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Pennington Biomedical Research Center
            Division of Education
                 Heli J. Roy, PhD
                Shanna Lundy, BS
         Phillip Brantley, PhD, Director
Information:
                   Omega-3 Fatty Acids

• Omega-3 FA’s are polyunsaturated, meaning they contain more
  than one double bond

• They are called omega-3 because the first double bond
  counting from the methyl end of the fatty acid is located at the
  third carbon atom




                              PBRC 2005
Omega-3 Fatty Acids
              Types


  Alpha-linolenic acid (ALA)
 Eicosapentaenoic acid (EPA)
 Docosahexaenoic acid (DHA)




            PBRC 2005
Alpha-linolenic acid                     (ALA)

• Scientific abbreviation is 18:3n-3

• The first part (18:3) suggests that ALA is an 18-carbon fatty
  acid with 3 double bonds

• The second part (n-3) tells you that ALA is an omega-3 fatty
  acid

• It is required for health, but cannot be synthesized in humans

• Must be obtained from the diet
                              PBRC 2005
Alpha-linolenic Acid
• Humans can synthesize other omega-3 fatty acids from ALA:

• Eicosapentaenoic acid (EPA): 20:5n-3
• Docosahexaenoic acid (DHA): 22:6n-3

• These two are usually referred to as marine-derived
  omega-3 fatty acids because they are abundant in
  certain species of fish

• Whereas, ALA is considered a plant-derived omega-3 fatty acid

                            PBRC 2005
Structures of the Omega-3
       Fatty Acids




          PBRC 2005
Alpha-linolenic acid: Sources
     Food           Serving         Alpha-linolenic
                                       acid (g)
 Flaxseed oil       1 tablespoon          8.5
Walnuts, English      1 ounce             2.6
  Flaxseeds         1 tablespoon          2.2
  Walnut Oil        1 tablespoon          1.4
  Canola Oil        1 tablespoon          1.2
 Mustard Oil        1 tablespoon          0.8
 Soybean Oil        1 tablespoon          0.9
Walnuts, Black        1 ounce             0.6
   Olive Oil        1 tablespoon          0.1
 Broccoli, raw     1 cup, chopped         0.1
EPA and DHA: Sources
           Food             Serving    EPA (g)   DHA (g)   Amt providing 1 g
                                                            of EPA + DHA
Herring, Pacific, cooked    3 ounces    1.06       .75     1.5 ounces
Salmon, chinook, cooked     3 ounces    .86        .62     2 ounces
Salmon, Atlantic, cooked    3 ounces    .28        .95     2.5 ounces
Oysters, Pacific, cooked    3 ounces    .75        .43     2.5 ounces
Salmon, sockeye, cooked     3 ounces    .45        .60     3 ounces
Trout, rainbow, cooked      3 ounces    .40        .44     3.5 ounces
Tuna, white, packed in      3 ounces    .20        .54     4 ounces
water
Crab, dungeness, cooked     3 ounces    .24        .10     9 ounces
Shrimp, cooked              3 ounces    .15        .12     11 ounces
Cod, Pacific, cooked        3 ounces    .09        .15     12.5 ounces
Fish oil, menhaden          1 gram      .13        .09     5 grams
Fish oil, salmon            1 gram      .13       .18      3 grams
Docosahexaenoic acid (DHA)

• Found in very high concentrations in the cell
  membranes of the retina

• It conserves and recycles DHA even when
  omega-3 fatty acid intake is low

• Studies in animals indicate that DHA is required for
  the normal development and function of the retina



                             PBRC 2005
Disease Prevention:
        Impaired Visual and Neural Development

• Because the last trimester of pregnancy is a critical period for the
  accumulation of DHA in the brain and retina, preterm infants are
  particularly vulnerable to adverse effects of insufficient DHA on visual
  and neural development

• Although preterm infants can synthesize DHA from ALA, they can’t
  synthesize enough to prevent declines in plasma and cellular DHA
  levels without additional dietary intake

