Lipid Profile Modulates Cardiometabolic Risk Biomarkers Including Hypertension in People with Type-2 Diabetes: A Focus on Unbalanced Ratio of Plasma Polyunsaturated/Saturated Fatty Acids.

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio is a likely contributor, but the mechanisms involved are not clearly elucidated. The aim of this study is to explore the association between plasma SFA/PUFA ratio and the clusters of cardiometabolic syndrome (CMS), including the atherogenic biomarkers, inflammatory status, feeding patterns, and physical activity in people with T2DM with or without essential hypertension. The study was conducted on 784 adult male and female participants, aged between 30 and 50 years, and divided into 3 groups: 100 T2DM without hypertension (D); 368 T2DM with hypertension (DM); and 316 hypertensive participants without T2DM (H). All Participants were phenotyped regarding CMS clusters according to the NCEP/ATPIII criteria. Insulin resistance was assessed by Homeostasis model assessment (HOMA model). Metabolic, atherogenic, and inflammatory parameters were analyzed by biochemical methods; NEFFA by microfluorimetry; SFA, PUFA-n6 and PUFA-n3 by gas phase chromatography. Dietary lipids and physical activity were analyzed through the use of validated questionnaires. The clusters of CMS were found in all groups. Dyslipidemia was correlated with accretion NEFFA levels in all groups, but more accentuated in the DH group (r = +0.77; p < 0.001). Similarly, plasma PUFA/SFA ratio and PUFA-3 level was lower, concomitantly with a higher plasma ApoB100/ApoA1 (p < 0.001), lipoprotein (a), homocysteine (p < 0.001), and pro-inflammatory cytokines (TNFα, IL-6, IL1-ß) in the DH group. Likewise, the depletion of PUFA-n3/PUFA-n6 ratio is associated with the decrease of omega 3-DHA (docosahexaenoic acid) and omega 3-EPA (eicosapentaenoic acid) (p < 0.001). It appears that the PUFAs-n3 ratio modulates cardiometabolic risk, inflammatory state and atherogenic biomarkers. The plasma unbalanced ratio of SFA/PUFA reflects dietary fatty acids intake. The contribution of dietary lipids is undisputed. Nutritional recommendations are required to determine the fatty acids ratio (saturated and unsaturated) provided in the diet.

FADS and PPARG2 Single Nucleotide Polymorphisms are Associated with Plasma Lipids in 9-Mo-Old Infants.

BACKGROUND: Dietary intake of polyunsaturated fatty acids (PUFAs), e.g., linoleic acid and n-3 (ω-3) long-chain PUFAs, has been shown in adults to affect plasma cholesterol and triglycerides (TGs), respectively. Little is known about the effects of PUFAs on plasma lipids in early life. OBJECTIVE: The aim of this study was to explore the associations between plasma concentrations of total, LDL, and HDL cholesterol and TGs in infants and 2 single nucleotide polymorphisms (SNPs) in the fatty acid desaturase genes (FADS) oppositely associated with docosahexaenoic acid (rs1535 and rs174448) and potential effect modification by a functional peroxisome proliferator-activated receptor-γ2 gene variant (PPARG2 Pro12Ala). METHODS: In 9-mo-old infants (n = 561) from 3 Danish cohorts, we analyzed associations between plasma lipids, erythrocyte PUFAs, and FADS SNPs, and interactions with PPARG2 Pro12Ala genotype, by multiple linear regression. We also examined potential effect modification by breastfeeding, as 46% of the infants were still being breastfed. RESULTS: Minor allele carriage of rs174448 was associated with lower total cholesterol (difference: -0.22 mmol/L; 95% CI: -0.37, -0.06 mmol/L; P = 0.006) and LDL cholesterol (difference: -0.15 mmol/L; 95% CI: -0.29, -0.01 mmol/L; P = 0.035), but no associations were observed with TGs or for rs1535. Minor allele carriage of both FADS SNPs was associated with 1 SD lower HDL cholesterol, but only in currently breastfed infants (rs174448 × breastfeeding, P = 0.080; rs1535 × breastfeeding, P = 0.030) and PPARG2 minor allele carriers (rs174448 × PPARG2, P = 0.001; rs1535 × PPARG2, P = 0.004). Erythrocyte arachidonic acid and eicosapentaenoic acid were inversely associated with LDL cholesterol [estimated effect (ß): -0.3 mmol/L; 95% CI: -0.06, -0.00 mmol/L per percentage of fatty acids (FA%); P = 0.035] and TGs (ß: -0.23 mmol/L; 95% CI: -0.41, -0.05 mmol/L per FA%; P = 0.015), respectively. CONCLUSIONS: The observed associations with FADS variants indicate that PUFAs are involved in plasma lipid regulation in 9-mo-old infants. Observed FADS SNP differences and interactions with breastfeeding and PPARG2 warrant additional studies to explore the effects of individual FADS SNPs on PUFA status and potential genetic modification of dietary PUFA effects.

