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Comparison of n-3 polyunsaturated fatty acids from vegetable oils, meat, and fish in raising platelet eicosapentaenoic acid levels in humans
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... For this reason, pregnant women must eat a diet containing adequate amounts of omega-3 and omega-6 fats for her own needs and also for those of the developing fetus. The DHA and arachidonic acid derived from essential fatty acids are especially vital, as they are building materials for the structure of nervous tissue of growing fetus, including the brain and retina in late pregnancy [21]. Breast milk contains 3-10 times more ALA than DHA, depending on the mother's diet [20]. ...
... For this reason, pregnant women must eat a diet containing adequate amounts of omega-3 and omega-6 fats for her own needs and also for those of the developing fetus. The DHA and arachidonic acid derived from essential fatty acids are especially vital, as they are building materials for the structure of nervous tissue of growing fetus, including the brain and retina in late pregnancy [21]. Breast milk contains 3-10 times more ALA than DHA, depending on the mother's diet [20]. ...
Flaxseed is one of the most important oilseed crops for industrial as well as food, feed, and fiber purposes. The seed provides oil rich in essential fatty acids, digestible proteins, and lignans. Being one of the richest sources of α-linolenic acid oil and lignans, flaxseed has considerable potential as a functional food. It delivers health benefits beyond their traditional nutrient content. Phytoestrogen of flaxseed is in focus for their benefits for a wide range of health conditions and may possess chemo-protective properties in animals and humans. This paper presents a review for the nutritional composition of flaxseed, its health benefits for disease prevention specially those relevant to cardiovascular system, diabetes, menopause, cancer, arthritis and dry eye.
... This process is quite inefficient. It has been shown that 15·4 g a-linolenic acid/d is required to cause an equivalent increase in platelet eicosapentaenoic acid levels as 70 mg eicosapentaenoic acid/d (Li et al. 1999). There is little information in relation to the conversion of a-linolenic acid into DHA, but it can be assumed that this is even less efficient. ...
Low n-3 polyunsaturated fatty acid (PUFA) status may be associated with neuro-degenerative disorders, in particular Alzheimer's disease, which has been associated with poor dietary fish or n-3 PUFA intake, and low docosahexaenoic acid (DHA) status. The present case-control study used an established biomarker of n-3 PUFA intake (serum cholesteryl ester-fatty acid composition) to determine n-3 PUFA status in patients with Alzheimer's disease, who were free-living in the community. All cases fulfilled the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Detailed neuropsychological testing and neuroimaging established the diagnosis in all cases. The subjects (119 females and twenty-nine males) aged 76.5 (SD 6.6) years had a clinical dementia rating (CDR) of 1 (SD 0.62) and a mini mental state examination (MMSE) score of 19.5 (SD 4.8). The control subjects (thirty-six females and nine males) aged 70 (SD 6.0) years were not cognitively impaired (defined as MMSE score <24): they had a mean MMSE score of 28.9 (SD 1.1). Serum cholesteryl ester-eicosapentaenoic acid and DHA levels were significantly lower (P<0.05 and P<0.001 respectively) in all MMSE score quartiles of patients with Alzheimer's disease compared with control values. Serum cholesteryl ester-DHA levels were progressively reduced with severity of clinical dementia. DHA levels did not differ in patients with Alzheimer's disease across age quartiles: all were consistently lower than in control subjects. Step-wise multiple regression analysis showed that cholesteryl ester-DHA and total saturated fatty acid levels were the important determinants of MMSE score and CDR. It remains to be determined whether low DHA status in Alzheimer's disease is a casual factor in the pathogenesis and progression of Alzheimer's disease.
Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33.0%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA + DHA in erythrocyte equivalents. Regions with high EPA + DHA blood levels (> 8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤ 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA + DHA and the very low to low range of blood EPA + DHA for most of the world may increase global risk for chronic disease.
