Work by Chapkin et.al. (references 1-4) has identified the potent synergistic relationship between GLA, an omega-6 fatty acid, and the well-known omega-3 fatty acids. Chapkin has shown that, rather than simply the quantity of dietary omega-3’s, it is the ratio of omega-6 to omega-3 fatty acids that is important in achieving full cardiovascular health and inflammatory control. Furthermore, he has identified the ideal ratio. That ratio is now available to you through Pathways Omega Plus from Health Products Distributors, Inc. Our product is produced by the actual supplier of material used in some of Chapkin’s research. The following materials describe research findings and product specifications, and include abstracts of Chapkin’s published research.
Polyunsaturated fatty acids have been extensively researched. They include the essential fatty acids linoleic acid (an omega-6) and alpha linolenic acid (an omega-3). Omega-3’s are not abundant in our food chain. There is none in corn oil and very little in soy oil, the two most widely used food oils. Therefore, nearly all the early research with polyunsaturated oils utilized omega-6 fatty acids, predominantly as linoleic acid. Fish oils were neglected out of ignorance or because the investigators chose to pass over these cholesterol-containing oils. Concern eventually developed over the close association between increasing incidence of mammary tumors and high intake of omega-6 polyunsaturated fatty acids. After some years, researchers finally turned their investigations to the interrelationship between dietary omega-6 and omega-3 fatty acids. Research now shows that the omega-6 fatty acid, linoleic acid, should be taken in at a level of about 3 grams per day to provide only about l% to 2% of each day’s calories. Our current consumption is about six times per day greater than the amount required for the prevention of deficiency symptoms. Americans may be consuming too much linoleic acid. The overall health effect may be negative.
Eicosanoids are prostaglandins that affect many aspects of health both positively and, in some cases, negatively. All known eicosanoids and prostaglandins are formed from the essential fatty acids linoleic acid (omega-6, or n-6), linolenic acid (omega-3, or n-3), their “enhanced” derivatives, and from the omega-3 fatty acids in fish oils. It is now known that the ratios of these dietary fatty acids are very important. Consumption of linoleic acid leads to production of the enhanced fatty acid, arachidonic acid (20:4n-6). Eicosanoids based on arachidonic acid exacerbate stress and inflammatory states, and suppress immunoprotective functions (i.e. resistance to disease). Too much linolenic acid and other omega-3’s may cause excessive bleeding during injury, surgery, or childbirth. Large amounts of any of these unsaturated fatty acids in the diet without a compensatory increase in antioxidant nutrients, can speed oxidative damage to tissues, resulting in accelerated aging while increasing the risk of degenerative diseases. Yet a balanced ratio of both omega-3 and omega-6 fatty acids in the diet offers very positive health benefits. When omega-3 fatty acids predominate, the body will produce less arachidonic acid (20:4n-6). Immunity improves and inflammation subsides. Unfortunately, our western diet is almost devoid of omega-3 fatty acids. Creating the optimum intake of omega 3-to-omega 6 unsaturated fatty acids has become, therefore, an issue of prime importance for anyone concerned with health. We need to evaluate carefully the amounts of linoleic acid (n-6) we consume relative to our intake of alpha linolenic acid (18:3n-3) and fish oils (EPA:20:5n-3 and DHA:22:6n-3).
Researchers from the University of California at Davis and at Texas A&M have published their work dealing with the importance of mixed diets supplying both linoleic and linolenic acids. To underscore the importance of these two fatty acids, refined oil supplements rich in enhanced forms were used. “Enhanced forms” are fatty acids derived from the original. They are one or more steps closer to the actual eicosanoid. In the human body, alpha linolenic acid (18:3n-3) is eventually converted to eicosapentaenoic acid (EPA, 20:5n-3) and linoleic acid (18:2n-6) is converted to gamma-linolenic (GLA, 18:3n-6) as its first enhanced form. Both enhanced fatty acids are precursors to eicosanoids. In the UC Davis research, superior health benefits were delivered by the mixed diet that supplied the eicosanoid precursors in a specific ratio. The balanced ratio of enhanced omega 6 (GLA)-to-omega 3 (EPA) fatty acids was 1:4.
