13 ingredients for healthy joint cartilage

13 ingredients for healthy joint cartilage

Two mechanisms are usually targeted for joint health: supporting cartilage structure via glucosamine and its relatives, and quelling inflammation with more novel ingredients such as curcumin and astaxanthin. Jack Challem investigates a baker's dozen of natural nutrients to consider.

Osteoarthritis, the most common form of arthritis, affects approximately 12 per cent of adults (21 million people) in the United States.1 In Great Britain, about six per cent of adults (2.6 million) have frequent knee pain and X-ray evidence of osteoarthritis; this number increases to 12 per cent (5.2 million) among people over age 65.2 The disease is characterized by a thinning of the cartilage pads in the knees and, less frequently, at other joints. Symptoms include pain, stiffness, inflammation and a lack of physical mobility.

Two nutritional approaches, or a combination of them, offer many benefits to people with osteoarthritis. As such, they provide a conceptual framework for formulating dietary supplements.

One approach focuses on nutritional compounds that enhance the structure of articular (joint) cartilage, which provides both cushioning and lubrication at joints. The rationale is that the body's physical structure and biochemistry ultimately depend on nutrition. Nutritional precursors to cartilage can help the body maintain and sometimes stimulate the regeneration of articular cartilage.

The other approach reduces inflammation to control pain and limit the breakdown of cartilage. Inflammation is part of the body's natural mechanism to remove dead or damaged chondrocytes, the body's cartilage-making cells. However, chronic inflammation leads to the breakdown of cartilage, and it can result from an imbalance in the body's pro- and anti-inflammatory compounds, such as prostaglandins and leuko-trienes. Once again, these substances depend on nutritional precursors.

Supporting cartilage structure

Eighty per cent of articular cartilage consists of water, which provides much of the cushioning effect of the tissue's cushioning properties. The remaining 20 per cent consists of both collagen and noncollagen proteins. The outer regions of cartilage have greater resiliency, whereas cartilage becomes more mineralised and denser close to bone.

Collagen type 2 cartilage provides 90-98 per cent of the collagen protein, with the remainder consisting of type 5, 6, 9, 10 and 11 collagens. In contrast, the noncollagen proteins have a complicated 'Russian doll' structure. To explain, proteoglycans form the main type of noncollagen protein, and aggrecan is the predominant type of proteoglycan. Proteoglycans consist of several types of glycosaminoglycans, including chondroitin sulphate, hyaluronic acid, keratan sulphates 1 and 2, and heparin sulphate.

Sulphur is one of the common denominators in many supplements —?including glucosamine sulphate, chondroitin sulphate, and methylsulfonylmethane (MSM) — that have been shown to enhance the structure of articular cartilage and reduce pain. In fact, glycosaminoglycan production depends on the presence of sulphur, and one study found that glucosamine sulphate supplements increased blood levels of sulphur, but not glucosamine.3 Although sulphur is not recognised as an essential dietary mineral, it is the third most abundant mineral in the body (after calcium and phosphorus). Its functionality may be related to the organic molecule to which it is attached.4

Glucosamine may not be the newest ingredient in joint health, but it does work. More than 40 clinical trials have found that glucosamine sulphate supplements can reduce pain, and two studies reported X-ray evidence showing the growth of new articular cartilage.5 In a recent study, published in Osteoarthritis and Cartilage, researchers followed patients in earlier clinical trials who had taken either glucosamine sulphate or placebos daily for one to three years. People who had taken glucosamine sulphate were half as likely (compared with those who had taken placebos) to undergo total knee-replacement surgery over the subsequent eight years.6

The controversial Gluosamine/Chondroitin Arthritis Intervention Trial (GAIT) was widely reported as showing no benefits for glucosamine hydrochloride. However, the combination of glucosamine and chondroitin sulphate together brought substantial pain relief to patients with the most severe symptoms. The combination worked better than either supplement by itself or the pharmaceutical drug celecoxib.7

Chondroitin sulphate is a structural component of cartilage. Considerable clinical research has also shown that it reduces pain and helps maintain articular cartilage.8 A meta-analysis published in Current Medical Research and Opinion found that chondroitin provided significant clinical benefits to patients with osteoarthritis. One of the studies showed that chondroitin sulphate supplements led to a reduced need for analgesic medications.9

Methylsulfonylmethane (MSM) is chemically related to dimethyl sulfoxide (DMSO), which has a long history of use as a topical analgesic in veterinary and alternative medicine. Taken orally, MSM has been found to reduce pain in people with osteoarthritis. One study reported significant improvements with 3g/day MSM taken for 12 weeks.10 Taking 1,500mg/day MSM in combination with 1,500mg/day glucosamine sulphate was more effective in reducing pain and swelling and in improving the functional ability of joints than the individual agents.11

Hyaluronic acid is a constituent of joints. Intra-cartilage injections of hyaluronic acid are occasionally used to treat osteoarthritis, but many experts have questioned whether it can be absorbed orally. In a study published in Nutrition Journal, researchers reported that 80mg/day oral hyaluronic acid significantly lessened pain and improved mobility. The hyaluronic acid was derived from chicken combs.12

Type 2 collagen is the predominant type of collagen protein (as opposed to noncollagen protein) in joints. Intuitively, oral supplements would benefit people with osteoarthritis by providing some of the biochemical building blocks of cartilage. In laboratory studies, type 2 collagen stimulates the synthesis of chondrocytes,13 and a small study found that supplements of type 2 collagen did lead to less pain and greater mobility in patients.14 However, the benefits of type 2 collagen appear greater in patients with rheumatoid arthritis.15,16

Pycnogenol is a proprietary extract of French maritime pine trees that is the beneficiary of research on anti-inflammation properties, joints and much more. It is a rich trove of antioxidant and anti-inflammatory polyphenols. It blunts the activity of inflammation-promoting COX-1 and COX-2 enzymes.17 In a recent study, Pycnogenol supplements reduced pain and stiffness in people with osteoarthritis.18 In another study, this one focusing on asthma, children taking Pycnogenol gained better lung function, and many were able to reduce or stop using their medications.19

Quelling inflammation in osteoarthritis

Given the appropriate dietary building blocks, the body can manufacture a variety of pro- and anti-inflammatory compounds. Many of these compounds, such as prostaglandins and leukotrienes, are downstream products of essential fatty acids. In addition, antioxidants modulate the inflammatory response, such as by diminishing the activity of adhesion molecules. Many nutrients support the body's systemic ability to control inflammation, and some have documented benefits in osteoarthritis.

The omega-6 and omega-3 ratio is a powerful determinant of the body's ability to regulate inflammation. As a general (though not completely accurate) rule, omega-6 fatty acids are considered pro-inflammatory, whereas omega-3 fatty acids are considered anti-inflammatory.

Traditionally, the omega-6:omega-3 dietary ratio has been approximately 1:1. With the widespread consumption of processed foods and oils (particularly corn, safflower, peanut and soybean oils), this ratio is now approximately 20:1, favouring the omega-6s and resulting in a predisposition toward greater inflammation. This change has been further amplified by the widespread consumption of trans fats, which inhibit some of the enzymes in the fatty acid pathways.20,21

Omega-3 fatty acids lead to the production of prostaglandin E3 and leuko-triene B5, both of which are anti-inflammatory. Cell studies have found that the omega-3s inhibit the activity of aggrecanases, the enzymes that break down aggrecan (the principal noncollagen protein in cartilage).22 In one study, using cultured cells from the knees of osteoarthritis patients, researchers confirmed that the omega-3 fatty acids reduced cyclo-oxygenase-2 (COX-2) enzyme activity and blocked the breakdown of chondrocytes.23

Gamma-linolenic acid (GLA) is an omega-6 PUFA, yet it has significant anti-inflammatory properties. Under normal circumstances, GLA is rapidly converted to dihomo-GLA, which can enter two pathways. In one, it quickly converts to prostaglandin E1, which is anti-inflammatory. In the other, dihomo-GLA converts to arachidonic acid, which is pro-inflammatory.

Elevated insulin levels (characteristic of insulin resistance, prediabetes, diabetes and abdominal obesity) increase the conversion of dihomo-GLA to arachidonic acid, which ultimately leads to pro-inflammatory prostaglandin E2 and leukotriene B4. Studies have found GLA supplements helpful in reducing inflammation stemming from athletic injuries and rheumatoid arthritis,24,25 and they may have general benefits in osteoarthritis.

Trans fats interfere with the production of GLA by inhibiting the delta-6-desaturase enzyme. GLA specifically leapfrogs the delta-6-desaturase enzyme.

