Borage Seed Oil GLA Gamma Linolenic Acid Dietary Food Supplement Health Benefits
Learn how GLA or Gamma Linolenic Acid from Borage Seed Oil is one of the most important food supplements you can take to reverse chronic inflammation, reduce insulin resistance and improve your health.
Borage Seed Oil is the second of the four most important diet supplements, which are: Fish Oil, Borage Seed Oil, Green Tea and Magnesium. These four products correct major deficiencies in the average American's diet. Together with a balanced diet that follows our Food Guide Football™, Borage Seed Oil can lead to significant improvements in health. They include dramatic weight loss when needed, and imrovement or reversal of major diseases. The benefits stem from reductions in low-level inflammation. Then, less inflammation leads to lower insulin resistance. For a detailed discussion of the inflammatory health cycle, read our article "The 3 Levels of Health: How Infection & Today's High Sugar/Starch, High Fat Diet Leads to a Cycle of Increasing Inflammation, Insulin Resistance, Low Metabolism, Obesity and Major Diseases".
How Borage Seed Oil Improves Your Health: Borage oil contains an essential fatty acid called GLA that your body does not make efficiently for itself (read this report about why). The GLA or gamma linolenic acid, is easy converted into DGLA or dihomagamma linolenic acid. From DHLA, the body rapidly makes PGE-1 or Series-1 Prostaglandins. These PGE-1 molecules are about 1/2 of your inflammation-fighting capability. Without them, you have a persistent tendancy toward inflammation, which often leads to insulin resistance, obesity and many deadly diseases.
Common Diseases Associated with
Chronic Low-Level Inflammation
or Insulin Resistance Syndrome**
GLA Gamma Linolenic Acid -- The three best sources of GLA are Borage Seed Oil, Black Currant Oil, and Evening Primrose Oil. Borage Seed Oil (usually about 24% GLA) contains about 5% more GLA than Black Currant Oils, and more than twice as much GLA per capsule as Evening Primrose Oil (which usually contains about 10% GLA). As a result of its high percentage of GLA, when you take Borage Seed Oil, you end up taking less of the undesirable Omega-6 (lenoleic acid) vegetable oils. Omega-6 oils are most of the remainder of the oil contained in each of the supplements. GLA is the immediate precursor to your body's production of PGE-1 or Prostaglandin Series 1, which is vital to the body's ability to handle blood lipids, cholesterol and triglycerides, and amounts to about 1/2 of your total inflammation fighting arsenal. We recommend Borage Seed Oil, because it is easier to take to get the needed amount of GLA than the other sources. However, many studies have also supported somewhat larger daily doses of Evening Primrose Oil.
Two Ways Delta-6 Deficiency Happens
|Inherited Problem Making Delta-6 Enzyme|
|Extra Thymidine Molecule1 in D6D-Making Gene - This or similar genetic mutations may be a major cause underlying inherited types of cardiovascular, diabetic, cancerous, insulin resistant, and/or inflammation associated diseases.43 The frequency of this kind of mutation is still being investigated. However, since inflammatory and insulin resistant conditions add up to 73% of all fatal diseases annually, any significant contributing factor to inflammation or insulin resistance is a very serious matter.|
|Dietary or Disease & Lifestyle Factors|
Producing Functional Delta-6 Deficiency
|When people without inherited deficiencies do in fact make enough Delta-6, the enzyme can be blocked from being utilized by many factors relating to their diet, disease, and substance abuse or other lifestyle, behavior or habits. (See "Hypoglycemia and Essential Fatty Acids", Hypoglycemic Association Newsletter, September, 1996, Pgs. 7-13.)|
Best Gamma Linolenic Acid Sources: The best sources of GLA are Borage Seed Oil (24%), Black Currant Oil (19%) and Evening Primrose Oil (9%). As you can see, Borage Seed Oil contains just a bit more GLA than does Black Currant Oil, and almost 2-1/2 times as much GLA as Evening Primrose Oil. If you want to take fewer pills, take Borage Seed Oil. The cost per pill is usually about the same, but you may want to shop around. We've found a month's supply of Borage Seed Oil, which is about (60) 1,200mg capsules containing 300mg of GLA per capsule, usually costs between $10-$15. Brands we like include Now Foods, Vitamin Shoppe, Twin Labs, and Life Extension Foundation.
