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Prostaglandins, Leukotrienes, and... Apr 2015This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid... (Review)
Review
The effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.
This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid (ALA) and omega-6 polyunsaturated fatty acid (n-6 PUFA) linoleic acid (LA) intakes on n-3 long-chain polyunsaturated fatty acid (LCPUFA) status in adult humans. The results suggest that it is possible to increase n-3 LCPUFA status by reducing LA and/or increasing ALA intake in humans, although decreasing LA intake to below 2.5%E may be required to specifically increase levels of the n-3 LCPUFA docosahexaenoic acid (DHA). The majority of studies in this area to date have been relatively poor in quality, which limits the ability to draw robust conclusions, and we present a series of recommendations to improve the quality of future studies in fatty acid nutrition in humans.
Topics: Adult; Clinical Trials as Topic; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Female; Humans; Linoleic Acid; MEDLINE; Male; alpha-Linolenic Acid
PubMed: 25687496
DOI: 10.1016/j.plefa.2015.01.001 -
Integrative Cancer Therapies May 2014Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may... (Review)
Review
BACKGROUND
Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer.
RESULTS
Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (P< .05) and decreased HER2 expression (P< .05) and cell proliferation (Ki-67 index; NS) among newly diagnosed breast cancer patients when compared with placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot flashes, cell proliferation, atypical cytomorphology, and mammographic density, as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients.
CONCLUSIONS
Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer.
Topics: Breast Density; Breast Neoplasms; Butylene Glycols; Cell Proliferation; Dietary Supplements; Female; Flax; Glucosides; Hot Flashes; Humans; Menopause
PubMed: 24013641
DOI: 10.1177/1534735413502076 -
BMJ (Clinical Research Ed.) Jun 2013To investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of breast cancer and to evaluate the potential... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To investigate the association between intake of fish and n-3 polyunsaturated fatty acids (n-3 PUFA) and the risk of breast cancer and to evaluate the potential dose-response relation.
DESIGN
Meta-analysis and systematic review of prospective cohort studies.
DATA SOURCES
PubMed and Embase up to December 2012 and references of retrieved relevant articles.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Prospective cohort studies with relative risk and 95% confidence intervals for breast cancer according to fish intake, n-3 PUFA intake, or tissue biomarkers.
RESULTS
Twenty six publications, including 20,905 cases of breast cancer and 883,585 participants from 21 independent prospective cohort studies were eligible. Eleven articles (13,323 breast cancer events and 687,770 participants) investigated fish intake, 17 articles investigated marine n-3 PUFA (16,178 breast cancer events and 527,392 participants), and 12 articles investigated alpha linolenic acid (14,284 breast cancer events and 405,592 participants). Marine n-3 PUFA was associated with 14% reduction of risk of breast cancer (relative risk for highest v lowest category 0.86 (95% confidence interval 0.78 to 0.94), I(2)=54), and the relative risk remained similar whether marine n-3 PUFA was measured as dietary intake (0.85, 0.76 to 0.96, I(2)=67%) or as tissue biomarkers (0.86, 0.71 to 1.03, I(2)=8%). Subgroup analyses also indicated that the inverse association between marine n-3 PUFA and risk was more evident in studies that did not adjust for body mass index (BMI) (0.74, 0.64 to 0.86, I(2)=0) than in studies that did adjust for BMI (0.90, 0.80 to 1.01, I(2)=63.2%). Dose-response analysis indicated that risk of breast cancer was reduced by 5% per 0.1g/day (0.95, 0.90 to 1.00, I(2)=52%) or 0.1% energy/day (0.95, 0.90 to 1.00, I(2)=79%) increment of dietary marine n-3 PUFA intake. No significant association was observed for fish intake or exposure to alpha linolenic acid.
CONCLUSIONS
Higher consumption of dietary marine n-3 PUFA is associated with a lower risk of breast cancer. The associations of fish and alpha linolenic acid intake with risk warrant further investigation of prospective cohort studies. These findings could have public health implications with regard to prevention of breast cancer through dietary and lifestyle interventions.
Topics: Body Mass Index; Breast Neoplasms; Fatty Acids, Omega-3; Female; Humans; Prospective Studies; Risk Factors; Seafood; alpha-Linolenic Acid
PubMed: 23814120
DOI: 10.1136/bmj.f3706 -
Annals of Nutrition & Metabolism 2013Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to assess the role of gender in determining the fatty acid composition of human samples, like plasma and erythrocyte membrane lipids, and adipose tissue.
METHODS
The method included a structured search strategy on MEDLINE, Scopus and the Cochrane databases, with formal inclusion/exclusion criteria, data extraction procedure and meta-analysis.
