Sarah K Gebauer

n−3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits

Dietary recommendations have been made for n-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) to achieve nutrient adequacy and to prevent and treat cardiovascular disease. These recommendations are based on a large body of evidence from epidemiologic and controlled clinical studies. The n-3 fatty acid recommendation to achieve nutritional adequacy, defined as the amount necessary to prevent deficiency symptoms, is 0.6-1.2% of energy for ALA; up to 10% of this can be provided by EPA or DHA. To achieve recommended ALA intakes, food sources including flaxseed and flaxseed oil, walnuts and walnut oil, and canola oil are recommended. The evidence base supports a dietary recommendation of approximately 500 mg/d of EPA and DHA for cardiovascular disease risk reduction. For treatment of existing cardiovascular disease, 1 g/d is recommended. These recommendations have been embraced by many health agencies worldwide. A dietary strategy for achieving the 500-mg/d recommendation is to consume 2 fish meals per week (preferably fatty fish). Foods enriched with EPA and DHA or fish oil supplements are a suitable alternate to achieve recommended intakes and may be necessary to achieve intakes of 1 g/d.

The Diversity of Health Effects of Individual trans Fatty Acid Isomers

There are multiple adverse effects of trans fatty acids (TFA) that are produced by partial hydrogenation (i.e., manufactured TFA), on CVD, blood lipids, inflammation, oxidative stress, endothelial health, body weight, insulin sensitivity, and cancer. It is not yet clear how specific TFA isomers vary in their biological activity and mechanisms of action. There is evidence of health benefits on some of the endpoints that have been studied for some animal TFA isomers, such as conjugated linoleic acid; however, these are not a major TFA source in the diet. Future research will bring clarity to our understanding of the biological effects of the individual TFA isomers. At this point, it is not possible to plan diets that emphasize individual TFA from animal sources at levels that would be expected to have significant health effects. Due to the multiple adverse effects of manufactured TFA, numerous agencies and governing bodies recommend limiting TFA in the diet and reducing TFA in the food supply. These initiatives and regulations, along with potential TFA alternatives, are presented herein.

Dietary stearic acid and risk of cardiovascular disease: Intake, sources, digestion, and absorption

Individual FA have diverse biological effects, some of which affect the risk of cardiovascular disease (CVD). In the context of food-based dietary guidance designed to reduce CVD risk, fat and FA recommendations focus on reducing saturated FA (SFA) and trans FA (TFA), and ensuring an adequate intake of unsaturated FA. Because stearic acid shares many physical properties with the other long-chain SFA but has different physiological effects, it is being evaluated as a substitute for TFA in food manufacturing. For stearic acid to become the primary replacement for TFA, it is essential that its physical properties and biological effects be well understood.

Pistachios Increase Serum Antioxidants and Lower Serum Oxidized-LDL in Hypercholesterolemic Adults

Pistachios are high in lutein, beta-carotene, and gamma-tocopherol relative to other nuts; however, studies of the effects of pistachios on oxidative status are lacking. We conducted a randomized, crossover controlled-feeding study to evaluate 2 doses of pistachios on serum antioxidants and biomarkers of oxidative status in 28 hypercholesterolemic adults (LDL-cholesterol >or=2.86 mmol/L). Participants consumed 3 isoenergetic diets for 4 wk each after a 2-wk baseline Western diet. Experimental diets included a lower-fat control diet without pistachios (25% total fat) with 1 serving/d (i.e. 32-63 g/d; energy adjusted) of pistachios (1 PD; 10% energy from pistachios; 30% total fat) or with 2 servings/d (63-126 g/d; energy adjusted) of pistachios (2 PD; 20% energy from pistachios; 34% total fat). When participants consumed the pistachio-enriched diets, they had higher plasma lutein (P < 0.0001), alpha-carotene, and beta-carotene (P < 0.01) concentrations than after the baseline diet. After consuming the pistachio diets, participants had greater plasma lutein (P < 0.001) and gamma-tocopherol (P < 0.05; 2 PD only) relative to the lower-fat control diet. After the 2 PD diet period, participants also had lower serum oxidized-LDL concentrations than following the baseline diet period (P < 0.05). After both the 1 PD and 2 PD diet periods, they had lower serum oxidized-LDL concentrations than after the control diet period (P < 0.05). The change in oxidized-LDL from baseline correlated positively with the change in LDL-cholesterol across all treatments (r = 0.42; P < 0.005). After controlling for the change in serum LDL-cholesterol as a covariate, increases in serum lutein and gamma-tocopherol following the 2 PD period were still modestly associated with decreases in oxidized-LDL (r = -0.36, P = 0.06 and r = -0.35, P = 0.08, respectively). This suggests that a heart-healthy diet including pistachios contributes to the decrease in the serum oxidized-LDL concentration through cholesterol-lowering and may provide an added benefit as a result of the antioxidants the pistachios contain.