• Preterm infants fed formulas with DHA added had significantly
  improved measures of visual function compared to preterm infants fed
  DHA-free formulas in 5 out of 5 randomized controlled trials

                                 PBRC 2005
Fish Consumption
                And Coronary Heart Disease



• One study followed 1,822 men for 30 years and found that
  mortality from CHD was 38% lower in men who consumed an
  average of at least 35 g (1.2 ounces) of fish daily than in men
  who did not eat fish, while mortality from myocardial infarction
  (MI) was 67% lower




                              PBRC 2005
ALA Consumption
                 And Coronary Heart Disease

• In a prospective study of 43,757 male health professionals followed
  for 6 years, a relatively small increase in ALA intake (1% of total
  energy) was associated with a 59% decrease in the risk of acute MI

• Women who consumed oil and vinegar salad dressings 5-6 times
  weekly had a risk of fatal CHD that was 54% lower than those who
  rarely consumed it even after adjusting the analysis for vegetable
  intake

• Although the evidence is limited, it is indicated that increased ALA
  intakes may decrease the risk for CHD, especially in populations with
  relatively low levels of fish consumption
                                PBRC 2005
CHD Treatment

• Results of randomized controlled trials in individuals with
  documented coronary heart disease suggest a beneficial effect
  of dietary and supplemental omega-3 fatty acids

• Therefore, the American Heart Association has recommended
  that individuals with documented CHD consume 1 g/d of EPA
  and DHA combined



                            PBRC 2005
Fish Consumption
                  And Sudden Cardiac Death

• Several studies have found inverse relationships between
  fish consumption and sudden cardiac death

• In a prospective study, omega-3 fatty acid intakes equivalent to two
  fatty fish meals per week were associated with a 50% decrease in the
  risk of primary cardiac arrest

• Plasma levels of EPA and DHA were found to be inversely related to
  the risk of sudden death, supporting the idea that omega-3 fatty acids
  are at least partially responsible for the beneficial effect of fish
  consumption and sudden cardiac death

                                PBRC 2005
Fish Consumption
                              And Stroke

• A stroke is a result of impaired blood flow to a region of the
  brain, which may be due to obstruction of a blood vessel by a blood
  clot (thrombotic or ischemic stroke) or the rupture of a blood vessel
  (hemorrhagic stroke)

• Even though the effects of increased omega-3 fatty acid intake and
  the incidence of stroke have not been studied as thoroughly as the
  relationship with CHD, what is available suggests that increased fish
  intake may decrease the risk of thrombotic or ischemic stroke but not
  hemorrhagic


                                PBRC 2005
Cancer
• Marine-derived fatty acids have been found to inhibit proliferation and
  promote apoptosis in breast, prostate, and colon cancer cell lines
  cultured outside the body
• Studies in animal models of cancer also indicate that increased intake
  of EPA and DHA decreases the occurrence and progression of
  mammary, prostate, and intestinal tumors
• However, in humans few have demonstrated significant inverse
  relationships between fish or omega-3 fatty acid intake and the risk for
  breast, prostate, or colorectal cancers




                                PBRC 2005
Diabetes Mellitus
• Cardiovascular diseases are the leading causes of death in
  individuals with diabetes

• Hypertriglyceridemia (fasting serum TG of 200 mg/dl or higher) is a
  common lipid abnormality in individuals with Type 2 diabetes

• A number of randomized controlled trials have found that fish oil
  supplementation significantly lowers serum triglyceride levels in
  diabetic individuals



                                PBRC 2005
Diabetes Mellitus
• But, few control trials have examined the effect of fish
  oil supplementation on cardiovascular disease outcomes
  in diabetics

• One prospective study, following 5103 women diagnosed with type 2
  DM but free of cardiovascular disease at the start of the study, found
  decreased risks

• Those with higher fish intakes were associated with significantly
  decreased risks of CHD over the 16 years that the study
  lasted for, suggesting that increasing EPA and DHA levels may be
  beneficial to diabetic individuals, especially those with elevated serum
  triglycerides
                                 PBRC 2005
Inflammatory Diseases
                    Rheumatoid arthritis
• Rheumatoid arthritis is the most common
  systemic inflammatory rheumatic (joint) disease

