Life Extension Magazine®

Natural Arthritis Relief With Omega-3 Fatty Acids

Advanced carnitine formulations improve cellular energy while supporting optimal brain function, protecting critical heart muscle, fighting sexual dysfunction, and stimulating nerve cell growth.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in October 2024. Written by: Life Extension Editorial Staff.

New research demonstrates that omega-3 fatty acids—long recognized for their remarkable ability to protect against cardiovascular disease—may confer a wealth of additional benefits for human health, guarding against depression, cancer, osteoporosis, arthritis, and other crippling diseases of aging.

For years, Life Extension has shared with its members compelling scientific studies that meticulously document the many ways in which omega-3 fatty acids promote cardiac health. This knowledge has finally made its way to the medical mainstream, such that physicians now routinely recommend fish oil for their patients with high triglycerides and heart arrhythmias. Even the American Heart Association and other mainstream groups now endorse omega-3 fatty acids for reducing the risk of coronary heart disease.

While many people are aware of the heart-protective effects of omega-3s, even the most health-conscious adults may not realize that these fatty acids provide a vast array of additional health benefits. In the following mini-articles, we examine a multitude of published, peer-reviewed scientific studies demonstrating that omega-3 fats may alleviate depression, inhibit cancer, boost bone health, and reduce the pain of arthritis. Amazingly, adding this low-cost supplement to your daily nutritional regimen may help to elevate mood, protect cardiovascular health, support healthy bone mass, avert cancer, and alleviate inflammatory pain!

Recently, the FDA issued troubling warnings about fish toxicity, advising Americans to limit their intake of fresh fish to two servings per week. The bad news is, this caution may well limit our ability to consume enough omega-3 fatty acids from fish to support optimal health and secure the extraordinarily broad range of benefits associated with fish oil. The good news is, supplementing with high-grade, ultra-purified fish oil is an ideal way to guard against fish toxicity while still reaping the innumerable benefits of omega-3 fatty acids.

On the following pages, we present a portfolio of five mini-articles detailing the latest scientific research on the diverse, health-promoting properties of omega-3 fatty acids from fish oil.

In this article, I will share with you the extraordinary success story of Stacy—a patient who came to me with a cholesterol level at a whopping 594 mg/dL and triglycerides that were off the chart at 2,893 mg/dL—and her amazing turnaround in blood test results achieved through the use of fish oil.

A Patient at Risk: Stacy’s Frightening Blood Test Results

Stacy, a 40-year-old physical therapist, was terrified to learn the results of her most recent cholesterol tests: dangerously elevated total cholesterol of 594 mg/dL and sky-high triglycerides of 2,893 mg/dL. Because these values were so high, her levels of dangerous low-density lipoprotein (LDL) and beneficial high-density lipoprotein (HDL) could not be determined.

When I met with Stacy, she was in a panic. In tears, she declared, “I don’t understand it. I take good care of myself. I don’t eat fatty foods, I exercise, I don’t do anything wrong!”

She was correct. Her frightening lipid levels were not due to anything “bad” she had done, but instead were a combination of genetics (“familial hypertriglyceridemia”) and modest dietary excesses. However, these levels of triglycerides and cholesterol posed risks for liver disease and pancreatic disease (pancreatitis), as well as heightened long-term risk for heart disease and stroke. Stacy also showed some features of the metabolic syndrome: her blood sugar was slightly elevated at 114 mg/dL, her blood pressure was high at 140/88 mmHg, and she showed an excess of abdominal fat, standing 5 feet, 5 inches tall and weighing 160 pounds.

Fish Oil Lowers Triglycerides

Dangerously high levels of triglycerides have become more common as Americans develop metabolic syndrome. Elevated triglycerides greatly increase risk for heart disease. Omega-3s can significantly reduce triglyceride levels and help correct other cardiac risk factors that accompany metabolic syndrome.1-3 In fact, omega-3 fatty acids derived from fish oils are now available in the form of a prescription drug called Omacor®, which has been approved specifically for the treatment of elevated triglycerides.4 (For more on this subject, see this month’s “As We See It.”)

Omega-3s Inhibit Inflammatory Compounds

Hidden, imperceptible inflammation is now recognized for its role in triggering a chain of events leading to heart disease and other illnesses. Omega-3 fatty acids suppress multiple steps in this inflammatory process, inhibiting the production of inflammatory cytokines and prostaglandins. Furthermore, omega-3 fats boost production of anti-inflammatory compounds. These anti-inflammatory effects may have important implications for fighting heart disease and numerous other disease processes associated with excessive inflammation.10-16

An important marker of inflammation in the body known as C-reactive protein (CRP) is associated with an increased risk of cardiovascular disease. Measuring high-sensitivity CRP is an emerging method of detecting hidden inflammation and its associated cardiovascular disease risk.17 Some scientists have observed that people who consume a greater amount of omega-3 fatty acids demonstrate lower levels of this cardiovascular risk factor, suggesting that omega-3 supplementation might help prevent cardiovascular disease by fighting inflammation.18

Fish Oils Rich in Omega-3s Fight After-Meal Surges in Blood Fats

An exciting area of research focuses on post-meal elevated blood fat (lipid) levels, known as post-prandial hyperlipidemia. This is essentially the flood of fat in the blood that occurs following a meal, which scientists suspect may be a potent contributor to atherosclerosis (and acute heart attack).5 A unique effect of omega-3 fatty acids (found in cold-water fish oil) is to accelerate the clearance of fat-containing particles from the blood following meals. Fish oil’s profound fat-clearing ability has important implications for cardiovascular disease prevention.6

Omega-3s Slow Plaque Growth and Prevent Blood Clots

Heart attacks can result from unstable atherosclerotic plaque. The rupturing of unstable plaque inside a coronary artery has been compared to a kernel of popcorn bursting open and occluding (blocking) the flow of blood through the vessel. These kinds of heart attacks can occur suddenly, without typical symptoms such as angina and shortness of breath. Omega-3s from fish oil may help to modify the structure of atherosclerotic plaque in ways that make it less dangerous. In fact, studies show that omega-3s can slow the rate of atherosclerotic plaque growth.7,8

Fish Oils Help Improve Endothelial Function

Cutting-edge scientists know that one of the instigating factors in cardiovascular disease is endothelial dysfunction, in which the delicate cells lining the blood vessels cannot dilate in response to increased demand for blood flow.

Fish oils are rich in omega-3 fatty acids. A recent study found that greater intake of omega-3s was clearly correlated with lower levels of blood markers associated with dangerous endothelial dysfunction.18 A past study showed that fish oil rich in omega-3 fatty acids contributes to healthy vascular function by increasing the production of an important blood vessel-dilating substance in the endothelial cells.7

A fascinating study showed that omega-3 supplementation actually changed the composition of unstable atherosclerotic plaque, making it less likely to rupture and thus less dangerous. Subjects who had severe carotid plaque and were scheduled to have it surgically removed received either fish oil or sunflower oil prior to surgery. When the plaque was removed at surgery and examined, researchers found that those who took fish oil had less plaque inflammation as well as more stable plaque. By contrast, those who took sunflower oil had more unstable, rupture-prone plaque.9

The omega-3 fatty acids found in fish oil also help reduce certain proteins that promote abnormal blood clotting and inhibit platelet aggregation, two effects that reduce the likelihood of clot formation on active, ruptured coronary plaque that could result in a heart attack.19

Although the blood-thinning effect of fish oil is modest, people who suffer from an abnormal bleeding tendency or use blood-thinning drugs such as Coumadin® should consult a physician before taking fish oil. The best way of determining if one is taking the optimal dose of Coumadin® and fish oil is to have a doctor perform a template bleeding time test. (Details about this test can be found in the Thrombosis Prevention chapter of the Disease Prevention and Treatment book. )

Omega-3s Normalize Heart Rhythm, Prevent Sudden Cardiac Death

One of the most dramatic benefits of fish oil is its ability to prevent sudden death, particularly sudden cardiac death. Scientists believe that omega-3 fatty acids from cold-water fish may help prevent these sudden deaths by reducing potentially fatal abnormal heart rhythms, or arrhythmias.

To investigate the life-saving benefits of fish oil, scientists studied more than 2,000 men who had previously suffered a heart attack. Some of the men were advised to regularly consume cold-water fish, while others did not receive this dietary advice. After two years, the difference in mortality between the two groups was dramatic: men who ate fish twice a week had a 29% lower rate of death than those who did not. Scientists believe that fish oil helped prevent death by suppressing dangerous, abnormal heart rhythms in these men with a history of heart muscle damage.20

Fish Oils and Omega-3s Counter Dangerous Metabolic Syndrome

Fish oils rich in omega-3 fatty acids provide special benefits for people with metabolic syndrome, an increasingly prevalent condition associated with a greatly elevated risk for heart disease and diabetes. Approximately 47 million US adults are affected by this condition, which is characterized by low levels of beneficial high-density lipoprotein (HDL), increased triglycerides, high blood pressure, insulin resistance, and elevated C-reactive protein. Omega-3 supplementation provides important cardiovascular benefits in people with metabolic syndrome by improving both blood pressure and insulin sensitivity.1,2

Another important study showed that people dying from sudden cardiac death had lower blood levels of omega-3 fatty acids than those who did not. Eating one or more servings of fish each week produced important heart-protective benefits, reducing the risk of sudden cardiac death by a stunning 52%.21

A major clinical study provides more good news about fish oil. In this large study of more than 11,000 adults, those who consumed 1000 mg of EPA and DHA daily had a 30% reduced rate of cardiovascular death and a 20% lower rate of sudden death. Moreover, the protective benefits of fish oil were apparent after only a few months of supplementation.22

Fish oil’s ability to promote healthy heart rhythms is so impressive that some cardiologists now recommend it for their patients who have the implanted devices known as defibrillators to prevent life-threatening heart arrythmias.23,24 In this patient population, the goal of supplementation with omega-3 fatty acids is to reduce rhythm instability.

