by Eric Cressey

Of all the lousy things that can happen, this has to be one of the worst. Imagine...You've just completed the most successful bulking cycle of your life, adding twenty pounds of mass; you're on top of the world. Now, all you have to do is train properly and eat plentifully in order to solidify your gains. With your knowledge of diet and training, it should be a snap. Then everything hits the fan... Your girlfriend is so proud of you for making such great gains and transforming your physique that she can't keep her hands off of you. The day before, she had shared a soda with a friend who had just come from the gym. That friend had taken a sip from the water fountain at the gym and accidentally touched her lips to the spout. Ten minutes earlier, that skanky "human sweat gland" guy who spends five hours on the elliptical cross trainer each day had just made out with that same water fountain. That morning, he had kissed his wife goodbye before leaving for his job at the DMV. That wife is the teacher of a kindergarten class. Incidentally, that class happened to be riddled with the flu, and some kid had blown chunks all over her nice new blouse the day before. Sure she cleaned it up, but she still wound up with the flu. Thanks to this incredibly unlikely downward spiral, you are now home sick from work, pitying yourself as you watch the same episode of Sportscenter eight times in a row. All the while, you're thinking about how you would much rather be deadlifting like a madman and showing off your gains at the gym! Unfortunately, you cannot go back in time to prevent yourself from coming down with the flu. Although it may be beneficial to look back and figure out if there was anything you could have done to strengthen your immune system (avoiding overtraining, paying attention to post-workout nutrition, taking certain supplements, getting plenty of sleep, etc.), you need to focus on the task at hand: beating the flu! You see, bodybuilders, powerlifters, and other athletes have to take into account how sickness affects performance and physical appearance, whereas normal folks just worry about "getting rid of their sniffles." Before we get to the specifics, though, I should mention that the term "flu" that we so often use is short for influenza. Influenza (also known as Grippe or Grip) is really only one of several common kinds of viral respiratory infections. Also including on this list are the common cold (upper respiratory infection or acute coryza), pharyngitis, laryngitis, tracheobronchitis, and viral pneumonia (1). Regardless of the clear differences in the nuts and bolts of each infection, they are generally all lumped together and called the flu by the general public. While this oversimplification is erroneous, the human immune system must be strong to prevent and in many cases overcome any type of infection. And, if you're anything like me, you detest the idea of getting loaded up on medications, sugary cough syrups, and lozenges just because your nose is running faster than a sprinter with a rocket up his butt. All that being said, let's get to work on finding a universal approach to maintaining your gains and getting back to optimal health as soon as possible. Diet Proper diet seems like a no-brainer, right? One would think so, but I'm constantly amazed at how people vehemently adhere to this primitive urge that tells them to stuff themselves full of crap foods just because they feel like crap! These crap foods are usually "comfort" foods: Mom's cookies, white toast with cinnamon, sugar, and butter, hot chocolate, a whole gallon of ice cream?. These foods may have made you feel better as a kid when they were used to take your mind off the "boo-boo" on your knee, but they'll only make thing worse when you are a sick adult. They might make you feel all warm and toasty on the inside, but they'll quickly make you soft and fluffy on the outside if you overindulge. So what should you eat and what should you avoid? For starters, remember that total calories are of foremost importance. Don't fall into the trap of dropping calories too low out of fear of gaining fat while "on the shelf." Instead, it's important to assume the mindset of maintaining the status quo physique-wise while bringing the immune system up to par. If you gain a little fat, don't sweat it. Remember, it's a lot easier to shed a little fat than it is to regain a few pounds of lost muscle. In reaching your daily caloric goal, as usual, spread your intake out over six smaller meals. Maintenance caloric intake is highly variable, so rather than multiplying your body weight by a certain number to find your target, base your intake on slightly below (100-150 calories) what you would take in on a normal rest day. This decrease should account for the extra time spent on the couch or in bed. Specific macronutrient recommendations are also of little value in this instance due to individual variations in terms of carb tolerance. As such, adhere to your typical macronutrient ratios with the only exception being a slight reduction in carb intake to compensate for the diminutive calorie reduction and reduced training effect. Furthermore, make sure that you keep protein high (1-1.5g/lb lean body mass) in order to remain in positive nitrogen balance and stop muscle protein catabolism in its tracks. From all our cutting cycles, we're all well aware that protein needs increase during times of stress, and sickness is certainly one of those times. In a study of critically ill children in hypermetabolic and catabolic states, researchers found that a higher protein intake was associated with positive nitrogen balance, whereas a low intake (with total calories held constant) led to a continued state of negative nitrogen balance and muscle protein catabolism (2). A big steak probably won't sound too appealing when you're sick, though, so low carb protein powders (such as Xtreme Ultra Peptide), cottage cheese, omelets, and other "easy to get down" protein sources might turn out to be your best friends. Next, only consume low-glycemic carbs. When you're sick, your body isn't primed for sucking up simple sugars like it is when you've just completed a training session. So, the typical bodybuilding "no-no" foods should be even more off-limits than usual. Your best bet is to focus carb intake early in the day when muscle cells are most receptive to storing glycogen. Keep fats (especially healthy fats) up as well - possibly at the expense of carbohydrates. In the aforementioned study of critically ill children, fat was used preferentially for oxidation. Meanwhile, a high carbohydrate intake was associated with lipogenesis (fat formation) and decreased fat oxidation (2). Thirty percent of total calories is a good figure in order to support endogenous testosterone and overall energy levels (as fat is the primary source of energy at rest). Your body will be forming plenty of new immune cells as you fight off sickness, and fatty acids constitute an important component of each new cell membrane. Therefore, in order to give the body the best raw materials available, make sure that you're getting plenty of omega-3 fatty acids. However, don't fall into the trap of overdoing the omega-3s or fat in general; very high fat diets are associated with impaired lymphocyte (one of the five kinds of leukocytes, or white blood cells) function (3). Furthermore, while fish oil has proven effective in enhancing immune function in certain clinical situations (e.g. rheumatoid arthritis, ulcerative colitis) and in animals, studies of healthy humans are yet to yield consistently favorable results to substantiate the claim that omega-3s enhance immunity (4). As such, there does not appear to be any greater benefit (at least not yet) to increasing omega-3 PUFA intake during times of sickness. Simply stick to your normal intake levels, relying on healthy sources such as fish oil and flaxseed oil for your supplemental fat intake. The last dietary concern that warrants mention is water intake. You might think that because you aren't training, you don't need to worry much about pushing the H2O- big mistake. The body loses a significant amount of fluids each day independent of training. We're constantly losing water as we dissipate heat through our skin and in our breathing without even knowing it. Factor in increased mucus production, the sweating that may be associated with a fever, the fact that your body is constantly constructing new cells (especially during sickness), not to mention your higher protein intake, and you can begin to realize the importance of really emphasizing water intake. Shoot for at least one gallon (preferably more) of water daily. Supplementation First and foremost, be sure to get a flu shot each fall. The optimal time to do so is mid-September through November, as it takes at least a week for the shot to really kick into protective-mode. If you need proof that the influenza vaccine is worth the fee (if you even have to pay for it), look no further than a study conducted on a Brazilian airline company's employees. As I'm sure you can imagine, flight attendants and those in related roles are a population segment that is extremely susceptible to the flu due to their interactions with so many customers (often in confined spaces). Prior to flu season, each of 813 employees received either an influenza vaccination or a placebo. Seven months later, the employees who had received the vaccines showed 39.5% fewer episodes of flu-like illness than the placebo. Additionally, the vaccine group was absent from work due to sickness 26% less often than the placebo group (5). From a weight-training standpoint, that 26% corresponds to a lot of missed training sessions. In addition to the flu shot and your regular multivitamin, you should definitely include the following: Vitamin C Vitamin C (ascorbic acid) is the first immune-booster that comes to mind. A vital component of every cell in the human body, ascorbic acid is perhaps most notably found in high concentrations in leukocytes (white blood cells). The leukocytes are constantly being produced in the bone marrow as safeguards against bad