How Much Borage Seed Oil GLA Gamma Linolenic Acid Should You Take per Day? Take at least 2 large 1,000 to 1,200mg capsules of Borage Seed Oil per day, one in the morning and evening. Ensure that each capsule contains at least 245mg of the GLA active ingredient. A small amount of Vitamin-E should also be listed on the label to prevent possible oxidation of the vital fatty acid ingredients during storage. Very sick, obese or people with high levels of C-Reactive Protein should consider taking up to double the regular daily dose of GLA.
Safety Issues: - Borage seed oil is generally considered safe. You should be concerned about its freshness, and always refrigerate it after opening. Look for brands with a small amount of Vitamin-E added to the capsule as a preservative. Borage oil acts moderately as an anti-clotting agent or blood thinner. While usually considered advantageous, its anti-clotting actions may add to the thinning power of other blood thinners if you are takng them. As always, we recommend you consult your doctor or other health care professional before adding this or any other supplement to your diet. You may want to print this page to show to your phsician, dietitian or other authorized health professional, as many will not have had time to read this much detail on the subject due to their busy schedules.*
Level1Diet.com's Current Recommendation
for Borage Seed Oil GLA Supplementation
Jarrow Formulas' Borage GLA 240, 120 Capsules - about $21.36. Jarrow Formulas' Borage Oil is an excellent quality brand, often sold in the national chain stores. We highly recommend this product for consistent quality and purity. Jarrow includes 10mg of Gamma Tocopherol Vitamin-E in each capsule to ensure that your GLA does not become oxidized before you consume it. This price is a super low Amazon.com value. The large 120 count bottle provides about 24 days' supply for one adult at 5 capsules/day. Five capsules will provide over 1.2 grams per day of total GLA. Jarrow has filtered the product to remove hexane that may be present in the raw borage oil products from other vendors.
Scientific Research Supporting Gamma Lenolenic Acid (GLA) Supplementation -- (1) For a discussion of GLA supplementation and its role in helping control or improve metabolic, insulin resistant or inflammatory disease read this PDF report written by Jur Plesmon in the Hypoglycemic Health Association Newsletter, September, 1996. (2) Read over 45 scientific studies reported at Pubmed.org (the web page of the National Library of Medicine, National Institutes of Health, NIH) reporting research about Gamma Linolenic Acid (GLA) and Inflammation. (3) Read over 200 scientific studies reported at Pubmed.org about Gamma Linolenic Acid (GLA) and Cancer. (4) Read over 60 scientific studies reported at Pubmed.org about Gamma Linolenic Acid (GLA) and Cardiovascular Heart Disease. (5) Read over 90 scientific studies reported at Pubmed.org about Gamma Linolenic Acid (GLA) and Diabetes.
Scientific Reviews of the Role of Gamma Linolenic Acid in Health
1. Phytother Res. 2009 Dec;23(12):1647-62.
Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part 2: Rheumatoid arthritis.
Cameron M, Gagnier JJ, Little CV, Parsons TJ, Bl�mle A, Chrubasik S.
School of Sport and Exercise Science, Centre for Ageing, Rehabilitation, Exercise and Sport (CARES), Victoria University, Melbourne, Australia. firstname.lastname@example.org
Herbal medicinal products (HMPs) that interact with the mediators of inflammation are used in the treatment of rheumatoid arthritis (RA). The aim of this study was to update a previous systematic review published in 2000. We searched electronic databases (MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane registers) to June 2007, unrestricted by date or language, and included randomized controlled trials that compared HMPs with inert (placebo) or active controls in patients with rheumatoid arthritis. Five reviewers contributed to data extraction. Disagreements were discussed and resolved by consensus with reference to Cochrane guidelines and advice from the Cochrane Collaboration. Twenty studies (10 identified for this review update, and 10 of the 11 studies of the original review) investigating 14 HMPs were included. Meta-analysis was restricted to data from previous seven studies with oils from borage, blackcurrant and evening primrose containing gamma linolenic acid (GLA). GLA doses equal or higher than 1400 mg/day showed benefit in the alleviation of rheumatic complaints whereas lower doses ( approximately 500 mg) were ineffective. Three studies compared products from Tripterygium wilfordii (thunder god vine) to placebos and returned favorable results but data could not be pooled because the interventions and measures differed. Serious adverse effects occurred in one study. In a follow-up study all side effects were mild to moderate and resolved after the intervention ceased, but time to resolution was variable. Two studies comparing Phytodolor NR to placebo were of limited use because some measures were poorly defined. The remaining studies, each considering differing HMPs, were assessed individually. For most HMPs used in the treatment of RA, the evidence of effectiveness was insufficient to either recommend or discourage their use. Interventions with HMPs containing GLA or Tripterygium wilfordii extract appear to produce therapeutic effects but further investigations are warranted to prove their effectiveness and safety.