Fish oil is particularly effective in fighting the common but worrisome heart arrhythmia known as atrial fibrillation. This is especially important, as atrial fibrillation increases the risk of stroke. One study showed that fish oil effectively reduced the incidence of atrial fibrillation by a remarkable 54% in people recovering from bypass surgery.25

Scientists have observed that people who suffer heart arrhythmias often demonstrate low levels of omega-3 fatty acids in their blood, further suggesting that omega-3 supplementation is clinically useful for promoting healthy heart rhythm.24

Fish Oil: Best Source of Omega-3s

Omega-3 Dosing Strategies

In order to help my patients reduce their cardiovascular disease risk factors, I suggest 1200 mg per day of omega-3 fatty acids (EPA + DHA). In my clinical practice, I have noted that this dose yields measurable improvements in cardiovascular risk factors. Omega-3 doses of 1800 mg per day may provide even greater benefits, and this is the dose we commonly use in our program to help reverse heart disease. To address elevated triglyceride levels, my clinic often recommends 1200-3000 mg per day of omega-3 fatty acids.

Fish oil and cold-water fish are the most concentrated sources of EPA and DHA. A secondary, much less concentrated source is alpha-linolenic acid from flaxseed, flaxseed oil, walnuts, and canola oil. However, only a small portion of ingested alpha-linolenic acid is converted into active EPA or DHA.26 Although linolenic acid may provide unique health benefits of its own, fish oil remains by far the most abundant source of heart-healthy omega-3s.

Success Story: Remarkable Changes in Stacy’s Blood Test Results

I advised Stacy to take 2700 mg of omega-3 fatty acids every day. She chose a low-potency, low-cost fish oil that required nine capsules to be consumed each day. She accomplished this by taking three capsules three times per day with meals. Stacy required more than most people, due to her unusually high triglycerides. Within several weeks, however, she was out of immediate danger: the omega-3s caused her triglycerides to plummet to 344 mg/dL.

Over the next few months, we counseled Stacy on reducing her intake of processed carbohydrates like crackers, pretzels, breakfast cereals, and other wheat-containing products. We also advised her to avoid high-fructose corn syrup, a common food additive that contributes to elevated triglyceride levels, and to reduce her weight by about 20 pounds. Stacy accomplished all this. Her most recent blood panel showed total cholesterol of 165 mg/dL, triglycerides of 144 mg/dL, HDL of 70 mg/dL, and LDL of 66 mg/dL.

Although an extreme case, Stacy’s experience demonstrates that omega-3 fatty acids such as EPA and DHA can form the foundation of a powerful strategy to dramatically reduce dangerously high blood lipid levels without the use of prescription drugs.

No prescription medication can provide the profound results that Stacy obtained from the omega-3 fatty acids in fish oil. If we did not have fish oil at our disposal, she would have required at least three additional prescription medications and yet would have achieved less than 50% of the benefit. 

If I were forced to choose one supplement to prevent heart disease, I would choose omega-3 fatty acids from fish oil without hesitation. When you witness the hidden genetic and acquired causes of heart disease that we identify in our heart disease-reversal program, you develop new respect for the power of fish oil. In many instances, fish oil not only corrects but eliminates these patterns. It has been responsible for much of our success.

Conclusion

Omega-3 polyunsaturated fatty acids such as EPA and DHA protect cardiovascular health in myriad ways, combating several critically important cardiovascular risk factors.

 

“In terms of its potential impact on health in the Western world, the ‘omega-3’ story may some day be viewed as one of the most important in the history of modern nutritional science.”

Dr. William Harris
St. Luke’s Mid-America Heart Institute
University of Missouri-Kansas City

Research clearly demonstrates that these crucial fats help prevent deadly heart arrhythmias and sudden cardiac death. Omega-3s show efficacy in fighting disease-provoking inflammatory processes and averting the insidious phenomenon of endothelial dysfunction. Omega-3 fatty acids have potent triglyceride-reducing effects and provide the additional benefit of reducing the after-meal flood of fat in the bloodstream, an emerging risk factor for cardiovascular disease. Furthermore, omega-3 fatty acids help stabilize dangerous atherosclerotic plaque and prevent dangerous blood clots.

These multifaceted heart-protective effects of omega-3 fatty acids make fish oil part of the foundation of a nutritional strategy to guard against cardiovascular disease and stroke.

Dr. William Davis is an author, lecturer, and cardiologist practicing in Milwaukee, WI. He is founder of Track your Plaque, a heart disease-prevention program that shows how to use CT heart scans to control coronary plaque. He can be contacted through www.trackyourplaque.com.

References

1. Menuet R, Lavie CJ, Milani RV. Importance and management of dyslipidemia in the metabolic syndrome. Am J Med Sci. 2005 Dec;330(6):295-302.

2. Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM, Tejero ME. Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project. Int J Circumpolar Health. 2005 Sep;64(4):396-408.

3. Balk EM, Lichtenstein Ah, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: A systematic review. Atherosclerosis. 2006 Mar 9; [Epub ahead of print]

4. Harris WS, Ginsberg HN, Arunkul N, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997 Oct-Dec;4(5-6):385-91.

5. Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis. 1994 Mar;106(1):83–97.

6. Westphal S, Orth M, Ambrosch A, Osmundsen K, Luley C. Postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia are lowered more effectively than are chylomicron remnants after treatment with n–3 fatty acids. Am J Clin Nutr. 2000 Apr;71(4):914–20.

7. Connor SL, Connor WE. Are fish oils beneficial in the prevention and treatment of coronary artery disease? Am J Clin Nutr. 1997 Oct;66(4 Suppl):1020S-31S.

8. Abeywardena MY, Head RJ. Longchain n-3 polyunsaturated fatty acids and blood vessel function. Cardiovasc Res. 2001 Dec;52(3):361-71.

9. Thies F, Garry JM, Yaqoob P, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomized controlled trial. Lancet. 2003 Feb 8;361(9356):477–85.

10. Watkins BA, Li Y, Lippman HE, Seifert MF. Omega-3 polyunsaturated fatty acids and skeletal health. Exp Biol Med. 2001 Jun;226(6):485–97.

11. Ciubotaru I, Lee YS, Wander RC. Dietary fish oil decreases C-reactive protein, interleukin-6, and triacylglycerol to HDL-cholesterol ratio in postmenopausal women on HRT. J Nutr Biochem. 2003 Sep;14(9):513–21.

12. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int. 2003 Jan;23(1):27-36.

13. Solomon DH. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Arthritis Rheum. 2005 Jul;52(7):1968–78.

14. Hippisley-Cox J, Coupland C. Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005 Jun 11;330(7504):1366.

15. Cleland LG, James MJ. Marine oils for anti-inflammatory effect—time to take stock. J Rheumatol. 2006 Feb;33(2):207–9.

16. Leaf A. On the reanalysis of the GISSI-Prevenzione. Circulation. 2002 Apr 23;105(16):1874–5.

17. Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol. 2004 Aug;29(8):439-93.

18. Lopez-Garcia E, Schulze MB, Manson JE, et al. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr. 2004 Jul;134(7):1806-11.

19. Vanschoonbeek K, Feijge MAH, Paquay M, et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol. 2004 Sept;24(9):1734–40.

20. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989 Sept 30;2(8666):757-61.

21. Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998 Jan 7;279(1):23-8.

22. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999 Aug 7;354(9177):447-55.

23. Leaf A, Albert CM, Josephson M, et al. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation. 2005 Nov 1;112(18):2762–8.

24. Christensen JH, Riahi S, Schmidt EB, et al. n-3 fatty acids and ventricular arrhythmias in patients with ischaemic heart disease and implantable cardioverter defibrillators. Europace. 2005 Jul;7(4):338–44.

25. Calo L, Bianconi L, Colivichi F, et al. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol. 2005 May 17;45(10):1723-8.

26. Burdge GC, Calder PC. Conversion of alpha-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Reprod Nutr Dev. 2005 Sep-Oct;45(5):581-97.

Owing to the limitations of conventional cancer treatments, a growing number of researchers have turned their attention to nutritional therapies that interfere with cancer cell propagation via different mechanisms. Among these promising therapies are omega-3 fatty acids, which exhibit a variety of striking biochemical effects that may be valuable in preventing and even helping to treat certain cancers.1-3

For example, researchers have uncovered remarkable evidence that these fatty acids may impede cancer cell proliferation, potentially preventing it from spreading (metastasizing) throughout the body.4 For those who have already been treated for cancer, omega-3 fatty acids may even support recovery by preventing some of the debilitating complications that can follow surgery to remove cancer.5

In this article, we survey recent studies illuminating the promising role of omega-3s in fighting the deadly scourge of cancer.

Higher Omega-3 Intake Tied to Lower Cancer Risk

In light of limited success in treating deadly cancers, cancer prevention has become a major focus in the war on cancer. For more than three decades, scientists have accumulated evidence that diets rich in fish may have protective effects against cancer.

For example, people living in areas where high fish consumption is the norm, such as Japan and Norway, have markedly lower rates of cancer than people elsewhere in the world.6-8 By contrast, a “Western-style” diet that is relatively low in omega-3 fatty acids from fish oil is associated with rising cancer rates,9 possibly due to its content of saturated and trans fatty acids and its overabundance of omega-6 fatty acids.10

Omega-3 Fats Induce Varied Cancer-Preventive Effects

Scientists are now beginning to understand the specific mechanisms by which omega-3 fatty acids may help prevent cancer. For example, these protective fats alter genetic signaling in cells, preventing them from becoming cancerous in the first place.11 Omega-3 fats may also “reprogram” damaged genes so that they are no longer able to contribute to the initiation of cancer.12 Furthermore, omega-3 fatty acids reduce the production of inflammatory molecules that are considered vital in the initiation and progression of cancer.13,14 In fact, these essential fats work to “switch off” production of certain molecules needed for cancer cell growth,13,15 while “switching on” genes that cause cells to die before they can begin to form full-blown tumors.16

Omega-3 fatty acids may also fight cancer by promoting a healthy balance of fatty acids in the body. Omega-6 fatty acids, which are found in foods such as vegetable oils, eggs, and poultry, are very common in the American diet. However, an abundance of omega-6 fats relative to omega-3 fats can set the stage for cancer as well as heart disease.17 While omega-6 fats contribute to the production of pro-inflammatory compounds, omega-3 fats help produce anti-inflammatory compounds. Thus, an imbalance of omega-6 relative to omega-3 fatty acids contributes to inflammation. Omega-3s can counteract many of the effects of omega-6 fatty acids, so that anti-inflammatory compounds predominate in the body.18 Suppressing inflammation may prevent many deleterious health effects, including cancer formation.

