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Paper: Effects of Omega 3 Supplementation

Hello all. Heres the scoop: I’m doing a research paper for my nutrition class on the effects of omega 3 fatty acid supplementation. If anyone is interested, I will post the paper on here once I finish it up. So far looks like tons of support for taking Flameout. Thanks…

one of the best collection of resources on omega-3 research - with tons of supporting references - can be found in the following link. you may find this useful.


Ok, here is the paper. Handed it in Friday. Took me pretty much 12 hrs straight, between reading and then writing the paper. Spike is awesome, but walking around like a zombie for half a day is not. Just noticed a few mistakes, but will post as is.

Going to be a long post.

Effects of Omega-3 Fatty Acid Supplementation
Introduction: The effects of Omega-3 Fatty Acids on humans are wide ranging. Omega 3 fatty acids all have a similarity in their chemical structure. In most situations omega-3 fatty acids oppose omega-6 fatty acids. It is through this opposition that some of the major effects of omega-3 fatty acids are known such as roles in inflammation, and cancer. Specific cases of inflammation include rheumatoid arthritis, asthma, and some cardiovascular diseases. The most notable omega-3 fatty acids are EPA, DHA, CLA, GLA, and ALA.
When describing fatty acids, they are refered to by name as well as chemical structure. The main focus of this paper will be on the effects of EPA, DHA, ALA, and CLA. EPA, or Eiconsapentaenoic acid has a chemical structure of 20:5N-3 (Christie 2). The number 20 on the left side of the colon signifies the amount of carbon atoms. The next number 5, located on the right of the colon, corresponds to the number of double bonds present. Finally the N stands for chain length, and the number after the dash represents the number of carbon atoms from the last double bond (2). For the current paper we will only be discussing the N-3 or omega 3 polyunsaturated fats. Another important long chain fatty acid in addition to EPA is DHA, or Docosahexaenonic acid. The chemical structure of DHA is 22:6N-3. Two more pivotal omega-3 fatty acids are Alpha-Linolenic acid, 18:3N-3, and Congugated Linoleic Acid or CLA. Many variations of CLA exist, and they are all dienoic isomers of linoleic acid (Brismar 1516). These are not the only Omega-3 fatty acids, but they will be the main focus.
When discussing Omega-3 fatty acids it is necessary at times to include Omega-6 (N-6) Fatty acids in the discussion. This is because, many of the positive aspects of Omega-3’s are inversely related to Omega-6’s. Supplemental omega-3 fatty acids partially replace omega-6 fatty acids in the cell membranes of almost all cells (Simopolous 496).
Additionally, both of these fatty acids are metabolizted to eicosanoid products (Callaghan 149). When an omega-6 fatty acid AA, or arachidonic acid, and EPA are both consumed, these two compounds compete to producce eicosanoids (Simopolous 496). The inflammatory properties of the eicosanoids produced vary greatly between omega-3 and omega-6.
These eicosanoids have a large impact in cases of rheumatoid arthritis as well (149). In these cases, there is a strong inflammation reaction. There have been several documented human studies of omega-3 fatty acids used to treat rheumatoid arthritis. In one study individuals were given supplemental EPA + DHA mixtures upwards of 2.4 grams per day. This supplementation reduced production of cytokines involved in inflammation (154).
During these reactions were eicosanoids are produced, cytokines are also produced and some have many undesirable qualities (Callaghan 150). Some cytokines have been shown to induce weight loss or a decrease in weight gain (284). Many studies have shown that the omega-3 fatty acid CLA can prevent this from happening. In one study, researchers injected TNF, the most catabolic cytokine into CLA fed mice, and the CLA the wasting damage (287). It is necessary to distinguish between specific diseases as the mechanisms of CLA are very specific in regard to specific pathogens (288). One of these compounds, PGE, has many negative aspects. It is pro-inflammatory, it potentiates pain caused by other agents, and it increases local pyrexia (Callaghan 150).
Another inflammatory process that involves omega-3 fatty acids is asthma (Simopoulos 501). According to Simopoulos, asthma is ?a mediator driven inflammatory process in the lungs.? Additionally, these mediators include the previously mentioned cytokines and eicosanoids produced by either AA or EPA being metabolized.
Altering the contents of fatty acids ingested can modify these effects. For instance, when EPA, DHA, and GLA are ingested, the presence of PGE2 as well as LTB4 decreases. LTB4 is another cytokine that has been shown to induce inflammation (152). Because of these, and other findings, a few important changes to diet are reccomended. A reccomendation for the ratio of omega-6 to omega-3 fatty acids in the diet is 1-4 to 1 instead of the current 16-20 to 1 common to most western diets (Simopolous 502).