PMID: 19941324 [PubMed - indexed for MEDLINE]
2. Am J Clin Nutr. 2008 Feb;87(2):498S-503S.
Mechanisms by which botanical lipids affect inflammatory disorders.
Chilton FH, Rudel LL, Parks JS, Arm JP, Seeds MC.
Center for Botanical Lipids, Wake Forest University, Winston Salem, NC, USA. email@example.com
Changes in diet over the past century have markedly altered the consumption of fatty acids. The dramatic increase in the ingestion of saturated and n-6 fatty acids and concomitant decrease in n-3 fatty acids are thought to be a major driver of the increase in the incidence of inflammatory diseases such as asthma, allergy, and atherosclerosis. The central objective of the Center for Botanical Lipids at Wake Forest University School of Medicine and the Brigham and Women's Hospital is to delineate the mechanisms by which fatty acid-based dietary supplements inhibit inflammation leading to chronic human diseases such as cardiovascular disease and asthma. The key question that this center addresses is whether botanical n-6 and n-3 fatty acids directly block recognized biochemical pathways or the expression of critical genes that lead to asthma and atherosclerosis. Dietary supplementation with flaxseed oil, borage oil, and echium oil affects the biochemistry of fatty acid metabolism and thus the balance of proinflammatory mediators and atherogenic lipids. Supplementation studies have begun to identify key molecular and genetic mechanisms that regulate the production of lipid mediators involved in inflammatory and hyperlipidemic diseases. Echium oil and other oils containing stearidonic acid as well as botanical oil combinations (such as echium and borage oils) hold great promise for modulating inflammatory diseases.
PMID: 18258646 [PubMed - indexed for MEDLINE]
3. Przegl Lek. 2007;64(2):91-9.
[Biology of essential fatty acids (EFA)]
[Article in Polish]
Dobryniewski J, Szajda SD, Waszkiewicz N, Zwierz K.
Oddzial III Og�lnopsychiatryczny z Pododdzialem Psychogeriatrii SPPZOZ w Choroszczy. firstname.lastname@example.org
Essential Fatty Acids (EFA), are unsaturated fatty acids not produced by human being, but essential for proper functioning of the human body. To EFA-s belongs: linoleic acid (LA) (18:2,cis detla(9,12), omega6)--precursor o f gamma-linolenic acid (GLA), gamma-linolenic acid (GLA) (18:3,cisA6,9,12, )6) and alpha-linolenic acid (ALA)(18:3,cisdelta(9, 12, 15), omega3)--product of dehydrogenation of linoleic acid (LA). Most important EFA is gamma-linolenic acid (GLA)--18 carbons, one-carboxylic, non-branched fatty acid with 3 double cis-bonds (the last is situated by 6-th carbon from methylic end). The diet devoided of EFA leads to decreased growth, skin and kidney injury and infertility. Modern research of GLA and others EFA's is concerned mainly on therapeutic impact on the inflammatory process. The biogenic amines, cytokines, prostaglandins, tromboxanes and leukotrienes are the main inflammatory mediators. The last three are described with the common name eicosanoides (eico-twenty). Eicosanoides are synthesized from 20-carbon unsaturated fatty acids: dihomo-gamma-linoleic (DGLA) (20:3, cis delta(8,11,14), omega6), arachidonic acid (AA-20:4, cis delta(5,8,11,14), omega6), and eicosapentaenoic acid (EPA-20:5, cis delta(5,8,11,14,17, omega3). Derivatives of gamma and gamma-linolenic acids regulate the inflammatory process, through their opposed activity. PG2, leucotrien C4 and tromboxan A2 have the strongest proinflammatory action. Derivatives of alpha-linolenic acid 15-HETE and prostaglandin E1 (PGE1) have weak pro-inflammatory action, or even anti-inflammatory (PGE1), and additionally, they inhibit the transformation of arachidonic acid (AA) to leukotriens. delta6-desaturase (transformes linolenic acid into gamma-linolenic acid by making additional double bond) is the slowest step of the fatty acid metabolism. It's activity is impaired by many physiological and pathologic factors and leads to gamma-linolenic acid (GLA) deficiency. The gamma-linolenic acid supplementation in diet allows to omitt the inefficient delta6-desaturase system which has an effect in rising of dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA) and their derivatives. This article describes biology of essential fatty acids and particularly the role of gamma-linolenic acid.
