Maggie Laidlaw and Bruce J Holub. Effects of supplementation with fish oil?derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J of Clinical Nutrition, 2003;77(1)37-42

Background:
Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and gamma-linolenic acid (GLA) have lipid-modifying and antiinflammatory properties. The effects of supplement mixtures of these fatty acids on plasma lipids and the fatty acid compositions of serum phospholipids have received little attention.

Objective:
The objective was to determine the effects of different levels of GLA supplementation together with a constant intake of EPA plus DHA on the triacylglycerol-lowering effect of EPA plus DHA alone and on the fatty acid patterns (eicosanoid precursors) of serum phospholipids.

Design:
Thirty-one women were assigned to 1 of 4 groups, equalized on the basis of their fasting triacylglycerol concentrations. They received supplements providing 4 g EPA+DHA (4:0, EPA+DHA:GLA; control group), 4 g EPA+DHA plus 1 g GLA (4:1), 2 g GLA (4:2), or 4 g GLA (4:4) daily for 28 d. Plasma lipids and fatty acids of serum phospholipids were measured on days 0 and 28.

Results:
Plasma triacylglycerol concentrations were significantly lower on day 28 than on day 0 in the 4:0, 4:1, and 4:2 groups. LDL cholesterol decreased significantly (by 11.3%) in the 4:2 group. Dihomo-gamma-linolenic acid increased significantly in serum phospholipids only in the 4:2 and 4:4 groups; however, total n-3 fatty acids increased in all 4 groups.

Conclusions:
A mixture of 4 g EPA+DHA and 2 g GLA favorably altered blood lipid and fatty acid profiles in healthy women.
On the basis of calculated PROCAM values, the 4:2 group was estimated to have a 43% reduction in the 10-y risk of myocardial infarction.

Belch JJF, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am. J. Clinical Nutrition, 2000;71 (1): 352S-356S.

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 LTB4, 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--linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE1. 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.

Ziboh VA, Fletcher MP. Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear- neutrophil biosynthesis of leukotriene B4. Am J Clinical Nutr., 1992;55:39-45.

The dose-dependent effect of dietary supplemented gamma-linolenic acid (GLA, 18:3n-6)-enriched borage oil (Bor) and black-currant oil on the ability of calcium ionophore-activated human polymorphonuclear neutrophils (PMN) to generate leukotriene B4 (LTB4) was investigated in adult healthy human volunteers.

Significant (P less than 0.05) elevation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6), an elongation product of GLA, was revealed in PMN phospholipids after ingestion of either 0.48 or 1.5 g GLA-enriched oil/d.

This elevation of DGLA in the PMN phospholipids paralleled the decreased capacity of calcium ionophore-activated PMN to generate LTB4.

Although the inhibition of LTB4 was greater with the ingestion of 1.5 g GLA-enriched BOR/d, it was not significantly different from the ingestion of 0.48 g/d.

Taken together, dietary ingestion of GLA-fortified oils does modulate PMN generation of proinflammatory LTB4.

Jiang WG, Bryce RP, et al. Regulation of tight junction permeability and occludin expression by polyunsaturated fatty acids. Biochem Biophys Res Comm, 1998;244(2):414-420

Tight junctions (TJ) are the topical most structure in epithelial and endothelial cells and play a key role in the control of permeability and prevention of tumour cell invasion of endothelium.

In this study we examined the effects of a range of polyunsaturated fatty acids on the function of TJs and the expression of occludin, a key molecule in the TJs of the human vascular endothelial cell line, ECV304.

Treatment of the endothelial cells with gamma linolenic acid, an anti-cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the paracellular permeability to large molecules.

The effects were seen without any changes in the viability of the endothelial cells.

Occludin, a recently identified molecule, which plays a major role in tight junctions was up-regulated by this fatty acid as revealed by both Western blotting and immunofluorescence.

Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an up-regulatory effect, but LA and AA down-regulated the expression.

We conclude that GLA and EPA which also have other anti-cancer effects, regulate the expression of occludin in endothelial cells and thus contribute to the modification of the TER of these cells.

Pacht ER, DeMichele SJ, et al. Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients. Crit Care Med, 2003; 31(2):491-500

OBJECTIVE: Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation.

DESIGN: Prospective, randomized, double-blind, controlled clinical trial.

PATIENTS: A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome.

INTERVENTIONS: A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days.

MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4.

CONCLUSIONS: This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.

Calder P, Zurier R. Polyunsaturated fatty acids and rheumatoid arthritis.
Curr Opin Clin Nutr Metab Care, Mar 2001; 4(2): 115-21.