Our bodies are best protected from disease when we supply a mixed diet of both omega-3 and omega-6 fatty acids. Studies show that we do not need to consume large amounts of fatty acids if the ratio is correct. These findings indicate that, for a typical human body, a ratio of 15 mg GLA (18:3n-6) to 60 mg EPA (20:5n-3) taken daily will provide for the optimum production of the three major prostaglandins. These amounts in the correct ratio is contained in our Omega Plus capsules and is now available to you.
Chapkin RS Somers SD Erickson KL
Dietary manipulation of macrophage phospholipid classes: selective increase of dihomogammalinolenic acid.
In: Lipids (1988 Aug) 23(8):766-70
Because alterations in the dietary content of fatty acids are an important method for modulating macrophage eicosanoid production, we have quantitated the levels of n-6 and n-3 polyunsaturated fatty acids in peritoneal macrophage individual phospholipids from mice fed diets (3 wk) with either safflower oil (SAF), predominantly containing 18:2n-6, borage, (BOR) containing 18:2n-6 and 18:3n-6, fish (MFO) containing 20:5n-3 and 22:6n-3, and borage/fish mixture (MIX) containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. Dietary n-3 fatty acids were readily incorporated into macrophage phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The increase in n-3 fatty acid levels was accompanied by a decrease in the absolute levels of 18:2n-6, 20:4n-6 and 22:4n-6 in PC, PE and PS. Interestingly, PI 20:4n-6 levels were not significantly lowered (P greater than 0.05) in MIX and MFO macrophages relative to SAF and BOR. These data demonstrate the unique ability of this phospholipid to selectively maintain its 20:4n-6 levels. In BOR and MIX animals, 20:3n-6 levels were significantly increased (P less than 0.05) in all phospholipids relative to SAF and MFO. The combination of borage and fish oils (MIX diet) produced the highest 20:3n-6/20:4n-6 ratio in all phospholipids. These data show that the macrophage eicosanoid precursor levels of 20:3n-6, 20:4n-6 and n-3 acids can be selectively manipulated through the use of specific dietary regimens. This is noteworthy because an increase in phospholipid levels of 20:3n-6 and 20:5n-3, while concomitantly reducing 20:4n-6, may have therapeutic potential in treating inflammatory disorders.
Institutional address: Department of Human Anatomy School of Medicine University of California Davis 95616.
Chapkin RS Carmichael SL
Effects of dietary n-3 and n-6 polyunsaturated fatty acids on macrophage phospholipid classes and subclasses.
In: Lipids (1990 Dec) 25(12):827-34
This study examined the effects of n-3 and n-6 polyunsaturated fatty acid alimentation on murine peritoneal macrophage phospholipids. Mice were fed complete diets supplemented with either corn oil predominantly containing 18:2n-6, borage oil containing 18:2n-6 and 18:3n-6, fish/corn oil mixture containing 18:2n-6, 20:5n-3 and 22:6n-3, or fish/borage oil mixture containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. After two weeks, the fatty acid levels of glycerophosphoserines (GPS), glycerophosphoinositols (GPI), sphingomyelin (SPH), and of the glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) phospholipid subclasses were determined. We found that mouse peritoneal macrophage GPC contain primarily 1-O-alkyl-2-acyl (range for the dietary groups, 24.6-30.5 mol %) and 1,2-diacyl (63.2-67.2 mol %), and that GPE contains 1-O- alk-1′-enyl-2-acyl (40.9-47.4 mol %) and 1,2-diacyl (44.2-51.2 mol %) subclasses. In general, fish oil feeding increased macrophage 20:5n-3, 22:5n-3 and 22:6n-3 levels while simultaneously reducing 20:4n-6 in GPS, GPI, GPE and GPC subclasses except for 1-O-alk-1′-enyl-2-acyl GPC. Administration of 18:3n-6 rich diets (borage and fish/borage mixture) resulted in the accumulation of 20:3n-6 (2-carbon elongation product of 18:3n-6) in most phospholipids. In general, the novel combination of dietary 18:3n-6 and n-3 PUFA produced the highest 20:3n-6/20:4n-6 phospholipid fatty acid ratios. This study demonstrates that marked differences in the responses of macrophage phospholipid classes and subclasses exist following dietary manipulation.