PMID: 17892040 [PubMed - indexed for MEDLINE]
4. Prostaglandins Leukot Essent Fatty Acids. 2007 May;76(5):251-68. Epub 2007 Apr 26.
A defect in the activity of Delta6 and Delta5 desaturases may be a factor in the initiation and progression of atherosclerosis.
UND Life Sciences, Shaker Heights, OH 44120, USA.
Atherosclerosis is a dynamic process. Dyslipidemia, diabetes mellitus, hypertension, obesity, and shear stress of blood flow, the risk factors for the development of atherosclerosis, are characterized by abnormalities in the metabolism of essential fatty acids (EFAs). Gene expression profiling studies revealed that at the sites of atheroslcerosis-prone regions, endothelial cells showed upregulation of pro-inflammatory genes as well as antioxidant genes, and endothelial cells themselves showed changes in cell shape and proliferation. Uncoupled respiration (UCP-1) precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis. UCP-1 expression in aortic smooth muscle cells causes hypertension, enhanced superoxide anion production and decreased the availability of NO, suggesting that inefficient metabolism in blood vessels causes atherosclerosis without affecting cholesterol levels. Thus, mitochondrial dysfunction triggers atherosclerosis. Atherosclerosis-free aortae have abundant concentrations of the EFA-linoleate, whereas fatty streaks (an early stage of atherosclerosis) are deficient in EFAs. EFA deficiency promotes respiratory uncoupling and atherosclerosis. I propose that a defect in the activity of Delta6 and Delta5 desaturases decreases the formation of gamma-linolenic acid (GLA), dihomo-DGLA (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from dietary linoleic acid (LA) and alpha-linolenic acid (ALA). This, in turn, leads to inadequate formation of prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, neuroprotectin D1 (NPD1), NO, and nitrolipids that have anti-inflammatory and platelet anti-aggregatory actions, inhibit leukocyte activation and augment wound healing and resolve inflammation and thus, lead to the initiation and progression atheroslcerosis. In view of this, it is suggested that Delta6 and Delta5 desaturases could serve as biological target(s) for the discovery and development of pharmaceuticals to treat atherosclerosis.
PMID: 17466497 [PubMed - indexed for MEDLINE]
5. Curr Pharm Biotechnol. 2006 Dec;7(6):531-4.
Gamma linolenic acid: an antiinflammatory omega-6 fatty acid.
Kapoor R, Huang YS.
Science & Technology, Bioriginal Food & Science Corp., 102 Melville Street, Saskatoon, SK. S7J 0R1, Canada. email@example.com
Inflammation plays an important role in health and disease. Most of the chronic diseases of modern society, including cancer, diabetes, heart disease, arthritis, Alzheimer's disease, etc. have inflammatory component. At the same time, the link between diet and disease is also being recognized. Amongst dietary constituents, fat has gained most recognition in affecting health. Saturated and trans fatty acids have been implicated in obesity, heart disease, diabetes and cancer while polyunsaturated fatty acids (PUFAs) generally have a positive effect on health. The PUFAs of omega-3 and omega-6 series play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid, C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme delta-6-desaturase. Preformed GLA is present in trace amounts in green leafy vegetables and in nuts. The most significant source of GLA for infants is breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA) which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3). GLA and its metabolites also affect expression of various genes where by regulating the levels of gene products including matrix proteins. These gene products play a significant role in immune functions and also in cell death (apoptosis). The present review will emphasize the role of GLA in modulating inflammatory response, and hence its potential applications as an anti-inflammatory nutrient or adjuvant.
PMID: 17168669 [PubMed - indexed for MEDLINE]
6. Curr Pharm Biotechnol. 2006 Dec;7(6):467-82.
Essential Fatty acids - a review.
UND Life Sciences, 13800 Fairhill Road, Shaker Heights, OH 44120, USA. firstname.lastname@example.org
Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.
PMID: 17168664 [PubMed - indexed for MEDLINE]
7. Respir Care Clin N Am. 2006 Dec;12(4):547-66, vi.
A nutritional strategy to improve oxygenation and decrease morbidity in patients who have acute respiratory distress syndrome.
DeMichele SJ, Wood SM, Wennberg AK.
Strategic and International R & D, Ross Products Division, Abbott Laboratories, 625 Cleveland Avenue, Columbus, OH 43215, USA. email@example.com
Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.