• Studies have been conducted to determine the effects of
  omega-3 fatty acids on rheumatoid arthritis

• Clinical benefits were observed at a minimum dose of 3 g/day
  of EPA + DHA, and were not apparent until at least 12 weeks of
  supplementation



                            PBRC 2005
Inflammatory Diseases
                     Rheumatoid arthritis



• Some investigators report that patients taking omega-3 fatty
  acid supplementation were able to lower their doses of
  nonsteroidal anti-inflammatory drugs (NSAIDS), but not all
  findings on this issue were consistent




                             PBRC 2005
Inflammatory Bowel Disease
          Ulcerative colitis and Crohn’s Disease


• Clinical trial results were less consistent with inflammatory
  bowel diseases than in patients with rheumatoid arthritis

• A significantly higher proportion of Crohn’s disease patients
  supplemented with 2.7 g/day of EPA + DHA remained in
  remission over a one-year period than those given placebo

                 Ileocecal region




                                    PBRC 2005
Inflammatory Bowel Disease
          Ulcerative colitis and Crohn’s Disease


• In 3 randomized controlled trials of EPA + DHA
  supplementation in Ulcerative colitis patients, significant
  improvements were reported in at least one outcome
  measure, including decreased corticosteroid use, decreased
  production of inflammatory mediators, and improvements in
  disease activity scores, histology scores, and weight gain  Crohn’s
                                                                 disease




                                PBRC 2005
                                            Ulcerative Colitis
Asthma

• Although there is some evidence that omega-3 fatty acid
  supplementation can decrease the production of inflammatory
  mediators in asthmatic patients, evidence that omega-3 fatty
  acid supplementation decreases the clinical severity of asthma
  in controlled trials has been inconsistent




                             PBRC 2005
Immunoglobulin A
                    nephropathy
• A kidney disorder that results from the deposition of the
  immune system protein IgA in the glomeruli (filtering region) of
  the kidney

• The cause is unclear, but progressive renal failure may
  eventually develop in 15-40% of patients

• Since glomerular IgA deposition results in increased production
  of inflammatory mediators, it is thought that omega-3 fatty acid
  supplementation could potentially modulate the inflammatory
  response and preserve renal function

                              PBRC 2005
Immunoglobulin A
                      nephropathy
• Several studies have been conducted showing no real significant
  benefits, and continuing declines in renal functioning in some

• However, the probability of a minor beneficial effect was high enough
  (75%) to provide support for a large placebo-controlled trial of at least
  two years duration

• Currently, researchers are conducting this study, comparing fish oil to
  alternate day prednisone treatment and a placebo in children and
  young adults


                                 PBRC 2005
Major Depression
                       And Bipolar Disorder

• Several small studies have found omega-3 fatty acid levels to be
  lower in the plasma and fat of individuals suffering from depression
  compared to controls

• In one study conducted, for 30 individuals, with bipolar
  disorder, consuming large amounts of EPA (6.2 g/d) and DHA (3.4
  g/d), they had a significantly longer period of remission than those on
  an olive oil placebo over a 4 month period

• Patients who took the EPA + DHA supplement also
  experienced less depression than those who took
  the placebo
                                 PBRC 2005
Major Depression
                     And Bipolar Disorder


• Although these very limited pilot studies produce somewhat
  optimistic results, larger and long-term randomized trial are
  needed to determine the efficacy of marine-derived omega-3
  fatty acid supplementation on major depression




                             PBRC 2005
Schizophrenia
• Schizophrenia is a chronic disabling brain disorder that affects
  approximately 1% of the population

• A pilot study in 45 schizophrenic patients found
  that the addition of 2 g/day of EPA to standard
  antipsychotic therapy was superior to the addition of
  a 2 g/day to DHA or a placebo in decreasing residual symptoms