A Prenatal DHA Test to Help Identify Women at Increased Risk for Early Preterm Birth: A Proposal.

Fish intake and docosahexaenoic acid (DHA), a nutrient found in fish, have been favorably linked to several pregnancy outcomes. The risk of early preterm birth (ePT, <34 weeks gestation) is associated with low fish intake and DHA blood levels and can be reduced by supplemental DHA. Here, we summarize the evidence linking blood DHA levels with risk for ePT birth, and based on the available studies, propose that women who are pregnant or trying to become pregnant aim for a red blood cell (RBC) DHA value of at least 5% (of total RBC fatty acids). In the US, ~70% of women of childbearing age are likely below this cut-point, and dietary intake data suggest that this group, including pregnant women, consumes ~60 mg/day DHA and that >90% of this group do not take an omega-3 supplement. Since the recommendations for women to consume fish and to take a 200 mg DHA supplement during pregnancy are not being heeded generally, there is a need to motivate practitioners and pregnant women to attend to these recommendations. Having an objective prenatal blood DHA test could provide such motivation. More research is needed to test the clinical utility of this proposed target prenatal DHA level.

Supplementation-Dependent Effects of Vegetable Oils with Varying Fatty Acid Compositions on Anthropometric and Biochemical Parameters in Obese Women.

Fatty acid (FA) composition is a determinant of the physiological effects of dietary oils. This study investigated the effects of vegetable oil supplementation with different FA compositions on anthropometric and biochemical parameters in obese women on a hypocaloric diet with lifestyle modifications. Seventy-five women (body mass index, BMI, 30⁻39.9kg/m²) were randomized based on 8-week oil supplementation into four experimental groups: the coconut oil group (CoG, n = 18), the safflower oil group (SafG, n = 19), the chia oil group (ChG, n = 19), and the soybean oil placebo group (PG, n = 19). Pre- and post-supplementation weight, anthropometric parameters, and body fat (%BF), and lean mass percentages (%LM) were evaluated, along with biochemical parameters related to lipid and glycidemic profiles. In the anthropometric evaluation, the CoG showed greater weight loss (Δ% = -8.54 ± 2.38), and reduced BMI (absolute variation, Δabs = -2.86 ± 0.79), waist circumference (Δabs = -6.61 ± 0.85), waist-to-height ratio (Δabs = -0.041 ± 0.006), conicity index (Δabs = -0.03 ± 0.016), and %BF (Δabs = -2.78 ± 0.46), but increased %LM (Δabs = 2.61 ± 1.40) (p < 0.001). Moreover, the CoG showed a higher reduction in biochemical parameters of glycemia (Δabs = -24.71 ± 8.13) and glycated hemoglobin (Δabs = -0.86 ± 0.28) (p < 0.001). The ChG showed a higher reduction in cholesterol (Δabs = -45.36 ± 0.94), low-density lipoprotein cholesterol (LDLc; Δabs = -42.53 ± 22.65), and triglycerides (Δabs = -49.74 ± 26.3), but an increase in high-density lipoprotein cholesterol (HDLc; abs = 3.73 ± 1.24, p = 0.007). Coconut oil had a more pronounced effect on abdominal adiposity and glycidic profile, whereas chia oil had a higher effect on improving the lipid profile. Indeed, supplementation with different fatty acid compositions resulted in specific responses.

Absorption rate of krill oil and fish oil in blood and brain of rats.

