Replacement Of Saturated Fatty Acids Research Articles

Perspective on the health effects of unsaturated fatty acids and commonly consumed plant oils high in unsaturated fat.

Epidemiological and clinical trial evidence indicates that n-6 polyunsaturated fatty acid (PUFA) intake is cardioprotective. Nevertheless, claims that n-6 PUFA intake promotes inflammation and oxidative stress prevail. This narrative review aims to provide health professionals with an up-to-date evidence overview to provide the requisite background to address patient/client concerns about oils containing predominantly unsaturated fatty acids (UFA), including MUFA and PUFA. Edible plant oils, commonly termed vegetable oils, are derived from vegetables, nuts, seeds, fruits and cereal grains. Substantial variation exists in the fatty acid composition of these oils; however, all are high in UFA, while being relatively low in saturated fatty acids (SFA), except for tropical oils. Epidemiological evidence indicates that higher PUFA intake is associated with lower risk of incident CVD and type 2 diabetes mellitus (T2DM). Additionally, replacement of SFA with PUFA is associated with reduced risk of CVD and T2DM. Clinical trials show higher intake of UFA from plant sources improves major CVD risk factors, including reducing levels of atherogenic lipids and lipoproteins. Importantly, clinical trials show that increased n-6 PUFA (linoleic acid) intake does not increase markers of inflammation or oxidative stress. Evidence-based guidelines from authoritative health and scientific organisations recommend intake of non-tropical vegetable oils, which contain MUFA and n-6 PUFA, as part of healthful dietary patterns. Specifically, vegetable oils rich in UFA should be consumed instead of rich sources of SFA, including butter, tallow, lard, palm and coconut oils.

Variation of LDL cholesterol in response to the replacement of saturated with unsaturated fatty acids: a nonrandomized, sequential dietary intervention; the Reading, Imperial, Surrey, Saturated fat Cholesterol Intervention (“RISSCI”-1) study

BackgroundSerum low density lipoprotein (LDL) cholesterol shows marked interindividual variation in response to the replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs). ObjectivesTo demonstrate the efficacy of United Kingdom guidelines for exchanging dietary SFAs for UFAs, to reduce serum LDL cholesterol and other cardiovascular disease (CVD) risk factors, and to identify determinants of the variability in LDL cholesterol response. MethodsHealthy males (n = 109, mean ± SD age 48 ± 11 y; BMI 25.1 ± 3.3 kg/m2), consumed a higher-SFA/lower-UFA diet for 4 wk, followed by an isoenergetic, lower-SFA/higher-UFA diet for 4 wk (achieved intakes SFA:UFA as % total energy 19.1:14.8 and 8.9:24.5, respectively). Serum LDL cholesterol, CVD risk markers, peripheral blood mononuclear cell (PBMC) gene expression, and dietary intakes were assessed at baseline and the end of each diet. ResultsTransition from a higher-SFA/lower-UFA to a lower-SFA/higher-UFA diet significantly reduced fasting blood lipids: LDL cholesterol (−0.50 mmol/L; 95% confidence interval [CI]: −0.58, −0.42), high-density lipoprotein (HDL) cholesterol (−0.11 mmol/L; 95% CI: −0.14, −0.08), and total cholesterol (TC) (−0.65 mmol/L; 95% CI:−0.75, −0.55). The dietary exchange also reduced apolipoprotein (apo)B, TC:HDL cholesterol ratio, non-HDL cholesterol, E-selectin (P < 0.0001), and LDL subfraction composition (cholesterol [LDL-I and LDL-II], apoB100 [LDL-I and LDL-II], and TAG [LDL-II]) (P < 0.01). There was also an increase in plasma biomarkers of cholesterol intestinal absorption (β-sitosterol, campesterol, cholestanol), and synthesis (desmosterol) (P < 0.0001) and fold change in PBMC LDL-receptor mRNA expression relative to the higher-SFA/lower-UFA diet (P = 0.035). Marked interindividual variation in the change in serum LDL cholesterol response (−1.39 to +0.77 mmol/L) to this dietary exchange was observed, with 33.7% of this variation explained by serum LDL cholesterol before the lower-SFA/higher-UFA diet and reduction in dietary SFA intake (adjusted R2 27% and 6.7%, respectively). APOE genotype was unrelated to serum LDL cholesterol response to SFA. ConclusionsThese findings support the efficacy of United Kingdom SFA dietary guidelines for the overall lowering of serum LDL cholesterol but showed marked variation in LDL cholesterol response. Further identification of the determinants of this variation will facilitate targeting and increasing the efficacy of these guidelines.The RISSCI-1 study was registered with ClinicalTrials.Gov (No. NCT03270527).