• Although limited evidence does suggest that EPA supplementation
  may be a useful adjunct to antipsychotic therapy in schizophrenic
  patients, larger long-term studies addressing clinically relevant
  outcomes are needed
                                 PBRC 2005
References
•   Ascherio A, et al. BMJ. 1996;313(7049):84-90.
•   Daviglus ML, Stamler J, Orencia AJ, et al. N Engl J Med. 1997;336(15):1046-1053
•   Siscovick DS et al. JAMA. 1995;274(17):1363
•   Albert CM et al. N Engl J Med. 2002;346(15):1113.
•   Rose DP, Connolly JM. Pharmacol Ther. 1999;83(3):217-244.
•   Bartsch H, Nair J, Owen RW. Carcinogenesis. 1999;20(12):2209-2218.
•   Terry PD, Rohan TE, Wolk. Am J Clin Nutr. 2003;77(3):532-543
•   Montori VM, Farmer A, Wollan PC, Dinneen SF. Diabetes Care. 2000;23(9):1407-1415.
•   Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE. Circulation. 2003;107(14):1852-1857.
•   Kremer JM. Am J Clin Nutr. 2000;71(1 Suppl):349S-351S.
•   Kjeldsen-Kragh J, Lund JA, Riise T, et al. J Rheumatol. 1992;19(10):1531-1536.
•   Lau CS, Morley KD, Belch JJ. Br J Rheumatol. 1993;32(11):982-989.

                                           PBRC 2005
References
•   Aslan A, Triadafilopoulos G. Am J Gastroenterol. 1992;87(4):432-437.
•   Hawthorne AB, Daneshmend TK, Hawkey CJ, et al. Gut. 1992;33(7):922-928.
•   Stenson WF, Cort D, Rodgers J, et al. Ann Intern Med. 1992;116(8):609-614.


•   Donadio JV, Grande JP. N Engl J Med. 2002;347(10):738-748.
•   Wyatt RJ, Hogg RJ. Pediatr Nephrol. 2001;16(2):156-167
•   Stoll AL, Severus WE, Freeman MP, et al. Arch Gen Psychiatry. 1999;56(5):407-412.
•   Peet M, Brind J, Ramchand CN, Shah S, Vankar GK. Schizophr Res. 2001;49(3):243-
    251.
•   Joy CB, Mumby-Croft R, Joy LA. Cochrane Database Syst Rev. 2000(2):CD001257


•   http://lpi.oregonstate.edu/infocenter/othernuts/omega3fa/index.html
•   http://www.google.com/imghp?hl=en&tab=wi&q=

                                            PBRC 2005

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Omega3fattyacids1 121225062726-phpapp02

