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  1. #1
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    Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Omega Fatty Acid Balance Can Alter Immunity And Gene Expression

    For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.
    See Also:
    Health & Medicine

    * Cholesterol
    * Dietary Supplement
    * Immune System
    * Obesity
    * Genes
    * Nutrition

    Reference

    * Saturated fat
    * Oily fish
    * Zone diet
    * Fatty acid

    Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.

    Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.

    This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.

    Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*

    1. Kelly L. Weaver‡§,
    2. Priscilla Ivester§,1,
    3. Michael Seeds‡,
    4. L. Douglas Case¶,
    5. Jonathan P. Arm? and
    6. Floyd H. Chilton§

    + Author Affiliations

    1.
    From the ‡Department of Internal Medicine, Section on Molecular Medicine, and
    2.
    Departments of §Physiology and Pharmacology and
    3.
    ¶Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the
    4.
    ?Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

    1. 1To whom correspondence should be addressed:
    Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157.
    Tel.: 336-716-7388; Fax: 336-716-8501; E-mail: ivester@wfubmc.edu.

    Abstract

    Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (?6) to ?3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased ?6/?3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the ?6/?3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NF?B, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain ?3 PUFA concomitant with a reduction in the ?6/?3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K? and PI3K? and the quantity of PI3K? protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.

  2. #2
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Good Link: http://www.perciavalle.com/wiki/Fish_Oil

    Fish Oil, as well as other omega-3 fatty acids, inhibit the conversion of arachidonic acid to prostaglandins and leukotrienes, decreasing the inflammatory response. [22] Supplementation with omega-3 also reduces serum levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1), both markers of inflammation. [23] [24] Additionally, DHA supplementation reduces inflammation as measured by decreased levels of C-reactive protein (CRP) and IL-6, both markers of inflammation. [25] These data suggest that omega-3 fatty acids are potent anti-inflammatory molecules.


    In another study, humans supplementing 9 grams of fish oil daily for four weeks displayed a 74% reduction in TNF-alpha and 80% decrease in IL-1 beta synthesis. [29] Patients with rheumatoid arthritis ameliorated their clinical symptoms and decreased their TNF-alpha and IL-1 beta levels when supplementing with high doses of fish oil daily. [30] In a mouse model of rheumatoid arthritis and autoimmune disease, mice fed a high fish oil diet had a reduction in symptoms and lower levels of pro-inflammatory cytokines

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  4. #4

    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Haha, nice little chart there. Knew the conversions for flax was really bad but heck, that's even worse than I thought!
    -Stopped my form of MPB through a simple diet change. At least 10% of the rest of you would respond from removing gluten from your diet as well.

    -The modern day high carb diet is somewhat idiotic, out of the three caloric food sources it's the only one that the body has ZERO need for.

  5. #5
    Senior Member Axl_Rose's Avatar
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Quote Originally Posted by Brains Expel Hair
    Haha, nice little chart there. Knew the conversions for flax was really bad but heck, that's even worse than I thought!
    Does that mean that flax supplements are pretty pointless then?

    Sorry i don't quite understand all this science talk haha.
    "Drink'n'drive white lightning faster baby
    Takin' your last ride
    Now better be so careful or you'll be dead before you time
    Sorry you took mother's car now"

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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Epigentics baby!

  7. #7
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Quote Originally Posted by purecontrol
    Epigentics baby!
    lol

  8. #8
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    J Steroid Biochem Mol Biol. 2002 Nov;82(4-5):393-400. Links
    5 alpha-reductase-catalyzed conversion of testosterone to dihydrotestosterone is increased in prostatic adenocarcinoma cells: suppression by 15-lipoxygenase metabolites of gamma-linolenic and eicosapentaenoic acids.Pham H, Ziboh VA.
    Department of Dermatology, School of Medicine, University of California at Davis, TB-192, One Shields Avenue, 95616, USA.

    Although the androgens, testosterone (T) and its highly active metabolite dihydrotestosterone (DHT) play a role in the development and progression of prostate cancer, the mechanism(s) are unclear. Furthermore, 5 alpha-reductase which catalyze the conversion of T to DHT, has been a target of manipulation in the treatment of prostatic cancer, hence synthetic 5 alpha-reductase activity inhibitors have shown therapeutic promise. To demonstrate that nutrients derived from dietary sources can exert similar therapeutic promise, this study was designed using benign hyperplastic cells (BHC) and malignant tumorigenic cells (MTC) derived from Lobund-Wistar (L-W) rat model of prostatic adenocarcinoma to test the effects of gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and their 15-lipoxygenase metabolites on cellular 5 alpha-reductase activity. Our data revealed: (i) that incubation of MTC with [3H]-T resulted in marked conversion to [3H]-DHT when compared to similar incubation with BHC; (ii) that DHT-enhanced activity of 5 alpha-reductase was inhibited 80% by 15S-hydroxyeicosatrienoic acid, the 15-lipoxygenase metabolite of GLA, when compared to 55% by 15S-hydroxyeicosapentaenoic acid, the 15-lipoxygenase metabolite of EPA; and (iii) that their precursor fatty acids, respectively, exerted moderate inhibition. Taken together, the study underscores the biological importance of 15-lipoxygenase metabolites of polyunsaturated fatty acids (PUFAs) in androgen metabolism.


    Br J Dermatol. 2007 Mar;156(3):428-32.Links
    Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes.
    Makrantonaki E, Zouboulis CC.

    Laboratory of Biogerontology, Dermatopharmacology and Dermatoendocrinology, Institute of Clinical Pharmacology and Toxicology, Charité University Medicine Berlin, Berlin, Germany.

    BACKGROUND: Despite the clinical evidence that androgens stimulate sebaceous lipids, androgens in vitro have shown no similar effects. This contradiction led to the assumption that cofactors may be required for lipid regulation and peroxisome proliferator-activated receptor (PPAR) ligands were suggested to be adequate candidates. OBJECTIVES: The influence of testosterone and linoleic acid, a PPAR ligand, as single agents and in combination with of LY191704, a 5alpha-reductase type I inhibitor, was examined on 5alpha-dihydrotestosterone (5alpha-DHT) synthesis and lipid content in human SZ95 sebocytes. METHODS: Cell proliferation and viability were measured by the 4-methylumbelliferyl heptanoate fluorescence assay and by the Boehringer Lactate Dehydrogenase Assay kit, respectively. 5alpha-DHT enzyme-linked immunosorbent assay was used for the detection of 5alpha-DHT synthesis in cell supernatants after treatment, whereas lipid production was documented by means of the Nile red lipid microassay and fluorescence microscopy. RESULTS:Testosterone promoted 5alpha-DHT synthesis (P < 0.001), whereas linoleic acid increased sebaceous lipids (P < 0.001). The combination of testosterone and linoleic acid exhibited a synergistic effect on the synthesis of 5alpha-DHT (P < 0.01 vs. testosterone) and sebaceous lipids (P < 0.01 vs. linoleic acid). Furthermore, LY191704 reduced 5alpha-DHT and sebaceous lipid levels (P < 0.01 and P < 0.001 in comparison with testosterone/linoleic acid, respectively). Cell proliferation and viability remained unchanged under treatment with all compounds tested. CONCLUSIONS: These data suggest a catalytic effect of PPAR ligands on cellular testosterone activation by 5alpha-reduction and the importance of the latter for the regulation of sebaceous lipids.

  9. #9
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Stacking fish oil with sesamin
    Life Extension has uncovered research that the addition of sesame lignans to fish oil enhances its beneficial effects.12 When fats are consumed, they are broken down into factors that either promote or suppress inflammatory reactions. Specialized enzymes in the body determine which inflammatory pathway fats will follow. Sesame lignans inhibit an enzyme (delta-5 desaturase) that causes dietary fats to be converted into arachidonic acid, a precursor to the toxic inflammatory factors prostaglandin E2 and leukotriene B4.13

    Sesame lignans also increases levels of desirable DGLA (di-homogamma linolenic acid), the precursor to prostaglandin E1. This prostaglandin has demonstrated numerous health benefits including suppression of inflammatory events.14

    Many people supplement with GLA (gamma linolenic acid) to increase their levels of DGLA and prostaglandin E1. When sesame lignans are combined with fish oil, DGLA levels rise dramatically and the inflammatory index of the fish oil greatly improves. We know sesamin (the lignan from sesame seeds) inhibits delta-5 desaturase activity resulting in an increase of DGLA which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. DGLA also suppresses inflammatory indices that inhibits production of dangerous inflammatory cytokines (such as tumor necrosis factor-alpha).14

    Health conscious people have been swallowing a lot of borage oil supplements to obtain GLA (gamma linolenic acid), the parent of the biologically active DGLA (di-homogamma linolenic acid). Sesame lignans not only increase beneficial DGLA (and prostaglandin E1), but it also reduces pro-inflammatory arachidonic acid and decreases the formation of destructive prostaglandin E2 and leukotriene B4.13 For consumers, this means that a modest dose fish oil concentrate with sesame lignans may provide better benefits than higher dose fish oil and borage oil supplements.

  10. #10
    Senior Member Jacob's Avatar
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    Re: Omega Fatty Acid Balance Can Alter Immunity And Gene Express

    Don't forget krill oil. Oops..Neptune krill oil

    Here's the next one I plan on trying for awhile: http://biopharmasci.com/patients/nanoepa/default.asp

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