BACKGROUND: Krill (Euphausia superba) is a small marine crustacean with a lipid content. The mechanism of Krill oil function is not clear yet and research reports on the absorption rate of the phospholipids of krill oil in the blood and brain are very poor. METHODS: We studied the effect of oral short-term and long-term administration of Krill oils (KOs) on bioavailability in the blood and brain of rats. For short-term testing of fish and KO bioavailability, rats were divided into four groups: normal, fish oil (FO), Krill oil 1 (KO), and Krill oil 2 (CKO). The blood and brain were collected at 2, 4, 8, 12, 24, and 48 h after oral administration (1000 mg/rat). Five hundred milligrams of FO, KO, and CKO were orally administered daily for 2 weeks for long-term administration, and then the brain and blood were collected. RESULTS: Two types of KOs showed high content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the PL. The EPA content of CKO and KO were 41.13 and 32.49%, respectively. After short-term KO administration, KO showed a higher EPA content than CKO in the blood after 2 h. KO showed higher content of DHA than CKO even after 2 h. FO increased until 8 h, but then decreased rapidly until 12 h. Although the total unsaturated fatty acid (UFA) content of KOs was lower than the total UFS content in FO, the remaining UFS content in the brain was higher than that in FO over time. Following oral administration of FO, KO, and CKO for 1 and 2 weeks, triglycerides (TG) and PL contents in the blood for KOs were slightly higher than for FO. EPA and DHA levels in the brain were slightly higher in KOs following long-term administration, but the difference was not significant. CONCLUSIONS: Base on these findings, KOs have functional potential for the brain and vascular diseases, and can be utilized as a multi-functional material composed mainly of functional ingredients.

Validation of an equation predicting highly unsaturated fatty acid (HUFA) compositions of human blood fractions from dietary intakes of both HUFAs and their precursors.

Proportions of omega-3 (n-3) and omega-6 (n-6) in 20- and 22-carbon highly unsaturated fatty acids with 3 or more double bonds (HUFA) accumulated in tissue HUFA (e.g., the %n-6 in HUFA) are biomarkers reflecting intakes of n-6 and n-3 fatty acids. An empirical equation, referred to here as the Lands' Equation, was developed previously to use dietary intakes of n-6 and n-3 HUFA and their 18-carbon precursors to estimate the %n-6 in HUFA of humans. From the PubMed database, we identified clinical trials reporting (a) dietary intake of at least linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and (b) the amounts of at least arachidonic acid (20:4n-6), eicosapentaenoic acid (20:5n-3), and docosahexaenoic acid (22:6n-3) in lipids of plasma, serum, or red blood cell. Linear regression analyses comparing reported and predicted %n-6 in HUFA gave a correlation coefficient of 0.73 (p<0.000000) for 34 studies with 92 subject groups. These results indicate that circulating HUFA compositions can be reliably estimated from dietary intake data that not only includes n-3 and n-6 HUFA consumption, but also includes consumption of 18 carbon n-3 and n-6 precursor fatty acids.

Effects of walnut oil on lipid profiles in hyperlipidemic type 2 diabetic patients: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The role of herbal medicine is now well documented in preventing and controlling diabetes mellitus. The main aim of this study was to evaluate the effects of walnut oil consumption on lipid profiles of hyperlipidemic patients with type 2 diabetes. METHODS: In a randomized, double-blind, placebo-controlled clinical trial, 100 hyperlipidemic type 2 diabetic patients aged 35-75 years were assigned to receive 15 cc Persian walnut oil or placebo every day for 90 days. The primary outcomes were the lipid profiles. RESULTS: Consumption of walnut oil by type 2 hyperlipidemic diabetic patients resulted in a significant decrease in total cholesterol levels (treatment difference (TD)=-30.04, P<0.001), triglyceride (TG) level (TD=-15.04, P=0.021), low-density lipoprotein (LDL) level (TD=-30.44, P<0.001) and total cholesterol to high-density lipoprotein (HDL) ratio (TD=-0.72, P<0.001) compared to the control group. There was a trend toward increasing HDL level with consumption of walnut oil (TD=2.28, P=0.06). Frequency of patients reaching a LDL level below 100 was higher in the case group (20 vs 0%). CONCLUSIONS: Addition of walnut oil in the daily diet of type 2 diabetic patients improves lipid profiles. Thus, it may be associated with a coronary artery disease risk factor modulation. Also, walnut oil may serve as a helpful natural remedy for hyperlipidemic patients with type 2 diabetes.

Maternal intake of dietary virgin coconut oil modifies essential fatty acids and causes low body weight and spiky fur in mice.