Comparing the effects of omega-3 to omega-6 fatty acid intake, scientists have noted lower cancer risks with higher omega-3 intake, and higher cancer risks with greater omega-6 intake.19,20 Supplementing with moderate amounts of omega-3 fatty acids may thus be a sensible approach to tipping the scales away from cancer development.

Omega-3s Fight Cancer in Laboratory and Animal Studies

Omega-3 fatty acids have shown impressive effects against laboratory models of cancer. Two of the most common of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have prevented the progression (continued growth) of breast and prostate cancer cells in both laboratory and animal studies.21,22 Furthermore, omega-3 fatty acids appear to inhibit the appearance of receptors on the surface of cells that are needed for tumor cells to proliferate and spread (metastasize) to other tissues.4,23,24

Scanning electron micrograph of human colon carcinoma, magnified 15,000 times.

Supplementation with omega-3 fatty acids may also help fight cancer by preventing angiogenesis, the formation of new blood vessels needed to fuel the growth of tumors.25 Inhibiting angiogenesis can stop or slow the growth of cancer cells. Scientists believe that it is the anti-inflammatory effect of omega-3 fatty acids that enables them to prevent angiogenesis.26,27 Although several pharmaceutical agents for fighting angiogenesis are currently under investigation, the dramatic influence of omega-3s in preventing angiogenesis, coupled with their excellent safety profile, could make them a first-line therapy in the fight against cancer proliferation.28

Omega-3s Show Potent Effects Against Prostate Cancer

Population studies suggest that dietary consumption of omega-3 fatty acids may have especially powerful effects in reducing the risk of prostate cancer.29,30 Furthermore, one study found that deaths from prostate cancer were lowest in populations that consumed higher quantities of foods containing omega-3 fatty acids.31

In an intriguing study published earlier this year, arachidonic acid, an omega-6 fatty acid, was found to increase the proliferation of malignant prostate cells, thereby increasing the risk of advanced prostate cancer. Remarkably, however, this effect was dramatically reversed by administration of the omega-3 fatty acid EPA.32

A notable study in animals showed that increased consumption of omega-3 fatty acids interfered with prostate tumor growth, while omega-6 consumption increased tumor growth. The research team found that omega-3s decreased the proliferation of cancer cells by causing them to naturally self destruct, or undergo apoptosis. Additionally, omega-3 fatty acids led to a decrease in prostate-specific antigen (PSA) doubling time, an important measure of disease progression and prognosis. In sum, these findings suggest that dietary consumption of omega-3 fatty acids may decrease the growth of prostate tumors and promote improved clinical outcomes.33

Omega-3s May Prevent and Inhibit Growth of Breast Cancer

Omega-3 fatty acids likewise show promise in fighting deadly breast cancer. Population studies examining the relationship between diet and cancer have found that higher dietary omega-3 content is associated with a lower incidence of breast cancers in various populations.1,3,34

Scanning electron micrograph of a breast cancer cell, the most common form of cancer in women. The tumor starts in the breast and spreads quickly when not treated. If it is found during the very early stages, it can be surgically removed.

Studies in animals and in the laboratory provide clues to how omega-3 fats may help avert breast cancer. In an animal model of human breast cancer, animals consuming a diet rich in omega-3 fatty acids had a dramatic 40% increase in the activity of a natural cancer-suppressing biochemical compared to animals that consumed a diet rich in omega-6 fats. Furthermore, tumors from the omega-3-fed group expressed elevated levels of a gene that helps induce self destruction, or apoptosis, in cancer cells. When scientists applied EPA and DHA to breast cancer cells grown in the laboratory, their growth was inhibited by 20-25%, and the cells displayed physical characteristics suggestive of their imminent death.16

In the laboratory, omega-3 fatty acids have reduced the growth of breast cancer cells. Researchers noted that by regulating genes that are involved in cellular reproduction, the omega-3 fats prevented the cells from exhibiting the uncontrolled growth that characterizes cancer cells.35

Furthermore, omega-3 fatty acids suppress the appearance of a certain growth factor receptor on cells that is associated with poorer clinical outcomes from breast cancer.36

Omega-3s Shield Skin Against UV Light-Induced Cancer

Exposure to ultraviolet (UV) light contributes to several kinds of skin cancer. For more than a decade, scientists have known that omega-3 fats help reduce the skin’s sensitivity to UV rays.37

Researchers recently discovered that omega-3s can help reduce the inflammatory skin response commonly known as sunburn, in part by lowering levels of an inflammatory prostaglandin. After adults supplemented with EPA for three months, they required much higher doses of UV radiation to redden their skin and did not experience the increased inflammation that usually follows sun exposure.38

A later study indicates that omega-3 fatty acids may reduce risk for skin cancer. In adults who supplemented with EPA daily for three months, omega-3 supplementation decreased the skin’s susceptibility to sunburn and reduced by 50% the expression of a gene associated with UV light-induced skin cancer. In addition, the supplemented individuals had significantly fewer UV light-induced breaks in DNA strands.

EPA supplementation may thus help protect against UV-induced DNA damage that can lead to cancer, and long-term supplementation may help to reduce the risk of skin cancer in humans.39

Omega-3s Enhance Effects of Cancer-Fighting Drugs

In the search for effective cancer-fighting regimens, scientists have explored the efficacy of combining omega-3 fatty acids with conventional pharmaceutical drugs. Exciting evidence suggests that omega-3s actually help to sensitize cancer cells to the effects of standard chemotherapy drugs. For example, researchers found that cancer cells with a higher concentration of DHA in their membranes were more susceptible to cell death from administration of the chemotherapy drug doxorubicin.40

Similar synergistic results were found when DHA was added to chemotherapy drugs in the taxane family, such as Taxol® and Taxotere®. Dramatic increases in tumor cell death occurred not only when DHA and the drug were administered together, but also when DHA was given before the drug. This suggests that DHA administration might help prepare patients for chemotherapy with taxane drugs, enhancing the drugs’ efficacy in fighting cancer.41

Omega-3s Inhibit Inflammatory Compounds

Hidden, imperceptible inflammation is now recognized for its role in triggering a chain of events leading to heart disease and other illnesses. Omega-3 fatty acids suppress multiple steps in this inflammatory process, inhibiting the production of inflammatory cytokines and prostaglandins. Furthermore, omega-3 fats boost production of anti-inflammatory compounds. These anti-inflammatory effects may have important implications for fighting heart disease and numerous other disease processes associated with excessive inflammation.10-16

An important marker of inflammation in the body known as C-reactive protein (CRP) is associated with an increased risk of cardiovascular disease. Measuring high-sensitivity CRP is an emerging method of detecting hidden inflammation and its associated cardiovascular disease risk.17 Some scientists have observed that people who consume a greater amount of omega-3 fatty acids demonstrate lower levels of this cardiovascular risk factor, suggesting that omega-3 supplementation might help prevent cardiovascular disease by fighting inflammation.18

Omega-3s Promote Healing From Cancer Surgery

Emerging research suggests that omega-3 fatty acids may help fight inflammation and prevent infection in individuals undergoing surgical treatment for cancer. Surgical treatment of any kind provokes a powerful, immediate inflammatory response, often coupled with immune suppression, which can lead to infections. Such inflammatory and immune challenges can drain the body’s resources for recovery.5 Omega-3 fatty acids may help support healing from cancer surgery.

Researchers have noted that omega-3 fatty acids reduce levels of inflammation while boosting beneficial immune responses, providing a “one-two punch” to suppress damaging post-operative inflammation and reduce the risk of post-operative infections.5

Omega-3 fatty acids may also be critically important for cancer patients who must undergo surgery.42 Omega-3 supplementation has been associated with fewer complications of surgery, as well as with shorter hospital stays.43,44 Because of the modest blood-thinning effects of omega-3 fatty acids, patients should consult with their surgeons before beginning supplementation.45

In one study, omega-3 fatty acids provided important benefits for patients who underwent surgery for intestinal cancers. Those who supplemented with omega-3 fatty acids before and after surgery experienced fewer complications and infections compared to patients who did not supplement. Additionally, the total costs of surgical treatment were substantially lower in the omega-3-supplemented group. Omega-3 fatty acids may thus help individuals to better tolerate surgical treatment of cancer.46

A similar study showed that patients who received omega-3 supplements before surgery for colorectal cancer demonstrated better immune responses and dramatically lower incidences of infection. Omega-3s thus helped promote rapid healing from surgery in cancer patients. This study may have broad implications for many types of patients undergoing surgery.47

Conclusion

Of the many health benefits conferred by omega-3 fatty acids, their ability to prevent the development of cancer by quelling dangerous inflammation and promoting healthy gene expression may be among the most significant.

These essential fats likewise hold equal promise for those who are already battling cancer, as new findings suggest that omega-3s may exert cancer-fighting effects alone or in combination with pharmaceutical therapies. Omega-3 fatty acids may help to prevent infection and complications in people undergoing surgical treatment for cancer, and may help relieve one of the most devastating manifestations of cancer, the fatigue and weight loss known as cachexia.

While additional studies are needed, the research findings to date suggest that omega-3 fatty acids may play an important role in both preventing cancer and augmenting the effectiveness of existing anti-cancer therapies.

