The Evidence for α-Linolenic Acid and Cardiovascular Disease Benefits: Comparisons with Eicosapentaenoic Acid and Docosahexaenoic Acid

Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n–3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n–3) and docosahexaenoic acid (DHA, 22:6n–3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n–3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction.     

Emerging Nutrition Science on Fatty Acids and Cardiovascular Disease: Nutritionists’ Perspectives

Recent dietary guidance for heart health recommends a reduction (by ∼50%) in saturated fatty acid (SFA) intake to reduce LDL cholesterol and to decrease risk of cardiovascular disease (CVD). The 2010 Dietary Guidelines for Americans recommends substituting unsaturated fat [both polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs, respectively)] for SFAs. There are many dietary options that can be implemented to replace SFAs, given the different sources of unsaturated fats in the food supply. Compelling evidence exists for the cardioprotective benefits of n–3 (ω-3) PUFAs, both marine- and plant-derived. In addition, the evidence of cardioprotective benefits of n–6 (ω-6) PUFAs is strong, whereas that for MUFAs is mixed, although there is emerging evidence of benefits. Quantitatively, lowering SFAs by 50% will require, in part, substituting food sources of n–6 and n–3 PUFAs and MUFAs for food sources of SFAs. The use of n–3 PUFAs as a replacement for SFAs will result in a shortfall in reaching the SFA goal because of the relatively low amounts that can be incorporated in the diet, even with very high n–3 PUFA substitution. SFAs also can be replaced with dietary carbohydrate and/or protein. Replacing SFAs with carbohydrate, specifically refined sources, however, has little impact on reducing CVD risk. There is evidence about the health benefits of dietary protein on CVD risk, which merits study. Dietary guidelines have advanced considerably with the “replacement of SFA with unsaturated fat message” instead of recommending decreasing SFAs alone. A key question that remains is what is the optimal mix of macronutrients to maximally reduce CVD risk.     

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines,Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners

Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.     

Twelve-Week Daily Consumption of ad hoc Fortified Milk with ω-3, D,and Group B Vitamins Has a Positive Impact on Inflammaging Parameters: A Randomized Cross-Over Trial

Background and Aim: A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with ad hoc fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters. Methods: A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63–80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission. Results: Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio. Conclusion: Twelve-week daily consumption of ad hoc fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.     

PUFAs,Bone Mineral Density,and Fragility Fracture: Findings from Human Studies

Osteoporosis is a global health problem that leads to an increased incidence of fragility fracture. Recent dietary patterns of Western populations include higher than recommended intakes of n–6 (ω-6) polyunsaturated fatty acids (PUFAs) relative to n–3 (ω-3) PUFAs that may result in a chronic state of sterile whole body inflammation. Findings from human bone cell culture experiments have revealed both benefits and detriments to bone-related outcomes depending on the quantity and source of PUFAs. Findings from observational and randomized controlled trials suggest that higher fatty fish intake is strongly linked with reduced risk of fragility fracture. Moreover, human studies largely support a greater intake of total PUFAs, total n–6 (ω-6) fatty acid, and total n–3 (ω-3) fatty acid for higher bone mineral density and reduced risk of fragility fracture. Less consistent evidence has been observed when investigating the role of long chain n–3 (ω-3) PUFAs or the ratio of n–6 (ω-6) PUFAs to n–3 (ω-3) PUFAs. Aspects to consider when interpreting the current literature involve participant characteristics, study duration, diet assessment tools, and the primary outcome measure.     

DHA-Containing Oilseed: A Timely Solution for the Sustainability Issues Surrounding Fish Oil Sources of the Health-Benefitting Long-Chain Omega-3 Oils

Benefits of long-chain (≥C₂₀) omega-3 oils (LC omega-3 oils) for reduction of the risk of a range of disorders are well documented. The benefits result from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); optimal intake levels of these bioactive fatty acids for maintenance of normal health and prevention of diseases have been developed and adopted by national and international health agencies and science bodies. These developments have led to increased consumer demand for LC omega-3 oils and, coupled with increasing global population, will impact on future sustainable supply of fish. Seafood supply from aquaculture has risen over the past decades and it relies on harvest of wild catch fisheries also for its fish oil needs. Alternate sources of LC omega-3 oils are being pursued, including genetically modified soybean rich in shorter-chain stearidonic acid (SDA, 18:4ω3). However, neither oils from traditional oilseeds such as linseed, nor the SDA soybean oil have shown efficient conversion to DHA. A recent breakthrough has seen the demonstration of a land plant-based oil enriched in DHA, and with omega-6 PUFA levels close to that occurring in marine sources of EPA and DHA. We review alternative sources of DHA supply with emphasis on the need for land plant oils containing EPA and DHA.     