RESULTS
We evaluated 51 publications, dated from 1975 to 2011. Meta-analysis showed significantly lower values of both arachidonic acid (AA) and docosahexaenoic acid (DHA) in total plasma lipids (32 and 33 studies) and in plasma phospholipids (PL; 21 and 23 studies) in men than in women. Primary analysis of the phospholipid fraction showed the mean difference in AA to be 0.42% weight/weight (95% CI: 0.18-0.65, n = 7,769) and in DHA 0.37% weight/weight (95% CI: 0.24-0.51, n = 8,541), while there was no gender difference in the values of linoleic acid and α-linolenic acid.
CONCLUSIONS
This systematic review based on 51 publications showed significantly lower contribution of AA and DHA to plasma total lipids and plasma PL in men than in women. Gender distribution should be regarded as a significant potential confounding factor in every study assessing data on fatty acid composition.
Topics: Adipose Tissue; Arachidonic Acid; Biomarkers; Cholesterol Esters; Databases, Factual; Docosahexaenoic Acids; Erythrocyte Membrane; Female; Humans; Linoleic Acid; Male; Nutritional Status; Phosphatidylcholines; Phosphatidylethanolamines; Sex Factors; Triglycerides; alpha-Linolenic Acid
PubMed: 23327902
DOI: 10.1159/000345599 -
The American Journal of Clinical... Dec 2012Prior studies of α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prior studies of α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and cardiovascular disease (CVD) risk have generated inconsistent results.
OBJECTIVE
We conducted a meta-analysis to summarize the evidence regarding the relation of ALA and CVD risk.
DESIGN
We searched multiple electronic databases through January 2012 for studies that reported the association between ALA (assessed as dietary intake or as a biomarker in blood or adipose tissue) and CVD risk in prospective and retrospective studies. We pooled the multivariate-adjusted RRs comparing the top with the bottom tertile of ALA using random-effects meta-analysis, which allowed for between-study heterogeneity.
RESULTS
Twenty-seven original studies were identified, including 251,049 individuals and 15,327 CVD events. The overall pooled RR was 0.86 (95% CI: 0.77, 0.97; I² = 71.3%). The association was significant in 13 comparisons that used dietary ALA as the exposure (pooled RR: 0.90; 95% CI: 0.81, 0.99; I² = 49.0%), with similar but nonsignificant trends in 17 comparisons in which ALA biomarkers were used as the exposure (pooled RR: 0.80; 95% CI: 0.63, 1.03; I² = 79.8%). An evaluation of mean participant age, study design (prospective compared with retrospective), exposure assessment (self-reported diet compared with biomarker), and outcome [fatal coronary heart disease (CHD), nonfatal CHD, total CHD, or stroke] showed that none were statistically significant sources of heterogeneity.
CONCLUSIONS
In observational studies, higher ALA exposure is associated with a moderately lower risk of CVD. The results were generally consistent for dietary and biomarker studies but were not statistically significant for biomarker studies. However, the high unexplained heterogeneity highlights the need for additional well-designed observational studies and large randomized clinical trials to evaluate the effects of ALA on CVD.
Topics: Biomarkers; Cardiovascular Diseases; Diet; Humans; Reproducibility of Results; Risk; alpha-Linolenic Acid
PubMed: 23076616
DOI: 10.3945/ajcn.112.044040 -
PloS One 2012Prospective cohort studies in relation to the associations between n-3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were inconsistent.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prospective cohort studies in relation to the associations between n-3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were inconsistent. Differences in tissue n-3 PUFA compositions in subjects with and without T2D were also inconsistent in both cohort and case-control studies. We conducted a systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with T2D risk. The differences in tissue n-3 PUFA compositions in subjects with and without T2D were investigated based on cohort and case-control studies.
METHODS AND FINDINGS
PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 was used to identify relevant studies, and reference lists from retrieved studies were reviewed. Two authors independently extracted the data. Random-effects models were used to pool the summary relative risk (RR). Twenty-four studies including 24,509 T2D patients and 545,275 participants were identified. For cohort studies, the summary RR of T2D for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha-linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20) and 0.93 (95% CI: 0.81, 1.07), respectively. Subgroup analyses indicated that summary RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96) for Asian populations, and 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28) for Western populations. Asian subjects with T2D had significantly lower tissue compositions of C22:6n-3 (SMD: -1.43; 95% CI: -1.75, -1.12) and total n-3 PUFA (SMD: -1.41; 95% CI: -2.23, -0.59) compared with those without T2D.
CONCLUSION
This systematic review and meta-analysis provides evidence that marine n-3 PUFA have beneficial effects on the prevention of T2D in Asian populations.