Diets Containing Pistachios Reduce Systolic Blood Pressure and Peripheral Vascular Responses to Stress in Adults With Dyslipidemia

Nut consumption reduces cardiovascular risk, and reductions in blood pressure and peripheral vascular resistance may be important mediators of this relationship. We evaluated effects of pistachios on flow-mediated dilation and blood pressure response to acute stress. Twenty-eight adults with dyslipidemia completed a randomized, crossover, controlled-feeding study. All of the meals were provided and calories were controlled. After 2 weeks on a typical Western diet (35% total fat and 11% saturated fat), test diets were presented in counterbalanced order for 4 weeks each, a low-fat control diet (25% total fat and 8% saturated fat), a diet containing 10% of energy from pistachios (on average, 1 serving per day; 30% total fat and 8% saturated fat), and a diet containing 20% of energy from pistachios (on average, 2 servings per day, 34% total fat and 8% saturated fat). None of the resting hemodynamic measures significantly differed from pretreatment values. When resting and stress levels were included in the repeated-measures analysis, average reductions in systolic blood pressure were greater after the diet containing 1 serving per day versus 2 servings per day of pistachios (mean change in systolic blood pressure, −4.8 vs −2.4 mm Hg, respectively; P<0.05). After the higher dose, there were significant reductions in peripheral resistance (−62.1 dyne·s×cm−5) and heart rate (−3 bpm) versus the control diet (P<0.0001). These changes were partially offset by increases in cardiac output. There was no effect of diet on fasting flow-mediated dilation. Reductions in peripheral vascular constriction and the resulting decrease in hemodynamic load may be important contributors to lower risk in nut consumers.

A moderate-fat diet containing pistachios improves emerging markers of cardiometabolic syndrome in healthy adults with elevated LDL levels

A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103μg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in β-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.

ESTIMATING THE SUBJECT BY TREATMENT INTERACTION IN NON-REPLICATED CROSSOVER DIET STUDIES

Researchers in human nutrition commonly refer to th e ‘consistent’ diet effect (i.e. the main effect of diet) and an ‘inconsistent’ diet effect (i.e. a subject by diet interaction). However, due to the non-replicated designs of most studies, one can onl y estimate the first part using ANOVA; the latter (interaction) is confounded with the residua l noise. In many diet studies, it appears that subjects do respond differently to the same diet, s o he subject by diet interaction may be large. In a search of over 40,000 published human nutritio n studies, most using a crossover design, we found that in none was a subject by diet interactio n effect estimated. For this paper, we examined LDL-cholesterol data from a non-replicated crossover study with four diets, the typical American diet, with and without added plant sterols , and a cholesterol-lowering Step-1 diet, with and without sterols. We also examined LDL-choleste rol data from a second crossover study with some replications with three diets, representi ng he daily supplement of 0, 1 or 2 servings of pistachio nuts. These two data sets were chosen be caus experience suggested that LDLcholesterol responses to diet tend to be subject-sp ecific. The second data set, with some replication, allowed us to estimate the subject by diet interaction term in a traditional ANOVA framework. One approach to estimating an interactio n effect in non-replicated studies is through the use of a multiplicative decomposition of the in teraction (sometimes called AMMI ―additive main effects, multiplicative interaction). In this type of analysis, residuals, formed after estimated main effects are subtracted from the data , are arrayed in a matrix with diets as columns and subjects as rows. A singular value decompositi on of the matrix is performed and the first, or first and second, principal component(s) are used a estimates of the interaction, and can be tested for significance using approximate F-tests. Using the R gnm package, we found large and significant subject by diet interaction effects in both data sets; estimates of the interaction in the second data set were similar to interaction estimat es from traditional ANOVA. Of an additional 26 dependent variables from the first and a third d ata set (the latter investigating the effect of mild alcohol consumption on blood variables), 19 ha d significant subject by diet interactions, based on the AMMI methodology. These results sugge st that the subject by diet interaction is often important and should not be ignored when anal yzing data obtained from non-replicated crossover designs ―the AMMI methodology works well and is readily avai lable in statistical software packages.

