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Can adults adequately convert ??-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)?

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Abstract

A diet including 2-3 portions of fatty fish per week, which corresponds to the intake of 1.25 g EPA (20:5n-3) + DHA (22:6n-3) per day, has been officially recommended on the basis of epidemiological findings showing a beneficial role of these n-3 long-chain PUFA in the prevention of cardiovascular and inflammatory diseases. The parent fatty acid ALA (18:3n-3), found in vegetable oils such as flaxseed or rapeseed oil, is used by the human organism partly as a source of energy, partly as a precursor of the metabolites, but the degree of conversion appears to be unreliable and restricted. More specifically, most studies in humans have shown that whereas a certain, though restricted, conversion of high doses of ALA to EPA occurs, conversion to DHA is severely restricted. The use of ALA labelled with radioisotopes suggested that with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%. It is thus reasonable to observe an n-6/n-3 PUFA ratio not exceeding 4-6. Restricted conversion to DHA may be critical since evidence has been increasing that this long-chain metabolite has an autonomous function, e.g. in the brain, retina and spermatozoa where it is the most prominent fatty acid. In neonates deficiency is associated with visual impairment, abnormalities in the electroretinogram and delayed cognitive development. In adults the potential role of DHA in neurological function still needs to be investigated in depth. Regarding cardiovascular risk factors DHA has been shown to reduce triglyceride concentrations. These findings indicate that future attention will have to focus on the adequate provision of DHA which can reliably be achieved only with the supply of the preformed long-chain metabolite.
... Additionally, the body has enzymes called delta-desaturases and elongases that convert short-chain omega-3 fatty acids-such as ALA, which is typically found in plants (e.g., chia seeds, flax seeds, and walnuts)-to long-chain fatty acids (e.g., DHA and EPA) [73]. The human body converts short-chain omega-3 fatty acids from plant-based sources to long-chain fatty acids with an average efficiency of approximately 5% [74]. ...
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The intake of linoleic acid (LA) has increased dramatically in the standard American diet. LA is generally promoted as supporting human health, but there exists controversy regarding whether the amount of LA currently consumed in the standard American diet supports human health. The goal of this narrative review is to explore the mechanisms that underlie the hypothesis that excessive LA intake may harm human health. While LA is considered to be an essential fatty acid and support health when consumed in modest amounts, an excessive intake of LA leads to the formation of oxidized linoleic acid metabolites (OXLAMs), impairments in mitochondrial function through suboptimal cardiolipin composition, and likely contributes to many chronic diseases that became an epidemic in the 20th century, and whose prevalence continues to increase. The standard American diet comprises 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids, with the majority of omega-6 intake coming from LA. As LA consumption increases, the potential for OXLAM formation also increases. OXLAMs have been associated with various illnesses, including cardiovascular disease, cancer, and Alzheimer's disease, among others. Lowering dietary LA intake can help reduce the production and accumulation of OXLAMs implicated in chronic diseases. While there are other problematic components in the standard American diet, the half-life of LA is approximately two years, which means the damage can be far more persistent than other dietary factors, and the impact of reducing excessive LA intake takes time. Therefore, additional research-evaluating approaches to reduce OXLAM formation and cardiolipin derangements following LA consumption are warranted.
... The parent fatty acid ALA (18:3 n-3), found in vegetable oils such as linseed or rapeseed oil, is used by the human body partly as an energy source and partly as a precursor of metabolites. However, the degree of endogenous conversion appears to be unreliable and limited [54]. Most human studies have shown that the conversion of high doses of ALA to EPA occurs, but to a limited extent, whereas the conversion to DHA is severely limited. ...
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Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology.
... Studies have shown that testicular function appears to be positively correlated with omega-3 PUFAs intake and negatively correlated with omega-6 PUFAs intake (90). Gerster found that the conversion of ALA to EPA and DHA was reduced by 40-50% when the ratio of omega-6/omega-3 PUFAs in the diet was elevated (91). Due to lack of research data, the appropriate ratio of omega-6/omega-3 PUFAs requires further research. ...