References

1. Caygill CP, Charlett A, Hill MJ. Fat, fish, fish oil and cancer. Br J Cancer. 1996 Jul;74(1):159-64.

2. Jude S, Roger S, Martel E, et al. Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers. Prog Biophys Mol Biol. 2006 Jan-Apr;90(1-3):299-325.

3. Kaizer L, Boyd NF, Kriukov V, Tritchler D. Fish consumption and breast cancer risk: an ecological study. Nutr Cancer. 1989;12(1):61-8.

4. Hardman WE. Omega-3 fatty acids to augment cancer therapy. J Nutr. 2002 Nov;132(11 Suppl):3508S-12S.

5. Calder PC. n-3 fatty acids, inflammation, and immunity—relevance to postsurgical and critically ill patients. Lipids. 2004 Dec;39(12):1147-61.

6. Hirose K, Takezaki T, Hamajima N, Miura S, Tajima K. Dietary factors protective against breast cancer in Japanese premenopausal and postmenopausal women. Int J Cancer. 2003 Nov 1;107(2):276-82.

7. Sakauchi F, Mori M, Washio M, et al. Dietary habits and risk of urothelial cancer incidence in the JACC Study. J Epidemiol. 2005 Jun;15 Suppl 2:S190-5.:S190-S195.

8. Wakai K, Tamakoshi K, Date C, et al. Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan. Cancer Sci. 2005 Sepb;96(9):590-9.

9. Roynette CE, Calder PC, Dupertuis YM, Pichard C. n-3 polyunsaturated fatty acids and colon cancer prevention. Clin Nutr. 2004 Apr;23(2):139-51.

10. Bartram HP, Gostner A, Reddy BS, et al. Missing anti-proliferative effect of fish oil on rectal epithelium in healthy volunteers consuming a high-fat diet: potential role of the n-3:n-6 fatty acid ratio. Eur J Cancer Prev. 1995 Jun;4(3):231-7.

11. Aktas H, Halperin JA. Translational regulation of gene expression by omega-3 fatty acids. J Nutr. 2004 Sep;134(9):2487S-91S.

12. Davidson LA, Nguyen DV, Hokanson RM, et al. Chemopreventive n-3 polyunsaturated fatty acids reprogram genetic signatures during colon cancer initiation and progression in the rat. Cancer Res. 2004 Sep 15;64(18):6797-804.

13. Bartram HP, Gostner A, Scheppach W, et al. Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology. 1993 Nov;105(5):1317-22.

14. Rao CV, Hirose Y, Indramie C, Reddy BS. Modulation of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res. 2001 Mar 1;61(5):1927-33.

15. Rao CV, Reddy BS. Modulating effect of amount and types of dietary fat on ornithine decarboxylase, tyrosine protein kinase and prostaglandins production during colon carcinogenesis in male F344 rats. Carcinogenesis. 1993 Jul;14(7):1327-33.

16. Wu M, Harvey KA, Ruzmetov N, et al. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer. 2005 Nov 10;117(3):340-8.

17. Abou-el-Ela SH, Prasse KW, Farrell RL, Carroll RW, Wade AE, Bunce OR. Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. Cancer Res. 1989 Mar 15;49(6):1434-40.

18. Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D. Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology. 2001 Aug;58(2):283-8.

19. Bagga D, Anders KH, Wang HJ, Glaspy JA. Long-chain n-3-to-n-6 polyunsaturated fatty acid ratios in breast adipose tissue from women with and without breast cancer. Nutr Cancer. 2002;42(2):180-5.

20. Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC. Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study. Br J Cancer. 2003 Nov 3;89(9):1686-92.

21. Rose DP. Dietary fatty acids and prevention of hormone-responsive cancer. Proc Soc Exp Biol Med. 1997 Nova;216(2):224-33.

22. Rose DP. Effects of dietary fatty acids on breast and prostate cancers: evidence from in vitro experiments and animal studies. Am J Clin Nutr. 1997 Decb;66(6 Suppl):1513S-22S.

23. McCarty MF. A wholly nutritional ‘multifocal angiostatic therapy’ for control of disseminated cancer. Med Hypotheses. 2003 Jul;61(1):1-15.

24. Tsuji M, Murota SI, Mortia I, et al. Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor. Prostaglandins Leukot Essent Fatty Acids. 2003 May;68(5):337-42.

25. Rose DP, Connolly JM. Regulation of tumor angiogenesis by dietary fatty acids and eicosanoids. Nutr Cancer. 2000;37(2):119-27.

26. De Caterina R, Massaro M. Omega-3 fatty acids and the regulation of expression of endothelial pro-atherogenic and pro-inflammatory genes. J Membr Biol. 2005 Jul;206(2):103-16.

27. Wallace JM. Nutritional and botanical modulation of the inflammatory cascade—eicosanoids, cyclooxygenases, and lipoxygenases—as an adjunct in cancer therapy. Integr Cancer Ther. 2002 Mar;1(1):7-37.

28. Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr. 2004 Dec;134(12 Suppl):3427S-30S.

29. Astorg P. Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence. Cancer Causes Control. 2004 May;15(4):367-86.

30. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther. 1999 Sep;83(3):217-44.

31. Hebert JR, Hurley TG, Olendzki BC, Teas J, Ma Y, Hampl JS. Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. J Natl Cancer Inst. 1998 Nov 4;90(21):1637-47.

32. Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW. Promotion of prostatic metastatic migration toward human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. Br J Cancer. 2006 Mar 27;94(6):842-53.

33. Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen KG, McHugh K. Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy. Neoplasia. 2006 Feb;8(2):112-24.

34. Hebert JR, Rosen A. Nutritional, socioeconomic, and reproductive factors in relation to female breast cancer mortality: findings from a cross-national study. Cancer Detect Prev. 1996;20(3):234-44.

35. Barascu A, Besson P, Le Floch O, Nougnoux P, Jordan ML. CDK1-cyclin B1 mediates the inhibition of proliferation induced by omega-3 fatty acids in MDA-MB-231 breast cancer cells. Int J Biochem Cell Biol. 2006 Feb;38(2):196-208.

36. Yee LD, Young DC, Rosol TJ, Vanbuskirk AM, Clinton SK. Dietary (n-3) polyunsaturated fatty acids inhibit HER-2/neu-induced breast cancer in mice independently of the PPARgamma ligand rosiglitazone. J Nutr. 2005 May;135(5):983-8.

37. Rhodes LE, O’Farrell S, Jackson MJ, Friedman PS. Dietary fish-oil supplementation in humans reduces UVB-erythemal sensitivity but increases epidermal lipid peroxidation. J Invest Dermatol. 1994 Aug;103(2):151-4.

38. Shahbakhti H, Watson RE, Azurdia RM, Ferreira CZ, Garmyn M, Rhodes LE. Influence of eicosapentaenoic acid, an omega-3 fatty acid, on ultraviolet-B generation of prostaglandin-E2 and proinflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 in human skin in vivo. Photochem Photobiol. 2004 Sep;80(2):231-5.

39. Rhodes LE, Shahbakhti H, Azurdia RM, et al. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers. Carcinogenesis. 2003 May;24(5):919-25.

40. Maheo K, Vibet S, Steghens JP, et al. Differential sensitization of cancer cells to doxorubicin by DHA: a role for lipoperoxidation. Free Radic Biol Med. 2005 Sep 15;39(6):742-51.

41. Menendez JA, Lupu R, Colomer R, et al. Exogenous supplementation with omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells. Eur J Cancer Prev. 2005 Jun;14(3):263-70.

42. Philpott M, Ferguson LR. Immunonutrition and cancer. Mutat Res. 2004 Jul 13;551(1-2):29-42.

43. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery. 1992 Jul;112(1):56-67.

44. Farreras N, Artigas V, Cardona D, Rius X, Trias M, Gonzalez JA. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 2005 Feb;24(1):55-65.

45. Nilsen DW, Almdahl SM, Svensson B, Vaage J, Rasmussen K, Osterud B. Lipopolysaccharide induced monocyte thromboplastin synthesis and coagulation responses in patients undergoing coronary bypass surgery after preoperative supplementation with n-3 fatty acids. Thromb Haemost. 1993 Dec;70(6):900-2.

46. Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg. 1999 Dec;134(12):1309-16.

47. Braga M, Gianotti L, Vignali A, Carlo VD. Preoperative oral arginine and n-3 fatty acid supplementation improves the immunometabolic host response and outcome after colorectal resection for cancer. Surgery. 2002 Nov;132(5):805-14.

48. Bauer J, Capra S, Battistutta D, et al. Compliance with nutrition prescription improves outcomes in patients with unresectable pancreatic cancer. Clin Nutr. 2005 Dec;24(6):998-1004.

49. Burns CP, Halabi S, Clamon GH, et al. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia. Cancer. 2004 Jul 15;101(2):370-8.

50. Burns CP, Halabi S, Clamon GH, et al. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res. 1999 Dec;5(12):3942-7.

51. Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003 Oct;52(10):1479-86.

52. Moses AW, Slater C, Preston T, Barber MD, Fearon GC. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer. 2004 Mar 8;90(5):996-1002.

Continued on Brain Food

More Americans suffer from depression today than ever before. Despite the wide array of antidepressant medications on the market, conventional psychiatric medicine is clearly failing to successfully manage the mood disorders that plague millions of adults.

Compelling new findings suggest that mental health disorders such as depression, attention deficit hyperactivity disorder (ADHD), and schizophrenia may in fact reflect severe deficiencies of omega-3 fatty acids.1-4 Although these essential fatty acids are critical in supporting healthy brain structure and function, they are shockingly scarce in the typical American diet.

Further exacerbating the problem is that many people who restrict their calorie intake with the goal of losing weight or extending life span may actually be endangering their mental health by depriving their brains of sufficient omega-3 fats.

In this article, we examine the latest research demonstrating the various ways in which omega-3 fatty acids help support optimal mood and attention while guarding against depression and other mental health disorders.