According to Artemis Simopoulous, ?The first evidence of the important role of dietary intake of omega-3 polyunsaturated fatty acids in inflammation was derived from epidemiological observations (495)?. A group of Eskimos in Greenland compared with a similar group of individuals from Dennmark displayed very low incidences of autoimmune and inflammatory disorders (496). The diet of these individuals was rich in long chain omega-3 fatty acids from seafood which may have lead to these low incidences.
These long chain omega-3 fatty acids, DHA and EPA, can be found in cold water fish, however the existence of mercury in some fish can outweigh the benefits of these fatty acids (Hauswirth 103). This creates a need for other sources other than fish for omega-3 fatty acids. Christa B. Hauswirth et al. Analyzed several varieties of cheese to determine differences in fatty acid profiles. They accomplished this by using gas chromatography on forty different cheeses. Because ALA has been hypothesized to protect individuals from cardiovascular disease, cheese from fresh alpine grass fed cow milk from Switzerland was used for 12 samples (103). The rest of the cheeses include: 7 commercial samples of cheddar cheese, 6 linseed supplemented swiss cheeses, and 8 cheeses from alpine grass and partial sillage fed cows. These cheeses were then given a fatty acid profile including linolenic acid, total omega-3 fatty acids, EPA, ratio of AA to EPA, omega-6 to omega-3 fatty acid ratios, and saturated fat. In all categories the cheese from alpine grass fed cows in Switzerland fared significantly better than other cheeses. Per 100g of cheese the alpine cheese had 495 +/- 73 mgs of Linolenic acid, compared to the next highest at 305 mg +/- 55 (104). Additionally, this cheese had the highest total omega-3 fatty acids, EPA content, the best ratio of AA to EPA, and the lowest saturated fat content. The presence of ALA is also important because ALA competes with LA for chain elongation to either EPA or AA respectively (106). According to Hauswirth:
The ratio of ALA to LA in human plasma and blood cell membranes is 1 to 100, but the enzymes involved in fatty acid chain elongation have much higher affinities for ALA (106).
Because of this, slight increases in ALA could lead to positive benefits. Additionally, ALA has been shown to slow heart rhythm, and also reduce the beating rate of isolated rat cardiac myocytes (105). This example provides some reason for the ?Swiss Paradox?. That is, the Swiss are one of the top cheese consumers in the world, which in turn causes a higher fat intake than other countries. Despite this higher fat intake, as a whole, the country has relatively low mortalities from cardiovascular diseases, which may be explained by the favorable fatty acid profile of alpine cheese (104).
Because many of the effects of Omega-3 fatty acids involve immune functions, the concern that these fatty acids may change the previously mentioned functions is legitimate. In order to evaluate this, Samatha Kew et al. conducted a placebo controlled double blind parrallel experiment with 150 healthy men and women (1287). Subjects were put into 5 different groups, which each received varying fats and oil capsules. One group was given a placebo, two groups were given ALA, and two groups were given an EPA and DHA combination. One of the ALA groups were given 4.5 grams per day, and one was given 9.5 grams per day. In the EPA and DHA groups, one group was given .77 grams per day, and the other was given 1.7 grams per day.
According to the researchers, cells like neutrophils, monocytes, and macrophages form part of the immune response (1287). Additionally, these cells destroy bacteria by phagocytosis, oxidative bursts, and Cytokine production, and it is by these mechanisms that the effects of omega-3 fatty acids on immune function are judged (1292). In Phagocytosis, there was no change in the amount of neutrophils and monocytes. Oxidative burst capacities and Cytokine production also remained unchanged. This study illustrates that ALA supplementation of up to 9.5 grams per day and EPA + DHA supplementation of up to 1.7 grams per day has no detrimental effect on immune function (1295). Additionally consumption of these omega-3’s could be increased without negative effects on immune function.
Omega-3 Fatty acids, specifically long chain omega 3’s such as EPA and DHA have been hypothesized to decrease cardiovascular diseases and have antiarrhythmic properties (Albert 1113). Additionally, fish consumption is associated with a reduced risk of sudden death caused by cardiac issues. In order to test this hypothesis, researchers analyzed healthy men in a Physician’s health study and followed up with them for up to 17 years. Blood levels of long chain omega-3’s were collected, and analyzed for 94 of these healthy individuals that died through sudden death of a cardiovascular nature.