stuff like cottage cheese gone sour, reruns of those obnoxious Subway commercials with Jared, curling in the squat rack, and, oh yeah, infections. During infection, in order to prevent oxidative damage, the vitamin C within the leukocytes is used up faster than a post-training shaker bottle full of Relentless (4)! Thus, it should come as no surprise that reduced leukocyte vitamin C levels are associated with less than optimal immune function. (6) In the worst vitamin C deficit scenario, scurvy, the immune response is entirely inadequate (and sometimes nonexistent) in each of the many components of the immune system. In fact, overall vitamin C status is often measured via an assessment of levels in the leukocytes (4). In terms of preventative supplementation, a true consensus has not yet been met regarding the efficacy of vitamin C in reducing the occurrence of common colds. Several respected studies have found that Vitamin C supplementation is of little value in preventing the common cold (7), whereas others have reported decreased incidences of reported common cold infection among individuals who received large doses of a vitamin C supplement (8,9). However, other studies have verified the assertions that supplementation with vitamin C improves several aspects of the human immune response, effecting positive changes in proliferation and/or function of in three of the five types of leukocytes: lymphocytes, neutrophils, and monocytes (10-16). Adequate vitamin C status is often defined as "a circulating pool of 1500mg" (7). Due to the fact that water-soluble vitamins like vitamin C are not stored by the body as well as fat-soluble vitamins, ascorbic acid must be continuously replenished through diet and supplementation. Doses of up to 10g per day have been used in numerous studies without serious toxicity symptoms. The side effects of such high consumption may include diarrhea and, in serious cases, kidney stones or urate crystals (due to increased uric acid release in the urine). Antonio and Stout state that these risks have "been greatly overstated" (7). Based on the available literature, I recommend 2-2.5g of supplemental vitamin C daily during normal training conditions and 4-5g daily during flu-like symptoms and times increased of training stress. Also, be sure to spread your intake throughout the day in 500mg doses. Dosages of 500mg are proven to increase cellular ascorbic acid absorption by up to 40%, whereas dosages greater do not increase this absorption (17). Vitamin E Perhaps as important as vitamin C is Vitamin E, which works synergistically with selenium in tissues to reduce lipid membrane damage by reactive oxygen species (ROS) during infections (4). Vitamin E has proven effective in improving various parameters of the immune function, including enhanced lymphocyte production, improved antibody response to vaccine, reduced pulmonary viral titers (a measure of virus prevalence in respiratory infections), and "preventing an influenza-mediated decrease in food intake and weight loss" (18-20). No decrease in food intake? Maybe that steak won't sound so bad after all! All that being said, even the slightest deficiency in vitamin E can easily compromise one's immune response. And, the current RDA of 30 IU is barely adequate in preventing deficiency in sedentary, normally healthy individuals, let alone in athletes, the elderly, and the sick and diseased. Granted, one may derive a considerable amount of vitamin E from diet alone, but in order to receive sufficient vitamin E to attain an enhanced immune benefit, one must supplement in excess of the RDA (especially on low-fat diets). Vitamin E is recognized as one of the least toxic vitamins, although one may experience some minor symptoms (nausea, diarrhea, muscle weakness) with very high dosages (7,21). As such, 800-1200 IU throughout the year (regardless of whether you're sick or healthy) is an optimal approach. Glutamine Glutamine is well known as the most abundant amino acid in the human body (including both the plasma and tissue pool). In fact, the intramuscular free amino acid pool is more than 60% glutamine, and the glutamine in skeletal muscle accounts for about 90% of the body's total glutamine pool. Although over 40% of the body's glutamine is devoted to fueling the GI tract, this amino acid also plays a role in the functioning of many other parts of the body, including the liver, brain, muscles (duh!), hair follicles, kidneys, and - you guessed it - the immune system (7,22-24). Adequate levels of glutamine are necessary to ensure optimal proliferation and function of lymphocytes, macrophages, and neutrophils (25,26). Traditionally, because the body can synthesize glutamine endogenously (mostly in the muscle tissue), it has been classified as a nonessential amino acid. However, this classification is made under the assumption that the body is not enduring a stressful physiologic trauma such as sickness (23). Many researchers have now begun to classify glutamine as a conditionally essential amino acid during times of sickness, infection, and malnutrition. Because glutamine is a crucial substrate for a variety of metabolic processes, it is only logical that the body requires increased amounts of the amino acid during infection in order to "bolster" the immune system while maintaining normal physiological functioning (24,26). Unfortunately, as you can see in many cancer patients, the body's response to infection, injury, and stress is protein catabolism. Initially, plasma glutamine levels are depleted. Next, in order to sustain its metabolic processes and replenish plasma glutamine levels, the body takes glutamine from skeletal muscle. Normally, this isn't a problem, as skeletal muscle glutamine synthesis matches glutamine release. However, during times of stress, there is a problem: numerous organs, including the liver and bowel, show marked increases in glutamine uptake during infection. These increases, in combination with the needs of the immune system, GI tract, and the regular metabolic processes, cause glutamine release from skeletal muscle to exceed glutamine synthesis. In fact, skeletal muscle glutamine release may double during infection (23,27). In summary, during infection: 1. Glutamine use increases 2. Glutamine supply decreases 3. A concentration gradient across the muscle cell membrane cannot be reached (23) 4. Your beloved quad sweep becomes fuel for your GI tract and, essentially, your body's lunch. Think about it for a second: when you're sick, is your body going to care more about ensuring appropriate internal organ functioning or maintaining sleeve-splitting biceps? Luckily, numerous studies have proven that exogenous glutamine can help to: maintain positive nitrogen balance (and glutamine levels in skeletal muscle), increase plasma glutamine levels, prevent decreases in ribosomal concentrations, improve muscle protein synthesis rates, and enhance immune function (through such mechanisms as encouraged lymphocyte proliferation) (7, 28-32). Also, let's not forget that glutamine?s "immunoenhancing" effects make it an effective year-round, recovery-promoting supplement (albeit in smaller doses) for hard training athletes who are more susceptible to infection, especially during and shortly after periods of intensive training (7,33,34). Glutamine supplementation is also associated with increased plasma GH concentration, which may also assist in immunity (7,35). During illness, shoot for 0.35-0.4g glutamine per kg body weight, and spread your intake out throughout the day in 3-5g doses. Based on the published clinical studies and for absorbability reasons, I recommend glutamine peptides. L-glutamine (free form), however, tastes better, generally costs less, and will also yield favorable results. Personally, I'll stick with peptides, but it's your call; just make sure to get it in you in some form! Zinc Although most people primarily associate zinc with growth and development, this trace mineral also plays a crucial role in proper immune function. A deficiency of zinc relates to diminished immune response, including low T- and B-cell (the two broad categories of lymphocytes) counts in bone marrow due to decreased proliferation, and reduced antibody production (just to name a few). In some mice, only thirty days of inadequate zinc intake caused an 80% reduction in immune capacity. As such, it should come as no surprise that zinc deficiencies are prevalent in numerous immune system-stressing chronic illnesses, including HIV, renal disease, and alcoholism (4,36). While the complications of zinc deficiency are well established, studies on the benefits of zinc supplementation in enhancing immune function have yielded mixed, but mostly favorable results. Numerous studies have found that zinc supplementation initiated upon the onset of a cold or upper respiratory tract infection decreases the sickness' duration and severity (7,37-39). In a study of twenty burn victims, fewer pulmonary infection rates and shorter hospital stays were observed in patients who received a trace mineral supplement that included zinc (40). Meanwhile, zinc supplementation in long distance runners prevented the typical increase in reactive oxidative species normally seen with endurance activity (41). In terms of preventative supplementation, researchers found that of 609 school children that were given either a zinc supplement or a placebo, those who supplemented with zinc had 45% fewer acute lower respiratory infections over the 120-day study (42). If you take nothing else from all these studies, at least walk away from this article cognizant of how important sufficient intake is, especially for athletes (who are more likely to be deficient than the general population). While high-dose supplementation can actually lead to immunosuppression, moderate supplementation throughout the year with slightly increased dosages beginning at the onset of flu- or cold-like symptoms is an effective and safe supplementation approach (7). During sickness, take at least 25mg zinc (but not more than 100mg) per day. An optimal approach would be to get this supplemental intake in the form of a ZMA