Effects of saturated fatty acid consumption on lipoprotein (a): a systematic review and meta-analysis of randomized controlled trials

BackgroundAn inverse relationship between saturated fatty acid (SFA) intake and Lp(a) concentration has been observed; however, there has been no quantification of this effect. ObjectivesThe objective was to determine whether SFA consumption alters Lp(a) concentrations among adults without atherosclerotic cardiovascular disease (ASCVD). MethodsA systematic review and meta-analysis of randomized controlled trials contrasting a lower SFA diet(s) with a higher SFA diet(s) among adults without ASCVD was conducted. PubMed, Cochrane Central Register of Clinical Trials, clinicaltrials.gov, and Web of Science databases and registers were searched through October 2023. The standardized mean difference (SMD) in Lp(a) between diets lower and higher in SFA [percentage of energy (%E)] was determined using random-effects meta-analysis. Analyses were also conducted to examine the effect of replacing SFA with carbohydrates (CHO), monounsaturated (MUFAs), polyunsaturated (PUFAs), or trans fatty acids (TFAs). ResultsIn total, 6255 publications were identified in the systematic search. Twenty-six publications reporting 27 randomized controlled trials, including 1325 participants and 49 diet comparisons, were included. The mean difference in SFA between lower and higher SFA diets was 7.6%E (3.7%–17.8%E). After lower SFA diets, Lp(a) concentration was higher (SMD: 0.14; 95% confidence interval [CI]: 0.03, 0.24) than after higher SFA diets. Subgroup analyses showed higher Lp(a) following diets where SFA was replaced by CHO (trials = 8; n = 539; SMD: 0.21; 95% CI: 0.02, 0.40) or TFAs (trials = 8; n = 300; SMD: 0.32; 95% CI: 0.17, 0.48). No differences in Lp(a) were observed when MUFA (trials = 16; n = 641; SMD: 0.04; 95% CI: −0.08, 0.16) or PUFA (trials = 8; n = 415; SMD: 0.09; 95% CI: −0.04, 0.22) replaced SFA. ConclusionsLower SFA diets modestly increase Lp(a) compared to higher SFA diets among individuals without ASCVD. This effect appeared to be driven by replacement of SFA with CHO or TFA. Research investigating the atherogenicity of diet-induced Lp(a) changes is needed to inform dietary management of lipid/lipoprotein disorders.This trial was registered with PROSPERO as CRD42020154169.

Replacement of Saturated Fatty Acids from Meat by Dairy Sources in Relation to Incident Cardiovascular Disease: The European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study

BackgroundProspective observational data revealed lower cardiovascular disease (CVD) incidence with modeled replacement of saturated fatty acids (SFA) from total meat by total dairy, but it is unknown what the associations are of replacing SFA from types of meat by types of dairy with CVD incidence. ObjectivesThis study aimed to investigate the associations of replacing SFA from total, red, processed, and poultry meat by SFA from total dairy, milk, cheese, and yogurt with the incidence of CVD. MethodsWe analyzed longitudinal data from 21,841 participants of the European Prospective Investigation into Cancer and Nutrition-Norfolk study (56.4% female; age, 40–79 years). Dietary data were collected by food frequency questionnaires at baseline (1993–1997). Incident fatal or nonfatal CVD (n = 5902), coronary artery disease (CAD; n = 4215), stroke (total: n = 2544; ischemic: n = 1113; hemorrhagic: n = 449) were identified up to 2018. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression for the risk associated with replacement of 2.5% of energy from SFA from meat by dairy, adjusted for sociodemographic, lifestyle, energy, dietary, and cardiometabolic factors. ResultsReplacing SFA from total meat by total dairy was associated with a lower CVD incidence (HR: 0.89; 95% CI: 0.82, 0.96) and CAD (HR: 0.88; 95% CI: 0.80, 0.96). Replacing SFA from processed meat by cheese was associated with lower CVD (HR: 0.77; 95% CI: 0.68, 0.88); CAD (HR: 0.77; 95% CI: 0.66, 0.90), and stroke (HR: 0.81; 95% CI: 0.67, 0.99). Similarly, replacing SFA from red meat by cheese was associated with lower CVD (HR: 0.86; 95% CI: 0.76, 0.97). Higher incidence of stroke was found with replacement of SFA from poultry by milk (HR: 2.06; 95% CI: 1.09, 3.89), yogurt (HR: 2.55; 95% CI: 1.27, 5.13), or cheese (HR: 1.96; 95% CI: 1.04, 3.70), but the CI were relatively large, owing to low, narrow range of poultry SFA intake. ConclusionsFindings indicate that different SFA-rich foods at baseline have differential associations with CVD risk. If confirmed by further studies, these findings could be used to inform specific food-based dietary guidance.