Oils rich in α-Linolenic Acid (ALA) are gaining increased attention because of the anticipated health benefits related to the cardioprotective effects of the fatty acid. Flax and perilla seed oils are the richest sources of ALA, followed by the seed oils of camelina, hempseed, red and black currants, sea buckthorn, lingonberry, blueberry, cranberry, cloudberry, raspberry, and walnut. This chapter discusses the relevant literature on flaxseed oil and the limited data on perilla and camelina seed oils. Limited research is available on the extraction and processing of flaxseed oil and other ALA-rich oils. However, oil destined for the paints and coating industry is refined by processes similar to those used for commercial edible oils. In contrast, edible flaxseed oil is expeller-pressed at temperatures lower than traditional solvent-extraction processes. Mechanical pressing is the preferred method for producing edible flaxseed oil due to the healthful perception of the oil. The high content of ALA in the flax, perilla, and camelina seed oils has attracted the attention of the health industry. However, high ALA also renders these oils vulnerable to oxidation. Thus, one must take special measures during their processing, storage, and use.
Flaxseed or linseed has been used for food and industrial fiber since ancient times. The terms, "flaxseed" and "linseed" are often used interchangeably, although North Americans use "flaxseed" to describe flax when it is eaten by humans and "linseed" to describe flax when it is used for industrial purposes, such as linoleum flooring. In Europe, the term, "flaxseed" describes the varieties grown for making linen. Flaxseed contains lipid (40%), protein (21%), dietary fiber (28%), ash (4%), and other soluble components such as sugars, phenolic acids, and lignans (ca 6%). The oil content in flaxseed represents between 29 and 45% of the seed depending on the cultivar, location, and agroclimatic conditions. This chapter focuses on the health benefits of flaxseed. The main nutritional advantage of flaxseed oil is related to the high level of ALA in the oil (50%-60%). About 20% of the flaxseed is a mucilagenous hull. Flaxseed mucilage is comprised of gum-like polysaccharides containing acidic (54.5% rhamnose and 23.4% galactose) and neutral arabinoxylan (62.8% xylose). Flaxseed contains about 1%-2% total phenolic compounds, of which the lignan secoisolariciresinol diglucoside (SDG) is a major component. SDG is present in the seed as a mixture of oligomers with hydroxymethylglutaric acid having an average molecular weight of 4000 Da.
Tissue arachidonic acid (AA) pools originate from the diet, and from hepatic and extrahepatic desaturation-elongation of dietary linoleic acid (LA). This review summarizes the roles of absorption, transport, and formation of AA in the buildup of tissue AA pools. In humans who ingest 0.2–0.3 g of AA and 10–20 g of LA per day on a Western diet, the formation of AA from LA exceeds the dietary supply of AA. A number of factors favor the partitioning of AA to tissue phospholipids rather than adipose tissue and plasma triglycerides. The characteristics of AA transport with lipoproteins are discussed with focus on the role of lipoprotein lipase, lecithin:cholesterol acyltransferase, hepatic lipase, and the scavenger receptor BI and LDL receptors in tissue uptake of AA. Liver-derived 2-acyl-lysophosphatidylcholine and plasma free AA are two important sources of AA for extrahepatic tissues which exhibit a low rate of uptake of lipoprotein AA. Desaturation-elongation of LA to produce AA occurs both in liver and in extrahepatic tissues, plasma free LA being an important substrate particularly during fasting.
The AA preference of the reacylation and transacylation reactions is crucial for the selective retention of AA in phospholipids.
Although epidemiologic studies suggest a role for alpha-linolenic acid (ALA) in the prevention of coronary heart disease and certain types of cancer, the findings of clinical studies suggest that ALA is inferior biologically to the n-3 long-chain fatty acids because its bioconversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is limited in humans and because the magnitude of its biologic effects is smaller than that of EPA and DHA. This paper reviews several methodologic issues that may confound the findings of clinical studies and complicate our interpretations of them: the ALA and EPA + DHA dietary enrichment levels; the choice of tissue; the choice of lipid species; and the method of reporting fatty acid composition. Although the ALA enrichment levels used in most clinical studies can be achieved by consuming ground flaxseed, flaxseed oil, canola oil and other ALA-rich plants as part of a typical dietary pattern, the EPA + DHA enrichment levels are not practical and can only be obtained from fish oil supplements. The lack of consistency in the choice of lipids species and the reporting of data makes it difficult to compare outcomes across studies. The choice of tissue (blood) for analysis is a limitation that probably cannot be overcome. The use of practical ALA and EPA + DHA dietary enrichment levels and some standardization of clinical study design would allow for greater comparisons of outcomes across studies and ensure a more realistic analysis of how individual n-3 fatty acids differ in their biologic effects in humans.