Long-Chain Polyunsaturated Fatty Acid Concentrations and Association with Weight Gain in Pregnancy

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women’s weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (−0.20, −0.12, and −0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).     

Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.     

Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

Omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with slower rates of cognitive decline. We investigated the association between omega-3 PUFAs and cognitive function in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase inhibitors (AChEIs). This was a prospective cohort study using registered data. Patients with AD receiving AChEIs were recruited from 1 May 2016 to 30 April 2019 and were followed up for two years. Their daily diet record and blood concentration of omega-3 PUFAs were analyzed. Multiple linear and binary logistic regression was used to determine the factors associated with cognitive decline (continuous and dichotomized cognitive change). In the research, 129 patients with AD were identified with a mean age of 76.5 ± 6.6. Patients with AD with lower baseline omega-3 PUFAs levels were associated with a higher risk of cognitive decline than those with higher levels (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.012, 1.125; p = 0.016) after adjustment. Patients with AD with a lower baseline DHA (OR = 1.131, 95% CI: 1.020, 1.254; p = 0.020), but not EPA, were associated with a higher risk of cognitive decline. We found that higher Mini-Nutritional Assessment scores (beta = −0.383, 95% CI = −0.182–−0.048, p = 0.001) and total fat (beta = −0.248, 95% CI = −0.067–−0.003, p = 0.031) were independently associated with slow cognitive decline in patients with AD receiving AChEIs. The baseline blood levels of omega-3 PUFAs were associated with cognitive decline in patients with AD receiving AChEIs. Future randomized controlled trials are needed to clarify whether this association is causal.     

The Role of Omega-3 Fatty Acids in Acute Pancreatitis: A Meta-Analysis of Randomized Controlled Trials

To determine whether treatment with omega-3 fatty acids (ω-3 FA) provides benefits to patients with acute pancreatitis (AP). The Cochrane Library, PubMed, Embase, Web of Science, and Chinese Biomedical Literature Database were searched. Data analysis was performed using Revman 5.2 software. A total of eight randomized controlled trials (RCTs) were included. Overall, ω-3 FA treatment resulted in a significantly reduced risk of mortality (RR 0.35; 95% CI 0.16 to 0.75, p < 0.05), infectious complications (RR 0.54; 95% CI 0.34 to 0.85, p < 0.05) and length of hospital stay (MD –6.50; 95% CI −9.54 to −3.46, p < 0.05), but not length of ICU stay (MD −1.98; 95% CI −6.92 to 2.96, p > 0.05). In subgroup analysis, only patients who received ω-3 FA parenterally had some statistically significant benefits in terms of mortality (risk ratio (RR) 0.37; 95% confidence interval (CI) 0.16 to 0.86, p < 0.05), infectious complications (RR 0.5; 95% CI 0.28 to 0.9, p < 0.05) and length of hospital stay (mean difference (MD) −8.13; 95% CI −10.39 to −5.87, p < 0.001). The administration of ω-3 FA may be beneficial for decreasing mortality, infectious complications, and length of hospital stay in AP, especially when used parenterally. Large and rigorously designed RCTs are required to elucidate the efficacy of parenteral or enteral ω-3 FA treatment in AP.     

Comparison of Formulas Based on Lipid Emulsions of Olive Oil,Soybean Oil,or Several Oils for Parenteral Nutrition: A Systematic Review and Meta-Analysis

Many studies have reported that olive oil–based lipid emulsion (LE) formulas of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) may be a viable alternative for parenteral nutrition. However, some randomized controlled clinical trials (RCTs) have raised concerns regarding the nutritional benefits and safety of SMOFs. We searched principally the MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to March 2014 for the relevant literature and conducted a meta-analysis of 15 selected RCTs that 1) compared either olive oil– or SMOF-based LEs with soybean oil–based LEs and 2) reported plasma concentrations of α-tocopherol, oleic acid, and ω-6 (n–6) and ω-3 (n–3) long-chain polyunsaturated fatty acids (PUFAs) and liver concentrations of total bilirubin and the enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase, and γ-glutamyl transferase. The meta-analysis suggested that SMOF-based LEs were associated with higher plasma concentrations of plasma α-tocopherol, oleic acid, and the ω-3 PUFAs eicosapentaenoic and docosahexaenoic acid. Olive oil– and SMOF-based LEs correlated with lower plasma concentrations of long-chain ω-6 PUFAs and were similar to soybean oil–based LEs with regard to their effects on liver function indicators. In summary, olive oil– and SMOF-based LEs have nutritional advantages over soybean oil–based LEs and are similarly safe. However, their performance in clinical settings requires further investigation.     

