Action of plant sterol intervention on sterol kinetics in hypercholesterolemic men with high versus low basal circulatory plant sterol concentrations.

BACKGROUND: The relationship between plant sterol (PS) absorption and circulatory concentrations with cholesterol absorption and biosynthesis during PS consumption has yet to be clearly elucidated in humans. It is therefore essential to examine campesterol, ß-sitosterol, and cholesterol absorption and cholesterol fractional synthesis rate (FSR) following PS consumption in individuals with high versus low basal circulatory PS concentrations. DESIGN: A randomized, crossover trial was conducted in 82 hypercholesterolemic men consuming spreads with or without 2 g/d of PS for two 4-week periods, each separated by a 4-week washout. Endpoint tracer enrichments after ingestion of (2)H-labeled campesterol or ß-sitosterol and (13)C-labeled cholesterol were determined by isotope ratio mass spectrometry. RESULTS: For both phases of dietary intervention, the endpoint cholesterol absorption index was positively correlated with campesterol (r = 0.5864, p < 0.0001) and ß-sitosterol (r = 0.4676, p < 0.0001) absorption indices; inversely, endpoint cholesterol FSR correlated negatively with the absorption indices of campesterol (r = -0.5004, p < 0.0009), ß-sitosterol (r = -0.4154, p < 0.05), and cholesterol (r = -0.4056, p < 0.0001). PS intervention reduced absorption indices of campesterol, ß-sitosterol, and cholesterol by 36.5% ± 2.7%, 39.3% ± 2.9%, and 34.3% ± 1.9%, respectively, but increased cholesterol FSR by 33.0% ± 3.3% relative to control. Endpoint circulatory PS levels (cholesterol adjusted) were positively associated with endpoint absorption indices of campesterol (r = 0.5586, p < 0.0001, for placebo; r = 0.6530, p < 0.0001, for PS intake) and cholesterol (r = 0.3683, p < 0.001 for placebo; r = 0.3469, p < 0.002, for PS intake) and were negatively associated with cholesterol FSR (r = -0.3551, p < 0.002, for placebo; r = -0.3643, p < 0.001, for PS intake). The cholesterol-lowering effect of PS was most pronounced among individuals falling within the 50th-75th percentiles of basal PS concentrations. CONCLUSION: These data suggest that basal PS concentrations indicate not only sterol absorption efficiency but also the extent of PS-induced cholesterol reduction and thus might be clinically useful to predict the extent of cholesterol response to PS intervention within a given individual.

The ratio of eicosapentaenoic acid to docosahexaenoic acid as a modulator for the cardio-metabolic effects of omega-3 supplements: A meta-regression of randomized clinical trials.

BACKGROUND: A large number of studies have demonstrated the effects of omega- 3 supplements containing mixtures of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), known to favorably affect many modifiable risk factors of coronary heart disease (CHD). These studies have used diverse ratios and doses of EPA and DHA. However, it is not known whether the ratio of EPA to DHA in omega-3 supplements affect their efficacy as modulators for cardiovascular risk factors. This meta-regression aimed to investigate the effect of different ratios of EPA to DHA on risk factors associated with CHD including lipid profile, blood pressure, heart rate, and inflammation. METHOD: A regression analysis was carried out on 92 clinical trials with acceptable quality (Jadad score ≥ 3) that were previously identified from two databases (PubMed and Cochrane Library). RESULTS: Data from studies that met the inclusion criteria for this analysis showed that the ratio of EPA to DHA was not associated with lipid profile, diastolic blood pressure, or heart rate. With all studies, the ratio of EPA to DHA was associated with C-reactive protein (CRP) (ß = -1.3121 (95 % CI: -1.6610 to -0.9543), that is, the higher the EPA to DHA ratio, the greater the reduction. Using only studies that supplied EPA and DHA in the range of 2 g-6 g, the ratio of EPA to DHA was also associated with CRP (ß = -2.10429 and 95 % CI: -3.89963 to -0.30895); that is, an even more pronounced reduction in CRP with a higher EPA to DHA ratio. Systolic blood pressure was only associated with an increasing EPA to DHA ratio in the 2 g-6 g range (ß = 5.47129 and 95 % CI: 0.40677-10.53580), that is, a higher EPA to DHA ratio within this dose range, the greater the increase in SBP. CONCLUSION: Current data suggest that the EPA to DHA ratio only correlates to the modulation of CRP by omega-3 supplementation of EPA and DHA, and SBP in studies that supplemented EPA and DHA in the range of 2 g-6 g, shedding light on potential differential effects of EPA vs. DHA on inflammation and systolic blood pressure.