Fat and fatty acids - a scoping review for Nordic Nutrition Recommendations 2023.

Two de novo NNR2022 systematic reviews (SRs) as well as 21 qualified SRs (qSRs) were available. A literature search yielded an additional ~70 SRs, meta-analyses and biomarker papers. Diets lower in total fat are associated with reductions in body weight and blood pressure compared with diets higher in total fat in adults. Partial replacement of saturated fatty acid (SFA) with n-6 polyunsaturated fatty acid (PUFA) improves blood lipid profile, decreases the risk of cardiovascular disease (CVD), improves glucose-insulin homeostasis and may decrease the risk of total mortality. Long-chain n-3 PUFAs (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) decrease triglycerides and are associated with lower risk of CVD. Dietary PUFAs, both n-3 and n-6, may be associated with reduced risk of type 2 diabetes (T2D). There is inconclusive evidence to suggest that the type of dietary fat is associated with blood pressure, risk of hypertension or musculoskeletal health. Higher intake of total PUFA is associated with lower mortality from any cancer. Long-chain n-3 PUFA is associated with reduced risk of breast cancer, whereas biomarker levels of n-6 PUFA are associated with lower risk of any cancer. Intake of long-chain n-3 PUFA during pregnancy increases length of gestation and child birth weight and reduces the risk of preterm delivery, but there is inconclusive evidence to suggest that it may influence child neurodevelopment, growth or development of allergic disease. In studies with higher versus lower dietary cholesterol intake levels, total blood cholesterol increased or were unaffected by the dietary cholesterol, resulting in inconclusive results. Trans fatty acid (TFA), regardless of source, impairs blood lipid profile compared to unsaturated fat. In observational studies, TFA is positively associated with CVD and total mortality but whether associations differ by source is inconclusive. Ruminant TFA, as well as biomarker levels of odd-chain fatty acids, might be associated with lower risk of T2D.

Replacement of saturated fatty acids with linoleic acid in western diet attenuates atherosclerosis in a mouse model with inducible ablation of hepatic LDL receptor

Dietary saturate fatty acids (SFAs) have been consistently linked to atherosclerosis and obesity, both of which are characterized by chronic inflammation and impaired lipid metabolism. In comparison, the effects of linoleic acid (LA), the predominant polyunsaturated fatty acid in the Western diet, seem to diverge. Data from human studies suggest a positive association between high dietary intake of LA and the improvement of cardiovascular risk. However, excessive LA intake has been implicated in the development of obesity. Concerns have also been raised on the potential pro-inflammatory properties of LA metabolites. Herein, by utilizing a mouse model with liver-specific Ldlr knockdown, we directly determined the effects of replacing SFAs with LA in a Western diet on the development of obesity and atherosclerosis. Specifically, mice treated with a Ldlr ASO were placed on a Western diet containing either SFA-rich butter (WD-B) or LA-rich corn oil (WD-CO) for 12 weeks. Despite of showing no changes in body weight gain or adiposity, mice on WD-CO exhibited significantly less atherosclerotic lesions compared to those on WD-B diet. Reduced lesion formation in the WD-CO-fed mice corresponded with a reduction of plasma triglyceride and cholesterol content, especially in VLDL and LDL, and ApoB protein levels. Although it increased expression of proinflammatory cytokines TNF-α and IL-6 in the liver, WD-CO did not appear to affect hepatic injury or damage when compared to WD-B. Collectively, our results indicate that replacing SFAs with LA in a Western diet could reduce the development of atherosclerosis independently of obesity.