supplement, as it will enable you to meet your zinc needs while increasing anabolic hormone levels, improving recovery, and promoting deep, restful sleep. Miscellaneous: the other stuff Here are a few other supplements that are often thrown into the immunity discussion, but will probably not be worthwhile additions to your immune effort: Vitamin A (preformed vitamin A is known as beta-carotene): Although vitamin A is of unquestionable importance to proper immune functioning, there is no definitive evidence to suggest that supplemental vitamin A offers additional benefits over normal dietary intake, especially in those with already adequate status. Excessive vitamin A intakes have been associated with suppression of T- and B-cell function, thus causing a greater susceptibility to infection. Toxicity can also become an issue with higher intakes. Vitamin A deficiency is very uncommon in wealthier nations. As such, if you feel that you need to get more beta-carotene than you diet alone provides, make sure to select a multivitamin with at least 5000 micrograms (4,7). Echinacea: Although a few studies have emerged that show slightly (and relatively insignificantly) shorter respiratory tract infection durations in patients treated with echinacea, most have demonstrated that the herbal product has little or no effect on preventing and treating sickness. This uncertainty is complicated by the fact that there are nine species of the plant, different parts (leaves, stem, roots, flowers) of the plant can be used, and different forms are available (e.g. powder, liquid extract, capsule). Essentially, even if echinacea was definitively proven effective, an argument would still exist over which species, form, and delivery produces the best results. At this point, there is not enough evidence to recommend echinacea as a worthy supplement (7,43-45). Arginine: This nonessential amino acid has shown promise in improving immune response and wound healing via improved lymphocyte production in individuals with compromised health status. Other studies, however, have shown that arginine supplementation is of no benefit in attempting to enhance the immune response, especially in healthy individuals (7). Given that some clinical trials use upwards of 20g L-arginine per day (mostly without appreciable immunity-related results), forty capsules per day seems like far too risky an investment even if you enjoy being a human guinea pig. Then again, even if you do decide to give arginine a try, be careful; excessive intakes can actually blunt the immune response (46). Lifestyle/Training An adequate amount of sleep during sickness is of the utmost importance. The old "8-hours at night" recommendation still holds true...as a minimum. You should also be shooting for a nap or two during the day. It seems like a no-brainer to say that you shouldn't be training when you're sick, but I'm constantly amazed at how many people still go the gym in spite of their wheezing, sore throats, and aches. Before you stumble off the couch and over to your local gym, ask yourself if your body could really recover from a heavy training session if it hasn't even recovered from the flu. The answer should be a resounding "NO!" If it isn't, maybe it will help to think about how your decision to go train will impact others; you'll probably make half the people in the gym sick just like the "human sweat gland" did to you. Stay home, if not for your own sake, then for the sake of everyone else who enjoys his or her health and visits to the gym. Get over the flu and then get back to the gym! Conclusion There you have it: a comprehensive approach to getting back to the gym as soon as possible. To recap: 1. No comfort foods 2. Maintenance calories (factoring in reduced activity level) 3. Normal protein intake 4. Slightly reduced carb intake, consisting of low GI carbs only 5. Normal healthy fat intake 6. Regular Multivitamin 7. 4-5g vitamin C in 500mg doses throughout the day 8. 800-1200 IU vitamin E in 400 IU doses throughout the day 9. 0.35-0.4g glutamine peptides/kg body weight in 3-5g doses throughout the day 10. ZMA supplement (or zinc equivalent providing 25-100mg/day) 11. No training until symptoms are gone 12. R&R It might not sound as appetizing or heart-warming as a bowl of chicken soup, but it beats Nyquil... References 1. The Merck Manual of Diagnosis and Therapy. http://www.merck.com/pubs/mmanual/section13/chapter162/162b.htm; 1995 accessed Sept 2002. 2. Coss-Bu JA et al. Energy metabolism, nitrogen balance, and substrate utilization in critically ill children. Am J Clin Nutr 2001 Nov;74(5):664-9. 3. Calder PC et al. Fatty acids and lymphocyte functions. Br J Nutr 2002 Jan;87 Suppl 1:S31-48. 4. Field C. et al. Nutrients and their role in host resistance to infection. J Leukoc Biol 2002 Jan;71(1):16-32. 5. Mixeu MA et al. Impact of influenza vaccination on civilian aircrew illness and absenteeism. Aviat Space Environ Med 2002 Sep;73(9):876-80 6. Schwager, J. et al. Modulation of interleukin production by ascorbic acid. Vet Immunol Immunopathol. 1998 Jun 30;64(1):45-57. 7. Antonio, J., & Stout, J. Sports Supplements. Lippincott Williams & Wilkins, 2001. 8. Hemila, H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int J Sports Med 1996 Jul;17(5):379-83. 9. Hemila, H. Vitamin C and acute respiratory infections. Int J Tuberc Lung Dis 1999 Sep;3(9):756-61. 10. Kennes, B. et al. Effect of vitamin C supplements on cell-mediated immunity in old people. Gerontology 1983;29(5):305-10. 11. Penn, ND. et al. The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial. Age Ageing 1991 May;20(3):169-74. 12. Shilotri PG, & Bhat KS. Effect of mega doses of vitamin C on bactericidal ativity [sic] of leukocytes. Am J Clin Nutr 1977 Jul;30(7):1077-81 13. de la Fuente, M. et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998 Apr;76(4):373-80. 14. Patrone, F. et al. Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils. Acta Vitaminol Enzymol 1982;4(1-2):163-8. 15. Prinz, W. The effect of ascorbic acid supplementation on some parameters of the human immunological defense system. Int J Vit Nutr Res 1977; 47:248-57. 16. Woollard, KJ. et al. Effects of oral vitamin C on monocyte: endothelial cell adhesion in healthy subjects. Biochem Biophys Res Commun 2002 Jun 28;294(5):1161-8. 17. Voldani, A. et al. New evidence for antioxidant properties of vitamin C. Cancer Detect Prev. 2000;24(6):508-23. 18. Meydani, SN et al. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr. 1990 Sep;52(3):557-63. 19. Meydani, SN et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997 May 7; 277(17):1380-6. 20. Han, SN et al. Effect of long-term dietary antioxidant supplementation on influenza virus infection. J Gerontol A Biol Sci Med Sci 2000 Oct;55(10):B496-503. 21. Beharka A. et al. Vitamin E status and immune function. Methods Enzymol 1997;282:247-63 22. Yeh, SL et al. Effects of glutamine-supplemented total parenteral nutrition on cytokine production and T cell population in septic rats. JPEN J Parenter Enteral Nutr. 2001 Sep-Oct;25(5):269-74. 23. van Acker, BA et al. Glutamine: the pivot of our nitrogen economy? JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5 Suppl):S45-8. Review. 24. Newsholme, P. Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J Nutr. 2001 Sep;131(9 Suppl):2515S-22S; discussion 2523S-4S. Review. 25. Saito, H. et al. Glutamine as an immunoenhancing nutrient. JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5 Suppl):S59-61. Review. 26. Ziegler, TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr. 2001 Sep;131(9 Suppl):2578S-84S; discussion 2590S. Review. 27. Karinch AM. et al. Glutamine metabolism in sepsis and infection. J Nutr 2001 Sep;131(9 Suppl):2535S-8S; discussion 2550S-1S. 28. Wilmore, DW. The effect of glutamine supplementation in patients following elective surgery and accidental injury. J Nutr. 2001 Sep;131(9 Suppl):2543S-9S; discussion 2550S-1S. Review. 29. Boelens PG. et al. Glutamine alimentation in catabolic state. J Nutr. 2001 Sep;131(9 Suppl):2569S-77S; discussion 2590S. Review. 30. Yoshida, S. et al. Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg. 1998 Apr;227(4):485-91. 31. Valencia, E. et al. Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers. Nutrition. 2002 May;18(5):367-70. 32. Yoshida, S. et al. Glutamine supplementation in cancer patients. Nutrition. 2001 Sep;17(9):766-8. 33. Castell LM., & Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition 1997 Jul-Aug;13(7-8): 738-42. 34. Rosene, MF. et al. Glutamine supplementation may maintain nitrogen balance in wrestlers during a weight reduction program. Med Sci Sports Exerc 1999;31(5): S123. 35. Welbourne, TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr. 1995 May;61(5):1058-61. 36. Fraker, PJ. et al. The dynamic link between the integrity of the immune system and zinc status. J Nutr 2000 May;130(5S Suppl):1399S-406S. 37. Prasad AS. et al. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2000 Aug 15;133(4):245-52. 38. Al-Nakib, W. et al. Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges. J Antimicrob Chemother. 1987 Dec;20(6):893-901. 39. Mossad, SB. et al. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996 Jul 15;125(2):81-8. 40. Berger MM. et al. Trace element supplementation modulates pulmonary infection rates after major burns: a double-blind, placebo-controlled trial. Am J Clin Nutr. 1998 Aug;68(2):365-71. 41. Singh A. et al. Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol 1994 Jun;76(6):2298-303. 42. Sazawal S. et al. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998 Jul;102(1 Pt 1):1-5. 43. Gunning, K. Echinacea in the treatment and prevention of upper respiratory tract infections. West J Med. 1999 Sep;171(3):198-200. 44. Brinkeborn RM. et al. Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial. Phytomedicine. 1999 Mar;6(1):1-6. 45. Grimm, W, & Muller, HH. A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections. Am J Med. 1999 Feb;106(2):138-43. 46. Wiebke EA. et al. Effects of L-arginine supplementation on human lymphocyte proliferation in response to nonspecific and alloantigenic stimulation. J Surg Res 1997 Jun;70(1):89-94.

