Osteoarthritis – Joint Pain

Basic practical facts

We now know that the anti-inflammatory drugs we take for osteoarthritis function to inhibit chemicals called prostaglandins (PGE2) that are derived from the foods we eat. In essence, over time, we eat ourselves into a state of chronic joint pain. The image below illustrates how the wrong foods can concentrate arachidonic acid/PGE2 in our joints, which leads to chronic pain.

For many readers, finding out about this relationship between specific foods and pain can be somewhat shocking, and almost unbelievable. For more information on osteoarthritis, read the More Detailed Information section below, and for practical, dietary information for reducing inflammation please consult our Deflaming Guidelines and the related MP3′s. In short, a diet rich in vegetables, fruits, lean meats, wild game, skinless chicken, all fresh fish except for farmed raised tilapia and catfish, and a modest amount of nut intake will not lead to the build up of arachidonic acid and PGE2 in our joints.

Regarding supplementation, in addition to the basic supplements that seem reasonable for us all to take (multi vitamin/mineral, magnesium, fish oil, vitamin D, and probiotics), the supplement of choice for osteoarthritis appears to be glucosamine/chondroitin. 

 

More detailed information

Most doctors and physical therapists have been trained to view osteoarthritis (OA) as a “non-inflammatory, wear and tear” disease of the joints. We learn this in pathology books that contrast OA with the highly inflammatory variety of arthritis called rheumatoid arthritis (RA).

While joint injury (wear-and-tear) can lead to OA, many people develop OA in multiple joints that were never injured, which suggests that the presence of OA may reflect a local joint manifestation that is part of a generalized systemic disorder as argued in the Lancet back in 2001 (1). “Systemic” disorder refers to widespread or a full-body problem, which we at deflame.com and others refer to as a chronic pro-inflammatory state.

As mentioned in other sections at deflame.com, the pro-inflammatory state manifests differently from person to person, depending on our genetic predispositions. This brief review will demonstrate that OA is, in fact, an inflammatory condition, and current research suggests that diet is likely to be the most important modulator of the disease.

The most common medications used to treat OA are non-steroidal anti-inflammatory drugs (NSAIDs), which should help direct us to view OA appropriately as an inflammatory condition. The main purpose for taking NSAIDs like aspirin, ibuprofen, Celebrex, and others is because they inhibit the COX (cyclo-oxygenase) enzyme that converts the arachidonic acid from our cell membranes into the inflammation- and pain promoting prostaglandin E2 (PGE2).

Importantly, it turns out that during our lives we can concentrate arachidonic acid in our joint tissues and levels of arachidonic acid have been correlated with histological severity of osteoarthritis, and this has been known since at least 1991 (2). More recent studies have confirmed this relationship (3).

Also very important to know is that young joint tissues are devoid of omega-6 fatty acids, and this was found to be the case for all species studied: young chicken, fetal calf, new born pig, rabbit, and human. They contain a unique omega-9 fatty acid called mead acid. However, as we age, the non-inflammatory omega-9 fatty acids are progressively depleted and replaced with inflammatory omega-6 fatty acid called arachidonic acid (4), which we get from our diet.

From a practical perspective, since dietary arachidonic acid converts into inflammation- and pain-producing PGE2, our consumption of arachidonic acid should be viewed as the consumption of PGE2. Clearly we should limit our dietary intake of arachidonic/PGE2.

 

Sources of dietary arachidonic acid

We accumulate arachidonic acid in two ways. First, we consume it directly whenever we eat grain/corn fed animals. Grains and corn contain linoleic acid, which when consumed by animals is converted into arachidonic acid. Modern grain/corn-fed domestic meat can up to 25% fat by weight compared to about 5% in wild game (5). Our over-fat meat, or obese meat, is a source of extra arachidonic acid. About 15-20% of the average American’s diet comes from arachidonic acid-rich animal products.

Second, like animals, whenever we humans consume grains and corn, we convert the linoleic acid into arachidonic acid. We also consume excessive amounts of seed oils (corn, safflower, sunflower, and cottonseed oils), which contain mostly linoleic acid. Peanut and soybean oils are also high in linoleic acid. Americans consume approximately 60 pounds of these omega-6 oils each year (7), which can convert into pain and inflammation producing arachidonic acid/PGE2. In contrast, back in 1900, we consumed about 15 pounds per year (7).