Low-Fat Craze Fuels Depression Epidemic

In the United States, longstanding conventional wisdom suggesting that all fats are unhealthy appears to have had an untold influence on rates of depression. Research indicates that when America went on its low-fat diet craze about 25 years ago, we threw out all dietary fats, including beneficial omega-3 fats like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Coinciding with this low-fat movement was an ever-increasing caseload of depression, ADHD, and other mental health conditions.5,6 In fact, rates of depression rose in every decade of the twentieth century.7 The United States spends nearly $44 billion a year on depression-related costs,8 and the mean out-of-pocket expense for elderly adults with depression was $1,835 in 1999.9

The observation that many Americans both limit their fat intake and suffer from depressed mood has led some investigators to suggest that some forms of depression and mental illness may be associated with a dietary deficiency of omega-3 fats.

Omega-3 Fats Fight Depression, Enhance Antidepressant Meds

Scientists first suspected a link between omega-3 fats and mood when they noticed that populations that consume the most seafood have the lowest rates of depression. For example, researchers at the National Institutes of Health have found that higher fish consumption in a nation correlates with lower rates of depression in its population.10 Researchers are now observing increasing rates of depression in areas of the world that are moving away from traditional diets rich in omega-3s to modern Western diets full of processed foods that typically supply miniscule amounts of beneficial fats.11

Low levels of omega-3 fatty acids may correlate with suicide, the most serious of all manifestations of depression. In fact, low blood levels of omega-3 fats have been linked to an increased risk of attempted suicide.12 In a recent study of medication-free depressed subjects over a two-year period, low blood levels of omega-3s predicted the risk of suicidal behavior.13 Supplementation with fish oil could potentially prevent many of the 765,000 suicide attempts and 30,000 suicides committed each year in the US.

Growing evidence likewise suggests a role for omega-3 fatty acids in helping to relieve disabling depression. After recently reviewing the most current scientific data, researchers noted that most well-designed studies show that omega-3 fatty acids benefit people who suffer depression. Importantly, they noted that omega-3 fatty acids showed positive results in a variety of patient populations, suggesting that these fatty acids may provide relief for people of all ages and genders who are afflicted by depression.2

Furthermore, omega-3 fatty acids may even benefit people who are already using antidepressant drugs but are not achieving optimal relief. In one study, people who used prescription antidepressants and supplemented with omega-3 fatty acids experienced improvements in numerous symptoms, including depression, anxiety, sleep disturbances, and poor libido.14

Similarly, a recent study from England examined the effects of omega-3 fatty acids on medicated patients suffering from depression related to bipolar disorder, or manic depressive illness. Those who took omega-3 fatty acid supplements in addition to their prescription antidepressants showed greater benefits compared to patients who took only antidepressants.15

These impressive studies indicate that omega-3 supplementation is not only beneficial against depressive disorders, but also may enhance the effects of prescription drugs used to fight conditions such as depression and bipolar disorder.

Improving Mood and Cognition Across Diverse Populations

In addition to aiding those who suffer depression, omega-3s appear to benefit non-depressed healthy subjects while helping to relieve symptoms of disorders such as ADHD, schizophrenia, and Alzheimer’s disease.

In a recent Italian study, a group of healthy volunteers who supplemented with omega-3s for just over a month demonstrated numerous benefits, including elevated mood, improved attention, and sharper cognition needed for complex information processing.16 These intriguing findings lend scientific support to the reputation of fish and its oils as “brain food.”

Omega-3s may prove to be invaluable in helping to prevent and manage ADHD, which affects a growing number of American children, adolescents, and even adults. When decreased blood levels of omega-3 fats were found in those suffering ADHD,3 researchers sought to investigate whether omega-3 supplementation could improve poor attention span and hyperactive behavior in ADHD patients. Omega-3 supplementation did in fact alleviate symptoms in children suffering from ADHD while improving academic achievement in kids with developmental coordination disorder, a condition characterized by poor coordination that sometimes occurs in concert with learning disorders.4

Another study suggests that omega-3 supplementation may complement prescription medications in those suffering from schizophrenia. In a study of patients with persistent, severe schizophrenia, combining omega-3 supplementation with antipsychotic drugs produced notable improvements compared to treatment with the drugs alone.17

In addition to being linked to ADHD, diminished blood levels of omega-3s are associated with Alzheimer’s disease, perhaps the most dreaded of all neurodegenerative disorders.3 Consumption of fish and its oils has been correlated with a decreased risk of developing dementia and Alzheimer’s, suggesting that maintaining healthy levels of omega-3 fats may help preserve cognitive function and prevent its deterioration with advancing age.18

These intriguing studies examining the effects of omega-3 fatty acids on disorders ranging from ADHD to Alzheimer’s suggest that omega-3s may well play an important role in promoting optimal mental health throughout the human life span, from childhood and adolescence well into advanced age.

Omega-3s Support Healthy Brain Structure, Function

Over the last decade, neuroscientists have found that essential fatty acids such as EPA and DHA are crucial to the very structure of the brain. Indeed, over 60% of the human brain consists of fat, which insulates nerve cells to support proper electrical signaling. More than one third of the brain’s fat is composed of omega-3 fatty acids such as those found in fish oil.19 Scientists believe that by upsetting the fatty make-up of the brain, deficiencies of essential fatty acids may contribute to mood disorders.

Omega-3 fats may also benefit brain health through their effects on blood flow to the brain. Omega-3 deficiency has been found to decrease normal blood flow to the brain in animals—an intriguing finding, as research shows that some patients with depression likewise suffer compromised blood flow to a number of brain regions.20,21 Omega-3 fatty acids may promote healthy mood by ensuring optimal blood flow to the brain.

Furthermore, omega-3 deficiency has been correlated with decreased levels of phosphatidylserine, an important brain compound that supports healthy memory and demonstrates depression-fighting effects in humans.22-24 Phosphatidylserine is a key nutrient for ensuring optimal brain function and may help to prevent cognitive decline with aging.19,25

Shortcomings of Prescription Antidepressants

Since the most expensive clinical study ever sponsored by the US government showed that popular antidepressant medicines such as Zoloft®, Effexor®, Wellbutrin®, and Celexa® benefited only 50% of the depressed patients who used them, many scientists and medical practitioners believe that it is time to re-evaluate the standard approach to mental health treatment.41 Clearly, medications alone are not sufficient to resolve depression. Furthermore, many popular antidepressants are associated with side effects such as nausea, vomiting, dizziness, and drowsiness.42

Fortunately, several reviews of the clinical evidence have concluded that omega-3 fatty acids from fish oil appear to work alone to combat depression while also enhancing the effectiveness of certain antidepressant drugs.2,14,29 Omega-3 fats may thus represent a crucial tool in the battle against ever-more common forms of depressive illness.

Omega-3s Aid Brain Health by Fighting Inflammation

A deficiency of omega-3s may also compromise brain health by promoting inflammation, which underlies degenerative diseases such as cancer, diabetes, arthritis, and heart disease that are commonly accompanied by clinical depression.26-30 Inflammation is associated with the production of certain cytokines that play a role in depressed mood.31-34

Omega-3 fatty acids reduce the production of pro-inflammatory compounds.35 By suppressing the inflammatory cascade, omega-3 fats may help reduce the incidence of depression.36,37 Lending support to the link between inflammation and depression, a recent study found that drugs that block inflammation show promise in managing depression.38 An additional advantage of omega-3 supplements is that they may have fewer side effects than anti-inflammatory medications.35

Together, these studies indicate that a deficiency in omega-3 fatty acids leads to biochemical imbalances and an increase in pro-inflammatory compounds that may contribute to the development of depression. Maintaining an optimal intake of omega-3 fatty acids may thus be crucial in supporting optimal brain health by suppressing harmful inflammation.

Optimal Omega-3 Sources and Dosages

The omega-3 fatty acid known as alpha-linolenic acid is abundant in flaxseed, canola oil, and walnuts. Unfortunately, humans convert only small amounts of alpha-linolenic acid into the EPA and DHA that are critical for inhibiting inflammation and supporting brain health. In fact, one study showed that only 5-15% of plant-derived alpha-linolenic acid was converted to DHA in the human body.39 Thus, fish oil or cold-water fish provide the best sources of these omega-3 fatty acids.

The average daily intake of EPA/DHA combined in North America is 130 mg—barely 10% of the 1000 mg recommended by the American Heart Association.40 Many health practitioners believe that doses of 1000-2000 mg a day of total omega-3 fatty acids may offer general support for health, mood, and cognition. Clinical studies suggest that 1000-4000 mg or more of omega-3s may be needed to improve mood in patients with depression.39

Fish Oil Caution

Individuals who use blood-thinning medications such as Coumadin® or who have increased bleeding tendencies should consult a physician before using fish oil.

Conclusion

Optimal intake of omega-3 fatty acids may provide invaluable support for ensuring healthy mood, attention span, and mental health in people of all ages.

By providing critical fats that support the brain’s very structure, omega-3 supplements promote healthy brain function. Emerging data suggest that omega-3 fatty acids not only fight depression, ADHD, and other mental disorders, but also may enhance the efficacy of prescription medications used to manage conditions such as depression and bipolar disorder.

These healthful fats should thus be considered essential nutrients for all who seek to achieve and maintain optimal mood and feelings of well-being.

References

1. Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65(8):1051-9.

2. Sontrop J, Campbell MK. Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med. 2006 Jan;42(1):4-13.

3. Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 2005 Jan-Feb;45(1):1-28.

4. Richardson AJ. Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. Int Rev Psychiatry. 2006 Apr;18(2):155-72.

5. Bruinsma KA, Taren DL. Dieting, essential fatty acid intake, and depression. Nutr Rev. 2000 Apr;58(4):98-108.

6. Wells AS, Read NW, Laugharne JD, Ahluwalia NS. Alterations in mood after changing to a low-fat diet. Br J Nutr. 1998 Jan;79(1):23-30.

