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The present findings showed that the daily intake levels of n-3 PUFAs, based on the new FFQ and FR, were significantly correlated; the correlation coefficients were between 0.771 and 0.827. Consistent with our findings, in several previous studies, a significant correlation was observed between the FFQ and FR results, although the correlation coefficients were comparable13,19,27. The time period covered by the FFQs differed among these validation studies, which assessed the dietary intake of healthy adults in the past 3 months, in the last year, and in the past 6 months13,19,27. The current study investigated the dietary intake of the participants in the past 6 months. All previously mentioned studies used the 3-day FR method, except for the study by Herter-Aeberli et al.13, which used the seven-day FR19,27; these factors may explain the difference between the correlation coefficients of FFQ and FR in these studies.

Almost all n-3 PUFA-rich foods, including fish and seafood as rich sources of EPA and DHA, meat as a source of DPA, and some plant-based foods (e.g., walnut and flaxseed) and some oils (flaxseed and canola oils) as sources of ALA were included in our new FFQ. Since the number of n-3 PUFA-fortified foods is very limited in Iran, they are not generally considered common dietary sources of n-3 PUFAs for people. Differences in n-3 PUFAs between the FFQ and FR might have contributed to day-to-day intake variabilities. For example, some participants might have consumed n-3 PUFA-rich foods several times in the last 6 months, which was not reported in the three-day FR. Another explanation for this finding is that people usually underreport their food intake when completing the FR. Similar reasons have been suggested by researchers in several similar studies13,19,27.

Healthcare providers can also assess omega-3 status indirectly by analyzing the fatty acid composition of red blood cells. This approach looks at the long-term dietary intake of fats over several months and may provide an idea of overall omega-3 intake (30).

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In a 2012 study, mice that received omega-3 supplements for 6 months appeared to have better retinal function and a lower risk of age-related vision loss than mice that did not receive the supplements.

Supplementation with EPA + DHA from fish oil capsules for approximately five months dose-dependently increased the omega-3 index in 115 healthy, young adults (ages, 20-45 years), validating the use of the omega-3 index as a biomarker of EPA + DHA intake (49). Before the omega-3 index can be used in routine clinical evaluation, however, clinical reference values in the population must be established (50). Additionally, fatty acid metabolism may be altered in certain disease states, potentially making the omega-3 index less relevant for some cardiovascular conditions (5).

Effect on children's risk of allergies and asthma: A 2018 meta-analysis of randomized controlled trials in 2,047 children followed for six months to 16 years found a 19% lower risk of wheezing and/or asthma with maternal supplementation of omega-3 PUFA (primarily EPA and DHA) from as early as the 20th week of gestation until delivery (67). However, there was no effect of prenatal supplementation when the analysis was restricted to the three trials that reported on the incidence of childhood asthma only (67). Another meta-analysis of nine trials in 3,637 children, including three trials in which maternal supplementation with omega-3 PUFA continued after birth, found no effect of prenatal supplements on the risk of any allergy (three trials), the risk of wheeze and/or asthma (seven trials), the risk of eczema (six trials), the development of allergic rhinitis (two trials), and the risk of food allergy (three trials) in children (68). There was, however, some evidence to suggest that prenatal supplementation could lower the incidence of sensitization to specific allergens, namely egg (three trials; -46%) and peanut (two trials; -38%) (68).

The last trimester of pregnancy and first six months of postnatal life are critical periods for the accumulation of DHA in the brain and retina (70). Human milk contains a mixture of saturated fatty acids (~46%), monounsaturated fatty acids (~41%), omega-6 PUFA (~12%), and omega-3 PUFA (~1.3%) (71). Although human milk contains DHA in addition to ALA and EPA, ALA was the only omega-3 fatty acid present in conventional infant formulas until the year 2001. Although infants can synthesize DHA from ALA, they generally cannot synthesize enough to prevent declines in plasma and cellular DHA concentrations without additional dietary intake. Therefore, it was proposed that infant formulas be supplemented with enough DHA to bring plasma and cellular DHA concentrations of formula-fed infants up to those of breast-fed infants (72).