Administration of an Intravenous Fat Emulsion Enriched with Medium-Chain Triglyceride/ω-3 Fatty Acids is Beneficial Towards Anti-Inflammatory Related Fatty Acid Profile in Preterm Neonates: A Randomized,Double-Blind Clinical Trial

Intravenous administration of pure soybean oil emulsions high in linoleic acid may lead to inflammation and lipid peroxidation in preterm neonates. We aimed to investigate the effects of a medium-chain triglyceride (MCT)/ω-3 polyunsaturated fatty acid (PUFA)-enriched intravenous fat emulsion (IVFE) on plasma fatty acid (FA) profile and serum interleukin-6 (IL-6) in preterm neonates. In this double-blind randomized study, 92 preterm neonates (gestational age < 32 weeks, birth weight < 1500 g) were assigned to receive either MCT/ω-3 PUFA-enriched IVFE (Intervention Group) or soybean oil-based IVFE (Control Group). Levels of FAs were measured at baseline (day 0) and day 15 of parenteral nutrition with gas-chromatography mass-spectrometry. Serum IL-6 was measured with sandwich ELISA in 59 neonates. Plasma FAs changed significantly over time; the MCT/ω-3 PUFA-IVFE group showed higher ω-3 PUFAs (p = 0.031), eicosapentaenoic acid (p = 0.000), and oleic acid (p = 0.003), and lower ω-6/ω-3 PUFAs ratio (p = 0.001) and ω-6 PUFAs (p = 0.023) compared to control group. Linoleic acid was higher in the soybean oil (SO)-based IVFE arm compared to the MCT/ω-3 PUFAs-IVFE arm (p = 0.006). Both fat emulsion types decreased IL-6 compared to baseline, but changes were insignificant between groups. Administration of MCT/ω-3 PUFA-enriched IVFE in preterm neonates is beneficial in changing the FA profile consistent with attenuated inflammatory response.     

Fish in the diet: A review

Fish plays a useful role in a healthy and balanced diet, and its consumption has long been associated with several health benefits. Fish provides a variety of nutrients, including protein and long‐chain omega‐3 polyunsaturated fatty acids (n‐3 PUFAs), as well as micronutrients including selenium, iodine, potassium, vitamin D and B‐vitamins. Intakes of some of these micronutrients, including iodine and vitamin D, are low in some population groups in the UK, which makes fish a valuable contributor to intakes of these. The long‐chain n‐3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present in oil‐rich fish and fish oil, have been suggested to be associated with beneficial health outcomes. In this paper, we review the evidence associating fish and long‐chain n‐3 PUFAs with various health outcomes. Evidence from observational studies shows a protective effect of fish intake on risk of cardiovascular disease (CVD; including stroke). Eating at least two portions of fish per week has been associated with a 23–25% lower risk of death from coronary heart disease (CHD) compared with those eating no or very little fish; eating fish once a week has been associated with a 15% lower risk of CHD death. Fish intake seems only moderately associated with lower risk of stroke, with results from meta‐analyses showing a risk reduction of between 6% and 18% in those eating fish 2–4 times per week compared with those eating none. There have been some inconsistencies in study findings relating to fish intake and risk of CVD. Differences in habitual fish intakes of the study populations may account for some of this inconsistency. Evidence from randomised controlled trials (RCTs) on the effect of long‐chain n‐3 PUFA supplementation on CVD risk has come mainly from secondary prevention studies and is inconsistent. While early studies support a protective effect, recent studies do not support the hypothesis that long‐chain n‐3 PUFA supplementation is beneficial in secondary prevention of CVD. Different study outcomes have been influenced by variations in study design and the characteristics of the study populations. Furthermore, the increased use of modern treatments for cardiovascular risk factors (e.g. statins) may not have been sufficiently controlled for in more recent studies. Treatment doses of long‐chain n‐3 PUFA also varied substantially between studies, ranging from 0.3 to 6.9 g/day. Current evidence suggests that there is no association between fish consumption and risk of type 2 diabetes. We also found no evidence to suggest that fish intake has a protective effect on several types of cancer (pancreas, prostate, bladder, stomach and ovaries). However, studies do suggest that maternal fish intake during pregnancy may reduce the risk of eczema and asthma in her baby, the evidence being somewhat more consistent for eczema. There may also be a link between fish intake during infancy and childhood and the risk of developing asthma and eczema later in childhood, although the evidence is inconsistent and more studies are needed to clarify the situation. The long‐chain fatty acid DHA is crucial for development of the brain and the central nervous system in early life. While studies suggest that fish intake in early life contributes to cognitive development, supplementation with EPA and DHA does not seem to have a beneficial effect on cognitive function in childhood. The European Food Safety Authority (EFSA) suggests that pregnant and breastfeeding women increase their intake of preformed DHA by 100–200 g/day in addition to the suggested average intake level of long‐chain n‐3 PUFA for adults (250 mg EPA + DHA combined). EFSA proposes that an intake of 1–2 portions of oil‐rich fish per week should be compatible with an adequate DHA supply during pregnancy and lactation. There is some evidence to suggest that higher fish intake, dietary DHA intake and DHA levels in the blood among older adults may be positively associated with a lower risk of dementia and Alzheimer's disease (AD). In some prospective studies, risk of AD and dementia in those having the highest fish intake, or the highest blood DHA levels, was about half that of those who ate a little or no fish or had a low blood DHA level. In one prospective study, eating fish once a week was associated with a 60% lower risk of AD compared with those who rarely or never ate fish. However, some studies have found no association, and more evidence will be needed to draw reliable conclusions. Fish intake may be associated with slower cognitive decline, but the evidence is very limited and more studies are needed. Data from RCTs do not suggest that long‐chain n‐3 PUFA supplements are effective in preventing cognitive decline. There is some evidence from cohort and cross‐sectional studies that fish intake may be associated with better bone health, but not all studies have found such an association. Oil‐rich fish, in particular, is an important dietary source of vitamin D, which is important for bone health, and fish consumed with soft bones are a good source of calcium, which is the most abundant mineral in the skeleton. When making recommendations on fish intake, consideration has to be given to the sustainability of fish supplies. Much work has been done already to ensure that fish stocks are not depleted and more efforts will be required to ensure supplies of fish for future generations. Overall, it is evident that including fish in the diet is associated with several health benefits. The extent to which long‐chain n‐3 PUFA per se contributes to these various effects has yet to be established. It is likely that other components in fish, such as selenium, potassium, vitamin D or B‐vitamins, and other dietary aspects (i.e. foods typically eaten with fish or foods displaced by fish) contribute to the positive health effects.     