7. Weissman MM, Klerman GL. Depression: current understanding and changing trends. Annu Rev Public Health. 1992;13:319-39.

8. Greenberg PE, Stiglin LE, Finkelstein SN, Berndt ER. The economic burden of depression in 1990. J Clin Psychiatry. 1993 Nov;54(11):405-18.

9. Harman JS, Kelleher KJ, Reynolds CF, Pincus HA. Out-of-pocket healthcare expenditures of older Americans with depression. J Am Geriatr Soc. 2004 May;52(5):809-13.

10. Hibbeln JR. Fish consumption and major depression. Lancet. 1998 Apr 18;351(9110):1213.

11. McGrath-Hanna NK, Greene DM, Tavernier RJ, Bult-Ito A. Diet and mental health in the Arctic: is diet an important risk factor for mental health in circumpolar peoples?—a review. Int J Circumpolar Health. 2003 Sep;62(3):228-41.

12. Huan M, Hamazaki K, Sun Y, et al. Suicide attempt and n-3 fatty acid levels in red blood cells: a case control study in China. Biol Psychiatry. 2004 Oct 1;56(7):490-6.

13. Sublette ME, Hibbeln JR, Galfalvy H, Oquendo MA, Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry. 2006 Jun;163(6):1100-2.

14. Peet M, Horrobin DF. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 2002 Oct;59(19):913-9.

15. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry. 2006 Jan;188:46-50.

16. Fontani G, Corradeschi F, Felici A, Alfatti F, Migliorini S, Lodi L. Cognitive and physiological effects of omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest. 2005 Nov;35(11):691-9.

17. Emsley R, Myburgh C, Oosthuizen P, van Rensburg SJ. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002 Sep;159(9):1596-8.

18. Uauy R, Dangour AD. Nutrition in brain development and aging: role of essential fatty acids. Nutr Rev. 2006 May;64(5Pt 2):S24-33; discussion S72-91.

19. Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol. 2005;21:633-57.

20. Ellis EF, Police RJ, Dodson LY, McKinney JS, Holt SA. Effect of dietary n-3 fatty acids on cerebral microcirculation. Am J Physiol. 1992 May:262(5pt.2):H1379-86.

21. Kennedy SH, Javanmard M, Vaccarino FJ. A review of functional neuroimaging in mood disorders: positron emission tomography and depression. Can J Psychiatry. 1997 Jun;42(5):467-75.

22. Hamilton L, Greiner R, Salem N, Jr., Kim HY. n-3 fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues. Lipids. 2000 Aug;35(8):863-9.

23. Maggioni M, Picotti GB, Bondiolotti GP, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand. 1990 Mar;81(3):265-70.

24. Cartwright IJ, Pockley AG, Galloway JH, Greaves M, Preston FE. The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers. Atherosclerosis. 1985 Jun;55(3):267-81.

25. Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano). 1993 Apr;5(2):123-33.

26. Kiecolt-Glaser JK, Glaser R. Depression and immune function: central pathways to morbidity and mortality. J Psychosom Res. 2002 Oct;53(4):873-6.

27. Plante GE. Depression and cardiovascular disease: a reciprocal relationship. Metabolism. 2005 May;54(5 Suppl 1):45-8.

28. Frasure-Smith N, Lesperance F, Julien P. Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Biol Psychiatry. 2004 May 1;55(9):891-6.

29. Pouwer F, Nijpels G, Beekman AT, et al. Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of omega-3 polyunsaturated fatty acids? A review of the evidence. Diabet Med. 2005 Nov;22(11):1465-75.

30. Singh RB, Pella D, Mechirova V, Otsuka K. Can brain dysfunction be a predisposing factor for metabolic syndrome? Biomed Pharmacother. 2004 Oct;58 Suppl :S56-68.

31. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan;27(1):24-31.

32. Wichers MC, Kenis G, Leue C, Koek G, Robaeys G, Maes M. Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment. Biol Psychiatry. 2006 Jul 1;60(1):77-9.

33. Schaefer M, Schwaiger M, Pich M, Lieb K, Heinz A. Neurotransmitter changes by interferon-alpha and therapeutic implications. Pharmacopsychiatry. 2003 Nov;36 Suppl 3:S203-6.

34. Hayley S, Poulter MO, Merali Z, Anisman H. The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity. Neuroscience. 2005;135(3):659-78.

35. Smith WL. Cyclooxygenases, peroxide tone and the allure of fish oil. Curr Opin Cell Biol. 2005 Apr;17(2):174-82.

36. Schiepers OJ, Wichers MC, Maes M. Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):201-17.

37. O’Brien SM, Scott LV, Dinan TG. Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol. 2004 Aug;19(6):397-403.

38. Muller N, Schwarz MJ, Dehning S, et al. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4.

39. Logan AC. Omega-3 fatty acids and major depression: a primer for the mental health professional. Lipids Health Dis. 2004 Nov 9;3:25.

40. Holub BJ. Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care. CMAJ. 2002 Mar 5;166(5):608-15.

41. Rubinow DR.Treatment strategies after SSRI failure—good news and bad news. N Engl J Med. 2006 Mar 23;354(12):1305-7.

42. Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry. 2004 Aug;19(8):754-62.

As we age, preserving strong, healthy bones becomes a top priority. Today, mainstream medical doctors routinely recommend minerals such as calcium and vitamin D, and drugs like Fosamax®, to help maintain healthy bone mass.

However, accumulating research indicates that traditional prescriptions for preserving bone health may be missing one vital ingredient: omega-3 fatty acids from fish oil. Exciting studies show that omega-3 fatty acids improve bone structure by enhancing calcium absorption, reducing bone loss, and maintaining bone mineral density. In fact, scientists now know that optimal levels of omega-3 fats such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) help support healthy bone tissue throughout life.1

In this article, we survey the latest findings pointing to omega-3 fatty acids as an essential yet largely overlooked component of a strategy to ensure lifelong bone health.

Bone: A Dynamic Body Tissue

While many people imagine that their bones are inert, static tissues, nothing could be further from the truth! In fact, bones are dynamic, living structures that continuously undergo a remodeling process that involves building and breaking down. Healthy bone structure and density depend on this delicate balance between bone building (formation) and bone breakdown (resorption). Omega-3 fatty acids appear to help maintain healthy bone mass by playing integral roles in this dynamic process.2-5

Omega-3s Prevent Bone Loss

Just how do omega-3s influence bone loss?

To determine the effects of omega-3 fatty acid consumption on bone loss in aging males, scientists have conducted experiments in an animal model of male aging. Beginning with a group of middle-aged rats, the researchers analyzed bone mineral density and then divided the remaining animals into several groups. One group received a diet rich in fish oil, another group received omega-6 fatty acids from safflower oil along with omega-3 fatty acids from fish oil, and a third group received only omega-6 fatty acids.6

After 20 weeks, all three groups demonstrated some age-associated loss of bone mineral density. However, the animals fed supplemental omega-3 fatty acids alone had higher bone mineral content and density compared to animals fed the omega-3-plus-omega-6 diet or the omega-6-only diet.6

The scientists also measured levels of various hormones and other biochemicals involved in bone production, maintenance, and destruction. Here again, the omega-3-fed rats had higher values for substances related to good bone health, while the omega-6-fed animals had higher levels of biochemicals related to bone loss.

While human studies are needed, these findings in animals lend considerable support to the positive role of omega-3 fatty acids in preventing age-induced bone loss.6

Omega-3s Increase Calcium Absorption

Omega-3 fatty acids have also been shown to increase the absorption of calcium, one of the key minerals that are incorporated in bone matrix to provide it with rigidity and strength.3

In another animal study, researchers noted that rats fed a diet rich in fish oil had significantly healthier bones than those fed a diet rich in corn oil, which supplies omega-6 fatty acids. In fact, several markers of bone health—including calcium absorption, bone mineral density, and bone calcium content—were markedly higher in the animals fed fish oil. Interestingly, DHA increased the incorporation of calcium in bone significantly more than did EPA.3

This study suggests that another mechanism by which omega-3s positively influence bone health is by increasing the absorption of bone-protective calcium.

Omega-3s Maintain Bone Mass

Since bone loss particularly affects women after menopause, scientists have also examined the effects of omega-3 fatty acids on bone health in an animal model of postmenopausal osteoporosis.

Once again, animals that consumed a diet rich in the omega-3 fatty acid DHA demonstrated notably less bone loss compared to animals whose diet was low in DHA. These intriguing findings suggest that DHA helped preserve bone mineral content in the absence of estrogen, as would be experienced by postmenopausal women.7

To determine whether the bone-protective effects of omega-3 fatty acids apply to people as well as animals, scientists examined data collected during a long-term investigation of the effects of nutrition on health. Conducted between 1988 and 1992, this study examined the nutritional habits of more than 1,500 men and women. Bone mineral density was measured using an imaging technique known as dual-energy x-ray absorptiometry, and the test results were then compared with nutritional intake data.8

The researchers concluded that subjects with the highest ratios of omega-6 to omega-3 fatty acid intake had the lowest bone mineral density. In other words, people who consumed the least omega-3s had the weakest bones. These findings strongly suggest that consuming plentiful omega-3 fatty acids may be critical in preserving healthy bone mass in aging adults.8

Another intriguing study suggests that omega-3 fatty acids may be particularly important in preserving bone mass in people suffering from rheumatoid arthritis, a painful inflammatory condition associated with a greatly increased risk of osteoporosis. Using an animal model of human rheumatoid arthritis, scientists found that subjects consuming a diet rich in fish oil had much greater bone mineral density than similar animals fed a diet deficient in omega-3 fats. The omega-3-fed animals also displayed less inflammation of the joints than did those that did not receive omega-3 fats. This study indicates that omega-3 fats can help maintain bone mineral density as well as help curtail inflammation in individuals with rheumatoid arthritis.9

Omega-3s May Promote Dental Health

Periodontal disease, one of the most common dental problems faced by adults, involves inflammation that can result in weakened bone in the jaw and erosion of the bony ridges that help secure teeth in the bone of the jaw. Emerging research suggests that a recently discovered, powerful anti-inflammatory compound derived from omega-3 fatty acids may help protect against the inflammation that can trigger tooth and bone loss.