Fan YY Chapkin RS
Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by dietary gamma-linolenic acid.
In: J Nutr (1992 Aug) 122(8):1600-6
The ability of dietary gamma-linolenic acid [18:3(n-6)] to modulate prostaglandin biosynthesis in mouse resident peritoneal macrophages was determined. Mice were fed diets containing corn oil, borage oil or evening primrose oil or a mixture of borage and fish oils. After 2 wk, resident peritoneal macrophages were isolated and stimulated with unopsonized zymosan to induce prostaglandin synthesis. Borage oil, primrose oil and fish-borage oil mixture dietary groups (containing 25.6, 11.9 and 19.5 g gamma-linolenic acid/100 g fatty acids, respectively) had significantly (P less than 0.05) enhanced prostaglandin E1 synthesis (39.7, 29.4 and 73.0 nmol prostaglandin E1/mg protein, respectively) compared with corn oil-fed (containing less than 0.1 g gamma-linolenic acid/100 g fatty acids) animals, which synthesized less than 0.1 nmol prostaglandin E1/mg protein. Borage oil- and fish-borage oil mixture-fed mice had the highest biosynthetic ratio of prostaglandin E1/prostaglandin E2 (E1/E2 approximately 0.2). Macrophages from borage oil-fed mice synthesized the lowest amount of prostacyclin (198.7 nmol 6-keto-prostaglandin F1 alpha/mg protein) compared with corn oil-, primrose oil- and fish- borage oil mixture-fed mice (379.7, 764.8 and 384.2 nmol 6-keto- prostaglandin F1 alpha/mg protein, respectively). In addition, borage oil-, primrose oil- and fish-borage oil mixture-fed mice had significantly (P less than 0.05) higher levels of dihomo-gamma- linolenic acid [20:3(n-6)] in membrane phospholipids (5.5, 3.5 and 5.7 mol/100 mol, respectively) relative to corn oil-fed mice (2.0 mol/100 mol).
Fan YY Chapkin RS Ramos KS
Dietary lipid source alters murine macrophage/vascular smooth muscle cell interactions in vitro.
In: J Nutr (1996 Sep) 126(9):2083-8
This study was conducted to compare the impact of dietary lipids on the ability of macrophages to modulate vascular smooth muscle cell (SMC) DNA synthesis in vitro. C57BL/6 female mice were fed six different diets (6 mice/diet) containing 10% fat from corn oil (CO), borage oil (BO), primrose oil (PO), fish-corn oil mix (FC, 9:1, w/w), fish-borage oil mix (FB, 1:3, w/w), or fish-primrose oil mix (FP, 1:3, w/w) for 2 wk. Peritoneal macrophages were isolated from these mice, stimulated with zymosan or vehicle, and subsequently co-cultured with naive mouse aortic SMC in the presence of 3H-thymidine to measure SMC DNA synthesis. In this co-culture system, macrophages were seeded on 25-mm culture inserts (upper chamber) and SMC were seeded on 35-mm culture dishes (lower chamber). The two cell types were separated by a semipermeable membrane with a 30-kD cut-off. When quiescent SMC were co-cultured with macrophages, only the PO and FP diet groups had significantly (P < 0.05) lower SMC DNA synthesis compared with the control CO group whose diet contained no gamma- linolenic acid (GLA) or (n-3) polyunsaturated fatty acids (PUFA). In contrast, when cycling SMC were co-cultured with diet-modulated macrophages, all dietary groups except for those fed FC had significantly lower (P < 0.05) SMC DNA synthesis relative to the CO group. Although the level of GLA in PO and BO diets was different (11.5 and 22.3 g/100 g fatty acids, respectively), these treatments exerted comparable inhibitory effects on SMC DNA synthesis. The FP treatment consistently exhibited the lowest SMC DNA synthetic profile among the six dietary groups irrespective of SMC growth conditions. These data suggest that BO and PO alone or in combination with fish oil influence macrophage/smooth muscle cell interactions in a manner consistent with favorable modulation of the atherogenic process.
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