An important question for mammalian nutrition is the relative efficiency of C18 versus C20 essential fatty acids (EFAs) for supporting the tissue composition of n-3 and n-6 pathway end products. One specific question is whether C22 EFAs are made available to tissues more effectively by dietary α-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) or by dietary eicosapentaenoic acid (20:5n-3) and dihomo-γ-linolenic acid (20:3n-6). To address this question in a direct manner, four stable isotope compounds were given simultaneously in a novel paradigm. A single oral dose of a mixture of ²H5-18:3n-3, ¹³C-U-20:5n-3, ¹³C-U-18:2n-6, and ²H5-20:3n-6 was administered to rats given a defined diet. There was a preferential in vivo conversion of arachidonic acid (20:4n-6) to docosatetraenoic acid (22:4n-6) and of 22:4n-6 to n-6 docosapentaenoic acid (22:5n-6) when the substrates originated from the C18 precursors. However, when the end products docosahexaenoic acid (22:6n-3) or 22:5n-6 were expressed as the total amount in the plasma compartment divided by the dosage, this parameter was 11-fold greater for 20:5n-3 than for 18:3n-3 and 14-fold greater for 20:3n-6 than for 18:2n-6.
Thus, on a per dosage basis, the total amounts of n-3 and n-6 end products accreted in plasma were considerably greater for C20 EFA precursors relative to C18.
Enteropathy defines abnormalities of the small intestinal mucosa of various etiologies in which nutrition has a causal or a therapeutic role. Breast milk is the gold-standard feeding during infancy for optimal nutrition in health and the majority of diseases. Therapeutic formulae have decreased the need for enteral or parenteral support. Gastrointestinal infections are worldwide the most frequent cause of enteropathy by increasing mucosal permeability, local expression of costimulatory molecules allowing antigen penetration in the mucosa, and T-cell activation leading sometimes to disruption of oral tolerance. Concomitant malnutrition impairs not only the immunologic response but also the recovery of damaged mucosa with secondary intestinal and pancreatic enzymatic reductions. Optimal nutritional rehabilitation is the cornerstone of the management of persisting diarrhea. Celiac disease and cow's milk protein allergy are examples of chronic enteropathy. Multiple food allergies, even during breast-feeding, are increasingly reported due to an impaired development of oral tolerance. The dietary approach to allergic disease is currently evolving from passive allergen avoidance to active modulation of the immune system to (re)establish tolerance. The gastrointestinal flora provides maturational signals for the lymphoid tissue, improves balance of inflammatory cytokines, reduces bacterial invasiveness and dietary antigen load, and normalizes gut permeability. The clinical effects of nucleotides and zinc merit further clinical evaluation. Major attention has recently focused on the immune effects of dietary lipids in terms of possible prevention of allergic sensitization by downregulating inflammatory response and protecting the epithelial barrier and host-microbe interactions modifying the adherence of microbes to the mucosa.