Omega-3 Index and Cardiovascular Health

Recent large trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the cardiovascular field did not demonstrate a beneficial effect in terms of reductions of clinical endpoints like total mortality, sudden cardiac arrest or other major adverse cardiac events. Pertinent guidelines do not uniformly recommend EPA + DHA for cardiac patients. In contrast, in epidemiologic findings, higher blood levels of EPA + DHA were consistently associated with a lower risk for the endpoints mentioned. Because of low biological and analytical variability, a standardized analytical procedure, a large database and for other reasons, blood levels of EPA + DHA are frequently assessed in erythrocytes, using the HS-Omega-3 Index^® methodology. A low Omega-3 Index fulfills the current criteria for a novel cardiovascular risk factor. Neutral results of intervention trials can be explained by issues of bioavailability and trial design that surfaced after the trials were initiated. In the future, incorporating the Omega-3 Index into trial designs by recruiting participants with a low Omega-3 Index and treating them within a pre-specified target range (e.g., 8%–11%), will make more efficient trials possible and provide clearer answers to the questions asked than previously possible.     

Importance of EPA and DHA Blood Levels in Brain Structure and Function

Brain structure and function depend on a constant and sufficient supply with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by blood. Blood levels of EPA and DHA reflect dietary intake and other variables and are preferably assessed as percentage in erythrocytes with a well-documented and standardized analytical method (HS-Omega-3 Index^®). Every human being has an Omega-3 Index between 2 and 20%, with an optimum of 8–11%. Compared to an optimal Omega-3 Index, a lower Omega-3 Index was associated with increased risk for total mortality and ischemic stroke, reduced brain volume, impaired cognition, accelerated progression to dementia, psychiatric diseases, compromises of complex brain functions, and other brain issues in epidemiologic studies. Most intervention trials, and their meta-analyses considered EPA and DHA as drugs with good bioavailability, a design tending to produce meaningful results in populations characterized by low baseline blood levels (e.g., in major depression), but otherwise responsible for many neutral results and substantial confusion. When trial results were evaluated using blood levels of EPA and DHA measured, effects were larger than comparing EPA and DHA to placebo groups, and paralleled epidemiologic findings. This indicates future trial design, and suggests a targeted use EPA and DHA, based on the Omega-3 Index.     

Eicosapentaenoic Acid Is Associated with Decreased Incidence of Alzheimer’s Dementia in the Oldest Old

Background. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties. Methods. We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer’s disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD. Results. During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia. Conclusions. Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.     