While scientists have long appreciated the anti-inflammatory properties of omega-3 fatty acids, they recently discovered another way in which these fats suppress inflammation. Harvard University researchers found that the omega-3 fatty acid EPA serves as a molecular building block for an anti-inflammatory compound that has been dubbed resolvin E1. This novel compound works by putting the brakes on runaway inflammation, with important implications for periodontitis (infection or inflammation of the gums).11-14

In an animal model of human periodontal disease, EPA-derived resolvin E1 offered dramatic protection against the tissue inflammation and bone loss associated with periodontitis.15 This finding suggests that omega-3 fats may be an important part of a strategy to guard against periodontal disease.

Periodontal disease has been linked with other chronic inflammatory disorders, such as diabetes, cardiovascular disease, asthma, and arthritis. This has led scientists to speculate that nutritional therapeutics such as omega-3 fatty acids that benefit periodontal disease may hold promise in treating other inflammation-related illnesses.15-17

Epidemic of Low Bone Mass Threatens Aging Women and Men

Osteoporosis is widely viewed as a disease of older adults, and especially of postmenopausal women, in whom it is linked to declining levels of estrogen. However, aging men are also susceptible to the ravages of this bone-weakening disease. Of the 10 million Americans believed to have osteoporosis, at least 2 million are men.10

According to the National Osteoporosis Foundation, another 34 million Americans have low bone mass, a condition known as osteopenia that increases their risk for osteoporosis. Thus, more than half of all people 50 years of age or older are at risk of suffering bone fractures due to low bone mass.10

Osteoporosis is often called a “silent disease” because it is a gradual, painless process that becomes evident only after fractures occur. As bone loses its mineral content, it loses mass and becomes more porous. This leads to structural weakening and an increase in the likelihood of fractures, which most commonly occur in the bones of the spine, hip, and wrist. Hip fractures usually require hospitalization and major surgery, and may lead to prolonged or permanent disability, and even death. Spinal fractures are similarly serious, potentially resulting in severe pain, disability, loss of height, or permanent deformity.

To assess a patient’s risk of osteoporosis, physicians may recommend specialized examinations called bone mineral density tests, which measure bone density at various sites of the body. Generally, the higher the mineral content of bone, the denser the bone. Denser bone is associated with a lower risk of fractures.

Conclusion

Although scientists are only just beginning to unravel the important benefits of omega-3 fatty acids for bone health, preliminary study findings in animals and humans offer compelling evidence that these fish oil-derived nutrients play a crucial role in promoting and preserving bone strength and integrity, especially as we age.18-21

These initial findings suggest that, among other effects, omega-3 fatty acids may prevent age-related declines in bone mineral density while increasing the absorption of bone-protective calcium. The bone-strengthening and anti-inflammatory effects of omega-3 fatty acids may hold special value for postmenopausal women at risk for crippling osteoporosis, as well as for aging adults suffering such maladies as rheumatoid arthritis and periodontitis.

While much remains to be learned about how omega-3 fatty acids affect bone health, the scientific findings to date lend considerable support to including optimal levels of fatty acids such as EPA and DHA as part of a nutritional regimen for preserving strong, healthy bones over a lifetime.

Boron Complements Bone Health Benefits of Omega-3 Fatty Acids

In emerging research studies, scientists are learning that the bone health benefits of omega-3 fatty acids may be greatly magnified when these essential fats are combined with the critical trace mineral boron.22

Boron promotes healthy bones by supporting the utilization of vitamins and minerals that are crucial to bone tissue, including calcium, magnesium, vitamin D, and phosphorus.23-31 Intriguing new research findings suggest that boron’s bone-supporting effects may be greatest when omega-3 fatty acids are also available.

For example, when laboratory animals consumed a diet rich in both omega-3 fatty acids and boron, they demonstrated greater bone mineral density and stronger bones compared to animals fed other dietary fats and boron. These findings suggest that omega-3 fatty acids and boron may work together to support dense, strong bones.22

While boron has not yet been classified as an essential nutrient, this may soon change. Growing evidence suggests that boron plays many essential roles in maintaining skeletal health.

Boron beneficially affects the compositional and functional properties of bone, while boron deprivation adversely affects these parameters of bone health.23,27,32 In humans, boron deprivation is associated with increased excretion of calcium in urine, signifying loss of calcium from bone.33 Other studies suggest that boron plays an important role in preventing osteoporosis and alleviating osteoarthritis pain.23

Scientists from the US Dept. of Agriculture note that most adults do not consume more than 1 mg of boron a day, while larger doses of 1-13 mg per day may be needed to support optimal bone health.31

The studies just cited offer powerful support for optimizing intake of boron and omega-3 fatty acids as part of a nutritional strategy for maintaining strong, healthy bones.

References

1. Watkins BA, Li Y, Seifert MF. Nutraceutical fatty acids as biochemical and molecular modulators of skeletal biology. J Am Coll Nutr. 2001 Oct;20(5 Suppl):410S-416S; discussion 417S-420S.

2. Kettler DB. Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss? Altern Med Rev. 2001 Feb;6(1):61-77.

3. Kruger MC, Schollum LM. Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability? Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):327-34.

4. Reinwald S, Li Y, Moriguchi T, Salem N Jr, Watkins BA. Repletion with (n-3) fatty acids reverses bone structural deficits in (n-3)-deficient rats. J Nutr. 2004 Feb;134(2):388-94.

5. Baggio B. Fatty acids, calcium and bone metabolism. J Nephrol. 2002 Nov-Dec;15(6):601-4.

6. Shen CL, Yeh JK, Rasty J, Li Y, Watkins BA. Protective effect of dietary long-chain n-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats. Br J Nutr. 2006 Mar;95(3):462-8.

7. Watkins BA, Li Y, Seifert MF. Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats. J Nutr Biochem. 2006 Apr;17(4):282-9. Epub 2005 Jun 21.

8. Weiss LA, Barrett-Connor E, von Muhlen D. Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr. 2005 Apr;81(4):934-8.

9. Bhattacharya A, Rahman M, Banu J, et al. Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids. J Am Coll Nutr. 2005 Jun;24(3):200-9.

10. Available at: http://www.nof.org/osteoporosis/diseasefacts.htm. Accessed on July 5, 2006.

11. Arita M, Clish CB, Serhan CN. The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids. Biochem Biophys Res Commun. 2005 Dec 9;338(1):149-57.

12. Arita M, Yoshida M, HIng S, et al. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7671-6.

13. Arita M, Bianchini F, Aliberti J, et al. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005 Mar 7;201(5):713-22.

14. Arita M, Oh S, Chonan T, et al. Metabolic inactivation of resolvin E1 and stabilization of its anti-inflammatory actions. J Biol Chem. 2006 Jun 6; [Epub ahead of print]

15. Hasturk H, Kantarci A, Ohira T, et al. RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB J. 2006 Feb;20(2):401-3. Epub 2005 Dec 22.

16. Kantarci A, Van Dyke TE. Resolution of inflammation in periodontitis. J Periodontol. 2005 Nov;76(11 Suppl):2168-74.

17. Serhan CN. Novel omega -- 3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther. 2005 Jan;105(1):7-21.

18. Sun D, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G. Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res. 2003 Jul;18(7):1206-16.

19. Watkins BA, Li Y, Lippman HE, Feng S. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):387-98.

20. Corwin RL. Effects of dietary fats on bone health in advanced age. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):379-86.

21. Watkins BA, Li Y, Seifert MF. Lipids as modulators of bone remodelling. Curr Opin Clin Nutr Metab Care. 2001 Mar;4(2):105-10.

22. Nielsen FH. Dietary fat composition modifies the effect of boron on bone characteristics and plasma lipids in rats. Biofactors. 2004;20(3):161-71.

23. [No authors listed] Monograph. Boron. Altern Med Rev. 2004 Dec;9(4):434-7.

24. Dupre JN, Keenan MJ, Hegsted M, Brudevold AM. Effects of dietary boron in rats fed a vitamin D-deficient diet. Environ Health Perspect. 1994 Nov;102 Suppl 7:55-8.

25. Hunt CD, Herbel JL, Idso JP. Dietary boron modifies the effects of vitamin D3 nutrition on indices of energy substrate utilization and mineral metabolism in the chick. J Bone Miner Res. 1994 Feb;9(2):171-82.

26. Hunt CD, Herbel JL, Nielsen FH. Metabolic responses of postmenopausal women to supplemental dietary boron and aluminum during usual and low magnesium intake: boron, calcium, and magnesium absorption and retention and blood mineral concentrations. Am J Clin Nutr. 1997 Mar;65(3):803-13.

27. Nielsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J. 1987 Nov;1(5):394-7.

28. Beattie JH, Peace HS. The influence of a low boron diet and boron supplementation on bone, major mineral and sex steroid metabolism in postmenopausal women. Br J Nutr. 1993 May3;69(3):871-84.

29. Hunt CD. Dietary boron modified the effects of magnesium and molybdenum on mineral metabolism in the cholecalciferol-deficient chick. Biol Trace Elem Res. 1989 Nov;22(2):201-20.

30. Meacham SL, Taper LJ, Volpe SL. Effects of boron supplementation on bone mineral density and dietary, blood, and urinary calcium, phosphorus, magnesium, and boron in female athletes. Environ Health Perspect. 1994 Nov;102 Suppl 7:79-82.

31. Nielsen FH. The justification for providing dietary guidance for the nutritional intake of boron. Biol Trace Elem Res. 1998 Winter;66(1-3):319-30.