By Eric Cressey

It's time to pick up where I left off last month in Part I.  To "reset" the stage, I'll just say that fish oil is good because it helps with:

• Belluzzi et al (1996) found that 2.7 g of fish oil per day for one-year significantly reduced the incidence of relapse in Crohn's patients in remission. Thirty-nine of the patients received the fish oil, while 39 others received a placebo; the relapse rate was 41% lower in the former group. Regression analysis indicated that the positive effects of fish oil were independent of patient age, sex, previous surgery history, disease duration, and smoking status (34).

• Barbosa et al (2003) hypothesized that omega-3 fatty acids from fish oil tend to exert their anti-inflammatory effects in ulcerative colitis via decreases in plasma oxidative stress, acting as free radical scavengers (35).
• In a study of eighteen patients with active ulcerative colitis (characterized by diarrhea and rectal inflammation; ain't that a pretty picture?), four months of 5.4 g combined EPA and DHA supplementation (vs. placebo) led to significantly "reductions in rectal dialysate leukotriene B4 levels, improvements in histologic findings, and weight gain (36)." English translation: their rectums looked, felt, and performed better.

• Nagakura et al (2000) found that ten months of EPA and DHA supplementation lessened asthma symptoms and acetylcholine sensitivity in 29 children with severe bronchial asthma (in collaboration with a controlled environment and diet) (37).
• Three weeks of 5.4 g combined EPA and DHA markedly blunted exercise-induced asthma in ten elite athletes and improved post-exercise pulmonary function significantly (38).

• In a study of thirty cystic fibrosis patients that received EPA and DHA supplementation as 1.3% of their total calories for eight months, researchers noted significant decreases in markers of inflammation. Subtle improvements in forced expiratory volume (a measure of pulmonary function) were noted as well. Furthermore, in comparison with the previous eight-month period, the patients (collectively) required much fewer days (392 vs. 721) of antibiotic therapy during the eight months on EPA and DHA (39).

• Shahar et al (1994) examined the relationship between dietary omega-3 fatty acid intake and COPD in 8,960 smokers, finding that combined EPA and DHA intake was "inversely related to the risk of COPD in a quantity-dependent fashion (40)." In other words, if you're going to smoke, you might as well complement that metallic cough with some fish breath; it'll probably protect you from COPD down the road.
• Romieu and Trenga (2001) observed that "data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements" in both children and adults (41).

• In patients with sickle cell disease, omega-3 fatty acid supplementation at 0.1 g/kg per day "reduced the frequency of pain episodes requiring presentation to the hospital from 7.8 events during the preceding year to 3.8 events/year." Conversely, subjects receiving dietary olive oil (the control group) experienced 7.1 pain events/year, only slightly less than the 7.6 event average from the previous year. This reduction in pain episodes was likely attributable to the effects of EPA and DHA on reducing prothrombotic activity (42).
• A study of Nigerian children found that omega-3 fatty acid concentrations were 40-50% lower in the phospholipid membranes of children with sickle cell disease than in those of healthy children. The researchers noted that "the phospholipids of the children with SCD are less fluid relative to those of their healthy counterparts. (43)"

• In a Danish study, low intakes of omega-3 fatty acids were correlated with more severe menstrual symptoms. Dysmenorrhea correlations were also observed in low omega-3: omega-6 ratios and vitamin B12 deficiencies. The body utilizes omega-3s to create type-3 prostaglandins that are less "aggressive" than those formed from other fatty acids. The net result of utilizing omega-3s as raw materials appears to be milder symptoms. Prostaglandins act like hormones, controlling uterine contractions and pains (44).

• Ninety days of DHA with vitamins E and B significantly improved computerized visual field (CVF) and retinal contrast sensitivity in thirty chronic glaucoma patients. The researchers concluded that such a supplement merits inclusion in an intervention to prevent the progression of glaucoma-related damage (45).

• Cunnane et al (1989) found that in comparison with their healthy counterparts, MS patients had lower omega-3 fatty acids in their plasma (46).
• As a follow-up, Gallai and colleagues (1995) found that omega-3 supplementation in MS patients led to decreases in proinflammatory eicosanoids, indicating potential for fish oil in modulating some immune function decrements associated with MS (47).