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021

Oxidative stress and inflammation have been recognized as important contributors to the risk of chronic non-communicable diseases. Polyunsaturated fatty acids (PUFAs) may regulate the antioxidant signaling pathway and modulate inflammatory processes. They also influence hepatic lipid metabolism and physiological responses of other organs, including the heart. Longitudinal prospective cohort studies demonstrate that there is an association between moderate intake of the omega-6 PUFA linoleic acid and lower risk of cardiovascular diseases (CVDs), most likely as a result of lower blood cholesterol concentration. Current evidence suggests that increasing intake of arachidonic acid (up to 1500 mg/day) has no adverse effect on platelet aggregation and blood clotting, immune function and markers of inflammation, but may benefit muscle and cognitive performance. Many studies show that higher intakes of omega-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a lower incidence of chronic diseases characterized by elevated inflammation, including CVDs. This is because of the multiple molecular and cellular actions of EPA and DHA. Intervention trials using EPA + DHA indicate benefit on CVD mortality and a significant inverse linear dose–response relationship has been found between EPA + DHA intake and CVD outcomes. In addition to their antioxidant and anti-inflammatory roles, omega-3 fatty acids are considered to regulate platelet homeostasis and lower risk of thrombosis, which together indicate their potential use in COVID-19 therapy.     

The effect of long-term supplementation with different dietary ω-6/ω-3 ratios on mineral content and ex vivo prostaglandin E2 release in bone of growing rabbits

BACKGROUND/OBJECTIVES

The aim of this research was to study the different long term effects of consumption of dietary oil sources with varying omega-6/omega-3 (ω-6/ω-3) polyunsaturated fatty acids (PUFAs) ratios on bone marrow fatty acid level, ex vivo prostaglandin E₂ (PGE₂) release, and mineral content of bone in rabbits.

MATERIALS/METHODS

For this purpose, weaning and female New Zealand white rabbits were purchased and randomly divided into five groups and offered ad libitum diets containing 70 g/kg of added oil for 100 days. The dietary lipid treatments were formulated to provide the following ratios of ω-6/ω-3 fatty acids: 8.68 soy bean oil (SBO control), 21.75 sesame oil (SO), 0.39 fish oil (FO), 0.63 algae oil (DHA), and 0.68 algae oils (DHA/ARA). DHA and ARA are two types of marine microalgae of the genus Crypthecodinium cohnii.

RESULTS

The dietary treatments had significant effects on the bone marrow fatty acids of rabbits. Rabbits fed the FO diet, containing the highest ω-3 PUFA concentration, and those fed the SBO diet showed the highest ω-6 PUFA. On the other hand, a positive correlation was observed between Ex vivo PGE₂ level and the ω-6/ω-3 dietary ratio. Significant effects of dietary treatment on femur Ca, P, Mg, and Zn contents were observed in both genders.

CONCLUSIONS

Findings of the current study clearly demonstrated that dietary PUFA, particularly ω-6/ω-3 and ARA/EPA ratios are important factors in determining bone marrow fatty acid profile, and this in turn determines the capacity of bone for synthesis of PGE₂, thereby reducing bone resorption and improving bone mass during growth.     

β-Carotene Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

β-carotene is widely available in plant-based foods, while the efficacy of β-carotene supplementation on cardiovascular disease (CVD) risk remains controversial. Hence, we performed a systematic review and meta-analysis on randomized controlled trials to investigate the associations between β-carotene supplementation and CVD risk as well as mortality. We conducted literature searches across eight databases and screened the publications from January 1900 to March 2022 on the topic of β-carotene treatments and cardiovascular outcomes. There were 10 trials and 16 reports included in the meta-analysis with a total of 182,788 individuals enrolled in the study. Results from the random-effects models indicated that β-carotene supplementation slightly increased overall cardiovascular incidence (RR: 1.04; 95% CI: 1.00, 1.08) and was constantly associated with increased cardiovascular mortality (RR: 1.12; 95% CI: 1.04, 1.19). Subgroup analyses suggested that, when β-carotene treatments were given singly, a higher risk of cardiovascular outcomes was observed (RR: 1.06; 95% CI: 1.01, 1.12). In addition, cigarettes smoking was shown to be a risk behavior associated with increased cardiovascular incidence and mortality in the β-carotene intervention group. In sum, the evidence of this study demonstrated that β-carotene supplementation had no beneficial effects on CVD incidence and potential harmful effects on CVD mortality. Further studies on understanding the efficacy of multivitamin supplementation in nutrient-deficient or sub-optimal populations are important for developing the tolerable upper intake level for β-carotene of different age and sex groups.