As mentioned earlier, linoleic and arachidonic acids are omega-6 fatty acids. These need to be consumed in modest quantities and in balance with the anti-inflammatory omega-3 fatty acids.

Ideally a 1:1 ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids is best, and less than 4:1 is acceptable (6). Below are two tables that contain n-6:n-3 ratios in common foods.

 

n-6:n-3 fatty acid ratios in select foods

Foods with anti-inflammatory ratios
Food n-6:n-3 Ratio
Fruit 3:1 or better
Green vegetables 1:1
White potato 3:1
Sweet potato 4:1
Grass-fed meat 3-5:1
Wild game 3:1 or better
Fresh fish 1:1 or better
Farmed-raised salmon 1:1 or worse
Flax seeds 1:3.6
Hemp seeds 2.5:1
Chia seeds 1:3

 

Foods with pro-inflammatory ratios
Food n-6:n-3 Ratio
Nuts 5:1 or worse
Grain-fed meat 5:1 or worse
Grain-fed chicken (white meat) 15:1
Grain-fed chicken (dark meat) 17:1
Grains (wheat, rye, oats, rice, barley, etc.) 20:1
Potato chips
(and similar foods with added n-6 seed oils)
60:1 or worse
n-6 Seeds and seed oils
(corn, sunflower, safflower, cottonseed, peanut)
70:1 or worse
  • Hands ES. Nutrients in food. Philadelphia: Lippincott Williams & Wilkins; 2000
  • Enig MG. Know your fats. Silver Spring: Bethesda Press; 2000: p. 123, 142, 280-292
  • Cordain L, Watkins BA, Florant GL, Kehler M, Rogers L, Li Y. Fatty acid analysis of wild ruminant tissues: Evolutionary implications for reducing diet-related chronic disease. Eur J Clin Nutr, 2002; 56:181-191

 

Based on the best evidence we have about fatty acids in the context of joint degeneration and arthritis, we should clearly focus our consumption on foods with acceptable ratios of n-6 to n-3 fatty acids. The problem with our excessive omega-6 fatty acid consumption has concerned researchers, such that a special NIH website has been developed to educate us about n-6 fatty acids (8).

 

The pro-inflammatory state of osteoarthritis

In addition to the arachidonic acid/PGE2 issue described above, several other pro inflammatory factors are involved in the expression of osteoarthritis. The nature of this soup of mediators has been reviewed recently (9). In particular, pro-inflammatory cytokines (interleukin-1 and tumor necrosis factor), matrix metalloproteinases, growth factors, and neuronal mediators (substance P) are involved (9). In addition, it is thought that free radicals also participate in osteoarthritis (10). Auto-immune factors may also be involved, which is a relatively new finding (11-13).

It is not so important that you understand the biochemistry of these mediators…the point to appreciate is that the chemistry of osteoarthritis is complex [See Figure 1 below]. And due to the complexity of the chemistry of osteoarthritis, we should come to the conclusion that a single therapy, called a mono-therapy, is not likely to have much of a long-term benefit. Indeed, envision yourself drinking gallons of corn oil with pounds of obese meat each year, and then you take an anti-inflammatory drug to combat this brutally pro-inflammatory diet – the drug would likely be minimally effective at best.

 

From: Bonnet CS, Walsh DA. Osteoarthritis, angiogenesis and inflammation. Rheumatology. 2005;44(1):7-16

 

What are pro-inflammatory cytokines?

Examples are interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The figure above illustrates IL-1 and TNF in the joint tissue. IL-1 and TNF help to promote inflammation, pain, and direct the matrix metalloproteinases (MMPs) to degrade connective tissue.

What are matrix metalloproteinases?

Their abbreviation is MMPs, and their function is to degrade connective tissue (collagen and proteoglycans) that make up joint tissues. The loss of joint space between the adjacent bones that develops in osteoarthritis is due to the activity of the MMPs.

What are growth factors?