PMID: 17150431 [PubMed - indexed for MEDLINE]
8. Biotechnol J. 2006 Apr;1(4):420-39.
Essential fatty acids: biochemistry, physiology and pathology.
UND Life Sciences, Shaker Heights, OH 44120, USA. firstname.lastname@example.org
Essential fatty acids (EFAs), linoleic acid (LA), and alpha-linolenic acid (ALA) are essential for humans, and are freely available in the diet. Hence, EFA deficiency is extremely rare in humans. To derive the full benefits of EFAs, they need to be metabolized to their respective long-chain metabolites, i.e., dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs) and resolvins that have potent anti-inflammatory actions. Furthermore, EFAs and their metabolites may function as endogenous angiotensin-converting enzyme and 3-hdroxy-3-methylglutaryl coenzyme A reductase inhibitors, nitric oxide (NO) enhancers, anti-hypertensives, and anti-atherosclerotic molecules. Recent studies revealed that EFAs react with NO to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors. The metabolism of EFAs is altered in several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer. Thus, EFAs and their derivatives have varied biological actions and seem to be involved in several physiological and pathological processes.
PMID: 16892270 [PubMed - indexed for MEDLINE]
9. Postepy Hig Med Dosw (Online). 2006;60:129-41.
[Cyclooxygenase and prostanoids--biological implications]
[Article in Polish]
Burdan F, Chalas A, Szumilo J.
Pracownia Teratologii Doswiadczalnej Zakladu Anatomii Prawidlowej Czlowieka Akademii Medycznej im. Prof. Feliksa Skubiszewskiego w Lublinie. email@example.com
Arachidonic acid is the main precursor of eikosanoids, which regulate the function of various organs and systems. It is released from cellular membrane phospholipids by phospholipase A2 or indirectly by phospholipases C and D. Prostaglandins, prostacyclin (PGI2), and thromboxane A2 (TAX2) are synthesized from arachidonic acid on a metabolic pathway dependent on prostaglandin H2 synthase activity, also known as cyclooxygenase (COX). Of the 12 prostaglandins, the most potent are PGD2, PGE2, and PGF2. The others are synthesized in a primary step of arachidonic acid transformation (PGG2, PGH2), by degradation of the above-mentioned prostaglandins, or are not presented physiologically and may be chemically generated (PGK2, PGL2). Similar compounds could originate from dihomo-gamma-linolenic, alpha-linoleic, and eicosapentaenoic acids. Three primary COX isoenzymes are distinguished: COX-1 (constitutive), COX-2 (inducible), and COX-3, which is detected mainly in the central nervous system. A number of partial forms of COX-1 and COX-2 are also known, but their biological functions have not been well evaluated. Although they differ in genes, transcription factors, primary protein structure, reactivity to substrates, and drugs which inhibit enzyme activity, the crystal structure is similar for all the izoenzymes. In contrast to the COX-1 gene, whose expression is typical for most of the cells, constant COX-2 expression was detected in the placenta and fetal tissue in late pregnancy. In the postnatal period, COX-2 expression decreases rapidly physiologically, and is observed in kidney, forebrain, spinal cord, as well as some other organs, but to a minor degree. It increases in inflammatory, degenerative, and neoplastic processes.
PMID: 16552393 [PubMed - indexed for MEDLINE]
10. Lipids. 2003 Apr;38(4):323-41.
Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3.
School of Chemical and Life Sciences, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, United Kingdom. L.Harbige@gre.ac.uk
The essentiality of n-6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20:4n-6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (1 8:2n-6, LA) for membrane phospholipids. Low n-6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2-like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer-chain n-6 PUFA produced by gamma-linolenic acid (18:3n-6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n-6 PUFA, GLA, dihomo-gamma-linolenic acid (20:3n-6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T-regulatory cell activity, e.g., transforming growth factor (TGF)-beta-producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha production. Low intakes of long-chain n-3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and Th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long-chain n-3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long-chain n-3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, whereas high-fat LA-rich diets increase disease severity. In experimentally induced T cell-mediated autoimmune disease, EFAD diets or diets supplemented with long-chain n-3 PUFA augment disease, whereas n-6 PUFA prevent or reduce the severity. In contrast, in both T cell- and antibody-mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n-6 and n-3 families are clinically useful in human autoimmune-inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n-6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.