Generic and product-specific health claim processes for functional foods across global jurisdictions.

Worldwide consumer interest in functional foods and their potential health benefits has been increasing over the past 10 y. To respond to this interest, regulatory bodies have developed guidelines for assessing health claims on functional foods. The objective of this article is to investigate the type and amount of evidence needed in various jurisdictions on a worldwide basis to substantiate both generic and product-specific health claims. Two types of health claims were examined using separate case studies. Analysis of generic health claims was highlighted by (n-3) fatty acids and their relation to heart health; whereas examination of product-specific health claims was conducted using probiotics and their association with gastrointestinal well-being. Results showed a common core for use of convincing high-quality human data, especially in the form of randomized controlled trials (RCT), but there was significant variability in the type and amount of scientific evidence needed to substantiate health claims, both generic and product specific, across different jurisdictions. Product-specific claims tended to use human RCT as the main basis for claims, whereas generic claims tended to base their statements on a wider spectrum of literature.

Conjugated linoleic acids: why the discrepancy between animal and human studies?

Conjugated linoleic acids (CLA) are positional and geometric isomers of linoleic acid. In animals, CLA consumption reduces body fat but results in humans are less conclusive. This review of the literature on CLA and loss of body fat or body weight in humans was conducted to explore the reasons for the discrepancy between animal and clinical trials. It indicates that the incongruity between human and animal data is largely related to methodological differences in the experimental design, including age and gender and, to a lesser extent, to CLA dose and isomers. The relatively unknown metabolic fate of CLA in humans may also be a contributing factor that helps explain the lack of consistency for CLA efficacy across studies.

Genetic variation in ABC G5/G8 and NPC1L1 impact cholesterol response to plant sterols in hypercholesterolemic men.

ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

Best practices for design and implementation of human clinical trials studying dietary oils.

Dietary oils are a significant contributor to overall energy and fatty acid intakes. Changes in the amount and/or type of dietary oils consumed have the potential to impact human health. Clinical trials represent the gold standard for testing the health impacts of such changes in dietary oils. The objective of this review is to explore best practices for clinical trials examining impacts of dietary oils including 1) pre-clinical topics such as research question generation, study design, participant population, outcome measures and intervention product selection and/or preparation; 2) clinical trial implementation topics such as recruitment, trial management, record keeping and compliance monitoring; and 3) post-clinical trial topics dealing with sample analysis and storage as well as management, publication and data access. The use of digital case report forms, and the best practices in reporting and publishing results are also addressed. In summary, properly designed and implemented clinical trials studying dietary oils produce strong scientific evidence-guiding their use.

Health benefits and evaluation of healthcare cost savings if oils rich in monounsaturated fatty acids were substituted for conventional dietary oils in the United States.

The impact of nutritional behaviors on health is beyond debate and has the potential to affect the economic outputs of societies in significant ways. Dietary fatty acids have become a central theme in nutrition research in recent years, and the popularity of dietary oils rich in healthy fatty acids, such as monounsaturated fatty acid (MUFA), for cooking applications and use in food products has increased. Here, the objective is to summarize the health effects of MUFA-rich diets and to systematically estimate the potential healthcare and societal cost savings that could be realized by increasing MUFA intakes compared with other dietary fat intakes in the United States. Using a scoping review approach, the literature of randomized controlled clinical trials was searched and a 4-step cost-of-illness analysis was developed, which included estimates of success rate, disease biomarker reduction, disease incidence reduction, and cost savings. Findings revealed improvements in established biomarkers and in incidence of coronary heart disease and type 2 diabetes, along with potentially substantial annual healthcare and societal cost savings when recommendations for daily MUFA intake were followed. In summary, beyond the beneficial health effects of MUFA-rich diets, potential economic benefits suggest practical implications for consumers, food processors, and healthcare authorities alike.