Curcumin is an extract of the herb turmeric with broad anti-inflammatory benefits. Although curcumin's role in osteoarthritis research is limited, researchers do have a clear understanding of how this nutritional ingredient works. Curcumin reduces inflammation through 97 different biochemical pathways, which are listed in a detailed review in Biochemical Pharmacology.26 It blocks the activity of nuclear factor kappa beta (NF-kappaB, a gene transcription factor), interleukin-6 (a cytokine), and COX-2 (a pro-inflammatory enzyme). In addition, recent cell and animal experiments have found that curcumin enhances the effects of pharmaceutical analgesics.27

Rose hips were popular in the 1970s. Although a source of 15 pro-anthocyandins, they have largely receded in the supplement marketplace.28 A meta-analysis of three studies, published in Osteoarthritis and Cartilage in 2008, found that 5g/day rose hips led to substantial decreases in pain (twice that of the placebo groups) in more than 300 patients with osteoarthritis.29

Avocado / Soybean unsaponifiables (ASU) is an extract of avocado and soybean. It has been shown to reduce pain, slow the breakdown of cartilage and stimulate the synthesis of new cartilage.30,31,32 A recent Danish review of four published studies found that ASU reduced pain in people with knee osteoarthritis.33 Another study reported that a combination of ASU, glucosamine and chondroitin sulphate reduced the activity of genes involved in making interleukin-6 and tumour necrosis factor, both promoters of inflammation.34,35

Astaxanthin inhibits NF-kappaB, which would otherwise stimulate the expression of inflammation-promoting genes.36 Cell and animal studies have documented the anti-inflammatory benefits of this antioxidant carotenoid. It also blocks other inflammation promoters, including tumour necrosis factor alpha, interleukin-1B, COX-1 and COX-2 enzymes, and prostaglandin E2.37,38

Boswellia is an herb known more formally as Boswellia serrata, with a long history of medicinal use in Ayurvedic traditions. Its biologically active constituents are known as boswellic acids. Many of boswellia's anti-inflammatory benefits appear related to its ability to inhibit 5-lipoxygenase, an enzyme involved in the production of pro-inflammatory leukotrienes.39,40 This mode of action is different from most natural and pharmaceutical products, which inhibit the activity of COX enzymes.

Because of the research, product formulators have many different options in designing natural and safe products for people with osteoarthritis. They can focus on individual ingredients, or they can use formulas to differentiate their products in the marketplace. Such formulas could focus on preventing and reversing the breakdown of cartilage, or on reducing inflammation —?or both.

Jack Challem is the author of The Food-Mood Solution, and Stop Prediabetes Now, both published by John Wiley & Sons.

Functional ingredients

Astaxanthin: inhibits pro-inflammatory gene activation
Avocado/Soybean Unsaponifiables: good in combination
Boswellia: Ayurvedic herb for inflammation
Chondroitin: glucosamine's partner in many formulations
Curcumin: turmeric extract is a broad anti-inflammatory
GLA: an omega-6 that acts like an omega-3
Glucosamine: the oldie but goodie
Hyaluronic acid: appears to work, but large molecule size is an issue
MSM: No. 3 ingredient in the product-developer arsenal
Omega-3s: another category opens for this blockbuster
Pycnogenol: targets both inflammation and rheumatoid
Rose hips: gone, but not forgotten?
Type 2 collagen: especially helpful for rheumatoid arthritis

Research keys new product launches

In the joint-health category, there are glucosamine and chondroitin, and there are the also-rans. Many suppliers hope their new and novel ingredients can be the ones added to 'new and improved' mainstream glucosamine-chondroitin formulations. And there's only one way of getting there: science.

Dan Lifton"We take a more opportunistic approach to developing our patented ingredient portfolio," says Dan Lifton, director of business development at Maypro, which offers hyaluronic acid, boswellia and MSM. "We look for natural ingredients that are supported by clinical studies that mainstream MDs would consider to be convincing. That's a very high bar to meet and there are very few ingredients in our industry that meet this criteria. In our view, one of the key factors that led to co-Q10 becoming one of the top-selling ingredients in the industry is because mainstream cardiologists accepted that it should be taken by patients who are on statins."

Some look merely to develop ingredients that work. Others go for a more targeted approach: developing an ingredient that complements the mechanism of action of glucosamine and chondroitin, which is why it pays to understand both the composition and mechanism of action of ingredients.

"With chondroitin and glucosamine, cartilage is regenerated on an inflamed joint, which continues to be painful with stiffness and functional impairment," explains Tina Sampalis, MD, PhD, chief scientific officer at Neptune Technologies and Bioressources. The company markets Neptune Krill Oil, which reduces inflammatory C-reactive protein levels. "Furthermore, it might take up to six weeks before any actual improvements in cartilage density are observed, at which time most patients have given up and terminated their treatment."

Also helpful are efficacious ingredients that are easy for supplements formulators to integrate into existing products.

Paul DijkstraInterHealth's patented undenatured collagen ingredient, UC-II, is a good fit with glucosamine-chondroitin combinations because it works on underlying inflammation. "The recommended small 40mg daily dosage of UC-II allows manufacturers to easily add value to multi-ingredient formulations of existing or new joint-health products," says Paul Dijkstra, CEO of InterHealth. "Science is the key to differentiating safe and effective products from the rest."