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.

Huang YS, Drummond R, Horrobin DF. Protective effect of gamma-linolenic acid on aspirin-induced gastric hemorrhage in rats. Digestion, 1987;36(1):36-41

The effects of feeding with gamma-linolenic acid (GLA) in comparison with linoleic acid on aspirin-induced gastric hemorrhage were studied in the rat. Gastric damage was examined macroscopically and histologically.

Intragastric administration of 100 mg aspirin daily for 4 weeks produced hemorrhage in 3 of 8 rats receiving a linoleic-acid-enriched diet, but none in 8 rats receiving GLA-enriched diet.

The levels of linoleic acid in plasma and liver phospholipids were significantly increased, whereas those of arachidonic acid (AA) were reduced in plasma and liver phospholipids of aspirin-treated animals fed linoleic acid. Similar, more pronounced changes occurred in those animals with hemorrhage.

The reduced ratios of arachidonate/linoleate suggest that fatty acid desaturation in these animals was depressed. Treatment with GLA prevented these changes.

Our results demonstrated that GLA could protect the gastric mucosa from aspirin-induced damage by bypassing the depressed delta-6-desaturation and thus providing a precursor for the synthesis of AA and prostaglandins.

Menendez JA, Vellon L, et al. Effect of -Linolenic Acid on the Transcriptional Activity of the Her-2/neu (erbB-2) Oncogene. J. Nat. Cancer Institute, 2005; 97 (21):1611-1615.

The omega-6 polyunsaturated fatty acid gamma-linolenic acid (GLA; 18:3n-6), which is found in several plant oils and is used as an herbal medicine, has antitumor activity in vitro.

We examined the effect of GLA on the expression of the Her-2/neu (erbB-2) oncogene, which is involved in development of numerous types of human cancer.
Flow cytometric and immunoblotting analyses demonstrated that GLA treatment substantially reduced Her-2/neu protein levels in the Her-2/neu, overexpressing cell lines BT-474, SK-Br3, and MDA-MB-453 (breast cancer), SK-OV3 (ovarian cancer), and NCI-N87 (gastrointestinal tumor derived).

GLA exposure led to a dramatic decrease in Her-2/neu promoter activity and a concomitant increase in the levels of polyomavirus enhancer activator 3 (PEA3), a transcriptional repressor of Her-2/neu, in these cell lines.

In transient transfection experiments, a Her-2/neu promoter bearing a PEA3 site mutated sequence was not subject to negative regulation by GLA in Her-2/neu overexpressing cell lines.

Concurrent treatments of Her-2/neu overexpressing cancer cells with GLA and the anti Her-2/neu antibody trastuzumab led to synergistic increases in apoptosis and reduced growth and colony formation.

Yang-Yi Fan and Robert S. Chapkin. Importance of Dietary Gamma-Linolenic Acid in Human Health and Nutrition. J of Nutrition, 1998;128(9):1411-1414

Considerable debate remains regarding the distinct biological activities of individual polyunsaturated fatty acids (PUFA). One of the most interesting yet controversial dietary approaches has been the possible prophylactic role of dietary gamma-linolenic acid (GLA) in treating various chronic disease states.

This strategy is based on the ability of diet to modify cellular lipid composition and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis.

Recent studies demonstrate that dietary GLA increases the content of its elongase product, dihomo-gamma-linolenic acid (DGLA), within cell membranes without concomitant changes in arachidonic acid (AA).

Subsequently, upon stimulation, DGLA can be converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1.

This is noteworthy because these compounds possess both anti-inflammatory and antiproliferative properties.

Although an optimal feeding regimen to maximize the potential benefits of dietary GLA has not yet been determined, it is the purpose of this review to summarize the most recent research that has focused on objectively and reproducibly determining the mechanism(s) by which GLA may ameliorate health problems.

Thies F, Nebe-von-Caron G, et al. Dietary Supplementation with gamma-Linolenic Acid or Fish Oil Decreases T Lymphocyte Proliferation in Healthy Older Humans. J of Nutrition,2001;131:1918-1927

Animal and human studies have shown that greatly increasing the amounts of flaxseed oil [rich in the (n-3) polyunsaturated fatty acid (PUFA) -linolenic acid (ALNA)] or fish oil [FO; rich in the long chain (n-3) PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease mitogen-stimulated lymphocyte proliferation.

The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA or FO on the proliferation of mitogen-stimulated human peripheral blood mononuclear cells (PBMC) and on the production of cytokines by those cells.