In all of these individuals this sudden death was the first occurrence of cardiovascular problems. In all of the men who died suddenly in this study, mean levels of EPA and DHA were much lower than the control, 4.82 +/ 1.31 versus 5.24 +/- 1.32 (1115). Additionally, no other fatty acids differed significantly in these groups. This study produced a significant inverse relation ship between the level of EPA and DHA, and the risk of sudden cardiac death. The fact that over 50 percent of sudden death from cardiac causes happen in individuals with no prior history of cardiac problems illustrates the value of this type of research, and potential benefits of DHA and EPA supplementation (1118).
The omega-3 fatty acid ALA has also been shown to have cardiac benefits such as reduce risk of arrhythmia (Hu 890). One study examined the connection between ALA consumption, and risk of fatal ischemic heart disease amongst women. This study used a 116 item food frequency questionaire, and then a 10 year follow up to determine any connection. This study concluded that a higher intake of ALA corresponded with a lower risk of FIHD. The findings that ALA is associated with a reduced risk fatal ischemic heart disease amongst women agree with the proposed antiarrhythmic effects of ALA (896). Aside from these benefits, ALA can be metabolized to EPA and DHA, which haven numerous health benefits (896).
Around 70% of the ALA in this study came from vegetable or plant sources, mainly salad dressings containing oil or vinegar, and certain vegetable oils (892). The implementation of fat-free salad dressings can be problematic as they eliminate a large source of ALA in the diet. Because ALA is very susceptible to oxidation, sources may frequently be hydrogenated which can turn these unsaturated fatty acids into trans fatty acids (896). These trans fatty acids have a negative impact on cardiovascular health and so addition of Vitamin E would be a more logical antioxidant for ALA to preserve the positive benefits.
The omega-3 fatty acid CLA has other uses as well, it has also been shown to produce antidiabetes and antiobesity effects in some animals ( Brismar 1516). Kerstin Brismar et al. examined the effects of CLA, and more specifically the trans10cis12 isomer of CLA that has been shown to cause the previously mentioned effects as well as improved insulin sensitivity (1516). They accomplished this by using a ,?randomized, double blind controlled trial. ? 60 different abdominally obese males were given either 3.4 grams of CLA a day, purified trans10cis12 CLA, or a placebo. At 12 weeks the males were evaluated. In the aspect of body composition, no significant differences occurred between the three groups in weight body fat or lean body mass (1518). The insulin sensitivity between groups did vary however. In the trans10cis12 CLA group, insulin sensitivity decreased more so than the placebo group. Both CLA groups resulted in a decrease in HDL cholesterol levels (1519). Overall, studies that produced positive results as far as insulin sensitivity and other effects of CLA in rats were not able to be reproduced in humans. One key point is that the effects of CLA are specific to individual isomers so additional CLA isomers need to be evaluated in the future. Low HDL cholesterol is a cardiovascular risk factor and combined with the other negative results of this study, supplemental CLA may not be nutritionally sound.
In addition to all of the already mentioned effects, some omega-3 fatty acids have been proposed to have suppress effects on some cancers (Rose 1751). An experiment on this subject conducted by David Rose and fellow researchers evaluated the effect of omega-3 fatty acids on the progression of human breast cancer cells in mice. Previous studies have shown that diets high in LA stimulate the growth of MDA-MB-435, which is the human breast cancer cell used in this model (1751).
Initially mice were fed a diet consisting of 7% LA for a week before being injected with the human breast cancer cell in this experiment. As the tumor progressed towards a surface area of .7 cm^2, the mice were put in the following diet categories: 7% LA, 8% EPA, 4% EPA, 2% EPA, 8% DHA, 4% DHA, and 2% DHA. After another week, the tumors were removed. After 8 weeks, the mice were killed and evaluated for local reoccurences and lung metastases. In this experiment the 4% EPA and the 4% DHA groups inhibited the formation of lung metastases (1754). Additionally, locoregional progression and macroscopic lung metastases were decreased by EPA and DHA diets (1755). This once again demonstrates the opposing nature of omega-6 and omega-3 fatty acids.
Omega-3 fatty acids also have an effect on bones as well (Watkins 388). Dietary lipids have been shown in the past to have an impact on bone modeling and remodeling, as well as bone metabolism. A previous study that examined omega-3’s effect on bone mineral density in elderly women found encouraging results. GLA and EPA were both shown to increase bone density through the same mechanism of competeting with AA. More research is needed to quantify the specific amounts needed of different omega-3 fatty acids, in different individuals (395).