PMID: 12848277 [PubMed - indexed for MEDLINE]
11. Ann Allergy Asthma Immunol. 2003 Apr;90(4):371-7; quiz 377-8, 421.
Diet and asthma: has the role of dietary lipids been overlooked in the management of asthma?
Spector SL, Surette ME.
University of California-Los Angeles, Los Angeles, California, USA. firstname.lastname@example.org
OBJECTIVE: This article discusses the role of diet in the management of asthma. Readers will gain an understanding of how evolution of the western diet has contributed to increased asthma prevalence and how dietary modification that includes management of dietary lipids may reduce symptoms of asthma. DATA SOURCES: Relevant studies published in English were reviewed. STUDY SELECTION: Medline search to identify peer-reviewed abstracts and journal articles. RESULTS: Asthma and obesity, which often occur together, have increased in prevalence in recent years. Studies suggest adaption of a western diet has not only contributed to obesity, but that increased intake of specific nutrients can cause changes in the frequency and severity of asthma. Increased asthma prevalence has also been proposed to arise from increased exposure to diesel particles or lack of exposure to infectious agents or endotoxins during childhood, generating a biased Th2 immune response, and increased cytokine and leukotriene production. Antagonists directed against these pro-inflammatory mediators include anticytokines and antileukotrienes. A reduction in the levels of inflammatory mediators associated with asthma has also been seen with dietary interventions, such as the administration of oils containing gamma-linolenic acid and eicosapentaenoic acid. CONCLUSIONS: Evidence suggests elevated body mass index and dietary patterns, especially intake of dietary lipids, contribute to symptoms of asthma. Dietary modification may help patients manage their asthma as well as contribute to their overall health.
PMID: 12722956 [PubMed - indexed for MEDLINE]
12. Br J Nutr. 2002 Jan;87 Suppl 1:S31-48.
Fatty acids and lymphocyte functions.
Calder PC, Yaqoob P, Thies F, Wallace FA, Miles EA.
Institute of Human Nutrition, University of Southampton, UK. email@example.com
The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.
PMID: 11895154 [PubMed - indexed for MEDLINE]
13. Z Rheumatol. 2001 Feb;60(1):17-27.
[Are there effective dietary recommendations for patients with rheumatoid arthritis?]
[Article in German]
Universit�tsklinikum Kr�llwitz, Klinik und Poliklinik f�r Innere Medizin I, Ernst-Grube-Str. 40, 06097 Halle/S. firstname.lastname@example.org
Patients with rheumatic diseases frequently ask the physician for diet recommendations. Although much has been written about this subject, scientifically validated studies investigating the impact of certain diets on rheumatoid arthritis are scant and often inconclusive. Elimination diets or total fasting is believed to eliminate food ingredients that cause or aggravate arthritis. In contrast, supplementation with fish oil, gamma-linoleic acid or vitamin E is directed at anti-oxidative and anti-inflammatory effects of these food compounds. So far, both approaches have failed to reveal a significant benefit with respect to objective signs of inflammation. Supplementation with other vitamins such as vitamin A and C, or with trace elements like selenium and zinc are of no proven influence on the disease activity as well. There is a higher request for calcium and vitamin D in patients with active RA under steroid treatment to prevent osteoporosis. In addition, patients with active RA have a slightly increased risk for cardiovascular events. Therefore, cholesterol-lowering diets and drugs should be applied early.
PMID: 11263011 [PubMed - indexed for MEDLINE]
14. Curr Opin Clin Nutr Metab Care. 2001 Mar;4(2):115-21.
Polyunsaturated fatty acids and rheumatoid arthritis.
Calder PC, Zurier RB.
Institute of Human Nutrition, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. email@example.com
Rheumatoid arthritis is characterized by infiltration of T lymphocytes, macrophages and plasma cells into the synovium, and the initiation of a chronic inflammatory state that involves overproduction of proinflammatory cytokines and a dysregulated T-helper-1-type response. Eicosanoids synthesized from arachidonic acid and cytokines cause progressive destruction of cartilage and bone. The n-6 polyunsaturated fatty acid gamma-linolenic acid is the precursor of di-homo-gamma-linolenic acid. The latter and the n-3 polyunsaturated fatty acid eicosapentaenoic acid, which is found in fish oil, are able to decrease the production of arachidonic acid-derived eicosanoids and to decrease the production of proinflammatory cytokines and reactive oxygen species, and the reactivity of lymphocytes. A number of double-blind, placebo-controlled trials of gamma-linolenic acid and fish oil in rheumatoid arthritis have shown significant improvements in a variety of clinical outcomes. These fatty acids should be included as part of the normal therapeutic approach to rheumatoid arthritis. However, it is unclear what the optimal dosage of the fatty acids is, or whether there would be extra benefit from using them in combination.