The study was randomized, placebo-controlled, double-blinded and parallel.
Healthy subjects ages 5575 y consumed nine capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA or DHA or FO.

Subjects in these groups consumed 2 g of ALNA or 770 mg of GLA or 680 mg of ARA or 720 mg of DHA or 1 g of EPA plus DHA (720 mg of EPA + 280 mg of DHA) daily from the capsules. Total fat intake from the capsules was 4 g/d.

The fatty acid composition of PBMC phospholipids was significantly changed in the GLA, ARA, DHA and FO groups. Lymphocyte proliferation was not significantly affected by the placebo, ALNA, ARA or DHA treatments.

GLA and FO caused a significant decrease (up to 65%) in lymphocyte proliferation. This decrease was partly reversed by 4 wk after stopping the supplementation.

None of the treatments affected the production of interleukin-2 or interferon-gamma by PBMC and none of the treatments affected the number or proportion of T or B lymphocytes, helper or cytotoxic T lymphocytes or memory helper T lymphocytes in the circulation.

We conclude that a moderate level GLA or EPA but not of other (n-6) or (n-3) PUFA can decrease lymphocyte proliferation but not production of interleukin-2 or interferon-gamma.

Fan Y-Y and Chapkin RS. Importance of Dietary -Linolenic Acid in Human Health and Nutrition. J. of Nutrition, 1998; 128 (9): 1411-1414

Considerable debate remains regarding the distinct biological activities of individual polyunsaturated fatty acids (PUFA).

One of the most interesting yet controversial dietary approaches has been the possible prophylactic role of dietary gamma-linolenic acid (GLA) in treating various chronic disease states.

This strategy is based on the ability of diet to modify cellular lipid composition and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis.

Recent studies demonstrate that dietary GLA increases the content of its elongase product, dihomo-gamma-linolenic acid (DGLA), within cell membranes without concomitant changes in arachidonic acid (AA).

Subsequently, upon stimulation, DGLA can be converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1.

This is noteworthy because these compounds possess both anti-inflammatory and antiproliferative properties.

Although an optimal feeding regimen to maximize the potential benefits of dietary GLA has not yet been determined, it is the purpose of this review to summarize the most recent research that has focused on objectively and reproducibly determining the mechanism(s) by which GLA may ameliorate health problems.

Barham JB, Edens MB, et al. Addition of Eicosapentaenoic Acid to Gamma-Linolenic Acid?Supplemented Diets Prevents Serum Arachidonic Acid Accumulation in Humans. J of Nutrition, 2000;130:1925-1931

Previous studies reveal that supplementation of human diets with gamma-linolenic acid (GLA) reduces the generation of lipid mediators of inflammation and attenuates clinical symptoms of chronic inflammatory disorders such as rheumatoid arthritis.
However, we have shown that supplementation with this same fatty acid also causes a marked increase in serum arachidonate (AA) levels, a potentially harmful side effect.

The objective of this study was to design a supplementation strategy that maintained the capacity of GLA to reduce lipid mediators without causing elevations in serum AA levels.

Initial in vitro studies utilizing HEP-G2 liver cells revealed that addition of eicosapentaenoic acid (EPA) blocked delta- 5-desaturase activity, the terminal enzymatic step in AA synthesis.

To test the in vivo effects of a GLA and EPA combination in humans, adult volunteers consuming controlled diets supplemented these diets with 3.0 g/d of GLA and EPA.
This supplementation strategy significantly increased serum levels of EPA, but did not increase AA levels.

EPA and the elongation product of GLA, dihomo-gamma-linolenic acid (DGLA) levels in neutrophil glycerolipids increased significantly during the 3-wk supplementation period.

Neutrophils isolated from volunteers fed diets supplemented with GLA and EPA released similar quantities of AA, but synthesized significantly lower quantities of leukotrienes compared with their neutrophils before supplementation.

This study revealed that a GLA and EPA supplement combination may be utilized to reduce the synthesis of proinflammatory AA metabolites, and importantly, not induce potentially harmful increases in serum AA levels.

Johnson MM, Swan DD, Surette ME, et al. Dietary Supplementation with gamma-Linolenic Acid Alters Fatty Acid Content and Eicosanoid Production in Healthy Humans. J of Nut.,1997;127(8):1435-1444.

To understand the in vivo metabolism of dietary gamma-linolenic acid (GLA), we supplemented the diets of 29 volunteers with GLA in doses of 1.5-6.0 g/d.