32. Rico H, Crespo E, Hernandez ER, Seco C, Crespo R. Influence of boron supplementation on vertebral and femoral bone mass in rats on strenuous treadmill exercise. A morphometric, densitometric, and histomorphometric study. J Clin Densitom. 2002 Summer;5(2):187-92.

33. Nielsen FH. Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Mag Trace Elem. 1990;9(2):61-9.

Recently, alarming studies documenting the potentially deadly side effects of prescription anti-arthritis drugs such as Vioxx® and Celebrex® have forced many to relinquish these medications. The result has been a frantic scramble among scientists and arthritis sufferers alike to find safe, effective agents that reduce inflammation and relieve arthritis pain.

Fortunately, groundbreaking research has uncovered new substances derived from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that resolve and protect against inflammation. These newly discovered substances, aptly called resolvins and protectins, may help provide arthritis relief without the side effects of conventional arthritis drugs.

Arthritis: A Family of Diseases Linked by Inflammation

Arthritis is not a single disorder, but rather a family of diseases, the most common of which are osteoarthritis and rheumatoid arthritis.

Osteoarthritis is considered the “wear and tear” arthritis, in which the cartilage that cushions our joints deteriorates, producing pain and discomfort. The most common type of joint disease, osteoarthritis is often associated with aging and exacerbated by obesity. By contrast, rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks the body’s own tissues, resulting in joint inflammation and tissue destruction. Both forms of arthritis are characterized by tenderness, stiffness, and inflammation in the joints. This pain can become severe, limiting mobility and adversely affecting one’s quality of life.1

Omega-3s Help Relieve Osteoarthritis Pain

Omega-3 fatty acids show promise in relieving the pain of osteoarthritis. In a preliminary study, individuals who supplemented with the omega-3 fatty acid EPA for six months reported less arthritis pain compared to people who did not supplement.2 This suggests that omega-3 fats could help restore mobility and quality of life to those who whose daily activities may be limited by arthritis pain.

In the laboratory, researchers have noted that adding omega-3 fatty acids to cartilage cells decreases their susceptibility to inflammation and degradation, such as occurs with osteoarthritis.3,4 Omega-3 fatty acids may thus guard against the degenerative joint destruction that accompanies osteoarthritis.

Powerful Pain Relief for Rheumatoid Arthritis

Abundant evidence suggests that omega-3s benefit people suffering from rheumatoid arthritis. Numerous studies document the rheumatoid arthritis-relieving effects of fish oil.5-10 The most commonly observed benefit is a decrease in swollen, painful joints,8 but improvements in morning stiffness, pain index, and grip strength are also reported.5,7 Several studies suggest that a minimum of 3 grams of omega-3 fatty acids daily for three months is needed to produce benefits.5-10

Earlier this year, scientists reported that omega-3 fatty acids administered intravenously quickly relieve rheumatoid arthritis pain. Patients with active rheumatoid arthritis received fish oil intravenously, in addition to standard prescription therapies. After just one week of once-a-day therapy, more than half of the patients experienced significant improvement in their symptoms. The therapy was well tolerated, and the research team recommended further investigation into the intravenous use of omega-3 fatty acids as a therapeutic option for rheumatoid arthritis patients.11

In a recent study from Brazil, rheumatoid arthritis patients reported markedly improved symptoms within three months by taking a daily dose of 3 grams of omega-3 fatty acids from fish oil. The patients experienced improvements in grip strength, pain intensity, ability to move easily, and fatigue. Interestingly, patients who also added olive oil to their daily regimen of fish oil supplements experienced even greater improvements in their symptoms, as determined by both self-reported and objective assessments of disease activity. The benefits of supplementation were even more pronounced after six months of therapy.12 This synergistic effect between olive oil and fish oil was reported in an earlier study by US researchers, who documented a significant decrease in production of inflammatory cytokines, as well as relief of rheumatoid arthritis symptoms, in patients who received fish oil and olive oil.13

Regular consumption of omega-3 fats from fish oil could help rheumatoid arthritis sufferers reduce their use of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs). Numerous studies have documented that when rheumatoid arthritis patients regularly consume fish oil, they can dramatically lessen their need for NSAIDs.14-16 A substantial number of individuals have experienced ongoing relief from rheumatoid arthritis symptoms with continued fish oil supplementation.15,16

Omega-3s Fight Pain by Quelling Inflammation

Omega-3s may be particularly helpful in managing arthritis because they reduce production of compounds that fuel the fires of inflammation, while increasing the production of biochemicals that limit inflammation.

New research reveals that EPA and DHA both serve as direct precursors of novel anti-inflammatory compounds aptly named resolvins and protectins.17,18 Groundbreaking work shows that various resolvins from EPA and DHA trigger resolution, or reduction, of inflammation, while protectins derived from DHA offer powerful protection against runaway inflammation.19 Furthermore, consumption of omega-3 fatty acids has been associated with reduced levels of two pro-inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 beta, in rheumatoid arthritis patients.20 EPA and DHA may thus help alleviate the inflammation that contributes to the pain and disability of arthritis.

Natural, Safe Relief—Without the Risks of Pharmaceuticals

Some physicians now consider fish oil an option preferable to NSAIDs such as ibuprofen or Celebrex® for relief from the inflammation of arthritis. For example, a group of Australian rheumatologists recently noted that fish oil has a number of advantages over NSAIDs. First, fish oil has not been associated with the potentially serious side effects of NSAIDs, such as upper digestive tract upset or upper gastrointestinal tract bleeding.21 (Since fish oil can produce a modest blood thinning effect, people who suffer from an abnormal bleeding tendency or use blood-thinning drugs such as Coumadin® should consult a physician before taking fish oil.22)

Furthermore, omega-3 fatty acids from fish oil benefit cardiovascular health, in contrast to some prescription arthritis medications, such as Bextra® and Vioxx®, that may harm the cardiovascular system.23 Thus, while fish oil works through several mechanisms to reduce risk for cardiovascular events, including cardiac death,24 numerous prescription drugs for arthritis actually increase the risk of cardiovascular events.23 For this reason, some physicians now recommend that their patients take the lowest possible dose, for the shortest possible time, when using NSAIDs to treat arthritis.21 By contrast, many nutritionally oriented physicians are now urging their patients to regularly consume fish oil in order to relieve the inflammation associated with arthritis and safeguard their cardiovascular health.

Conclusion

Growing clinical evidence indicates that supplemental omega-3 fatty acids from fish oil may help relieve the inflammation, pain, and immobility of arthritis. Unlike many commonly used prescription pain relievers, these essential fatty acids are safe and well tolerated.

Clearly, people seeking to prevent or relieve joint inflammation and its associated immobility and pain should consider including the omega-3 fatty acids EPA and DHA in their daily nutritional program.

References

1. Theodosakis J, Adderly B, Fox B. The Arthritis Cure: The Medical Cure That Can Halt, Reverse and May Even Cure Osteoarthritis. New York: St. Martin’s Press; 1997.

2. Stammers T, Sibblad B, Freeling P. Fish oil in osteoarthritis. Lancet. 1989. Aug 26;2(8661):503.

3. Curtis CL, Rees SG, Little CB, et al. Pathological indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum. 2002 Jun;466):1544-53.

4. Curtis CL, Rees SG, Cramp J, et al. Effects of n-3 fatty acids on cartilage metabolism. Proc Nutr Soc. 2002 Aug;61(3):381-9.

5. Hagfors L, Nilsson I, Skoldstam L, Johansson G. Fat intake and composition of fatty acids in serum phospholipids in a randomized, controlled, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr Metab (Lond). 2005 Oct 10;2:26.

6. Volker D, Fitzgerald P, Major G, Gang M. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol. 2000 Oct;27(10):2343-6.

7. James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum. 1997 Oct;27(2):85-97.

8. Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.

9. James MJ, Proudman SM, Cleland LG. Dietary n-3 fats as adjunctive therapy in a prototypic inflammatory disease: issues and obstacles for use in rheumatoid arthritis. Prostaglandins Leukot Essent Fatty Acids. 2003 Jun;68(6):399-405.

10. Fortin PR, Lew RA, Liang MH, et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol. 1995 Nov;48(11):1379-90.

11. Leeb BF, Sautner J, Andel I, Rintelen B. Intravenous application of omega-3 fatty acids in patients with active rheumatoid arthritis. The ORA-1 trial. An open pilot study. Lipids. 2006 Jan;41(1):29-34.

12. Berbert AA, Kondo CR, Alemendra CL, Matsuo T, Dichi I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition. 2005 Feb;21(2):131-6.

13. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum. 1990 Jun;33(6):810-20.

14. Belch JJ, Ansell D, Madhok R, O’Doud A, Sturrock RD. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis. 1988 Feb;47(2):96-104.

15. Lau CS, Morley KD, Belch JJ. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis—-a double-blind placebo controlled study. Br J Rheumatol. 1993 Nov;32(11):982-9.

16. Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis Rheum. 1995 Aug;38(8):1107-14.

17. Ariel A, Li PL, Wang W, et al. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering. J Biol Chem. 2005 Dec 30;280(52):43079-86.

18. Chiang N, Serhan CN. Cell-cell interaction in the transcellular biosynthesis of novel omega-3-derived lipid mediators. Methods Mol Biol. 2006;341:227-50.

19. Serhan CN, Gotlinger K, Hong S, et al. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol. 2006 Feb 1;176(3):1848-59.

20. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000 Jan;71(1 Suppl):343S-8S.

21. Cleland LG, James MJ. Marine oils for antiinflammatory effect— time to take stock. J Rheumatol. 2006 Feb;33(2):207-9.

22. Buckley MS, Goff AD, Knapp WE. Fish oil interaction with warfarin. Ann Pharmacother. 2004 Jan;38(1):50-2.

23. Motsko SP, Rascati KL, Busti AJ, et al. Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk. Drug Saf. 2006;29(7):621-32.

24. Oh R. Practical applications of fish oil (Omega-3 fatty acids) in primary care. J Am Board Fam Pract. 2005 Jan-Feb;18(1):28-36.