• Supplementation with DHA between the 24th and 28th week of pregnancy significantly increased (by roughly six days on average) the duration of gestation. Birth weight, length, and head circumference all increased slightly as well (48).
• A study of Norwegian children found that "use of cod liver oil in the first year of life was associated with a significantly lower risk of type 1 diabetes." Regression analysis implied that this effect was independent of the oil's vitamin D content, and was likely due to the omega-3 fatty acids in the oil (49).
• Malcolm et al (2003) noted an association between "the DHA status of infants at term and early postnatal development of the pattern-reversal VEP [visual evoked potential], indicating that DHA status itself may influence maturation of the central visual pathways" in infants. These assertions were based on results seen in a trial of one hundred women that received either fish oil capsules or a placebo (50).
• Uauy and colleagues (2003) found not only that long chain polyunsaturated fatty acid supplementation in newborns improved visual acuity at four months, but also there was "a significant relation between the total DHA equivalents provided and effectiveness (51)." In other words, more was better (to a certain point, of course). This effect is likely due to effects on physical properties of the membranes, neurotransmitters, and modulation of gene expression in the retina and brain (52).
• Because of the crucial role of essential fatty acids as structural components of all cell membranes, profound implications can be seen at the "brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LC-PUFA) (52)."
• Uauy et al (2001) asserted that "light sensitivity of retinal rod photoreceptors is significantly reduced in newborns with n-3 fatty acid deficiency, and that docosahexaenoic acid (DHA) significantly enhances visual acuity maturation and cognitive functions (52)." Furthermore, "DHA also has significant effects on photoreceptor membranes and neurotransmitters involved in the signal transduction process; rhodopsin activation, rod and cone development, neuronal dendritic connectivity, and functional maturation of the central nervous system (52)." It beats feeding potato chips to your kids, doesn't it?
• Data from Dunstan et al (2003) suggests that there may be a role for omega-3 fatty acids in the prevention of allergic disease. In a study of 83 atopic pregnant women receiving fish oil or placebo, the researchers noted that infants from the fish oil group had significantly less severe atopic dermatitis at age one, although no difference in the frequency of the disease was apparent between groups (53).
• Williams and colleagues (1995) described preeclampsia (affecting pregnant women) as "a systemic disease characterized by diffuse endothelial dysfunction, increased peripheral vascular resistance, coagulation abnormalities, antioxidant deficiency, persistent elevations of maternal leukocyte-derived cytokines, and hyperlipidemia (54)." These researchers conducted a study to examine the relationship between omega-3 fatty acid intake and preeclampsia. Women with the lowest omega-3 levels were 7.6 times more likely than those with the highest levels to have preeclampsia-related complications during their pregnancies. Moreover, "a 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia (54)."

• Psoriatic lesions are characterized by increased concentrations of arachidonic acid. EPA exerts an anti-inflammatory effect that likely works to counteract the pro-inflammatory effects of arachidonic acid and its metabolites. In a study of 83 patients with chronic plaque-type psoriasis, researchers found that omega-3 fatty acid infusions were superior to omega-6 infusions (the placebo) "with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient (55)."
• Grimminger et al (1993) observed that high dose intravenous omega-3 fatty acid supplementation exerted a rapid beneficial effect on inflammatory skin lesions in twenty patients hospitalized with acute guttate psoriasis. These effects were most likely mediated through eicosanoid metabolism regulation (56).

• Hydroa vacciniforme ?also known as photosensitivity ? is a serious skin disorder characterized by blistering (especially on the face) after even the slightest amount of sun exposure; it affects primarily children. In a small study, Rhodes and White reported that three months of fish oil supplementation reduced erythemal sensitivity to UVA and UVB (two types of ultraviolet radiation), and yielded modest improvements in overall symptoms (57).

• Increased oxidative stress is a hallmark of type 2 diabetes. Jain et al (2002) sought to determine the effects of very low dose omega-3 fatty acid supplementation (0.6 g combined EPA and DHA) on type 2 diabetics. Even at such a low dose, they found that the patients in the omega-3 group exhibited significantly greater improvements in glycemic status, blood pressure, lipid profiles, and reductions in markers of oxidative stress as compared to a placebo group of type 2 diabetics (58).
• It's well established that the various types of fatty acids are clearly involved in the onset of chronic conditions (such as insulin resistance and obesity) characterized by inflammation. In overweight subjects, higher concentrations of saturated fats and omega-6 and lower concentrations of omega-3 fatty acids are significantly associated with higher concentrations of circulating interleukin-6 (IL-6), a marker of inflammation. Interestingly, though, these associations are not apparent in lean subjects (59).
• In a 14-year study of 84,204 female nurses ages 34-59, the risk of type 2 diabetes was significantly positively associated with high consumptions of trans fatty acids and cholesterol, whereas the condition was negatively associated with omega-3 and omega-6 polyunsaturated fatty acids. The investigators estimated that "replacing 2% of energy from trans fatty acids isoenergetically with polyunsaturated fat would lead to a 40% lower risk" of type 2 diabetes (60). I guess it's time to replace the doughnuts in the nurses' lounge with canned salmon. Or, you could contact Krispy Kreme about introducing the chocolate frosted sardine filled doughnut!
• Chicco et al (1996) found that low-dose fish oil supplementation in rats led to significant reductions in blood lipids and plasma insulin levels without changes in glucose tolerance. The investigators hypothesized that because no changes in pancreatic insulin content were apparent, the lower insulin levels may have been due to improvements in peripheral insulin sensitivity (61).
• Unfortunately, studies attempting to demonstrate these effects in humans have been less impressive (62-64). In spite of the fact that omega-3 consumption in the form of fish increased HDL cholesterol and improved overall dyslipidemia in overweight patients, Mori et al (1999) found no independent effect of fish consumption on glucose or insulin (62). Others have come to similar conclusions with actual fish oil supplementation (63,64).

• Eric Noreen has done extensive work examining the effect of fish oil on resting metabolic rate (RMR). At the 2003 American College of Sports Medicine Annual Conference, Noreen presented the results of a study that compared RMR in subjects supplemented with 9g of safflower oil (predominately omega-6), 3, 6, or 9g of 60% concentrated fish oil. The fish oil groups saw daily RMR increases of 141 to 448 calories, whereas the safflower group's RMR actually decreased. As an added bonus, the fish oil group also lost a little bit of fat mass while gaining some lean body mass. (65)

• Leptin is a hormone released by adipocytes that has a great impact on body fat levels. In simple terms, the amount of leptin present in one's body serves as feedback to the brain about whether one is okay as far as nutritional status is concerned. As you get leaner, leptin levels drop; as you get pudgier, they go up. These are important responses, as high leptin concentrations are associated with decreased hunger and food intake and increased energy expenditure, all of which are important factors in getting and staying lean.
• Unfortunately, as you get leaner, leptin levels drop as your body essentially senses starvation-like conditions; this decrease makes it difficult to get and stay lean. Fish oil may be able to help with this problem, as rats fed high omega-3 diets demonstrate up-regulation in plasma leptin concentrations significantly above what is predicted based on body fat levels (66,67).
• In an overfeeding study of rats with 42% of their energy intakes as fish oil, safflower oil, olive oil, or beef tallow, the fish oil group had the greater lean body mass gains and the lowest fat mass gains (68). In other words, if you're going to stuff yourself, be sure to include some fish oil in the feast.