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Fatty acids (FAs) are classified into different types according to the degree of hydrocarbon chain saturation, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and omega-6 polyunsaturated fatty acids (omega-6 PUFAs), which play an important role in maintaining semen quality. This review focuses on the regulation of FAs in semen, diet and extender on semen quality, and expounds its effects on sperm motility, plasma membrane integrity, DNA integrity, hormone content, and antioxidant capacity. It can be concluded that there are species differences in the FAs profile and requirements in sperm, and their ability to regulate semen quality is also affected by the addition methods or dosages. Future research directions should focus on analyzing the FAs profiles of different species or different periods of the same species and exploring suitable addition methods, doses and mechanism of regulating semen quality.
... This is not altogether unsurprising, as ALA is a known precursor for longer chain PUFAs, is also utilised for β-oxidation, and is, therefore, not commonly stored [44,45]. However, the metabolism of ALA to EPA or DHA is considered to be poor [46]. This can be mediated by the amount consumed, with Goyens et al. [47] reporting that a low intake of LA increased ALA metabolism to EPA, while a high intake of ALA increased DHA production. ...
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Higher dietary intakes of Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have been linked to lower rates of preterm birth and preeclampsia. The aim of this analysis was to describe dietary intake and fractions of red blood cell (RBC) membrane LC-PUFAs during pregnancy in a cohort of Indigenous Australian women. Maternal dietary intake was assessed using two validated dietary assessment tools and quantified using the AUSNUT (Australian Food and Nutrient) 2011–2013 database. Analysis from a 3-month food frequency questionnaire indicated that 83% of this cohort met national n-3 LC-PUFA recommendations, with 59% meeting alpha-linolenic acid (ALA) recommendations. No nutritional supplements used by the women contained n-3 LC-PUFAs. Over 90% of women had no detectable level of ALA in their RBC membranes, and the median Omega-3 Index was 5.5%. This analysis appears to illustrate a decline in concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) across gestation in women who had preterm birth. However, there was no visible trend in LC-PUFA fractions in women who experienced hypertension during pregnancy. Further research is needed to better understand the link between dietary intake of n-3 LC-PUFA-rich foods and the role of fatty acids in preterm birth and preeclampsia.
... Moreover, the presence of higher levels of these fatty acids elevated the proportion of n-3 PUFA and n-6 PUFA in colostrum and n-3 PUFA in milk. Higher ratio of n-6:n-3 may limit the production of anti-inflammatory eicosanoids derived from eicosapentaenoic acid [37]. Maternal diets with varying n-6:n-3 PUFA ratios affected the antioxidant status, immune cell eicosanoid responses, immunoglobulins, fatty acids composition, and growth performance [38,39]. ...
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... Essential fatty acids are the ones that cannot be synthesized by the body. The long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be synthesized from LNA (Spector & Kim, 2019), but due to low conversion efficiency, they must be supplied from foods rich in EPA and DHA (Gerster, 1998). ...
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The goal of this study was to determine the essential fatty acids of the total lipids of the fillet, head and orbital cavity tissue from farmed tambaqui (Colossoma macropomum) fish from a Brazilian Amazon area. The tambaqui were acquired from different fish farms in the Roraima state, located at Western Brazilian Amazon. The meat, the head and the fatty tissue from orbital cavity were dissected for lipid extraction and analysis of fatty acids by gas chromatography. The fatty acids were quantified in mg g-1 of total lipids using C23:0 as an internal standard. The nutritional quality of the lipids was determined by using the atherogenicity and thrombogenicity indices, and also by the ratio between hypocholesterolemic / hypercholesterolemic fatty acids. The orbital cavity tissue had the higher concentration amount of linoleic and α-linolenic acid, whereas the fillet had higher docosahexaenoic acid (DHA). The eicosapentaenoic acid (EPA) concentration was: 1.28, 0.97, 1.71 mg g-1 of total lipids, in the filet, in head, and in orbital cavity tissue, respectively. All essential fatty acids were detected in the three parts analyzed. The nutritional quality of the total lipids from the head and from the orbital cavity tissue was similar to the fillet.
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It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals Follow-up Study. During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was 1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease.