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The Journal of Nutrition Mar 2021Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins.
OBJECTIVES
Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined.
METHODS
Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed.
RESULTS
ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA.
CONCLUSIONS
DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588.
Topics: Adult; Cross-Over Studies; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Male; Oxylipins; Sex Factors; Time Factors; Young Adult; alpha-Linolenic Acid
PubMed: 33097936
DOI: 10.1093/jn/nxaa294 -
International Journal of Molecular... Jul 2023A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the...
A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the influence of a low ratio of LA/ALA intake on lipid metabolism and endogenous fatty acid distribution in obese patients remains elusive. In this investigation, 8-week-old C57BL/6J mice were randomly assigned to four groups: low-fat diet (LFD) as a control, high-fat diet (HFD), high-fat diet with a low LA/ALA ratio (HFD+H3L6), and high-fat diet with a high LA/ALA ratio (HFD+L3H6) for 16 weeks. Our results show that the HFD+H3L6 diet significantly decreased the liver index of HFD mice by 3.51%, as well as the levels of triacylglycerols (TGs) and low-density lipoprotein cholesterol (LDL-C) by 15.67% and 10.02%, respectively. Moreover, the HFD+H3L6 diet reduced the pro-inflammatory cytokines interleukin-6 (IL-6) level and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and elevated the level of superoxide dismutase (SOD) in the liver. The HFD+H3L6 diet also resulted in the downregulation of fatty acid synthetase () and sterol regulatory element binding proteins-1c () expression and the upregulation of peroxisome proliferator-activated receptor-α () and acyl-CoA oxidase 1 () gene expression in the liver. The low LA/ALA ratio diet led to a notable increase in the levels of ALA and its downstream derivative docosahexaenoic acid (DHA) in the erythrocyte, liver, perienteric fat, epididymal fat, perirenal fat, spleen, brain, heart, and gastrocnemius, with a strong positive correlation. Conversely, the accumulation of LA in abdominal fat was more prominent, and a high LA/ALA ratio diet exacerbated the deposition effect of LA. In conclusion, the low LA/ALA ratio not only regulated endogenous fatty acid levels but also upregulated and and downregulated and gene expression levels, thus maintaining lipid homeostasis. Optimizing dietary fat intake is important in studying lipid nutrition. These research findings emphasize the significance of understanding and optimizing dietary fat intake.
Topics: Mice; Animals; Fatty Acids; Lipid Metabolism; alpha-Linolenic Acid; Linoleic Acid; Mice, Obese; Peroxisome Proliferator-Activated Receptors; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Liver; Diet, High-Fat; Obesity
PubMed: 37569494
DOI: 10.3390/ijms241512117 -
Nutrients Feb 2021Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether...
Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to equilibrate the n-6/n-3 polyunsaturated fatty acids (PUFA) ratio) might prevent obesity disorders, particularly by modulating the mucosa-associated microbiota. Wistar rats received a low fat diet (LFD; control) or high fat diet (HFD) for 16 weeks to induce obesity. Then, animals in the HFD group were divided in four groups: HFD (control), HFD + linseed oil (LO), HFD + HIIT, HFD + HIIT + LO. In the HIIT groups, rats ran on a treadmill, 4 days.week. Erythrocyte n-3 PUFA content, body composition, inflammation, and intestinal mucosa-associated microbiota composition were assessed after 12 weeks. LO supplementation enhanced α-linolenic acid (ALA) to docosahexaenoic acid (DHA) conversion in erythrocytes, and HIIT potentiated this conversion. Compared with HFD, HIIT limited weight gain, fat mass accumulation, and adipocyte size, whereas LO reduced systemic inflammation. HIIT had the main effect on gut microbiota β-diversity, but the HIIT + LO association significantly increased relative abundance. In our conditions, HIIT had a major effect on body fat mass, whereas HIIT + LO improved ALA conversion to DHA and increased the abundance of bacteria in the microbiota.
Topics: Adipocytes; Animals; Blood Glucose; Body Composition; Clostridiales; Docosahexaenoic Acids; Erythrocytes; Fatty Acids; Fatty Acids, Volatile; Feces; Gastrointestinal Microbiome; Glucose Tolerance Test; High-Intensity Interval Training; Intestinal Mucosa; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Wistar; alpha-Linolenic Acid
PubMed: 33673609
DOI: 10.3390/nu13030788 -
Journal of the International Society of... Nov 2020Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain...
BACKGROUND
Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain n-3 PUFAs, and it has pleiotropic effects, such as functioning as an energy substrate during long-term training when carbohydrate reserves are depleted. The purpose of this investigation was to study the link between the essential dietary and plasma ALA and aerobic performance, which is estimated via maximal fat oxidation (MFO), among skiers.
METHODS
Twenty-four highly trained male athletes from the Russian cross-country skiing team participated in the study. ALA intake was determined by an original program used to assess the actual amount and frequency of fat consumption. The plasma level of ALA was determined using gas-liquid chromatography. The skiers' aerobic performance was estimated via MFO and determined by indirect calorimetry using the system "Oxycon Pro".
RESULTS
The consumption of ALA in the diet in half of the skiers was below the recommended level at 0.5 ± 0.2 g/day. The deficiency of plasma ALA levels was on average 0.2 ± 0.1 Mol% for almost all participants. The consumption of ALA in the diet and its level in plasma were associated with MFO (r = 0.507, p = 0.011; r = 0.460, p = 0.023). Levels of ALA in plasma (p = 0.0523) and the consumption of ALA in the diet (p = 0.0039) were associated with high aerobic performance.
CONCLUSIONS
ALA in the diet of the athletes may be used as nutritional support to increase MFO and aerobic performance.
Topics: Adult; Athletic Performance; Calorimetry, Indirect; Dietary Fats; Exercise; Exercise Test; Heart Rate; Humans; Lipids; Male; Oxidation-Reduction; Recommended Dietary Allowances; Russia; Skiing; Sports Nutritional Physiological Phenomena; Young Adult; alpha-Linolenic Acid
PubMed: 33198755
DOI: 10.1186/s12970-020-00385-2 -
European Heart Journal Oct 2011Epidemiological studies report an inverse association between plant-derived dietary α-linolenic acid (ALA) and cardiovascular events. However, little is known about the...
AIMS
Epidemiological studies report an inverse association between plant-derived dietary α-linolenic acid (ALA) and cardiovascular events. However, little is known about the mechanism of this protection. We assessed the cellular and molecular mechanisms of dietary ALA (flaxseed) on atherosclerosis in a mouse model.
METHODS AND RESULTS
Eight-week-old male apolipoprotein E knockout (ApoE(-/-)) mice were fed a 0.21 % (w/w) cholesterol diet for 16 weeks containing either a high ALA [7.3 % (w/w); n = 10] or low ALA content [0.03 % (w/w); n = 10]. Bioavailability, chain elongation, and fatty acid metabolism were measured by gas chromatography of tissue lysates and urine. Plaques were assessed using immunohistochemistry. T cell proliferation was investigated in primary murine CD3-positive lymphocytes. T cell differentiation and activation was assessed by expression analyses of interferon-γ, interleukin-4, and tumour necrosis factor α (TNFα) using quantitative PCR and ELISA. Dietary ALA increased aortic tissue levels of ALA as well as of the n-3 long chain fatty acids (LC n-3 FA) eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The high ALA diet reduced plaque area by 50% and decreased plaque T cell content as well as expression of vascular cell adhesion molecule-1 and TNFα. Both dietary ALA and direct ALA exposure restricted T cell proliferation, differentiation, and inflammatory activity. Dietary ALA shifted prostaglandin and isoprostane formation towards 3-series compounds, potentially contributing to the atheroprotective effects of ALA.
CONCLUSION
Dietary ALA diminishes experimental atherogenesis and restricts T cell-driven inflammation, thus providing the proof-of-principle that plant-derived ALA may provide a valuable alternative to marine LC n-3 FA.
Topics: Animals; Atherosclerosis; Cell Differentiation; Cell Proliferation; Lymphocyte Activation; Male; Mice; Mice, Knockout; Plaque, Atherosclerotic; T-Lymphocytes; alpha-Linolenic Acid
PubMed: 21285075
DOI: 10.1093/eurheartj/ehq501 -
Molecular Nutrition & Food Research Feb 2022Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1...
SCOPE
Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L-cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP-1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP-1 release which results in a decrease food intake.
METHODS AND RESULTS
α-Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP-1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP-1 secretion. Single-dose orally given αLA loaded mesoporous particles increased plasma active GLP-1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice.
CONCLUSIONS
αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.
Topics: Animals; Colon; Eating; Glucagon-Like Peptide 1; Mice; Nutrients; alpha-Linolenic Acid
PubMed: 34882959
DOI: 10.1002/mnfr.202100978 -
Clinics (Sao Paulo, Brazil) Oct 2018Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and...
OBJECTIVES
Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and molecular changes induced by the omega-3 fatty acid α-linolenic acid (ALA), which is found in linseed oil, are not fully understood. In this study, we showed a correlation between ALA and insulin resistance, inflammation and endoplasmic reticulum stress (ERS).
METHODS
We studied 40 male mice (C57/BL6) divided into 4 groups: a control (C) group, a control + omega-3/ALA (CA) group, a high-fat diet (HFD) (H) group and a high-fat diet + omega-3/ALA (HA) group. For 8 weeks, the animals in the H and HA groups were fed a high-fat (60%) diet, while the animals in the C and CA groups received regular chow. The diets of the CA and HA groups were supplemented with 10% lyophilized ALA.
RESULTS
ALA supplementation improved glucose tolerance and reduced insulin resistance, as measured by intraperitoneal glucose tolerance tests and the homeostasis model assessment for insulin resistance, respectively. In addition, ALA reduced hepatic steatosis and modified the standard fat concentration in the liver of animals fed an HFD. Dietary ALA supplementation reduced the serum levels of interleukin 6 (IL-6), interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), increased the expression of important chaperones such as binding immunoglobulin protein (BIP) and heat shock protein 70 (HSP70) and reduced the expression of C/EBP-homologous protein (CHOP) and X-box binding protein 1 (XBP1) in hepatic tissues, suggesting an ERS adaptation in response to ALA supplementation.
CONCLUSIONS
Dietary ALA supplementation is effective in preventing hepatic steatosis; is associated with a reduction in insulin resistance, inflammation and ERS; and represents an alternative for improving liver function and obtaining metabolic benefits.
Topics: Animals; Diet, High-Fat; Dietary Supplements; Endoplasmic Reticulum Stress; Fatty Acids, Omega-3; Fatty Liver; Glucose Tolerance Test; Inflammation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; alpha-Linolenic Acid
PubMed: 30379219
DOI: 10.6061/clinics/2018/e150 -
Journal of Dairy Science Sep 2022Ruminal biohydrogenation (BH) of unsaturated fatty acids (FA) reduces absorption of essential FA and can result in formation of bioactive FA that cause milk fat...
Ruminal biohydrogenation (BH) of unsaturated fatty acids (FA) reduces absorption of essential FA and can result in formation of bioactive FA that cause milk fat depression. Rates of biohydrogenation of unsaturated FA are commonly observed using in vitro systems and are not well described in vivo. Seven ruminally cannulated cows were enrolled in a 3 × 3 Latin square design study to quantify biohydrogenation of 18:1n-9, 18:2n-6, and 18:3n-3 using a recently developed in vivo BH assay. All cows were fed a common high corn silage basal diet. Biohydrogenation was quantified using a perturbation model that consisted of a bolus dose of 200 g of an oil enriched in each unsaturated FA (oleic acid, OA = 87% 18:1n-9 sunflower oil; linoleic acid, LA = 70% 18:2n-6 safflower oil; and α-linolenic acid, ALA = 54% 18:3n-3 flaxseed oil) and 12 g of 17:0 as a marker of rumen outflow. Rumen contents were sampled before and after the bolus and enrichment of the bolused FA modeled. Using first-order kinetics to model FA disappearance, the fractional rates of disappearance of 18:1n-9 was 0.597 per hour, 18:2n-6 was 0.618 per hour, and 18:3n-3 was 0.834 per hour, similar to rates previously reported with this approach. Rumen turnover of 17:0 was 0.123 per hour, 0.065 per hour, and 0.106 per hour during the OA, LA, and ALA treatments, respectively. The extents of BH were calculated to be 82.8, 90.4, and 88.6% for 18:1n-9, 18:2n-6, and 18:3n-3, respectively. Finally, compartmental modeling was used to quantify the amount of each unsaturated FA metabolized through trans-10 and trans-11 BH pathways. The recently developed in vivo BH assay was able to predict rates of BH and provide insight into rumen metabolism of individual FA and may be useful to future investigations.