The Influence of Dietary Interventions on Arterial Stiffness in Overweight and Obese Subjects.

Arterial stiffness is often increased in overweight/obese subjects before the development of hypertension. It is also one of the earliest indicators of increased cardiovascular disease risk and can be considered a good predictor of the development of subclinical cardiovascular dysfunction. Arterial stiffness is a significant prognostic factor influencing cardiovascular risk, which dietary habits can modify. Obese patients should use the caloric-restricted diet because it augments aortic distensibility, diminishes pulse wave velocity (PWV), and increases the activity of endothelial nitric oxide synthases. High intake of saturated fatty acids (SFA), trans fats, and cholesterol, typical for the Western diet, impairs endothelial function and raises brachial-ankle PWV. The replacement of SFA with monounsaturated (MUFA) or polyunsaturated fatty acids (PUFA) derived from seafood and plants diminishes the risk of arterial stiffness. The dairy product intake (excluding butter) decreases PWV in the general population. The high-sucrose diet causes toxic hyperglycemia and increases arterial stiffness. Complex carbohydrates with a low glycemic index (including isomaltose) should be recommended to keep vascular health. The high sodium intake (>10 g/day), particularly associated with low potassium consumption, has a deleterious effect on arterial stiffness (↑ baPWV). Since vegetables and fruits are good sources of vitamins and phytochemicals, they should be recommended in patients with high PWV. Thus, the dietary recommendation to prevent arterial stiffness should be similar to the Mediterranean diet, which is rich in dairy products, plant oils, and fish, with a minimal red meat intake and five servings of fruits and vegetables daily.

Putting saturated fat in context-replacement and total intake matter.

The manuscript ‘Saturated Fat: Villain and Bogeyman in the Development of Cardiovascular Disease?’ was recently published in European Journal of Preventive Cardiology.1 Given the extraordinary importance of nutrition on health, we would like to contextualize this review and help avoid unnecessary public confusion. We agree with the authors that complexities exist in nutritional research. With regard to this specific review, it is important to consider what macronutrient may have replaced saturated fatty acids (SFA) in cited studies. Specifically, was SFA replaced with polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), or healthful carbohydrates such as whole grains? Or was SFA replaced with refined grains, sugar, or harmful trans unsaturated fats? Many of the SFA studies and reviews cited by the authors did not account for replacement or were in the context of replacement with refined carbohydrates or trans fat. When replacement is accounted for, the adverse effects of SFA on cardiovascular outcomes are much more consistent. The authors actually report several meta-analyses of observational studies and clinical trials showing that replacing SFA with PUFA is associated with reduced risk of cardiovascular disease, even though they conclude these beneficial effects ‘remain elusive’. This was also demonstrated in a 2015 study of over 120 000 individuals showing that replacement of SFA with PUFA as well as MUFA or whole-grain carbohydrates was associated with improved cardiovascular outcomes, while replacement with refined carbohydrates or smaller amounts of trans fat was associated with no difference.2 Though this particular study accounted for replacement macronutrients and met all inclusion criteria for the authors’ review, it was not cited. The authors also failed to mention that several older studies supposedly vindicating SFA, such as the Sydney Diet Heart Study from decades ago, included PUFA from vegetable oil products high in harmful trans fat. Fortunately, vegetable oils with artificial trans fat are now banned in most industrialized countries.

Replacement of saturated fatty acids from meats by dairy sources in relation to incident coronary heart diseases in the European Investigation into Cancer and Nutrition (EPIC)-Norfolk study

Replacement of saturated fatty acids from meats by dairy sources in relation to incident coronary heart diseases in the European Investigation into Cancer and Nutrition (EPIC)-Norfolk study

Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study.

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.