• Maes et al (1999) observed that there is a significant deficiency in omega-3 fatty acids serum phospholipids and red blood cell membranes in major depression. Furthermore, the deficiency is likely a result of abnormal omega-3 metabolism in depressed patients and may continue in spite of treatment with antidepressants (69). As such, fish oil treatment may serve as an important adjunct to ? or even a replacement for - traditional antidepressant therapy
• Hibbeln and Salem (1995) proposed that low concentrations of polyunsaturated fatty acids may be related to increased risks of suicide, depression, alcoholism, and post-partum depression (70).
• Four out of five trials of EPA in the treatment of schizophrenia have demonstrated significant reduction in patient episodes of severe mania and depression following supplementation (71).
• In an eight-week study of 28 clinically depressed patients receiving either 9.6 g omega-3 fatty acids per day or a placebo, there were significant decreases in scores on the Hamilton Rating Scale for Depression, an evaluative tool on which high scores indicate more severe feelings of depression (72).
• Zanarini and Frankenburg (2003) studied the effects of 1 g/day ethyl-EPA (or placebo) on thirty females with borderline personality disorder. The ethyl-EPA supplement proved "to be superior to placebo in diminishing aggression as well as the severity of depressive symptoms (73)."
• Attention-deficit/hyperactivity disorder (ADHD) may be related to an abnormality in polyunsaturated fatty acid metabolism. As such, both Richardson and Puri (2000) and Kidd (2000) have proposed that omega-3 fatty acid supplementation may have merits in the treatment of this condition, although more research is warranted in this regard (74,75).

• Here's one for the Type A folks out there. Delarue et al (2003) studied seven subjects on two occasions separated by three weeks. In the first session, these seven individuals were subjected to mental stress in the form of mental arithmetic and the Stroop task, and measures of sympathoadrenal activation (plasma cortisol, catecholamines, energy expenditure, and adipose tissue lipolysis) were taken thirty minutes after the stress. After this mental stress challenge, each subject supplemented with 7.2 g fish oil/day for three weeks, at which point they took the battery of tests again. In this second session, plasma epinephrine, cortisol, energy expenditure, and plasma non-esterified fatty acids concentrations, were all significantly lower than in the initial session. The investigators therefore concluded that omega-3 fatty acid supplementation "inhibits the adrenal activation elicited by a mental stress, presumably through effects exerted at the level of the central nervous system (76)." It appears that omega-3 fatty acids are able to partially inhibit the pro-inflammatory response to psychological stress (77). Ever get a racing heart or high blood pressure before a test, presentation, or job interview? Fish oil may be just what you need to get mellow!

• In a study of 27 adolescents with chronic migraines, supplementation with fish oil led to reductions of 87% in headache frequency, 74% in headache duration, and 78% in headache severity compared to a period prior to the study. Interestingly, olive oil (the placebo) produced similar results, although they were not quite as favorable (78).

• Many anticonvulsant medications for epileptics have highly undesirable side effects. In light of the profound roles of omega-3 fatty acids in immune and nervous system activities, Rabinovitz and colleagues (2004) compared the effects of carbamazepine (CBZ) and SR-3, a compound with a 1:4 omega-3: omega-6 ratio, on seizure control efficiency, and protection against cognitive impairment and cortisol elevation in rats. While the two treatments were equally effective in controlling seizures, SR-3 proved to be superior on the latter two measures (79). Treating epilepsy with omega-3 compounds is certainly a new frontier, so more research is warranted (especially in human subjects) to determine its true efficacy.

• The exact cause of CFS remains to be determined, but there is speculation that it could involve abnormalities at the immune, neuroendocrine, and autonomic levels. Because fish oil inhibits the production of certain pro-inflammatory substances, many experts believe that it holds great potential in the treatment of CFS. Research is ongoing (80).

• Several experts predict a role for omega-3 fatty acids in the treatment of fibromyalgia; anecdotal evidence supports this assertion, and further research is certainly warranted on this front (81).

• In chronic liver disease, widespread inflammation can cause the liver to become fibrotic. In light of the known anti-inflammatory benefits of omega-3 fatty acids, Hayashi et al (1999) studied the effect of EPA and DHA supplementation on four patients with hepatitis B infection, one with hepatitis C virus cirrhosis, and one with alcohol-related cirrhosis. Subtle reductions were observed in globulin (a marker of liver pathology) with simultaneous increases in HDL cholesterol and various apolipoproteins (protective agents against hepatitis-related liver disease) (82).

If you aren't taking fish oil, you're an idiot. Seriously. Okay, I'll leave you with a bit more practical wisdom instead. The typical fish oil capsule you'll encounter is 1000 mg fish oil; we, however, are more concerned with the EPA and DHA content of that 1000 mg. In most cases, you'll find 180 mg EPA and 120 mg DHA per capsule. A good rule of thumb (especially based on the results of the clinical trials) is to consume 3-6 g combined EPA and DHA per day; at this capsule size, you'd need 10-20 capsules per day. For this reason, liquid fish oil is a great alternative.

By Eric Cressey

If you're even remotely up-to-date on your nutrition-for-health reading, you're well aware of the benefits of fish oil. Moreover, if you're anything like me, you've also gone to great lengths--often to no avail--to convince people that they should be taking it even if it does sound "icky." In an effort to save you and I a lot of future time and energy, I've compiled the following for you to share with your relatives, mailman, proctologist, lunchlady, and anyone else with whom you associate that isn't currently "on da fish." Based on undeniable scientific evidence and anecdotal evidence, I strongly encourage you to incorporate into your diet two specific omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), commonly referred to as fish oils. EPA and DHA deficiencies have been linked to problems that include, but are certainly not limited to heart disease, hypertension, arthritis, cancer, immune disorders, chronic intestinal disorders, growth retardation, liver disorders, skin lesions, reproductive failure, visual problems, kidney disorders, and neurological disorders (1). Dietary alpha-linolenic acid can be converted to EPA and DHA in the body for utilization as important raw materials in healthy cell membranes. Significant amounts of alpha-linolenic acid can be found in the following oils: flaxseed, soybean, hempseed, pumpkinseed, canola, wheat germ and walnut. Products such as margarine and shortening that are derived from these oils also contain modest amounts of alpha-linolenic acid. Some nuts and seeds-- butternuts, walnuts, pumpkinseeds, and flaxseeds-- and vegetables (soybeans) are good sources as well (1). However, the conversion of alpha-linolenic acid to EPA and DHA is quite inefficient; estimates place the conversion rates at less than 5-10% for EPA and 2-5% for DHA (2). Lifestyle factors can also negatively influence these conversions. There is also evidence to suggest that females are more efficient at converting linolenic acid than men; this is likely due to increased demands for EPA and DHA during pregnancy and lactation (3). Even if you eat plenty of the aforementioned foods regularly, you still might come up short on EPA and DHA because the fatty acid quality is often degraded due to the typical overprocessing that occurs in commercial production (4). As such, it is best to get your EPA and DHA directly whenever possible. EPA and DHA are commonly referred to as fish oils because coldwater fish are by far the best sources. Although the terms EPA/DHA and fish oils are substituted for one another in writing and conversation, EPA and DHA are actually just two kinds of fatty acids contained in fish oils (5). These fish include, but are not limited to: salmon, mackerel, bluefish, tuna, mullet, herring, anchovy, and sardines. Infants receive plenty of EPA and DHA from their mothers' milk (1). Certainly, eating fish every day isn't appetizing for most people, and drinking human milk after the age of one is neither feasible nor socially acceptable! Plus, the typical vegetarian diet is extremely low in alpha-linolenic acid, so even if conversion was efficient, these individuals would still be coming up short (clinical studies have proven that vegetarians have insufficient levels of EPA and DHA) (2). Luckily, fish oil supplements in both liquid and softgel form are widely available to ensure that EPA and DHA requirements can be met easily. EPA and DHA exert their most powerful effects in an anti-inflammatory role. Arachidonic acid, which is created out of the omega-6 fatty acids in our diets, serves as the building block for certain eicosanoids that control the synthesis of cytokines that are pro-inflammatory and immunoregulatory; when these cytokines are overproduced, chronic inflammatory diseases (and even septic shock) can result. Omega-3 fatty acids, on the other hand, inhibit the production of arachidonic acid--thus preventing the production of certain mediators of inflammation--and serve as the raw materials for a healthier class of eicosanoids with anti-inflammatory properties (6). Given how out-of-whack the typical diet is in terms of the omega-6: omega-3 ratio, it should come as no surprise that the world is as unhealthy as it is! Here is some pretty impressive data on a variety of fronts: Cardiovascular Health/Atherosclerosis/Hyperlipidemia/Hypertension:

• An eleven year study of 20,557 male U.S. physicians showed that those who consumed fatty fish at least once per week were 52% less likely to suffer a sudden cardiac death than those who only ate it once per month or less (5).
• The typical Greenland Eskimo diet is devoid of fruits and vegetables and very high in fats from animal sources: not your traditional "heart healthy diet." However, the Eskimos had far lower instances of coronary heart disease (CHD) than a Denmark population of nearly identical ethnical composition (same ancestors). The Eskimo and Danish diets both consisted of a high percentage of calories from fat (39% and 42%, respectively), so why didn't the Eskimos suffer from such CHD like the Danes and everyone else? The secret lay with the types of fat that the Eskimos were eating. The typical Danish diet consisted of 22% of total calories from saturated fat and less than 1% from omega-3 polyunsaturated fatty acids (PUFAs). Meanwhile, only 9% of total calories in the Eskimo diet came from saturated fat. Perhaps more importantly, 4.2% of the Eskimos' total calories came from omega-3 PUFAs (5). Similar trends are readily apparent in coastal villages of Korea and Japan and throughout Scandinavian countries. Not surprisingly, they all rely extensively on coldwater fish in their everyday lives. Need further proof? A recent comparison of two Japanese villages: one fishing, one farming, found that the farming village had eight times more atherosclerotic plaques than their fishing counterparts (7).
• In a study of 59 patients with diagnosed heart disease, Durrington et al (2001) monitored the effects of 2 g daily of Omacor, a pharmaceutical grade fish oil concentrate. The researchers found that "there was a sustained significant decrease in serum triglycerides by 20-30% and in very low density lipoprotein (VLDL) cholesterol by 30-40% in patients receiving active Omacor at three, six, and 12 months compared either to baseline or placebo (8)."
• Not only do fish oils lower serum triglycerides and, in high dosages and combination with dietary modifications, low density lipoprotein (LDL) cholesterol, but they also decrease arterial platelet collection, which can lead to dangerous clots (5).
• Harper and Jacobsen (2001) reported that randomized clinical trials with fish oils "have demonstrated reductions in risk that compare favorably with those seen in landmark secondary prevention trials with lipid-lowering drugs (5)."
• Following coronary artery bypass surgery with venous grafts, patients that receive 4 g per day of omega-3 fatty acids have a significantly lower risk of graft occlusion (obstruction/closure) (9).

Hypertension:

• There are like 80 bizillion studies out there proving that fish oil reduces blood pressure (although you'll obviously derive greater benefits if you eat right and exercise, too). That said, 4 g omega-3 fatty acids per day is the minimum you'll need to see an improvement (9). You can expect not only reduced blood pressure, but also decreased vascular wall thickness (10). I've included a few more references (11-13) for those of you that either don't believe me or have a lot of time on your hands for extra reading.

Cardiac Arrhythmias:

• There is significant backing for the assertion that fish oils' antiarrhymthic capacity is the most important. Without sufficient EFAs, the body is forced to make cell membranes out of saturated fatty acids, which yield membranes that are far less elastic. When cardiac cells are made from EFAs (and are thus appropriately elastic), the heart has an easier time returning to a resting state. However, the rigid cell membranes made from saturated fatty acids can cause arrhythmias and alter the cardiac muscle cell contraction (5).

Inflammatory Diseases of Joints and Connective Tissues:

• In patients with degenerative and inflammatory joint diseases, supplementation with omega-3 fatty acids decreases both the "degradative and inflammatory aspects of chondrocyte metabolism, whilst having no effect on the normal tissue homeostasis (14)."
• Chondrocytes are the building blocks of articular cartilage and work with the extracellular matrix of collagen and proteoglycans to dissipate forces. If the cartilage is constantly eroding due to chondrocyte degradation, the structure tends to soften as its water content increases. Interventions with omega-3 fatty acids are effective in reducing these negative trends and their related symptoms in most patients with osteoarthritis (15,16).
• In more than two dozen studies, researchers have found that fish oil supplementation reduces fatigue and stiffness in rheumatoid arthritis (RA) afflicted individuals. In fact, some studies found the effects to be dramatic enough to allow for substantial decreases in nonsteroidal anti-inflammatory drug (NSAID) dosages (16-18). Generally speaking, in trials of 3 g combined EPA and DHA (the minimum recommended dose for RA patients), the benefits of fish oil supplementation were not noticeable until the 12-week mark, so be patient! On a microscopic level, the omega-3 supplementation tended to limit the release of leukotrien B(4) and interleukin 1 from neutrophils and monocytes. In plain English, this means that two inflammation-causing factors were present in lesser quantities (17).
• RA patients that supplemented with Vitamin E and fish oil showed an even greater decrease in NSAID requirements, indicating a synergistic effect between the two (18).
• Raynaud's Phenomenon is a vascular disorder that falls under the inflammatory diseases of joints and connective tissues. In this condition, tiny blood vessels that feed the skin periodically contract (called a "vasospasm"), limiting blood flow to the skin. As oxygen deprivation sets in, the skin--especially in the hands and feet--turns white and eventually blue. There is speculation that this phenomenon is due to the body's overreaction to cold, as the body excessively vasoconstricts these arteries to conserve heat. However, while cold atmospheres are most likely to cause a vasospasm, emotional stress can be a causative factor as well. Because omega-3 fatty acids "induce a favorable response to vascular ischemia," they have been investigated as a potential treatment for Raynaud's. DiGiacomo et al (1989) found that fish oil supplementation improved cold exposure tolerance and significantly delayed the onset of vasospasm in Raynaud's patients. Furthermore, this cold tolerance improvement was associated with a significantly increased digital systolic blood pressure in a cold atmosphere (20).
• Systemic lupus erythematosus (SLE) -- better known simply as lupus - is a chronic, autoimmune rheumatic disease with a wide variety of symptoms. Typically, this disease affects women of childbearing age (21). Symptoms include arthritis, skin rash, vascular inflammation, and profound effects on the central nervous, renal and cardiopulmonary systems (22). Mohan and Das (1997) found that concentrations of EPA and DHA were low in the plasma phospholipids of SLE patients; this supported pre-existing data that EPA and DHA supplementation could lead to clinical remission without side effects (22).
• In cases of pediatric SLE, dyslipoproteinemia -- essentially high triglycerides, low HDL, and high LDL - is often present. Provision of fish oil supplements has proven effective in significantly improving blood lipid profiles (decreased serum triglycerides concentrations) in these patients beyond dietary intervention alone (24).

Osteoporosis:

• Two short-term studies have found that a lower omega-6 to omega-3 fatty acid ratio (achieved via omega-3 supplementation) attenuates bone loss in patients with osteoporosis. These effects are likely due to decreases in the production of Prostaglandin E2 (PGE2), an eicosanoid widely implicated in bone resorption (25). Overall eicosanoid balance is largely dependent on fatty acid intake; so it's important to consider both the quantity of omega-3s and omega-6s present.