The human body has numerous growth factors, and when properly controlled they promote health. However, when not controlled properly they promote disease. Vascular endothelial growth factor (VEGF) has received a lot of attention in recent years, as it has been associated with the development of diverse diseases such as osteoarthritis, macular degeneration, endometriosis, and cancer.

The function of VEGF is to promote the development of new blood vessels so tissues can grow. We now know that VEGF is involved in osteoarthritis, as indicated in the image above. Typically blood vessel growth is accompanied by an increased nerve supply, which in the case of joint and disc injury, could lead to increased pain.

What are free radicals?

These are unstable reactive molecules that are produced normally in the body, but at a level that can be controlled. However, our pro-inflammatory diets are thought to promote an excessive amount of free radicals that are disease producing. In the case of joints, the joint cell called a chondrocyte seems to produce excessive free radicals that assist in the destruction of its surrounding joint tissue (10). Free radicals are not pictured above.

What is hsCRP?

Although not illustrated in the above figure, it is has recently been determined that hsCRP is commonly be elevated in knee osteoarthritis, and may even help predict osteoarthritis expression before it emerges symptomatically (14,15). hsCRP stands for high sensitivity C-reactive protein, and is most considered in the context of heart disease. hsCRP is a marker of ongoing inflammation in the body. More research is needed to better understand the relationship between hsCRP and musculoskeletal disease; however, in the meantime, we would still do well to keep our hsCRP levels as low as possible as it better predicts vascular disease than cholesterol levels (16).

The normal level of hsCRP is 1 mg/L or less. Levels of hsCRP are similar in men and women. The average hsCRP in middle-aged Americans is about 1.5 mg/L. Approximately 25% of the US population has levels of hsCRP greater than 3 mg/L, the cut point for high risk for heart attack and stroke (16). Clearly, the US population is inflamed and needs to deflame.

Inflammation synergy

All of the above-mentioned chemicals work together as an army and the outcome is inflammation, pain, and joint degradation. We now know that our inflammatory lifestyle leads to the overproduction of these various chemicals. Our goal with lifestyle should be to create a state that does not support the activity of the many inflammatory chemicals and the resultant expression a chronic inflammatory disease such as osteoarthritis.

 

The failure of mono-therapies for osteoarthritis

Most people who take anti-inflammatory drugs for musculoskeletal pains like osteoarthritis will continue to suffer. The drugs basically take the “edge” off the pain so it is more bearable. The same holds true for nutritional supplements such as glucosamine and chondroitin sulfate. A recent study demonstrated this to be case, wherein a 20% improvement in pain was considered a positive outcome for the placebo, Celebrex, or glucosamine/chondroitin (17). In other words, each of the mono-therapies tested was slightly effective at reducing knee pain; many subjects in each group achieved a 20% reduction in pain. We should appreciate that a 20% reduction in pain does not translate into significantly better physical function. Do you want a mere 20% relief in pain or would you like 50%, 75% or even 100% relief?

Regretfully, we are all programmed to think that a mono-therapy may exist for our given condition – and perhaps in the short term, so do exist; however, in the long run, the pro-inflammatory state will take its toll. It is important to keep in mind that approximately 60% of calories of the average American’s diet consist of refined sugar (20%), refined flour/grains (20%), and refined/omega-6 oils (20%) (7). Another 15-20% of calories appear to come from obese meat rich in arachidonic acid. This represents a tsunami of dietary inflammation that cannot be counteracted to any appreciable degree with medications or supplements.

 

Reducing the pro-inflammatory state

Diet for reducing inflammation

There is no special way to reduce inflammation if you have osteoarthritis versus a different inflammatory condition. Deflaming does not treat a specific disease. Deflaming reduces inflammation, and hopefully this will help promote a healing state for osteoarthritis.

From experience and based on evidence in the scientific literature, the information contained in the Deflaming Guidelines appears to offer us the best dietary chance for reducing inflammation. The Deflaming Guidelines will help you to create a diet that consists primarily of vegetation and healthy animal products.

 

Supplements for reducing inflammation

The goal with supplementation should be to support the diet in reducing the chronic pro-inflammatory state. What appear to be the most appropriate supplements to achieve this goal are listed below, as well as in the Deflaming Guidelines, and these supplements are described in the supplement section of deflame.com.