Abstract P059: Effects Of Saturated Fatty Acid On Lipoprotein(a): A Systematic Review And Meta-analysis

Background: Elevated lipoprotein(a) [Lp(a)] is a significant contributor to residual CVD risk. Replacement of saturated fatty acids (SFA) with mono- and polyunsaturated fatty acids (MUFA and PUFA), carbohydrates (CHO) has established effects on traditional lipid parameters related to CVD; however, the evidence for Lp(a) is inconsistent. Moreover, some evidence suggests replacing SFA with other macronutrients increases Lp(a). Objective: The aim was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of replacing SFA with MUFA, PUFA, trans fatty acids (TFA) and CHO on Lp(a). Methods: PubMed, Cochrane Central, ClinicalTrials.gov, and Web of Science were searched for RCTs with a duration of ≥13 days that included healthy adults ages 20-65 y and examined the effect of diets differing in SFA, MUFA, PUFA, or CHO on Lp(a). Exclusion criteria included changes in protein/alcohol and &gt;10% weight loss in last 6 months. Diet comparisons were extracted from trials to assess the effect of substitution of SFA for other macronutrients. Data are presented as weighted means. Data were analyzed using a mixed model approach (SAS 9.4). Results: Twenty-seven articles met criteria for inclusion and data were available for analysis for 15 articles. There were 39 comparisons between SFA and other macronutrients. Lp(a) was measured by macra, polyclonal, or sandwich enzyme linked immunosorbent assay (ELISA), particle enhanced turbidimetric immunoassay, or radioimmunoassay. SFA was substituted for TFA ( k =6), MUFA ( k =9), and PUFA ( k =3). Five trials compared a high SFA diet with a high CHO diet. A total of 539 adults (44.7 + 31.6 y) were included in the pooled sample. Overall, the mean displacement of SFA for other macronutrients was 6.7% of kcals. Mean Lp(a) across the included studies was 100.5 + 100.3 mg/dl. Replacement of SFA with MUFA, PUFA or CHO did not significantly affect Lp(a). Lp(a) was 6.1 mg/dl (p=0.021; 95% CI: -11.3, -0.9) lower when SFA replaced TFA. Conclusions: Overall, substitution of SFA for other macronutrients did not impact Lp(a) concentrations. Lower levels of Lp(a) were observed when 5% of kcals from TFA were replaced with SFA, although the clinical relevance of this finding is unclear. Further research examining the effect of SFA replacement on Lp(a) is needed due to the methodological quality of the available data and heterogeneity in Lp(a) measurement methods utilized.

Beneficial Role of Replacing Dietary Saturated Fatty Acids with Polyunsaturated Fatty Acids in the Prevention of Sarcopenia: Findings from the NU-AGE Cohort.

Dietary fat subtypes may play an important role in the regulation of muscle mass and function during ageing. The aim of the present study was to determine the impact of isocaloric macronutrient substitutions, including different fat subtypes, on sarcopenia risk in older men and women, while accounting for physical activity (PA) and metabolic risk. A total of 986 participants, aged 65–79 years, completed a 7-day food record and wore an accelerometer for a week. A continuous sex-specific sarcopenia risk score (SRS), including skeletal muscle mass assessed by dual-energy X-ray absorptiometry (DXA) and handgrip strength, was derived. The impact of the isocaloric replacement of saturated fatty acids (SFAs) by either mono- (MUFAs) or poly-unsaturated (PUFAs) fatty acids on SRS was determined using regression analysis based on the whole sample and stratified by adherence to a recommended protein intake (1.1 g/BW). Isocaloric reduction of SFAs for the benefit of PUFAs was associated with a lower SRS in the whole population, and in those with a protein intake below 1.1 g/BW, after accounting for age, smoking habits, metabolic disturbances, and adherence to PA guidelines. The present study highlighted the potential of promoting healthy diets with optimised fat subtype distribution in the prevention of sarcopenia in older adults.

The association of dietary macronutrients composition with the incidence of cardiovascular disease, using iso-energetic substitution models: Tehran lipid and glucose study

Background and aimsDietary macronutrient composition plays an important role in the prevention of cardiovascular disease (CVD). This study aimed at assessing the iso-energetic substitution of dietary macronutrients in relation to the incidence of CVD. Materials and resultsThis prospective study was conducted on 5102 individuals of Tehran lipid and glucose study participants, aged 20–70 years who were followed for 5.3 years. A valid and reliable semi-quantitative food frequency questionnaire was used to assess dietary intakes. The hazard ratio of CVD for each 5% of energy from macronutrients at the expense of another macronutrient was calculated using the substitution model.During follow-up, a total of 206 CVD outcomes were identified. Mean age of participants (44.2% men) was 47.0 ± 12 and 45.6 ± 11 for men and women, respectively. Substituting 5% of energy from all types of macronutrients by 5% percentage of energy from combined saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) was associated with a decrease in the risk of CVD by almost 20%. Higher energy intake from total-, starchy-, and nonstarchy carbohydrates replaced by other macronutrients was not significantly associated with the risk of CVD. Each 5% of energy from animal protein (HR: 1.09 and CI: 1.02–1.16) independently increased the risk of CVD in the adjusted Cox proportional hazard regression analyses. ConclusionHigher percentage of energy from animal protein independently increased the risk of CVD, replacement of SFA and MUFA together with other macronutrients was inversely associated with CVD risk.