BACKGROUND: Coconut oil is commonly used as herbal medicine worldwide. There is limited information regarding its effects on the developing embryo and infant growth. METHODS: We investigated the effect of virgin coconut oil post-natally and until 6 weeks old in mice (age of maturity). Females were fed with either standard, virgin olive oil or virgin coconut oil diets 1 month prior to copulation, during gestation and continued until weaning of pups. Subsequently, groups of pups borne of the respective diets were continuously fed the same diet as its mother from weaning until 6 weeks old. Profiles of the standard and coconut oil diets were analysed by gas chromatography flame ionization detector (GCFID). RESULTS: Analysis of the mean of the total weight gained/ loss over 6 weeks revealed that in the first 3 weeks, pups whose mothers were fed virgin coconut oil and virgin olive oil have a significantly lower body weight than that of standard diet pups. At 6 weeks of age, only virgin coconut oil fed pups exhibited significantly lower body weight. We report that virgin coconut oil modifies the fatty acid profiles of the standard diet by inducing high levels of medium chain fatty acids with low levels of essential fatty acids. Furthermore, pups borne by females fed with virgin coconut oil developed spiky fur. CONCLUSION: Our study has demonstrated that virgin coconut oil could affect infant growth and appearance via maternal intake; we suggest the use of virgin coconut oil as herbal medicine to be treated with caution.

Red blood cell PUFAs reflect the phospholipid PUFA composition of major organs.

Numerous clinical trials examining the use of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) on various health outcomes have been conducted, and fish oil remains one of the most widely used nutritional supplements. More recently, studies have begun to utilize the omega-3 index, defined as the sum of EPA+DHA in red blood cells (RBCs), as both a biomarker of n-3 LCPUFA exposure and a potential risk factor for coronary heart disease (CHD). Considerably less research evaluates whether RBC phospholipid fatty acids reflect the phospholipid fatty acid composition of other tissues across increasing intakes of n-3 LCPUFAs. We fed mice diets containing increasing amounts of EPA+DHA, equivalent to current recommendations by the American Heart Association on a percent of energy basis, and analyzed the phospholipid fatty acid composition of various tissues in relation to RBCs. We observed that RBCs, heart, muscle, spleen, lung, and adipose tissues all respond to dietary supplementation with EPA+DHA with increasing n-3 LCPUFA and decreasing n-6 LCPUFA levels. Furthermore, the n-3 LCPUFA profiles of all measured tissues had strong (r>0.7) and significant (p<0.001) correlations to RBCs. Interestingly, we also observed changes in saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) levels across various tissues in response to increased EPA+DHA intakes despite there being no change in dietary SFA and MUFA. Specifically, there were increases in RBC SFA and spleen MUFA and decreases in heart MUFA. These demonstrate that the RBC, including the omega-3 index, may serve as a marker for the relative levels of n-3 and n-6 LCPUFAs in phospholipids of certain tissues.

Dietary long-chain unsaturated fatty acids acutely and differently reduce the activities of lipogenic enzymes and of citrate carrier in rat liver.

The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fatty acids (PUFAs) are known to induce on hepatic de novo lipogenesis (DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fatty acids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 % w/w) diets (HFDs) enriched in saturated fatty acids (SFAs) or unsaturated fatty acids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fatty acid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect.

Polyunsaturated fats, carbohydrates and carotid disease: The Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.

BACKGROUND AND AIMS: Carbohydrates and fat intake have both been linked to development of atherosclerosis. We examined associations between glycemic index (GI) and fat intake with carotid atherosclerosis. METHODS: The Atherosclerosis Risk in Communities (ARIC) cohort enrolled participants during the period 1987-1989 and the Carotid MRI sub-study occurred between 2004 and 2006 (1672 participants attending both visits). Measures of carbohydrate quality (usual GI), fat intake (total, polyunsaturated and saturated) and overall dietary quality index (DASH Diet Score) were derived from a 66-item food frequency questionnaire administered at baseline. Trained readers measured lipid core presence and maximum wall thickness. Using multivariate logistic regression, we determined the odds of lipid core presence by quintile (Q) of energy-adjusted dietary components. Restricted cubic spline models were used to examine non-linear associations between dietary components and maximum wall thickness. RESULTS: Mean daily polyunsaturated fat intake was 5 g (SD 1.4). GI and polyunsaturated fat intake had a nonlinear relationship with maximum wall thickness. Low (1-4 g) and high (6-12 g) polyunsaturated fat intake were associated with a statistically significant decreased odds of lipid core presence compared to intake in a majority of participants (OR Q5 vs. Q2-4: 0.64, 95% CI 0.42 to 0.98; OR Q1 vs. Q2-4: 0.64, 95% CI 0.42, 0.96), however, the association with lipid core was attenuated by adjustment for maximum wall thickness, hypertension, hyperlipidemia, and diabetes. CONCLUSIONS: GI and polyunsaturated fat intake were not associated with high-risk plaque features, such as lipid core presence, independent of traditional vascular risk factors.