  • 1. Pennington Biomedical Research Center Division of Education Heli J. Roy, PhD Shanna Lundy, BS Phillip Brantley, PhD, Director
  • 2. Information: Omega-3 Fatty Acids • Omega-3 FA’s are polyunsaturated, meaning they contain more than one double bond • They are called omega-3 because the first double bond counting from the methyl end of the fatty acid is located at the third carbon atom PBRC 2005
  • 3. Omega-3 Fatty Acids Types Alpha-linolenic acid (ALA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) PBRC 2005
  • 4. Alpha-linolenic acid (ALA) • Scientific abbreviation is 18:3n-3 • The first part (18:3) suggests that ALA is an 18-carbon fatty acid with 3 double bonds • The second part (n-3) tells you that ALA is an omega-3 fatty acid • It is required for health, but cannot be synthesized in humans • Must be obtained from the diet PBRC 2005
  • 5. Alpha-linolenic Acid • Humans can synthesize other omega-3 fatty acids from ALA: • Eicosapentaenoic acid (EPA): 20:5n-3 • Docosahexaenoic acid (DHA): 22:6n-3 • These two are usually referred to as marine-derived omega-3 fatty acids because they are abundant in certain species of fish • Whereas, ALA is considered a plant-derived omega-3 fatty acid PBRC 2005
  • 6. Structures of the Omega-3 Fatty Acids PBRC 2005
  • 7. Alpha-linolenic acid: Sources Food Serving Alpha-linolenic acid (g) Flaxseed oil 1 tablespoon 8.5 Walnuts, English 1 ounce 2.6 Flaxseeds 1 tablespoon 2.2 Walnut Oil 1 tablespoon 1.4 Canola Oil 1 tablespoon 1.2 Mustard Oil 1 tablespoon 0.8 Soybean Oil 1 tablespoon 0.9 Walnuts, Black 1 ounce 0.6 Olive Oil 1 tablespoon 0.1 Broccoli, raw 1 cup, chopped 0.1
  • 8. EPA and DHA: Sources Food Serving EPA (g) DHA (g) Amt providing 1 g of EPA + DHA Herring, Pacific, cooked 3 ounces 1.06 .75 1.5 ounces Salmon, chinook, cooked 3 ounces .86 .62 2 ounces Salmon, Atlantic, cooked 3 ounces .28 .95 2.5 ounces Oysters, Pacific, cooked 3 ounces .75 .43 2.5 ounces Salmon, sockeye, cooked 3 ounces .45 .60 3 ounces Trout, rainbow, cooked 3 ounces .40 .44 3.5 ounces Tuna, white, packed in 3 ounces .20 .54 4 ounces water Crab, dungeness, cooked 3 ounces .24 .10 9 ounces Shrimp, cooked 3 ounces .15 .12 11 ounces Cod, Pacific, cooked 3 ounces .09 .15 12.5 ounces Fish oil, menhaden 1 gram .13 .09 5 grams Fish oil, salmon 1 gram .13 .18 3 grams
  • 9. Docosahexaenoic acid (DHA) • Found in very high concentrations in the cell membranes of the retina • It conserves and recycles DHA even when omega-3 fatty acid intake is low • Studies in animals indicate that DHA is required for the normal development and function of the retina PBRC 2005
  • 10. Disease Prevention: Impaired Visual and Neural Development • Because the last trimester of pregnancy is a critical period for the accumulation of DHA in the brain and retina, preterm infants are particularly vulnerable to adverse effects of insufficient DHA on visual and neural development • Although preterm infants can synthesize DHA from ALA, they can’t synthesize enough to prevent declines in plasma and cellular DHA levels without additional dietary intake • Preterm infants fed formulas with DHA added had significantly improved measures of visual function compared to preterm infants fed DHA-free formulas in 5 out of 5 randomized controlled trials PBRC 2005
  • 11. Fish Consumption And Coronary Heart Disease • One study followed 1,822 men for 30 years and found that mortality from CHD was 38% lower in men who consumed an average of at least 35 g (1.2 ounces) of fish daily than in men who did not eat fish, while mortality from myocardial infarction (MI) was 67% lower PBRC 2005
  • 12. ALA Consumption And Coronary Heart Disease • In a prospective study of 43,757 male health professionals followed for 6 years, a relatively small increase in ALA intake (1% of total energy) was associated with a 59% decrease in the risk of acute MI • Women who consumed oil and vinegar salad dressings 5-6 times weekly had a risk of fatal CHD that was 54% lower than those who rarely consumed it even after adjusting the analysis for vegetable intake • Although the evidence is limited, it is indicated that increased ALA intakes may decrease the risk for CHD, especially in populations with relatively low levels of fish consumption PBRC 2005