All infants: Although formulas enriched with DHA raise plasma and red blood cell DHA concentrations in preterm and term infants, the results of randomized controlled trials examining measures of visual acuity and neurological development in infants fed formula with or without added DHA have been mixed. For instance, a 2012 meta-analysis of randomized controlled trials (12 trials, 1,902 infants) comparing long-chain PUFA-supplemented and unsupplemented formula, started within one month of birth, found no effect of long-chain PUFA supplementation on infant cognition assessed at approximately one year of age (73). A lack of effect was observed regardless of the dose of long-chain PUFA or the prematurity status of the infant. With respect to visual acuity, a 2013 meta-analysis of randomized controlled trials (19 trials, 1,949 infants) found a beneficial effect of long-chain PUFA-supplemented formula, started within one month of birth, on infant visual acuity up to 12 months of age (74). Notably, two different types of visual acuity assessment were evaluated in the meta-analysis. Visual acuity assessed by using the Visually Evoked Potential (10 trials, 852 infants) showed a significant positive effect of long-chain PUFA-supplemented formula at 2, 4, and 12 months of age. When assessed by the Behavioral Method (12 trials, 1,095 infants), a significant benefit of long-chain PUFA-supplemented formula on visual acuity was found only at the age of two months. No moderating effects of dose or prematurity status were observed.

Randomized controlled trials: A 2018 Cochrane systematic review assessed the evidence for a cardioprotective effect of ALA and long-chain omega-3 PUFA in individuals either at low or high risk of CVD (103). Moderate-to-high quality evidence from randomized controlled trials (of at least 12 months) suggested no effect of omega-3 PUFA (either supplemented, enriched in meals, or advised to be consumed) on the risk of CHD events, CVD events, arrhythmia, stroke, CHD mortality, CVD mortality, or all-cause mortality. There was also no evidence of an effect on secondary outcomes, including major adverse cerebrovascular or cardiovascular events, MI, sudden cardiac death, angina pectoris, heart failure, revascularization, peripheral arterial disease, and acute coronary syndrome (103). A 2017 review and advisory from the American Heart Association found no evidence to suggest a benefit of long-chain omega-3 PUFA supplementation for the prevention of cardiovascular mortality in patients with or at risk of type 2 diabetes mellitus, the prevention of CHD in patients with atherosclerotic disease (e.g., with prior stroke, peripheral vascular disease, diabetes, hypercholesterolemia), the prevention of stroke in patients with or without a history of stroke, and the prevention of atrial fibrillation in patients with prior atrial fibrillation or in those undergoing cardiac surgery (104). There was some evidence to suggest that supplementation with long-chain omega-3 PUFA in patients with prior clinical CHD might reduce the risk of CHD death, possibly because of a reduction in the risk of ischemia-induced sudden cardiac death (104).

Often associated with metabolic disorders, nonalcoholic fatty liver disease (NAFLD) is a condition characterized by an excessive lipid accumulation in the liver (i.e., hepatosteatosis). NAFLD can progress to nonalcoholic steatohepatitis (NASH) in about one-third of the patients with NAFLD, thereby increasing the risk of cirrhosis and hepatocellular carcinoma (152, 153). An emerging feature of NAFLD is the decline in hepatic omega-3 and omega-6 PUFA with disease progression (154). Considering that C20-22 omega-3 PUFA can reduce fatty acid synthesis and inflammation, a possible therapeutic strategy would be to increase dietary intake of long-chain omega-3 PUFA. A 2018 meta-analysis of 18 randomized controlled trials in 1,424 participants with NAFLD found that omega-3 supplementation showed beneficial effects on liver fat, specific liver enzymatic activities, serum triglycerides, fasting glucose, and insulin resistance (155). However, there was no evidence of an effect on total cholesterol, LDL-cholesterol, HDL-cholesterol, fasting insulin, blood pressure, BMI, and waist circumference (155). Other recent meta-analyses have also reported that supplementation with long-chain omega-3 fatty acids from fish/seal oil (0.25-6.8 g/day for 3-25 months) improved hepatosteatosis and other metabolic disorders in both children and adults with NAFLD (reviewed in 153). Additional studies are needed to examine their efficacy in more severe cases of NASH. be457b7860

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