Monounsaturated Fatty Acids in a High-Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome.

Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega-3 long-chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega-3 long-chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)-induced metabolic syndrome are unknown. Male Lepob/ob LDLR-/- mice are fed a chow diet or HFDs based on milk cream (21%kcal), olive oil (21%kcal), or olive oil (20%kcal) plus 1%kcal from eicosapentaenoic and docosahexaenoic acids, including immediate-release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD+ signaling pathways by triggering NAD+ biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD+ and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD-induced obesity and metabolic syndrome.

Dietary fat composition: replacement of saturated fatty acids with PUFA as a public health strategy, with an emphasis on α-linolenic acid.

SFA intakes have decreased in recent years, both in Ireland and across other European countries; however a large proportion of the population are still not meeting the SFA recommendation of &lt;10% of total energy (TE). High SFA intakes have been associated with increased CVD and type-2 diabetes (T2D) risk, due to alterations in cholesterol homoeostasis and adipose tissue inflammation. PUFA, in particular EPA and DHA, have been associated with health benefits, including anti-inflammatory effects. It is well established that dietary fat composition plays an important role in biological processes. A recent review of evidence suggests that replacement of SFA with PUFA has potential to reduce risk of CVD and T2D. The public health and molecular impact of EPA and DHA have been well-characterised, while less is known of effects of α-linolenic acid (ALA). The current dietary guideline for ALA is 0·5% TE; however evidence from supplementation trials suggests that benefit is observed at levels greater than 2 g/d (0·6-1% TE). This review highlights the gap in the evidence base relating to effects of the replacement of SFA with ALA, identifying the need for randomised controlled trials to determine the optimal dose of ALA substitution to define the efficacy of dietary fat modification with ALA.

ω-6 Polyunsaturated Fatty Acids and Cardiometabolic Health: Current Evidence, Controversies, and Research Gaps.

ABSTRACTThe 2015 Dietary Guidelines for Americans recommend limiting the intake of saturated fatty acids (SFAs) to <10% of energy/d and replacing dietary SFAs with unsaturated fatty acids. A Presidential Advisory from the American Heart Association recently released its evaluation of the relation between dietary fats and cardiovascular disease (CVD), and also recommended a shift from SFAs to unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), in conjunction with a healthy dietary pattern. However, the suggestion to increase the intake of PUFAs in general, and omega-6 (n–6) PUFAs in particular, continues to be controversial. This review was undertaken to provide an overview of the evidence and controversies regarding the effects of ω-6 PUFAs on cardiometabolic health, with emphasis on risks and risk factors for CVD (coronary heart disease and stroke) and type 2 diabetes mellitus (T2D). Results from observational studies show that higher intake of ω-6 PUFAs, when compared with SFAs or carbohydrate, is associated with lower risks for CVD events (10–30%), CVD and total mortality (10–40%), and T2D (20–50%). Findings from intervention studies on cardiometabolic risk factors suggest that ω-6 PUFAs reduce concentrations of LDL cholesterol and non-HDL cholesterol in a dose-dependent manner compared with dietary carbohydrate, and have a neutral effect on blood pressure. Despite the concern that ω-6 fatty acids increase inflammation, current evidence from studies in humans does not support this view. In conclusion, these findings support current recommendations to emphasize consumption of ω-6 PUFAs as a replacement of SFAs; additional randomized controlled trials with cardiometabolic disease outcomes will help to more clearly define the benefits and risks of this policy.

Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study

The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries. We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events. Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all ptrend<0·0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all ptrend<0·0001, apart from ApoB [ptrend=0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol. Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk. Full funding sources listed at the end of the paper (see Acknowledgments).

Saturated fats, dairy foods and health: A curious paradox?