  • 13. CHD Treatment • Results of randomized controlled trials in individuals with documented coronary heart disease suggest a beneficial effect of dietary and supplemental omega-3 fatty acids • Therefore, the American Heart Association has recommended that individuals with documented CHD consume 1 g/d of EPA and DHA combined PBRC 2005
  • 14. Fish Consumption And Sudden Cardiac Death • Several studies have found inverse relationships between fish consumption and sudden cardiac death • In a prospective study, omega-3 fatty acid intakes equivalent to two fatty fish meals per week were associated with a 50% decrease in the risk of primary cardiac arrest • Plasma levels of EPA and DHA were found to be inversely related to the risk of sudden death, supporting the idea that omega-3 fatty acids are at least partially responsible for the beneficial effect of fish consumption and sudden cardiac death PBRC 2005
  • 15. Fish Consumption And Stroke • A stroke is a result of impaired blood flow to a region of the brain, which may be due to obstruction of a blood vessel by a blood clot (thrombotic or ischemic stroke) or the rupture of a blood vessel (hemorrhagic stroke) • Even though the effects of increased omega-3 fatty acid intake and the incidence of stroke have not been studied as thoroughly as the relationship with CHD, what is available suggests that increased fish intake may decrease the risk of thrombotic or ischemic stroke but not hemorrhagic PBRC 2005
  • 16. Cancer • Marine-derived fatty acids have been found to inhibit proliferation and promote apoptosis in breast, prostate, and colon cancer cell lines cultured outside the body • Studies in animal models of cancer also indicate that increased intake of EPA and DHA decreases the occurrence and progression of mammary, prostate, and intestinal tumors • However, in humans few have demonstrated significant inverse relationships between fish or omega-3 fatty acid intake and the risk for breast, prostate, or colorectal cancers PBRC 2005
  • 17. Diabetes Mellitus • Cardiovascular diseases are the leading causes of death in individuals with diabetes • Hypertriglyceridemia (fasting serum TG of 200 mg/dl or higher) is a common lipid abnormality in individuals with Type 2 diabetes • A number of randomized controlled trials have found that fish oil supplementation significantly lowers serum triglyceride levels in diabetic individuals PBRC 2005
  • 18. Diabetes Mellitus • But, few control trials have examined the effect of fish oil supplementation on cardiovascular disease outcomes in diabetics • One prospective study, following 5103 women diagnosed with type 2 DM but free of cardiovascular disease at the start of the study, found decreased risks • Those with higher fish intakes were associated with significantly decreased risks of CHD over the 16 years that the study lasted for, suggesting that increasing EPA and DHA levels may be beneficial to diabetic individuals, especially those with elevated serum triglycerides PBRC 2005
  • 19. Inflammatory Diseases Rheumatoid arthritis • Rheumatoid arthritis is the most common systemic inflammatory rheumatic (joint) disease • Studies have been conducted to determine the effects of omega-3 fatty acids on rheumatoid arthritis • Clinical benefits were observed at a minimum dose of 3 g/day of EPA + DHA, and were not apparent until at least 12 weeks of supplementation PBRC 2005
  • 20. Inflammatory Diseases Rheumatoid arthritis • Some investigators report that patients taking omega-3 fatty acid supplementation were able to lower their doses of nonsteroidal anti-inflammatory drugs (NSAIDS), but not all findings on this issue were consistent PBRC 2005
  • 21. Inflammatory Bowel Disease Ulcerative colitis and Crohn’s Disease • Clinical trial results were less consistent with inflammatory bowel diseases than in patients with rheumatoid arthritis • A significantly higher proportion of Crohn’s disease patients supplemented with 2.7 g/day of EPA + DHA remained in remission over a one-year period than those given placebo Ileocecal region PBRC 2005
  • 22. Inflammatory Bowel Disease Ulcerative colitis and Crohn’s Disease • In 3 randomized controlled trials of EPA + DHA supplementation in Ulcerative colitis patients, significant improvements were reported in at least one outcome measure, including decreased corticosteroid use, decreased production of inflammatory mediators, and improvements in disease activity scores, histology scores, and weight gain Crohn’s disease PBRC 2005 Ulcerative Colitis