Twenty-four subjects ate controlled eucaloric diets consisting of 25% fat; the remaining subjects maintained their typical Western diets. GLA and dihomo-gamma-linolenic acid (DGLA) increased in serum lipids of subjects supplemented with 3.0 and 6.0 g/d; serum arachidonic acid increased in all subjects.

GLA supplementation with 3.0 and 6.0 g/d also resulted in an enrichment of DGLA in neutrophil phospholipids but no change in GLA or AA levels.

Before supplementation, DGLA was associated primarily with phosphatidylethanolamine (PE) of neutrophil glycerolipids, and DGLA increased significantly in PE and neutral lipids after GLA supplementation. Extending the supplementation to 12 wk did not consistently change the magnitude of increase in either serum or neutrophil lipids in subjects receiving 3.0 g/d.

After GLA supplementation, A23187-stimulated neutrophils released significantly more DGLA, but AA release did not change. Neutrophils obtained from subjects after 3 wk of supplementation with 3.0 g/d GLA synthesized less leukotriene B4 (P < 0.05) and platelet-activating factor.

Together, these data reveal that DGLA, the elongase product of GLA, but not AA accumulates in neutrophil glycerolipids after GLA supplementation.

The increase in DGLA relative to AA within inflammatory cells such as the neutrophil may attenuate the biosynthesis of AA metabolites and may represent a mechanism by which dietary GLA exerts an anti-inflammatory effect.

Nassar BA, Huang YS, Manku MS et al. The influence of dietary manipulation with n-3 and n-6 fatty acids on liver and plasma phospholipid fatty acids in rats. Lipids,1986;21(10):652-656.

The interrelations between linoleic acid (LA) metabolites and fish oil fatty acids were studied.

Sprague-Dawley rats (200-220 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) of different combinations of evening primrose oil (EPO), a rich source of LA and gamma-linolenic acid, and polepa (POL), a marine oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids.

The combinations of supplement were as follows: 9% EPO-1% POL, 8% EPO-2% POL, 7% EPO-3% POL, 6% EPO-4% POL and 5% EPO-5% POL. After two weeks on the respective diets, the animals were killed, and the fatty acid compositions of liver and plasma phospholipids were examined.

The results showed that animals fed higher proportions of POL consistently contained higher levels of dihomo-gamma-linolenic acid (DGLA) (p less than 0.05), a metabolite of LA and GLA, and lower levels of arachidonic acid (AA) (p less than 0.01), a metabolite of DGLA through delta-5-desaturation.

Thus, an inverse relationship between AA/DGLA ratio and EPA levels was found to exist (r = -0.765 in plasma and -0.792 in liver). However, there was no such relationship between AA/DGLA ratio and DHA levels.

This result suggested that EPA but not DHA in fish oil exerts an inhibitory effect on the conversion of DGLA to AA.

McCarty MF. Vascular nitric oxide, sex hormone replacement, and fish oil may help to prevent Alzheimer's disease by suppressing synthesis of acute-phase cytokines. Med Hypotheses 1999;53(5):369-374.

The neurodegenerative plaques of Alzheimer's disease (AD) are characterized by a self-sustaining acute-phase reaction in which both interleukin-1 (IL-1) and interleukin-6 (IL-6) are up-regulated.

The fact that IL-6 is detectable in early stage diffuse plaques encourages the speculation that the acute-phase process is crucial to the pathogenesis of AD.

The epidemiological association of AD with estrogen deficiency, as well as with various disorders characterized by vascular endotheliopathy, suggest a protective role for vascular nitric oxide (NO).

NO has an autocrine anti-inflammatory impact on endothelium, owing in part to antagonism of NF-kappaB activity; since induction of IL-6 is dependent on NF-kappaB, this may explain recent evidence that NO inhibits macrophage IL-6 production.

It is reasonable to postulate that, analogously, cerebrovascular NO decreases IL-6 production in the brain.
Vascular NO may also have direct neuroprotective activity. Estrogen, in addition to promoting vascular NO synthesis, can block IL-6 production by a more direct mechanism in cells expressing estrogen receptors; since such receptors have been reported in brain glia and astrocytes, estrogen has the potential to limit brain IL-1 activity.
Testosterone likewise can inhibit IL-6 induction in androgen-responsive cells, which may include brain glia and astrocytes.

Since fish oil and gamma linolenic acid (GLA) suppress IL-1 production by stimulated monocytes, they conceivably could exert this effect in the brain as well; the comparatively low prevalence of AD in elderly Japanese is intriguing in this regard.

These considerations suggest that a healthy cerebrovascular endothelium, sex hormone activity, and dietary fish oil/GLA may slow or prevent AD onset by dampening acute-phase mechanisms in the brain.