N-3 essential fatty acid deficiency affects a number of biological and physiological processes. In this study, we investigated the effect of n-3 essential fatty acid status on two key pineal biochemical functions, melatonin production and lipoxygenation, using pineal glands from rats given an n-3-adequate or n-3-deficient diet. The pineal total lipid profile and phospholipid molecular species distribution altered by n-3 deficiency were evaluated in parallel. In pineal glands from n-3-deficient rats, an 87% reduction of 22:6n-3 (docosahexaenoic acid) was observed, and this decrease was accompanied by increases in 22:4n-6 (docosatetraenoic acid, 3-fold), 22:5n-6 (docosapentaenoic acid, 12-fold), and 20:4n-6 (arachidonic acid, 48%). The significant decrease of 22:6n-3 containing species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) was also evident. These decreases in 22:6n-3 containing PL species were compensated by substantial accumulations of 22:4n-6 or 22:5n-6 and slight increases in 20:4n-6 containing PL species in PC and PE. In PS, however, the accumulation of n-6 species was not adequate to compensate for the loss of 22:6n-3 species. N-3 deficiency significantly reduced non-esterified 20:4n-6 and 22:6n-3 levels in pineals (25% and 65%, respectively). Concomitantly, the endogenous 12-HETE level decreased by 35% in deficient pineals. In contrast, n-3 deficiency led to a more than 60% increase in the daytime pineal melatonin level. In conclusion, n-3 fatty acid deficiency not only has profound effects on pineal lipid profiles but also on pineal biochemical activities. These results suggest that n-3 fatty acids may play a critical role in regulating pineal function.
Recent evidence indicates that arachidonic acid (AA) and its metabolites play a fast messenger role in synaptic modulation in the CNS. 12-Lipoxygenase derivatives are released by Aplysia sensory neurons in response to inhibitory transmitters and directly target a class of K+ channels, increasing the probability of their opening. In this way, hyperpolarization is achieved and action potentials are shortened, leading to synaptic depression. Other types of K+ channels in vertebrate excitable cells have been found to be sensitive to arachidonic acid, lipoxygenase products, and polyunsaturated fatty acids (PUFA). In the mammalian CNS, arachidonic acid is released upon stimulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors. We found that arachidonic acid inhibits the rate of glutamate uptake in both neuronal synaptic terminals and astrocytes. Neither biotransformation nor membrane incorporation are required for arachidonic acid to exert this effect. The phenomenon, which is rapid and evident at low microM concentrations of AA, may involve a direct interaction with the glutamate transporter or its lipidic microenvironment on the outer side of the cell membrane. Polyunsaturated fatty acids mimic arachidonate with a rank of potency parallel to the degree of unsaturation. Since the effect of glutamate on the synapses is terminated by diffusion and uptake, a slowing of the termination process may potentiate glutamate synaptic efficacy. However, excessive extracellular accumulation of glutamate may lead to neurotoxicity.
The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The activation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.
Foods which increase tissue arachidonic acid levels have been proposed to increase thrombosis tendency, presumably through increased platelet aggregation. This study examined the effect of doubling the dietary arachidonic acid (20:4n-6) using meat- or fish-based diets on the systemic production of prostacyclin (PGI2) and thromboxane (TXA2) in 29 healthy, nonsmoking adults. There were three, 3-wk low-fat dietary periods (< 15% energy as fat) in which subjects consumed a vegetarian diet for 1 wk followed by 2 wk on diets containing meat or fish as sources of 20:4n-6. Between each diet period, there was a 3-wk washout period, during which subjects returned to their normal diets. The level of 20:4n-6 consumed during the last 2 wk of each study was approximately double the usual intake (mean 140 mg/d), while the mean eicosapentaenoic acid (20:5n-3) content of the diets varied from 1 mg/d on the white meat diet to 70 mg/d on the red meat diet and to 847 mg/d on the fish diet. The serum phospholipid (PL) 20:4n-6/20:5n-3 ratios were 11:1 on the vegetarian diet, 15:1 on the white meat diet, 8:1 on the red meat diet, and 2:1 on the fish diet (P < 0.001). Neither white nor red meat diets affected platelet 20:4n-6 levels, platelet aggregation, ex vivo platelet TXB2 production, or the systemic PGI2 or TXA2 production as measured by gas chromatography-mass spectrometry analysis of the excretion levels of the principal urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and 11-dehydro-TXB2 (TXA2-M), respectively. The fish diet decreased the 20:4n-6/20:5n-3 ratio in platelet PL from the baseline level of 45:1 to 13:1 (P < 0.001), had no effects on platelet aggregation, but significantly decreased platelet TXB2 production (collagen-stimulated) and TXA2-M production, while PGI2-M levels were unaltered. These results indicate that short-term diets which double the usual 20:4n-6 intake using white meat (175-330 g/d) or red meat (275-530 g/d) are not associated with an increased TXA2 production, but this does not rule out the adverse effects of 20:4n-6 at higher levels in the diet, or for more prolonged periods. Short-term diets containing fish (100-200 g/d with 90-210 mg/d 20:4n-6 and approximately 650-1000 mg/d 20:5n-3) led to significant increases in platelet 20:5n-3 levels and a decrease in the ex vivo and systemic TXA2 production.