  • 23. Asthma • Although there is some evidence that omega-3 fatty acid supplementation can decrease the production of inflammatory mediators in asthmatic patients, evidence that omega-3 fatty acid supplementation decreases the clinical severity of asthma in controlled trials has been inconsistent PBRC 2005
  • 24. Immunoglobulin A nephropathy • A kidney disorder that results from the deposition of the immune system protein IgA in the glomeruli (filtering region) of the kidney • The cause is unclear, but progressive renal failure may eventually develop in 15-40% of patients • Since glomerular IgA deposition results in increased production of inflammatory mediators, it is thought that omega-3 fatty acid supplementation could potentially modulate the inflammatory response and preserve renal function PBRC 2005
  • 25. Immunoglobulin A nephropathy • Several studies have been conducted showing no real significant benefits, and continuing declines in renal functioning in some • However, the probability of a minor beneficial effect was high enough (75%) to provide support for a large placebo-controlled trial of at least two years duration • Currently, researchers are conducting this study, comparing fish oil to alternate day prednisone treatment and a placebo in children and young adults PBRC 2005
  • 26. Major Depression And Bipolar Disorder • Several small studies have found omega-3 fatty acid levels to be lower in the plasma and fat of individuals suffering from depression compared to controls • In one study conducted, for 30 individuals, with bipolar disorder, consuming large amounts of EPA (6.2 g/d) and DHA (3.4 g/d), they had a significantly longer period of remission than those on an olive oil placebo over a 4 month period • Patients who took the EPA + DHA supplement also experienced less depression than those who took the placebo PBRC 2005
  • 27. Major Depression And Bipolar Disorder • Although these very limited pilot studies produce somewhat optimistic results, larger and long-term randomized trial are needed to determine the efficacy of marine-derived omega-3 fatty acid supplementation on major depression PBRC 2005
  • 28. Schizophrenia • Schizophrenia is a chronic disabling brain disorder that affects approximately 1% of the population • A pilot study in 45 schizophrenic patients found that the addition of 2 g/day of EPA to standard antipsychotic therapy was superior to the addition of a 2 g/day to DHA or a placebo in decreasing residual symptoms • Although limited evidence does suggest that EPA supplementation may be a useful adjunct to antipsychotic therapy in schizophrenic patients, larger long-term studies addressing clinically relevant outcomes are needed PBRC 2005
  • 29. References • Ascherio A, et al. BMJ. 1996;313(7049):84-90. • Daviglus ML, Stamler J, Orencia AJ, et al. N Engl J Med. 1997;336(15):1046-1053 • Siscovick DS et al. JAMA. 1995;274(17):1363 • Albert CM et al. N Engl J Med. 2002;346(15):1113. • Rose DP, Connolly JM. Pharmacol Ther. 1999;83(3):217-244. • Bartsch H, Nair J, Owen RW. Carcinogenesis. 1999;20(12):2209-2218. • Terry PD, Rohan TE, Wolk. Am J Clin Nutr. 2003;77(3):532-543 • Montori VM, Farmer A, Wollan PC, Dinneen SF. Diabetes Care. 2000;23(9):1407-1415. • Hu FB, Cho E, Rexrode KM, Albert CM, Manson JE. Circulation. 2003;107(14):1852-1857. • Kremer JM. Am J Clin Nutr. 2000;71(1 Suppl):349S-351S. • Kjeldsen-Kragh J, Lund JA, Riise T, et al. J Rheumatol. 1992;19(10):1531-1536. • Lau CS, Morley KD, Belch JJ. Br J Rheumatol. 1993;32(11):982-989. PBRC 2005
  • 30. References • Aslan A, Triadafilopoulos G. Am J Gastroenterol. 1992;87(4):432-437. • Hawthorne AB, Daneshmend TK, Hawkey CJ, et al. Gut. 1992;33(7):922-928. • Stenson WF, Cort D, Rodgers J, et al. Ann Intern Med. 1992;116(8):609-614. • Donadio JV, Grande JP. N Engl J Med. 2002;347(10):738-748. • Wyatt RJ, Hogg RJ. Pediatr Nephrol. 2001;16(2):156-167 • Stoll AL, Severus WE, Freeman MP, et al. Arch Gen Psychiatry. 1999;56(5):407-412. • Peet M, Brind J, Ramchand CN, Shah S, Vankar GK. Schizophr Res. 2001;49(3):243- 251. • Joy CB, Mumby-Croft R, Joy LA. Cochrane Database Syst Rev. 2000(2):CD001257 • http://lpi.oregonstate.edu/infocenter/othernuts/omega3fa/index.html • http://www.google.com/imghp?hl=en&tab=wi&q= PBRC 2005