PMID: 10616034

Das UN. Essential fatty acids and acquired immunodeficiency syndrome. Med Sci Monit., 2005;11(6):RA206-211

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) that is characterized by profound immunodeficiency, opportunistic infections and Kaposi's sarcoma.

As yet no effective therapy is available for AIDS, though retroviral drugs are able to prolong life and contain HIV proliferation to some extent.

I propose that essential fatty acids (EFAs) and their metabolites could be useful in the prevention and management of AIDS.

Linoleic acid (LA) and arachidonic acid (AA) inactivate enveloped viruses, linolenic acid-enriched macrophages are markedly tumoricidal, EFAs activate macrophages and neutrophils and induce free radical generation; and cytokines bring about some of their actions by inducing the release of EFAs; gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) prevent genetic damage and have tumoricidal actions as well; and are relatively non-toxic when administered orally or parentarally over long periods of time.

In view of this, I suggest that further studies with regard to the role of GLA, AA, EPA and/or docosahexaenoic acid (DHA) in the pathobiology of AIDS needs to be performed.

It is also proposed that possible use of these fatty acids in the prevention and treatment of AIDS needs serious consideration.

Mizock BA, DeMichele SJ. The Acute Respiratory Distress Syndrome: Role of Nutritional Modulation of Inflammation Through Dietary Lipids. Nutrition in Clinical Practice,2004;19(6):563-557.

The acute respiratory distress syndrome (ARDS) is the most serious form of acute hypoxic respiratory failure.

ARDS represents the expression of an acute, diffuse, inflammatory process in the lungs consequent to a variety of infectious and noninfectious conditions.
It is characterized pathologically by damage to pulmonary epithelial and endothelial cells, with subsequent alveolar- capillary leak and exudative pulmonary edema.
The main clinical features of ARDS include rapid onset of dyspnea, severe defects in gas exchange, and imaging studies demonstrating diffuse pulmonary infiltrates.

The role of nutrition in the management of ARDS has traditionally been supportive.

Recent research has demonstrated the potential of certain dietary oils (eg, fish oil, borage oil) to modulate pulmonary inflammation, thereby improving lung compliance and oxygenation, and reducing time on mechanical ventilation.

This article reviews the alterations in the immune response that underlie ARDS, discusses the physiology of dietary oils as immunonutrients, summarizes animal and human studies that explore the therapeutic effects of dietary oils, and provides clinical recommendations for their use.

Richardson A, Montgomery P. The Oxford-Durham Study: A Randomized, Controlled Trial of Dietary Supplementation With Fatty Acids in Children With Developmental Coordination Disorder. Pediatrics 2005, 115 (5):1360-1366

Background. Developmental coordination disorder (DCD) affects 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood.

Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation.

Methods. A randomized, controlled trial of dietary supplementation with -3 and -6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5?12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months.

Results. No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress.

Conclusions. Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

Claassen N, Coetzer H, et al. The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Prosta Leukot Essent Fatty Acids,1995;53(1):13-19

Prostaglandins (PGs) are known to have various effects on bone metabolism.

The supplementation of essential fatty acids (EFAs), the precursors of PGs, leads to increased intestinal calcium absorption and calcium balance.

It is, however, not known whether increased calcium absorption and calcium balance will enhance the calcium content in bone.

Male Sprague-Dawley rats (n = 40) aged 5-12 weeks were supplemented with EFAs. The main dietary EFAs, linoleic acid (LA) and alpha-linolenic acid (ALA) were administered in a ratio of 3:1 as a control group.

The conversion of LA ans ALA to the PG precursors is slow, with the first step, delta-6-desaturation being rate limiting.

Fatty acids beyond this rate-limiting step, gamma-linolenic acid (GLA, n-6) and eicoapentaenioc acid (EPA, n-3), were administered to different groups in the ratios 3:1, 1:1 and 1:3 to explore the impact of different ratios of n-6 and n-3 EFAs.

Intestinal calcium absorption (mg/24 h) increased by 41.5% in the 3:1 supplemented group, compared with the control group. The decrease in urinary calcium (mg/24 h) correlated with the increase in n-3 level.

The calcium balance (mg/24 h) and bone calcium (mg/g bone ash) increased significantly in the 3:1 (41.5% and 24.7%) group, compared with the control.

The increase in bone calcium might be attributed to an EFA-induced increase in circulating PGs.

An increased synthesis of PGs acting on target bone cells, as well as changes in membrane fluidity, may underlie these observations.