In this study, we demonstrate that astroglial 5-HT2A receptors are linked to the mobilization of polyunsaturated fatty acids (PUFA). Stimulation of C6 glioma cells, prelabeled with [3H]arachidonate (AA, 20:4n6) and [14C]docosahexaenoate (DHA, 22:6n3), with serotonin and the 5-HT(2A/2C) receptor agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) resulted in the mobilization of both [3H] and [14C] into the supernatant of the cell monolayers. The increased radioactivity in the supernatant was mainly associated with free fatty acids. Experiments using inhibitors of phosphoinositide-specific phospholipase C and PLA2, inhibited the DOI-stimulated mobilization of AA and DHA, suggesting the involvement of both phospholipases. Ketanserin (1 microM), a 5-HT(2A/2C) receptor antagonist, and MDL 100,907 (R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-pi peridine-methanol) (1 microM), a highly selective antagonist for 5-HT2A receptors, significantly decreased the DOI-stimulated release of AA and DHA. These results indicate that the 5-HT2A receptor is coupled to the mobilization of PUFA. The release of AA and DHA in response to serotonin may represent a mechanism through which astroglia provide these polyunsaturated fatty acids to neurons.
Docosahexaenoic acid (22:6n-3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n-3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n-3-deficient diet showed a dramatic reduction of 22:6n-3 content (1.7 +/- 0.1%) when compared with control animals (15.0 +/- 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n-6) content, which replaced the 22:6n-3 phospholipids with 22:5n-6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n-3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1-stearoyl-2-docosapentanoyl (18:0/22:5n-6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n-3-deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n-3-supplemented media (10-40 microM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n-3 may be a modulator of PS synthesis.
Stimulation of neuronal tissues with neurotransmitters results in the release of the polyunsaturated fatty acids 20:4n6 and 22:6n3. Astroglial cells hydrolyze 20:4n6 and 22:6n3 equally well under both stimulated and basal conditions. Despite the high abundance of 22:6n3 in neuronal membranes, 20:4n6 is preferentially hydrolyzed from neuronal cells. These results suggest that 22:6n3 may be of more physiological importance in neuronal membranes as a membrane component rather than as a released free fatty acid while in astroglia, release of 22:6n3 may also be a significant step involved in receptor-stimulated signaling processes. Oxygenation of these polyunsaturated fatty acids occurs in the brain. However, in contrast to the prevailing belief, lipid peroxidation rather than lipoxygenation is primarily responsible for their formation. In rodent brains, any significant lipoxygenation appears to occur only in the pineal. The production of hydroxylated polyunsaturated fatty acids in pineal may play a role in the pineal function especially in relation to melatonin synthesis.
The Effect of Short-Term Diets Rich in Fish
- N J Mann
- Aj Sinclair
- M Pille
- L Johnson
- G Warrick
- E Reder
- R Lorenz
Mann, N.J., Sinclair, AJ., Pille, M., Johnson, L., Warrick, G., Reder, E., and Lorenz, R. (1997) The Effect of Short-Term Diets Rich in Fish, Red Meat, or White Meat on Thromboxane and Prostacyclin Synthesis in Humans, Lipids 32, 635-644.
The Influence of Diet on Atherosclerotic and Thrombotic Risk Factors in Healthy Men
- D Li
- D. Li