—Todd Runestad

Omega pathways:

Omega-3 and omega-6 EFA's have important roles to play in the body's biochemistry. The metabolic pathway tracks the different forms omega-3 fatty acids take inside the body from consumption to ultimate absorption by the bloodstream. The chemistry is pictured in this schematic.

Dietary alpha-linolenic acid, upon reacting with the D-6-D enzyme, converts into stearidonic acid. The next step in the pathway is the conversion of stearidonic acid into eicosatetraenoic acid after reaction with elongase. This acid transforms into eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) after it reacts with D-5-D enzyme.

The omega-6 group contains large quantities of linoleic acid (LA). This is converted into arachidonic acid, which in turn leads to the production of many other chemicals. When these are over-produced, they can have negative effects, such as uncontrolled or excessive inflammation from a small trigger.

Select suppliers: targeting inflammation and joint health

Bergstrom Nutrition
OptiMSM-brand MSM has been produced in the US for more than 25 years in a GMP facility, and is third-party tested for quality and consistency.

Biocell Technology
BioCell Collagen II is a natural hydrolysed type 2 collagen comprised of collagen, chondroitin sulphate and hyaluronic acid. Its low molecular-weight ingredient is easily absorbed by the body.

This Spanish company provides the glucosamine and the chondroitin sulphate used in the landmark GAIT study of glucosamine and chondroitin for joint health.

Regenasure vegetarian-sourced glucosamine is US produced, GRAS for foods and beverages, kosher, halal, and produced in accordance to GMPs.

BioAstin-brand astaxanthin is produced from micro-algae on the Big Island of Hawaii. The world's best-selling brand of astaxanthin for humans, it relieves joint pain with a natural anti-inflammatory response.

Cyvex Nutrition
AvoVida avocado/soy unsaponifiables is a natural extract of phytosterols from avocado and soy, including beta-sitosterol, campesterol and stigmasterol, so it's effective for both joints and cholesterol levels.

Denomega Nutritional Oils
Fish oils are used in functional foods, supplements and pet nutrition. Its new Omega 360 logo is designed to incorporate the full spectrum of health benefits associated with its oils.

EPAX 4510 TG marine omega-3 DHA/EPA fatty acids is the company's joint health condition-specific formula. It has high levels of concentrated EPA to provide nutrition to joints, help reduce stiffness and support mobility.

ESM Technologies
NEM — Natural Eggshell Membrane — is a complex ingredient matrix composed of naturally occurring glucosamine, chondroitin, hyaluronic acid, collagen and other proteins. It is suitable for foods and supplements.

Fortigel is bioactive collagen peptides for supplements that stimulates cartilage metabolism and enhances the synthesis of cartilage cells, thus countering the progressive loss of cartilage tissue.

InterHealth Nutraceuticals
UC-II is undenatured native type 2 collagen derived from chicken sternum cartilage. It is supported by six human clinical trials and has four US patents and international patents pending to benefit those with osteoarthritis as well as rheumatoid arthritis.

Neptune Bioressources
NKO-brand krill has a recent clinical study demonstrating a daily dose of 300mg/day significantly inhibits inflammation and reduces arthritic symptoms within seven to 14 days.

Pycnogenol French maritime pine bark inhibits inflammation in arthritis by inhibiting the activation of pro-inflammatory gene NF-kappaB, inhibits COX-enzymes that cause joint pain, and lowers inflammatory marker C-reactive protein in osteoarthritis patients.

Ocean Nutrition Canada
MEG-3 fish oil is specially micro-encapsulated to prevent rancidity or off-flavours, and is effective for a range of conditions including joint health.

Osamine is a pharmaceutical-grade glucosamine distinguished by Drug Master Files recognized by more than 25 European countries.

Boswellin is an anti-inflammatory botanical (Boswellia serrata). Curcumin C3 Complex is a complex of three curcuminoids that act as anti-inflammatories — as well as a host of other benefits including anti-cancer potential.

Soft Gel Technologies
Injuv contains nine per cent low molecular-weight hyaluronic acid, which is believed to help body tissues retain moisture and keep joints lubricated.

Stolle Milk Biologics
Derived naturally from cows' milk, Stolle's patented ingredients have more than 250 worldwide patents, with properties that complement the body's anti-inflammatory response, help reduce tenderness in joints, enhance antibody function and more. Suitable for supplements and a range of functional-foods applications.

TSI Health Sciences
This company supplies a range of chondroitin sulphate salts from a variety of sources as well as glucosamine sulphate and HCl.


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