Kidney Disease/Renal Failure:

• Researchers at the Mayo Nephrology Collaborative Clinic found that fish oils slowed the progression of immunoglobin A nephropathy in patients at a high risk for kidney disease (26).
• Omega-3s have shown promise in reducing urinary calcium levels in kidney stone patients and preventing blood clots in hemodialysis patients (26).
• Hemodialysis patients given fish oil required 16% less erythropoietin while experiencing a 3.6% increase in serum albumin levels in comparison to a placebo group (27).
• The side effects (such as skin lesions and hyperlipidemia) of cyclosporine, a medication often prescribed for kidney transplant patients, are noticeably less significant when patients supplement with fish oil (28)

Prostate Cancer:

• A longitudinal study of 6,272 Swedish men showed that those who regularly consumed fish were approximately 50% less likely to be diagnosed with prostate cancer and roughly 70% less likely to die from it than those who avoided fish. Three servings per week appeared to be the minimum amount needed to attain such benefits (29).
• Augustsson et al (2003) validated the Swedish study with a larger sample size of 47,882, and noted that the strongest association also existed between fish consumption and metastatic cancer (meaning that it's extensive and spreads to other parts of the body via the blood vessels or lymphatic system). Those men that ate fish more than three times per week were 24% less likely to be diagnosed with metastatic cancer (30).

Colon Cancer:

• Collett et al noted that incidences of colon cancer in rats were reduced significantly with DHA supplementation in the form of fish oil (31).

Breast Cancer:

• In a five-year prospective study of 35,298 Singapore Chinese women ages 45-74, high levels of dietary omega-3 fatty acids (mostly from shellfish) were associated with a significantly reduced (26% lower) risk of breast cancer (32).

Skin Cancer:

• In animals, omega-3 fatty acids have been proven effective as protection against photocarcinogenesis, likely due to the fatty acids' ability to combat oxidative stress. Rhodes et al studied the effect of 4 g/day EPA supplementation "on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status" in 42 healthy subjects. The control group received oleic acid, a monounsaturated fatty acid, for the three-month study. Sunburn sensitivity was reduced in the EPA group only; likewise, other early markers of skin cancer diminished significantly with EPA supplementation. These results imply that there was protection against acute UVR-induced damage by dietary EPA; the researchers hypothesized that "longer-term supplementation might reduce skin cancer in humans (33)."

That concludes part one; hopefully, you've picked up some valuable information. Next month, I'll besiege you with another 8,471 references supporting my argument on a variety of different fronts. Stay tuned! References 1. Whitney, E.N. & Rolfes, S.R. Understanding Nutrition: (8th ed.). Belmont, CA: Wadsworth Publishing Company, 1999. 2. Davis BC, Kris-Etherton PM. Achieving optimal essential fatty acid status in vegetarians: current knowledge and practical implications. Am J Clin Nutr. 2003 Sep;78(3 Suppl):640S-646S. 3. Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002 Oct;88(4):411-20. 4. Colgan, M. Optimum Sports Nutrition. New York: Advanced Research Press, 1993. 5. Harper CR, Jacobson TA. The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med. 2001 Oct 8;161(18):2185-92. 6. Calder PC. n-3 polyunsaturated fatty acids and cytokine production in health and disease. Ann Nutr Metab. 1997;41(4):203-34. 7. Yamada T, Strong JP, Ishii T, Ueno T, Koyama M, Wagayama H, Shimizu A, Sakai T, Malcom GT, Guzman MA. Atherosclerosis and omega-3 fatty acids in the populations of a fishing village and a farming village in Japan. Atherosclerosis. 2000 Dec;153(2):469-81. 8. Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia. Heart. 2001 May;85(5):544-8. 9. Nordoy A, Marchioli R, Arnesen H, Videbaek J. n-3 polyunsaturated fatty acids and cardiovascular diseases. Lipids. 2001;36 Suppl:S127-9. 10. Engler MM, Engler MB, Pierson DM, Molteni LB, Molteni A Effects of docosahexaenoic acid on vascular pathology and reactivity in hypertension. Exp Biol Med (Maywood). 2003 Mar;228(3):299-307. 11. Passfall J, Philipp T, Woermann F, Quass P, Thiede M, Haller H. Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension. Clin Investig. 1993 Aug;71(8):628-33. 12. Bhatnagar D, Durrington PN.Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications. Int J Clin Pract. 2003 May;57(4):305-14 13. Holm T, Andreassen AK, Aukrust P, Andersen K, Geiran OR, Kjekshus J, Simonsen S, Gullestad L. Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients. Eur Heart J. 2001 Mar;22(5):428-36. 14. Curtis CL, Rees SG, Cramp J, Flannery CR, Hughes CE, Little CB, Williams R, Wilson C, Dent CM, Harwood JL, Caterson B. Effects of n-3 fatty acids on cartilage metabolism. Proc Nutr Soc. 2002 Aug;61(3):381-9. 15. Curtis CL, Rees SG, Little CB, Flannery CR, Hughes CE, Wilson C, Dent CM, Otterness IG, Harwood JL, Caterson B. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum. 2002 Jun;46(6):1544-53. 16. Cho SH, Jung YB, Seong SC, Park HB, Byun KY, Lee DC, Song EK, Son JH. Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel (Perna Canaliculus) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical trial. Allerg Immunol (Paris). 2003 Jun;35(6):212-6. 17. Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S 18. Tidow-Kebritchi S, Mobarhan S. Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Nutr Rev. 2001 Oct;59(10):335-8. 19. Rennie KL, Hughes J, Lang R, Jebb SA. Nutritional management of rheumatoid arthritis: a review of the evidence. J Hum Nutr Diet. 2003 Apr;16(2):97-109. 20. DiGiacomo RA, Kremer JM, Shah DM. Fish-oil dietary supplementation in patients with Raynaud's phenomenon: a double-blind, controlled, prospective study. Am J Med. 1989 Feb;86(2):158-64. 21. Ioannou Y, Isenberg DA. Current concepts for the management of systemic lupus erythematosus in adults: a therapeutic challenge. Postgrad Med J. 2002 Oct;78(924):599-606. 22. Das UN. Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network. Prostaglandins Leukot Essent Fatty Acids. 1994 Sep;51(3):207-13. 23. Mohan IK, Das UN. Oxidant stress, anti-oxidants and essential fatty acids in systemic lupus erythematosus. Prostaglandins Leukot Essent Fatty Acids. 1997 Mar;56(3):193-8. 24. Ilowite NT, Copperman N, Leicht T, Kwong T, Jacobson MS. Effects of dietary modification and fish oil supplementation on dyslipoproteinemia in pediatric systemic lupus erythematosus. J Rheumatol. 1995 Jul;22(7):1347-51. 25. Albertazzi P, Coupland K. Polyunsaturated fatty acids. Is there a role in postmenopausal osteoporosis prevention? Maturitas. 2002 May 20;42(1):13-22. 26. Donadio JV. n-3 Fatty acids and their role in nephrologic practice. Curr Opin Nephrol Hypertens. 2001 Sep;10(5):639-42. 27. Vergili-Nelsen JM. Benefits of fish oil supplementation for hemodialysis patients. J Am Diet Assoc. 2003 Sep;103(9):1174-7. 28. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991 Sep;54(3):438-63. 29. Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet. 2001 Jun 2;357(9270):1764-6. 30. Augustsson K, Michaud DS, Rimm EB, Leitzmann MF, Stampfer MJ, Willett WC, Giovannucci E. A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003 Jan;12(1):64-7. 31. Collett ED, Davidson LA, Fan YY, Lupton JR, Chapkin RS. n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. Am J Physiol Cell Physiol. 2001 May;280(5):C1066-75. 32. 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. 33. Rhodes LE, Shahbakhti H, Azurdia RM, Moison RM, Steenwinkel MJ, Homburg MI, Dean MP, McArdle F, Beijersbergen van Henegouwen GM, Epe B, Vink AA. 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.