Topics: Adult; Aged; Animals; Asian People; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Diet; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Male; Middle Aged; Prospective Studies; Risk
PubMed: 22984522
DOI: 10.1371/journal.pone.0044525 -
The British Journal of Nutrition Jun 2012The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources... (Meta-Analysis)
Meta-Analysis Review
The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood sources (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant sources (alpha-linolenic acid, ALA) and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95 % CI. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n = 13 studies; RR per 100 g/d = 1·12, 95 % CI = 0·94, 1·34); nor were consumption of EPA+DHA (n = 16 cohorts; RR per 250 mg/d = 1·04, 95 % CI = 0·97, 1·10) nor circulating levels of EPA+DHA biomarkers (n = 5 cohorts; RR per 3 % of total fatty acids = 0·94, 95 % CI = 0·75, 1·17). Both dietary ALA (n = 7 studies; RR per 0·5 g/d = 0·93, 95 % CI = 0·83, 1·04) and circulating ALA biomarker levels (n = 6 studies; RR per 0·1 % of total fatty acid = 0·90, 95 % CI = 0·80, 1·00, P = 0·06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I²~80 %) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity ( < 55 %) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-interaction ≤ 0·02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.
Topics: Animals; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Fatty Acids, Omega-3; Fishes; Humans; Plant Oils; Seafood
PubMed: 22591895
DOI: 10.1017/S0007114512001602 -
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 -
The American Journal of Clinical... Jul 2006Studies on the relation between dietary n-3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the... (Meta-Analysis)
Meta-Analysis Review
n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review.
Studies on the relation between dietary n-3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the literature on the effects of n-3 FAs (consumed as fish or fish oils rich in eicosapentaenoic acid and docosahexaenoic acid or as alpha-linolenic acid) on cardiovascular disease outcomes and adverse events was conducted. Studies from MEDLINE and other sources that were of > or =1 y in duration and that reported estimates of fish or n-3 FA intakes and cardiovascular disease outcomes were included. Secondary prevention was addressed in 14 randomized controlled trials (RCTs) of fish-oil supplements or of diets high in n-3 FAs and in 1 prospective cohort study. Most trials reported that fish oil significantly reduced all-cause mortality, myocardial infarction, cardiac and sudden death, or stroke. Primary prevention of cardiovascular disease was reported in 1 RCT, in 25 prospective cohort studies, and in 7 case-control studies. No significant effect on overall deaths was reported in 3 RCTs that evaluated the effects of fish oil in patients with implantable cardioverter defibrillators. Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes. The effects on stroke were inconsistent. Evidence suggests that increased consumption of n-3 FAs from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benefits of fish oil is stronger in secondary- than in primary-prevention settings. Adverse effects appear to be minor.
Topics: Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Dietary Supplements; Evidence-Based Medicine; Fatty Acids, Omega-3; Fish Oils; Humans; Primary Prevention; Randomized Controlled Trials as Topic; Retrospective Studies; Seafood; Treatment Outcome; alpha-Linolenic Acid
PubMed: 16825676
DOI: 10.1093/ajcn/84.1.5 -
Heart (British Cardiac Society) Feb 2006To determine whether dietary supplementation with alpha linolenic acid (ALA) can modify established and emerging cardiovascular risk markers. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine whether dietary supplementation with alpha linolenic acid (ALA) can modify established and emerging cardiovascular risk markers.
DESIGN
Systematic review and meta-analysis of randomised controlled trials identified by a search of Medline, Embase, Cochrane Controlled Trials Register (CENTRAL), and the metaRegister of Controlled Trials (mRCT).
PATIENTS
All human studies were reviewed.
MAIN OUTCOME MEASURES
Changes in concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglyceride, fibrinogen, and fasting plasma glucose, and changes in body mass index, weight, and systolic and diastolic blood pressure.
RESULTS
14 studies with minimum treatment duration of four weeks were reviewed. ALA had a significant effect on three of the 32 outcomes examined in these studies. Concentrations of fibrinogen (0.17 micromol/l, 95% confidence interval (CI) -0.30 to -0.04, p = 0.01) and fasting plasma glucose (0.20 mmol/l, 95% CI -0.30 to -0.10, p < 0.01) were reduced. There was a small but clinically unimportant decrease in HDL (0.01 mmol/l, 95% CI -0.02 to 0.00, p < 0.01). Treatment with ALA did not significantly modify total cholesterol, triglycerides, weight, body mass index, LDL, diastolic blood pressure, systolic blood pressure, VLDL, and apolipoprotein B.
CONCLUSIONS
Although ALA supplementation may cause small decreases in fibrinogen concentrations and fasting plasma glucose, most cardiovascular risk markers do not appear to be affected. Further trials are needed, but dietary supplementation with ALA to reduce cardiovascular disease cannot be recommended.
Topics: Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Fibrinogen; Humans; Risk Factors; Triglycerides; alpha-Linolenic Acid
PubMed: 15890766
DOI: 10.1136/hrt.2004.053538