Analysis of free hydroxytyrosol in human plasma following the administration of olive oil.

Hydroxytyrosol (HT) from olive oil, a potent bioactive molecule with health benefits, has a poor bioavailability, its free form (free HT) being undetectable so far. This fact leads to the controversy whether attained HT concentrations after olive oil polyphenol ingestion are too low to explain the observed biological activities. Due to this, an analytical methodology to determine free HT in plasma is crucial for understanding HT biological activity. Plasma HT instability and low concentrations have been major limitations for its quantification in clinical studies. Here, we describe a method to detect and quantify free HT in human plasma by using liquid chromatography coupled to tandem mass spectrometry. The method encompasses different steps of sample preparation including plasma stabilization, protein precipitation, selective derivatization with benzylamine, and purification by solid-phase extraction. A high sensitivity (LOD, 0.3ng/mL), specificity and stability of HT is achieved following these procedures. The method was validated and its applicability was demonstrated by analyzing human plasma samples after olive oil intake. A pharmacokinetic comparison was performed measuring free HT plasma concentrations following the intake of 25mL of ordinary olive oil (nearly undetectable concentrations) versus an extra-virgin olive oil (Cmax=4.40ng/mL). To our knowledge, this is the first time that an analytical procedure for quantifying free HT in plasma after olive oil dietary doses has been reported. The present methodology opens the door to a better understanding of the relationship between HT plasma concentrations and its beneficial health effects.

Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial.

The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14% as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic-euglycaemic-euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14%, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9%. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14% with the FO supplement, the enrichment in muscle membranes remained lower (8%; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.

Krill oil reduces plasma triacylglycerol level and improves related lipoprotein particle concentration, fatty acid composition and redox status in healthy young adults - a pilot study.

BACKGROUND: Lipid abnormalities, enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders. Krill oil (RIMFROST Sublime®) is a phospholipid-rich oil with eicosapentaenoic acid (EPA): docosahexaenoic acid (DHA) ratio of 1.8:1. In this pilot study we determined if krill oil could favourable affect plasma lipid parameters and parameters involved in the initiation and progression of atherosclerosis. METHODS: The study was conducted as a 28 days intervention study examining effect-parameters of dietary supplementation with krill oil (832.5 mg EPA and DHA per day). 17 healthy volunteers in the age group 18-36 (mean age 23 ± 4 years) participated. Plasma lipids, lipoprotein particle sizes, fatty acid composition in plasma and red blood cells (RBCs), plasma cytokines, antioxidant capacity, acylcarntines, carnitine, choline, betaine, and trimethylamine-N-oxide (TMAO) were measured before and after supplementation. RESULTS: Plasma triacylglycerol (TAG) and large very-low density lipoprotein (VLDL) & chylomicron particle concentrations decreased after 28 days of krill oil intake. A significant reduction in the TAG/HDL cholesterol resulted. Krill oil supplementation decreased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio both in plasma and RBCs. This was due to increased EPA, DHA and docosapentaenoic acid (DPA) and reduced amount of arachidonic acid (AA). The increase of n-3 fatty acids and wt % of EPA and DHA in RBC was of smaller magnitude than found in plasma. Krill oil intake increased the antioxidant capacity, double bond index (DBI) and the fatty acid anti-inflammatory index. The plasma atherogenicity index remained constant whereas the thrombogenicity index decreased. Plasma choline, betaine and the carnitine precursor, γ-butyrobetaine were increased after krill oil supplementation whereas the TMAO and carnitine concentrations remained unchanged. CONCLUSION: Krill oil consumption is considered health beneficial as it decreases cardiovascular disease risk parameters through effects on plasma TAGs, lipoprotein particles, fatty acid profile, redox status and possible inflammation. Noteworthy, no adverse effects on plasma levels of TMAO and carnitine were found.