PMID: 11224655 [PubMed - indexed for MEDLINE]
15. Am J Clin Nutr. 2000 Jan;71(1 Suppl):352S-6S.
Evening primrose oil and borage oil in rheumatologic conditions.
Belch JJ, Hill A.
Department of Medicine, Ninewells Hospital and Medical School, Dundee, United Kingdom. firstname.lastname@example.org
Diets rich in arachidonic acid (20:4n-6) lead to the formation of 2-series prostaglandins (PGs) and 4-series leukotrienes (LTs), with proinflammatory effects. Nonsteroidal antiinflammatory drugs are used in rheumatoid arthritis to inhibit cyclooxygenase (prostaglandin-endoperoxide synthase), thereby decreasing production of 2-series PGs. Lipoxygenase activity remains intact, however, allowing LT production (eg, synthesis of LTB(4), a potent inflammatory mediator) to continue. Altering the essential fatty acid (EFA) content of the diet can modify some of these effects. Ingestion of a diet rich in evening primrose oil elevates concentrations of dihomo-gamma-linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE(1). DGLA itself cannot be converted to LTs but can form a 15-hydroxyl derivative that blocks the transformation of arachidonic acid to LTs. Increasing DGLA intake may allow DGLA to act as a competitive inhibitor of 2-series PGs and 4-series LTs and thus suppress inflammation. The results of in vitro and animal work evaluating EFAs in inflammatory situations are encouraging, which has stimulated clinical workers to evaluate these compounds in rheumatoid arthritis. Several well-controlled, randomized clinical studies have now been completed in which various EFAs were evaluated as treatments. The results of most of these studies suggest some clinical benefit to these treatments; these data are reviewed here.
PMID: 10617996 [PubMed - indexed for MEDLINE]
16. Proc Nutr Soc. 1998 Nov;57(4):555-62.
Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease.
School of Chemical and Life Sciences, University of Greenwich, London, UK. Harbige@greenwich.ac.uk
Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be appreciated that linoleic acid does not reflect the functions of dihomo-gamma-linolenic and arachidonic acid, and that the endogenous rate of conversion of linoleic to arachidonic acid is slow (Hassam et al. 1975, 1977; Phylactos et al. 1994; Harbige et al. 1995). In addition to effects of dietary fatty acids on immunoregulation, inflammation as a consequence of immune activation in autoimmune disease may also be an important mechanism of action whereby dietary fatty acids modulate disease activity. In conclusion, regulation of gene expression, signal transduction pathways, production of eicosanoids and cytokines, and the action of antioxidant enzymes are all mechanisms by which dietary n-6 and n-3 fatty acids may exert effects on the immune system and autoimmune disease. Probably the most significant of these mechanisms in relation to our current understanding of immunoregulation and inflammation would appear to be via fatty acid effects on cytokines. The amount, type and balance of dietary fatty acids and associated antioxidant nutrients appear to impact on the immune system to produce immune-deviation or immunosuppressive effects, and to reduce immune-mediated inflammation which will in turn affect the susceptibility to, or severity of, autoimmune disease.
PMID: 10096116 [PubMed - indexed for MEDLINE]
17. Semin Arthritis Rheum. 1995 Oct;25(2):87-96.
Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis.
Rothman D, DeLuca P, Zurier RB.
Division of Rheumatology, University of Massachusetts Medical Center, Worcester 01655-0335, USA.
OBJECTIVE: This review discusses the rationale and experimental data that led to clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA), for the treatment of rheumatoid arthritis (RA). DATA SOURCES: Pertinent articles and reviews, and a bibliographic database in English using the following indexing terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and monocytes, were used. STUDY SELECTION: All clinical trials in which GLA was used to treat arthritis are included in this review. Data from appropriately peer reviewed in vitro and animal experiments evaluating the effects of botanical lipids as regulators of cell activation and immune responses are also reviewed. DATA SYNTHESIS: GLA treatment is associated with clinical improvement in patients with RA, as evaluated by duration of morning stiffness, joint pain and swelling, and ability to reduce other medications. However, studies vary in terms of duration, GLA dose, whether or not they were placebo controlled, and, if so, what placebo was used, criteria for evaluation, and use of concomitant medication. Studies done in vitro generally indicated that GLA reduces lymphocyte activation and production of mediators of inflammation. CONCLUSIONS: A small number of studies suggest that GLA is effective treatment for RA patients. Further controlled studies of its use in RA seem warranted.