Topics: Animals; Cattle; Diet; Fatty Acids; Fatty Acids, Unsaturated; Female; Hydrogenation; Lactation; Milk; Rumen; Silage; alpha-Linolenic Acid
PubMed: 35931484
DOI: 10.3168/jds.2022-21831 -
The American Journal of Clinical... May 2009alpha-Linolenic acid (ALA; 18:3n-3) has been associated inconsistently with an increased risk of prostate cancer. Additional studies have become available since the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
alpha-Linolenic acid (ALA; 18:3n-3) has been associated inconsistently with an increased risk of prostate cancer. Additional studies have become available since the publication of 2 previous meta-analyses.
OBJECTIVE
The objective was to review the published data on the relation between ALA and prostate cancer.
DESIGN
We conducted a systematic review to identify studies that included data on ALA and risk of prostate cancer. Data were pooled from studies that compared the highest ALA quantile with the lowest ALA quantile, and risk estimates were combined by using a random-effects model.
RESULTS
The relation between ALA and prostate cancer is inconsistent across studies. We pooled data from 8 case-control and 8 prospective studies. The summary estimate revealed that high ALA dietary intakes or tissue concentrations are weakly associated with prostate cancer risk (relative risk [RR]: 1.20; 95% CI: 1.01, 1.43). When examined by study type (ie, retrospective compared with prospective or dietary ALA compared with tissue concentration) or by decade of publication, only the 6 studies examining blood or tissue ALA concentrations revealed a statistically significant association. With the exception of these studies, there was significant heterogeneity and evidence of publication bias. After adjustment for publication bias, there was no association between ALA and prostate cancer (RR: 0.96; 95% CI: 0.79, 1.17).
CONCLUSIONS
Studies examining the relation between ALA and prostate cancer have produced inconsistent findings. High ALA intakes or high blood and adipose tissue concentrations of ALA may be associated with a small increased risk of prostate cancer. However, these conclusions are qualified because of the heterogeneity across studies and the likelihood of publication bias.
Topics: Adipose Tissue; Case-Control Studies; Humans; Male; Odds Ratio; Prospective Studies; Prostatic Neoplasms; Reproducibility of Results; Risk Factors; alpha-Linolenic Acid
PubMed: 19321563
DOI: 10.3945/ajcn.2009.26736E -
European Journal of Nutrition Jun 2022The aim was to investigate the cross-sectional association of dietary omega-3 polyunsaturated fatty acids PUFA (alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA),...
PURPOSE
The aim was to investigate the cross-sectional association of dietary omega-3 polyunsaturated fatty acids PUFA (alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)) intake with multiple physical functions, muscle mass and fat mass in older women.
METHOD
Study subjects were 554 women from the Osteoporosis Risk Factor and Prevention Fracture Prevention Study, with dietary intake assessed with 3-day food record. Body composition was measured by dual-energy X-ray absorptiometry. Physical function measures included walking speed 10 m, chair rises, one leg stance, knee extension, handgrip strength and squat. Short physical performance battery (SPPB) score was defined based on the European working group on sarcopenia criteria.
RESULTS
The multivariable adjusted models showed statistically significant associations for dietary ALA with higher SPPB (β = 0.118, P = 0.024), knee extension force at baseline (β = 0.075, P = 0.037) and lower fat mass (β = - 0.081, P = 0.034), as well as longer one-leg stance (β = 0.119, P = 0.010), higher walking speed (β = 0.113, P = 0.047), and ability to squat to the ground (β = 0.110, P = 0.027) at baseline. Total dietary omega-3 PUFA was associated with better SPPB (β = 0.108, P = 0.039), one-leg stance (β = 0.102, P = 0.041) and ability to squat (β = 0.110, P = 0.028), and with walking speed (β = 0.110, P = 0.028). However, associations for dietary EPA and DHA with physical function and body composition were not significant.
CONCLUSION
Dietary omega-3 and ALA, but not EPA and DHA, were positively associated with muscle strength and function in older women. The intake of omega-3 and its subtypes was not associated with muscle mass. Longitudinal studies are needed to show whether omega-3 intake may be important for muscle function in older women.
Topics: Aged; Cross-Sectional Studies; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Hand Strength; Humans; alpha-Linolenic Acid
PubMed: 34913105
DOI: 10.1007/s00394-021-02773-z