰ and bone health,²¹ and tendon health.”²² Research studies by Keith Baar suggested a 15-g/d dose of collagen for those who are trying to build stronger ligaments and healthier tendons.²³ 

Glucosamine and Chondroitin

Studies show glucosamine sulfate helps rebuild the cartilage matrix and decrease hyaluronidase activity, an enzyme that damages tissue.²⁴ “Glucosamine is one of the primary precursor building blocks for healthy joint cartilage,” said Nena Dockery, scientific and regulatory affairs manager, ESM Technologies. “It is not an inflammatory per se, but if there is healthy joint cartilage, inflammation will subside.

Chondroitin sulfate is a glycosaminoglycan and is a major component of healthy joint tissue, she explained. “There is some indication that chondroitin sulfate may help lower CRP levels,²⁵ an important indicator of general inflammation throughout the body.”

The largest glucosamine and chondroitin study to date, the National Institutes of Health (NIH)-sponsored multi-center Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) compared five treatment regimens in over 1,500 patients with osteoarthritis (OA) of the knee: 1,500 mg glucosamine HCL; 1,200 mg chondroitin sulfate; 1,500 mg glucosamine HCl plus 1,200 mg chondroitin sulfate; the prescription drug celecoxib; and placebo.²⁶ After 24 weeks, patients with moderate to severe OA taking glucosamine HCl plus chondroitin sulfate experienced significant improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, which assesses pain, stiffness and physical functioning. No significant improvement was noted in any of the other treatment groups or in those with mild OA.

MSM

Methylsulfonylmethane (MSM) is a sulfur-containing supplement purported to reduce inflammation and pain.²⁷ Sulfur is used to stabilize the connective tissue matrix within cartilage. Additionally, “sulfur is important in resolving the inflammatory cascade by reducing levels of certain critical pro-inflammatory mediators (cytokines),” Dockery said. The research on MSM is inconclusive, Wells added, though some evidence shows combining MSM with boswellia serrata AKBA may be effective for managing inflammation and joint degradation.²⁸

Eggshell Membrane

Eggshell membrane contains glucosamine, chondroitin, glycosaminoglycans, hyaluronic acid (HA) and types 1, 5 and 10 collagen. “Natural eggshell membrane (NEM) that is partially hydrolyzed has been shown to reduce inflammation through reductions in key pro-inflammatory cytokines, chemokines and metalloproteinases,” Dockery said.

Wells pointed to research showing 500 mg/d of NEM supports joint health in three key areas by: reducing exercise-related joint stiffness; providing relief from joint aches and pain from overexertion2; and protecting cartilage from degradation associated with normal wear and tear in healthy individuals.²⁹ The standard dose is 500 mg.

Curcumin

Curcumin works through several molecular targets to decrease inflammatory cytokines and indirect markers of muscle damage. The International Olympic Committee (IOC) Consensus Statement on Dietary Supplements and the High-Performance Athlete lists curcumin as a supplement that may help with training capacity, recovery, muscle soreness and injury management.³⁰

Curcumin has poor solubility, is not well absorbed, is metabolized quickly and eliminated from the body rapidly. Wells suggested taking consumers take a water-soluble form, a liposomal form, or combining it with black pepper to improve absorption. Doses range from 250 to 400 mg for a high-absorption form of curcumin and up to 1 to3 g for other forms of curcumin.

Lipoic Acid

Alpha-lipoic acid (ALA) is an antioxidant that performs several important functions throughout the body while also helping recycle other antioxidants, including glutathione.³¹

“Its role as an anti-inflammatory is probably indirect and related to its ability as an antioxidant to prevent cell damage,” Dockery said. “The dosing for alpha-lipoic acid is variable, as it is often combined with several other ingredients in formulations. When taken alone, the dose may range from 300 to1,800 mg, though much lower amounts (approximately 100 mg) may be used in formulations,” according to Dockery.

Tart Cherry

Tart cherry juice is a natural source of anthocyanins 1 and 2, plant-based compounds that inhibit COX-1 and COX-2 enzymes, which drive acute and chronic inflammation, respectively. Cherries, especially tart cherries, have more anthocyanins 1 and 2, than other fruits.^32,33,34

Tart cherry juice helps decrease inflammation, exercise-induced muscle pain and other symptoms of muscle damage.³⁵ Two bottles of tart cherry juice per day for five to eight days prior to running or a damaging bout of elbow flexion contractions led to lower levels of inflammatory markers while decreasing strength loss and pain.³⁶ “Tart cherry juice has the added benefit of improving sleep quality and duration,”³⁷ Wells noted. The typical dose is two bottles per day or 480 mg of tart cherry juice powder. 

Glutamine

Glutamine, one of the most abundant amino acids in the body, has anti-inflammatory.³⁸

“It works through interfering with the functioning or production of key pro-inflammatory prostaglandins.³⁹ It may also suppress pro-inflammatory signaling pathways,” Dockery said. However, the gastrointestinal (GI) tract is by far the greatest user of glutamine, where this amino acid supports healthy intestinal lining.⁴⁰ Glutamine is also used when healing from an injury or surgery as well as for muscle cell repair.⁴¹ “Intense exercise lowers glutamine levels, which can remain low if intense training is repeated without adequate recovery.⁴² Evidence suggests that supplemental L-glutamine can offset these conditions, and it also benefits GI health, supports wound healing and maintains immune health,”^43,44 Wells said. “The dose for L-glutamine is very highly variable, but common dietary supplement doses are from around 2 to 4 grams daily,” according to Dockery.

Cissus quadrangularis  

A few high-quality studies have been conducted on cissus quadrangularis, a common botanical in the grape family. “But, there is some indication it can help reduce the symptoms of joint conditions through reductions in key markers of inflammation,”⁴³ Dockery said. “The typical dose is 1 to 4 grams, and there was one study that focused on its effects in relieving the symptoms of osteoarthritis that employed 3,200 mg.”⁴⁵ 

Acute inflammation that doesn’t cause excess pain should be left to run its course so as not to shortcut the healing process. Furthermore, inflammation does not necessarily always lead to pain and limited functioning. “People experience pain differently and at different magnitudes; therefore, what works for one person may not work for the next—it is highly individualistic,” McKinley-Barnard said. For chronic inflammation, a diet full of plant-based foods and fatty fish may help while targeted functional ingredients, depending on the site of inflammation or dysfunction, may help an active adult return to play faster. 

Market Snapshot: Inflammation Innovation

New Hope’s NEXT Trend Database, which tracks products and claims at Natural Products Expo trade shows, showed diet and nutrition products targeting inflammation are showing modest growth overall, with share growth of 7% between Expo West 2017 and Expo West 2019. Specialty formula supplements maintain the lion’s share of diet and nutrition products targeting inflammation, representing 42% of the category at Expo West 2019 (36 of 85 total products). Digestive/fiber supplements, green supplements, and snack, energy & granola bars are emerging categories tackling inflammation reflected in their high  share growth among diet and nutrition products targeting inflammation between 2017 and 2019, indicating potential opportunities for innovation. Interestingly, data indicate sports nutrition brands could be moving away from inflammation as a targeted claim; energy, protein and muscle recovery drinks targeting inflammation decreased more than 40% between Expo West 2017 and 2019, from 13 products in 2017 to 9 in 2019.

Marie Spano, R.D., , is a sports dietitian, food industry consultant and freelance writer who covers everything from functional ingredients to the latest research on dietary fats. Marie has appeared on CNN, Fox, ABC, NBC and other network affiliates throughout the nation, and is currently working on a nutrition textbook.

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