PMID: 8578315 [PubMed - indexed for MEDLINE]
18. Clin Investig. 1992 Feb;70(2):167-71.
Treatment of atopic eczema with evening primrose oil: rationale and clinical results.
Kerscher MJ, Korting HC.
Dermatologische Klinik und Poliklinik Ludwig-Maximilians Universit�t M�nchen.
Recently a defect in the function of the enzyme delta-6-desaturase has been discussed as a major factor in the development of atopic eczema. Delta-6-desaturase is responsible for the conversion of linoleic acid to gamma linolenic acid. Several plants, including evening primrose, are known to be fairly rich in gamma linolenic acid. Hence, substitution of gamma linolenic acid in patients prone to developing atopic eczema seems like a feasible concept. During the last few years different clinical trials have been performed. Controlled trials following a parallel study design showed marked improvement in atopic eczema. Patients treated with the drug showed less inflammation, dryness, scaling and overall severity compared to controls. Although these findings have been supported by meta-analysis, there is still conflicting evidence in trials based on a crossover design alone, demonstrating a decrease in itching. At present, evening primrose oil in doses used for the treatment of atopic eczema is considered safe. However, still more trials addressing both efficacy and safety are needed to make a final decision.
PMID: 1318129 [PubMed - indexed for MEDLINE]
19. Hautarzt. 1989 Nov;40(11):685-92.
[A new concept of the etiopathogenesis and prevention of atopic dermatitis]
[Article in German]
Melnik B, Plewig G.
Hautklinik, Heinrich-Heine-Universit�t D�sseldorf.
The hypothesis proposed for the pathogenesis of atopy links the well-known alterations in cell-mediated and humoral immunity, the disturbances of mediator metabolism and the increased disposition of atopic epidermis for inflammation to a common underlying deficiency in the production of prostaglandin E1. The PGE1 deficiency is explained as the result of reduced delta-6-desaturase activity in atopic patients. The development of depressed cell-mediated immunity is regarded as a PGE1-dependent T-cell-maturation defect of the newborn's immune system post partum. Our hypothesis offers a novel approach to the prevention of atopy by administration of gamma-linolenic acid to newborns with increased risk of atopy and to nursing atopic mothers. Furthermore, it provides an explanation for the beneficial therapeutic effects of dietary supplementation of gamma-linolenic acid in patients with atopic dermatitis.
PMID: 2558092 [PubMed - indexed for MEDLINE]
20. Wien Klin Wochenschr. 1988 Jul 15;100(14):471-7.
Prostaglandin E1: physiological significance and clinical use.
Efamol Research Institute, Kentville, Canada.
Contrary to popular belief, prostaglandin (PG) E1 and its immediate precursor, dihomogammalinolenic acid (DGLA), are found in physiologically important amounts in humans. PGE1 has many desirable effects, particularly with regard to the cardiovascular system and to inflammation. PGE1 is difficult to use therapeutically because of its short life. Better clinical results may be obtained by administering its precursors such as DGLA and gamma-linolenic acid (GLA).
PMID: 3062904 [PubMed - indexed for MEDLINE]
21. J Am Coll Nutr. 1986;5(2):213-28.
Increased requirements for essential fatty acids in atopic individuals: a review with clinical descriptions.
Patients with atopic eczema and a mixture of allergic illnesses show biochemical evidence suggesting impairment in the desaturation of linoleic acid and linolenic acid by the enzyme delta-6 dehydrogenase. Consequences of this enzyme defect are 1) diminished synthesis of the 20-carbon polyunsaturated fatty acids, which are prostaglandin precursors and 2) a reduction in the concentration of double bonds in the cell membrane. A distortion in the production of prostaglandins and leukotrienes, which might result from this block, can account for the immunological defects of atopy and a variety of clinical symptoms experienced by atopic individuals. Dietary supplementation with essential fatty acids relieves the signs and symptoms of atopic eczema, may improve other types of allergic inflammation, and may also correct coexisting symptoms as diverse as excessive thirst and dysmenorrhea. Further research is suggested to test the hypothesis that some atopic states represent a condition of essential fatty acid dependency owing to defective desaturation of dietary fatty acids.
PMID: 2424959 [PubMed - indexed for MEDLINE]
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