The omega-3 fatty acids have a profound and extensive impact on human functions. EPA, DHA, ALA, and CLA are all omega-3 fatty acids that produce different results.
EPA is a long chain omega-3 acid that has many important properties. When metabolized, EPA competes with AA to produce eicosanoids. Eicosanoids are present in many situations in the body such as asthma, rheumatoid arthritis and other conditions involving inflammation. Supplemental EPA therefore is rational because eicosanoids produced by EPA are less inflammatory than those produced by AA. EPA, as well as DHA has also been shown to decrease the progress of cancer cells growing. EPA and DHA are also very effective in preventing sudden death of a cardiac nature.
ALA is another very important omega-3 fatty acid. ALA has been shown to cause a reduced risk of fatal ischemic heart disease in women, and can be metabolized into DHA or EPA. Additionally, ALA competes with LA in the same way that EPA competes with AA.
CLA has been shown to be beneficial in some situations, and not others. Studies have shown that CLA is effective in combating some cytokines. In regard to body composition, and insulin sensitivity however, CLA has not shown to be an effective supplement. In all cases examined, n-3 fatty acids had no effect on the ability of the immune system to fight bacteria, etc.
Works Cited
Adlof, R. O., J. L. Sebedio, and William W. Christie. Advances in Conjugated Linoleic Acid Research. Vol. 2. The American Oil Chemists Society, 2003. 1-337.
Albert, Christine M., Hannia Campos, Meir J. Stampfer, Paul M. Ridker, Joann E. Manson, Walter C. Willett, and Jing Ma. “Blood Levels of Long-Chain n-3 Fatty acids and the risk of sudden death.” New England Journal of Medicine 346 (2002): 1113-118.
Callaghan, Alison, and Margaret Rayman. Nutrition and Arthritis. Grand Rapids: Blackwell Limited, 2006.
Christie, Dr. William W. “What is a Lipid?” The Lipid Library. Scottish Crop Research Institute. http://www.lipidlibrary.co.uk/lipids/whatlip/index.htm.
Hauswirth, Christa B., Martin Scheeder, and Jurg H. Beer. “High w-3 Fatty Acid Content in Alpine Cheese.” 103-07.
Hu, Frank B., Meir J. Stampfer, Joann E. Manson, Eric B. Rimm, Alicja Wolk, Graham A. Colditz, Charles H. Hennekens, and Walter C. Willett. “Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women.” The American Journal of Clinical Nutrition (1999): 890-97.
Kew, Samantha, Tapati Banerjee, Anne M. Minihane, Yvonne E. Finnegan, Reto Muggli, Ruud Albers, Christine M. Williams, and Philip C. Calder. “Lack of effect of foods enriched with plant - or marine derived n-3 fatty acids on human immune function.” The American Journal of Clinical Nutrition (2003): 1287-295.
Marchioli, Roberto, Federica Barzi, Elena Bomba, Carmine Chieffo, Domenico D. Gregorio, Rocco D. Mascio, Maria G. Franzosi, Enrico Geraci, Giacomo Levantesi, Aldo P. Maggioni, Loredana Mantini, Rosa M. Marfisi, G. Mastrogiuseppe, Nicola Mininni, Gian L. Nicolosi, Massimo Santini, Carlo Schweiger, Luigi Tavazzi, Gianni Tognoni, Corrado Tucci, and Franco Valagussaa. “Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids after myocardial infarction: Time-COurse Analysis of the results…” Journal of the American Heart Association: 1897-903.
Riserus, Ulf, Peter Arner, Kerstin Brismar, and Bengt Vessby. “Treatment With Dietary trans10cis12 Conjugated Linoleic Acid Causes Isomer-Specific Insulin Resistance in Obese Men with the Metabolic Syndrome.” Diabetes Care 25 (2002): 1516-521.
Rose, David P., Jeanne M. Connolly, and Melissa Coleman. “Effect of Omega-3 Fatty Acids on the Progression of Metastases after the s.” Clinical Cancer Research 2 (1996): 1751-756.
Simopouulos, Artemis P. “Omega-3 Fatty Acids in Inflammation and Autoimmune Dieseases.” Journal of the American College of Nutrition 21 (2002): 495-505.
Watkins, Bruce A., Yong Li, Hugh E. Lippman, and Shulin Feng. “Modulatory effect of omega-3 polyunsaturatedfatty acids on osteoblast function and bone metabolism.” Prostaglandins Leukotrienes and Essential Fatty Acids: 387-98.