The primary supplement that may offer specific benefits for osteoarthritis is glucosamine/chondroitin. In a  recent study called the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), patients with painful osteoarthritis of the knees were blinded to their treatment, and received either placebo, glucosamine, chondroitin, glucosamine/chondroitin, or Celebrex. While there was no significant difference in pain outcome in the mild knee pain group, those with moderate to severe knee pain 

The following supplements that promote health and reduce chronic inflammation incude:

Multivitamin/mineral (Aved Multi w/o iron)
Mega-Magnesium

Concentrated Omega-3
Vitamin D
Probiotic Complete
Pro-Enz

Glucosamine/Chondroitin

If your finances are limited or if you do not wish to take large amounts of supplements, the most reasonable approach would be to follow the anti-inflammatory eating recommendations in the Deflaming Guidelines, and to take a multivitamin/mineral (Aved Multi w/o iron), Mega-Vitamin D, and glucosamine/chondroitin.

Another option for glucosamine/chondroitin is a new liquid product called Elations. I personally take so many supplements that drinking my glucosamine/chondroitin as Elations is an option I like. I typically use Elations [and water as needed] as the liquid portion in my meal shakes. Elations is unique in that it contains 3 mg of boron, which has anti-pain and anti-arthritis benefits (18,19).

 

References

1. Aspden RM, Scheven BA, Hutchison JD. Osteoarthritis is a systemic disorder involving stromal cell differentiation and lipid metabolism. Lancet. 2001;357:1118–1120.
2. Lippiello L, Walsh T, Fienhold M. The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism. 1991; 40(6):571-6.
3. Plumb MS, Aspden RM. High levels of fat and (n-6) fatty acids in cancellous bone in osteoarthritis. Lipids Health Dis. 2004, 3:12
4  Adkisson HD, Risener RS, Zarrinkar PP, Walla MD, Christie WW, Wuthier RE. Unique fatty acid composition of normal cartilage: discovery of high levels of n-9
eicosatrienoic acid and low levels of n-6 polyunsaturated fatty acids. FASEB J. 1991; 5(3):344-53.
5. O’Keefe JH Jr, Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century huntergatherer. Mayo Clin Proc. 2004; 79(1):101-8.
6. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999; 70(3 Suppl):560S-569S
7. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the western diet: health implications for the 21st century. Am J Clin Nutr. 2005;81:341-54.
8. National Institutes of Health (NIH) website on omega-6 and omega-3 fatty acids.
http://efaeducation.nih.gov/sig/eicosa3.html
9. Bonnet CS, Walsh DA. Osteoarthritis, angiogenesis and inflammation. Rheumatology. 2005;44(1):7-16
10. Tiku ML, Shah R, Allison GT. Evidence link chondrocyte lipid peroxidation to cartilage matrix protein degradation: possible role in cartilage aging and the pathogenesis of osteoarthritis. J Biol Chem 2000; 275: 20069-76.
11. Nishioka K. Autoimmune response in cartilage-derived peptides in a patient with osteoarthritis. Arth Res Ther. 2003; 6:6-7.
12. Nakamura H et al. T-cell mediated inflammatory pathway in osteoarthritis. Osteoarthritis Cart. 1999; 7:401-02.
13. Kato T, Xiang Y, Nakamura H, Nishioka K. Neoantigens in osteoarthritic cartilage. Curr Opin Rheumatol. 2004; 16:604-08.
14. Sharif M, Elson CJ, Dieppe PA, Kirwan JR. Elevated serum C-reactive protein levels in osteoarthritis. Brit J Rheumatol. 1997; 36:140-41
15. Sharif M, Shepstone L, Elson CJ, Dieppe PA, Kirwan JR. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dis. 2000;59;71-74
16. Ridker PM. Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke. Circulation. 2003; 108(12):e81-5.
17. Clegg DO, Reda DJ, Harris CL et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New Eng J Med. 2006; 354:795-808.
18. Newnham RE. Essentiality of boron for healthy bones and joints. Environ Health Perspect. 1994; 102(Suppl 7):83-85
19. Nielsen FH. Is boron nutritionally relevant? Nutr Rev. 2008;66(4):183-91