AbstractCardiovascular diseases (CVD) remain a major cause of death and morbidity worldwide. Dietary guidelines aim to restrict the intake of saturated fatty acids (SFA) as they are regarded as an important risk factor for CVD due to their association with increased blood cholesterol. As dairy foods are major contributors of dietary SFA, there have been guidelines to reduce consumption of these foods. However, it is now generally accepted that the effects of reducing intake of SFA are dependent on what replaces them in the diet. Reduced CVD risk has been associated with replacement of SFA with cis‐polyunsaturated fatty acids (cis‐PUFA) and/or cis‐monounsaturated fatty acids (cis‐MUFA), with replacement by carbohydrate leading to no reduction or even increased CVD risk. Most studies on the effect of diet/food on CVD risk have used total cholesterol (TC) and/or low‐density lipoprotein cholesterol (LDL‐C) in blood as the marker(s) of risk. However, because of potentially attenuating effects of dairy foods (e.g. effect of protein on blood lipids and blood pressure; food matrix effects on fat bioavailability), a wider range of markers is needed to more fully evaluate disease risk. Nevertheless, whilst prospective evidence shows no increase in CVD risk from high dairy consumption, it is still unclear whether replacing a proportion of SFA in dairy fat with cis‐MUFA will lead to reduced CVD risk. The relatively few randomised controlled trials that have examined this using TC/LDL‐C as risk markers give some indications of reduced CVD risk from consumption of milk and dairy products with modified fatty acid composition, compared with those of normal milk fat composition. The results of ongoing studies will add valuable new evidence on this issue.

Serum low‐density lipoprotein as a dietary responsive biomarker of cardiovascular disease risk: Consensus and confusion

AbstractThe replacement of saturated fatty acids (SFA) has been the mainstay of our dietary guidelines to help prevent cardiovascular disease (CVD) for over 30 years. However, the underlying evidence to support this guideline is now held in contentious disrepute on the grounds of an apparent lack of evidence, largely from meta‐analyses, for a direct relationship between saturated fat and CVD mortality. This can be explained by the fact that the relationship between dietary SFA and CVD is not direct, but indirect and mediated through the low‐density lipoprotein cholesterol (LDL‐C) raising effects of certain SFA, in certain foods. There is over 100 years of evidence to link raised serum cholesterol with CVD and to support the current consensus that serum LDL is causally related to CVD morbidity and mortality. Nevertheless, the role of LDL as a biomarker of CVD risk, as measured by its cholesterol content (LDL‐C), is often confused with its contribution to cardio‐metabolic risk by its conversion into small and dense LDL particles with increased potential to cause CVD. The clinical utility of serum LDL is outstanding as a biomarker for CVD, albeit through an increase in its cholesterol mass (LDL‐C), its small particle size or over‐abundance of these particles. What is of overriding importance is to identify and modify these characteristics in LDL at the earliest stage of their development and to reduce the associated CVD risk through appropriate and sustained changes in diet and lifestyle.

Clinical Outcomes of Dietary Replacement of Saturated Fatty Acids with Unsaturated Fat Sources in Adults with Overweight and Obesity: A Systematic Review and Meta-Analysis of Randomized Control Trials

Background: Obesity and dyslipidemia are frequently treated with dietary interventions before pharmacotherapy is given. Diets high in unsaturated fat have proven advantageous to disease treatment. Aims: The purpose of this systematic review and meta-analysis was to assess the evidence of the effect of saturated fatty acids (SFA) replacement with unsaturated fatty acids (UFA) in metabolically healthy adults with overweight and obesity on markers of dyslipidemia and body composition. Methods: Keyword search was performed in PubMed, CINAHL, and Cochrane Library for randomized controlled trials (RCTs) evaluating the effects of fatty acid substitution in adults with overweight and obesity. Meta-analysis was performed on interventions assessing lipoprotein levels and body composition. Publication bias was assessed by funnel plot inspection, Begg's, and Egger's test. Results: Eight RCTs enrolling 663 participants were included in the review, with intervention durations between 4 and 28 weeks. Although nonsignificant (p = 0.06), meta-analysis found UFA replacement to reduce total cholesterol concentrations by 10.68 mg/dL (95%CI -21.90 to 0.53). Reductions in low-density lipoprotein cholesterol and triglycerides were statistically nonsignificant. Conclusions: Due to null results and a small number of studies included, there is no strong evidence that replacement of SFA with UFA may benefit lipid profiles in this population.