Integration of molecular biology and nutrition: the role of nutritional genomics in optimizing dietary guidance in lipids

The evolution of the field of nutrition has largely been due to advancements in the techniques of molecular biology. Since the completion of the Human Genome Project, the fields of nutrigenomics, nutrigenetics, pharmacogenetics, metabolomics and proteomics have evolved. These fields provide immense potential to enhance the study of genes involved in health and chronic diseases and the interactions of nutrients on these genes. The emerging field of lipidomics will provide further insight into the roles of genetics, disease, drugs and diet on the regulation of lipid metabolism. Advances in molecular nutrition will continue to increase our understanding of the heterogeneity of individual lipid response to dietary interventions, allowing for a movement towards a more individualized approach for dietary guidance. The potential impact of molecular biology on clinical nutrition research of the future is inducing a shift in the focus of nutrition research from disease treatment and management to one of disease pr...

Impact of stearic acid and oleic acid on hemostatic factors in the context of controlled diets consumed by healthy men

The effects of stearic acid (STA) on cardiovascular disease risk beyond lipid and lipoprotein risk factors, including hemostasis, are unclear, particularly when compared with unsaturated fatty acids. The aim of the present study is to compare the effects of STA with those of oleic acid (OL) on markers of hemostasis. In a randomized crossover study, 50 men consumed six controlled diets for 5 weeks each (39% energy from fat, 15% energy from protein, 46% energy from carbohydrate (CHO)). Fat (8% energy) was replaced across diets by: STA, OL, CHO (control), trans fatty acids (TFAs), TFA/STA and 12:0–16:0 saturated fatty acids. Factor VIIc, plasminogen activator inhibitor-1 (PAI-1) and plasmin alpha-2-antiplasmin complex concentrations were not different between OL and STA (P>0.05). Compared with control, OL increased factor VIIc and PAI-1 (P⩽0.05), whereas there were no differences with STA (P>0.05). STA and OL similarly affect markers of hemostasis in healthy men, within the context of a highly controlled diet.

Dose-related effects of pistachios on emerging CVD risk factors in moderately hypercholesterolemic individuals

We previously found similar, significant decreases in LDL-C for both the 1 PD (-9%) and 2 PD (-12%) diets versus the CON (P < 0.05)3. Here we report significant differences (P < 0.05) in small-dense LDL levels (sdLDL) between the 2 PD (34.98 ± 1.71 mg/dl) and the CON (44.06 ± 2.50 mg/dl), and between the 2 PD and the 1 PD diet (42.37 ± 3.35 mg/dl), with no significant difference between the 1 PD and the CON. These differences in sdLDL are important since this is a strong predictor of CVD risk. Lower levels of the highly atherogenic sdLDL may decrease the rate of atherogenesis as these particles are more prone to oxidation. Previous results also showed no effect due to diet on HDL-C levels3. However, current results show a trend towards a significant effect (P = 0.057) on α-2 HDL levels, with numerically increased levels in the 2PD group over the 1PD and the CON groups. This trend indicates higher levels of large, cholesterol-rich α-2 HDL particles, after pistachio inclusion, that may have participated in reverse cholesterol transport and promoted atheroregression. We found no significant difference due to diet for other HDL subclasses (pre β1, α-4, α-3, or α-1), or for Lipoprotein (a). Our results provide new information about the role of bioactives in pistachios that affect these emerging CVD risk markers.