Similar eicosapentaenoic acid and docosahexaenoic acid plasma levels achieved with fish oil or krill oil in a randomized double-blind four-week bioavailability study.

BACKGROUND: Long-chain n-3 polyunsaturated fatty acids (LC n-3-PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) provide multiple health benefits for heart, brain and eyes. However, consumption of fatty fish, the main source of LC n-3-PUFAs is low in Western countries. Intakes of LC n-3-PUFA can be increased by taking dietary supplements, such as fish oil, algal oil, or krill oil. Recently, conflicting information was published on the relative bioavailability of these omega-3 supplements. A few studies suggested that the phospholipid form (krill) is better absorbed than the fish oil ethyl ester (EE) or triglyceride (TG) forms. Yet studies did not match the doses administered nor the concentrations of DHA and EPA per supplement across such comparisons, leading to questionable conclusions. This study was designed to compare the oral bioavailability of the same dose of both EPA and DHA in fish oil-EE vs. fish oil-TG vs. krill oil in plasma at the end of a four-week supplementation. METHODS: Sixty-six healthy adults (n = 22/arm) were enrolled in a double blind, randomized, three-treatment, multi-dose, parallel study. Subjects were supplemented with a 1.3 g/d dose of EPA + DHA (approximately 816 mg/d EPA + 522 mg/d DHA, regardless of formulation) for 28 consecutive days, as either fish oil-EE, fish oil-TG or krill oil capsules (6 caps/day). Plasma and red blood cell (RBC) samples were collected at baseline (pre-dose on Day 1) and at 4, 8, 12, 48, 72, 336, and 672 h. Total plasma EPA + DHA levels at Week 4 (Hour 672) were measured as the primary endpoint. RESULTS: No significant differences in total plasma EPA + DHA at 672 h were observed between fish oil-EE (mean = 90.9 ± 41 ug/mL), fish oil-TG (mean = 108 ± 40 ug/mL), and krill oil (mean = 118.5 ± 48 ug/mL), p = 0.052 and bioavailability differed by < 24 % between the groups. Additionally, DHA + EPA levels were not significantly different in RBCs among the 3 formulations, p = 0.19, providing comparable omega-3 indexes. CONCLUSIONS: Similar plasma and RBC levels of EPA + DHA were achieved across fish oil and krill oil products when matched for dose, EPA, and DHA concentrations in this four week study, indicating comparable oral bioavailability irrespective of formulation. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02427373.

Essential Fatty Acid Deficiency in 2015: The Impact of Novel Intravenous Lipid Emulsions.

The fatty acids, linoleic acid (18:2ω-6) and α-linolenic acid (18:3ω-3), are essential to the human diet. When these essential fatty acids are not provided in sufficient quantities, essential fatty acid deficiency (EFAD) develops. This can be suggested clinically by abnormal liver function tests or biochemically by an elevated Mead acid and reduced linoleic acid and arachidonic acid level, which is manifested as an elevated triene/tetraene ratio of Mead acid/arachidonic acid. Clinical features of EFAD may present later. With the introduction of novel intravenous (IV) lipid emulsions in North America, the proportion of fatty acids provided, particularly the essential fatty acids, varies substantially. We describe a case series of 3 complicated obese patients who were administered parenteral nutrition (PN), primarily using ClinOleic 20%, an olive oil-based lipid emulsion with reduced amounts of the essential fatty acids, linoleic and α-linolenic, compared with more conventional soybean oil emulsions throughout their hospital admission. Essential fatty acid profiles were obtained for each of these patients to investigate EFAD as a potential cause of abnormal liver enzymes. Although the profiles revealed reduced linoleic acid and elevated Mead acid levels, this was not indicative of the development of essential fatty acid deficiency, as reflected in the more definitive measure of triene/tetraene ratio. Instead, although the serum fatty acid panel reflected the markedly lower but still adequate dietary linoleic acid content and greatly increased oleic acid content in the parenteral lipid emulsion, the triene/tetraene ratio remained well below the level, indicating EFAD in each of these patients. The availability and use of new IV lipid emulsions in PN should encourage the clinician to review lipid metabolism based on the quantity of fatty acids provided in specific parenteral lipid emulsions and the expected impact of these lipid emulsions (with quite different fatty acid composition) on measured fatty acid profiles.

Invited commentary: dietary polyunsaturated Fatty acids and chronic systemic inflammation--a potentially intriguing link.

It remains largely unclear whether consumption of total and individual polyunsaturated fatty acids (PUFAs) is associated with chronic systemic inflammation in healthy, free-living individuals. While available evidence (stemming principally from mechanistic studies) has indicated that greater intake of n-6 PUFAs may lead to increased levels of inflammation-for instance, by their acting as precursors to proinflammatory eicosanoids and increasing levels of oxidized linoleic acid metabolites-n-3 PUFAs are precursors to some antiinflammatory eicosanoids. New human data from a Dutch prospective study, the Rotterdam Study-as presented by Muka et al. ( Am J Epidemiol. 2015;181(11):846-856) in this issue of the Journal-now make an important contribution to the relatively scarce literature on the association of dietary n-3 and n-6 PUFAs with serum levels of C-reactive protein (CRP), a key marker of inflammation, in a general population. The study by Muka et al. benefitted from repeated CRP measurements, comprehensive correction for potential confounding, and wide-ranging sensitivity analyses. The findings show no significant trend regarding n-3 PUFAs but indicate an important inverse association between n-6 PUFAs and chronic systemic inflammation. This study provides support for existing dietary guidelines, which encourage consumption of a combination of n-3 and n-6 PUFAs in the diet.

Polyunsaturated fatty acids and serum C-reactive protein: the Rotterdam study.

We aimed to investigate whether dietary intake of total or individual (n-3, n-6, and n-3:n-6 ratio) polyunsaturated fatty acids (PUFAs) was prospectively associated with serum levels of C-reactive protein (CRP), a marker of inflammation. We analyzed 4,707 participants (1,943 men and 2,764 women) from the Rotterdam Study, a prospective follow-up study of subjects aged 55 years or older in the Netherlands. At baseline (1989-1993), dietary intake of PUFAs was assessed by validated food frequency questionnaire. CRP was measured at baseline and at the third study visit (1997-1999). Regression coefficients (ß) and 95% confidence intervals were obtained using linear generalized estimating equations. Dietary intake of butter and margarine explained most of the variance in PUFA intake. After adjustment for possible confounding factors, higher intake of total PUFAs was associated with lower CRP levels (fourth quartile vs. first quartile: ß = -0.08, 95% confidence interval: -0.15, -0.01). Similarly, intake of n-6 PUFAs was inversely related to CRP (fourth quartile vs. first: ß = -0.09, 95% confidence interval: -0.16, -0.01). No consistent trends were observed regarding n-3 PUFAs or n-3:n-6 PUFA ratio and CRP. These findings suggest that high intakes of total PUFAs are associated with lower levels of CRP, reflecting diminished chronic systemic inflammation, which in our study was mainly driven by n-6 PUFAs.

Cyclic fatty acids found in frying oils are detoxified via classical drug metabolic pathway but also by ß-oxidation and eliminated as conjugates in rats.

Cyclic fatty acid monomers (CFAM) are mainly formed during heat treatments, such as frying, of edible oils. These fatty acids are mixtures of disubstituted five- or six-carbon-membered ring structures. Some earlier studies have suggested that some of these molecules could be metabolized and detoxified, but so far, neither the detoxification mechanisms nor the metabolite identifications have been elucidated. The objective of the present study was to identify the metabolites resulting from the metabolism and detoxification of CFAM. A deuterium-labeled CFAM, [9-(2)H]-10-(6-propyl-2-cyclohexenyl)-dodecenoic acid, was synthesized and fed to rats for 3 days, along with a standard chow diet while the control group was fed the same chow diet which did not contain any CFAM. Biological fluids (urine, blood) were collected for both groups of rats and analyzed using an untargeted metabolomic approach by ultra-performance liquid chromatography coupled with mass spectrometry. Two discriminant metabolites and 18 molecules derived from CFAM were identified or tentatively identified in plasma and urine samples, respectively. The structures of the metabolites suggest that CFAM having a six-carbon-membered ring could be detoxified by the classical drug metabolic pathway (phase I and phase II reactions), but our study also indicates that these are substrates for the ß-oxidation pathway and eliminated as glucuronide, sulphate, and/or nitrate conjugates. Urine metabolomics investigations without diet effects have indicated a higher excretion of medium-chain acylcarnitines in the D-CFAM diet group, which may indicate an incomplete ß-oxidation.