Optimizing clinical trial design for assessing the efficacy of functional foods.

Randomized clinical trial data are capable of providing strong experimental evidence to establish causal relationships between functional food components and health and disease/disease risk. However, clinical studies must be well designed in order to optimize the quality of the data they provide. The purpose of this review is to identify design elements that maximize the quality of clinical trials examining the efficacy of functional foods. Both observational studies and experimental trials can provide useful data for identifying diet-disease relationships. Two experimental designs are conventionally used: parallel and crossover. Each of these designs possesses advantages and disadvantages. For certain functional ingredients, selection of an appropriate control arm is straightforward, while for others it is challenging. Studies should be short enough to optimize subject compliance, be cost effective, and avoid high subject dropout rates, while being lengthy enough to ensure biological efficacy. The dose, frequency, and diurnal timing of intake of the active food ingredient all need to be chosen carefully. Randomized clinical trials testing the efficacy of functional foods may use both validated and emerging surrogate endpoints and should employ suitable statistical tests for data analysis. Paying attention to all these factors is crucial to the design of quality clinical trials that reliably evaluate food-health relationship validity. Accordingly, clinical studies that incorporate the optimal design elements discussed will yield robust results appropriate for the substantiation of health claims on functional foods.

Evolution of the human diet: linking our ancestral diet to modern functional foods as a means of chronic disease prevention.

The evolution of the human diet over the past 10,000 years from a Paleolithic diet to our current modern pattern of intake has resulted in profound changes in feeding behavior. Shifts have occurred from diets high in fruits, vegetables, lean meats, and seafood to processed foods high in sodium and hydrogenated fats and low in fiber. These dietary changes have adversely affected dietary parameters known to be related to health, resulting in an increase in obesity and chronic disease, including cardiovascular disease (CVD), diabetes, and cancer. Some intervention trials using Paleolithic dietary patterns have shown promising results with favorable changes in CVD and diabetes risk factors. However, such benefits may be offset by disadvantages of the Paleolithic diet, which is low in vitamin D and calcium and high in fish potentially containing environmental toxins. More advantageous would be promotion of foods and food ingredients from our ancestral era that have been shown to possess health benefits in the form of functional foods. Many studies have investigated the health benefits of various functional food ingredients, including omega-3 fatty acids, polyphenols, fiber, and plant sterols. These bioactive compounds may help to prevent and reduce incidence of chronic diseases, which in turn could lead to health cost savings ranging from $2 to $3 billion per year as estimated by case studies using omega-3 and plant sterols as examples. Thus, public health benefits should result from promotion of the positive components of Paleolithic diets as functional foods.

The effect of dietary oleic, linoleic, and linolenic acids on fat oxidation and energy expenditure in healthy men.

Studies have shown that the long chain fatty acid composition of a dietary fat influences whether it will be partitioned for either energy or storage. The objective of this study was to compare the effects of 3 oils differing in fatty acid composition on postprandial energy expenditure and macronutrient oxidation in healthy normal-weight men. Using a randomized crossover design, 15 subjects consumed breakfast meals containing 60% of energy as fat. The principal source of fat was (a) olive oil rich in oleic acid (18:1n-9), (b) sunflower oil rich in linoleic acid (18:2n-6), or (c) flaxseed oil rich in linolenic acid (18:3n-3). Measurements of resting metabolic rate, thermic effect of food, and postprandial energy expenditure were conducted with indirect calorimetry that recorded O(2) consumed and CO(2) produced one-half hour before meal consumption and 6 hours after meal consumption. Fat and carbohydrate oxidation rates were calculated from nonprotein gaseous exchange. Olive oil feeding showed a significant overall increase in energy expenditure compared with flaxseed oil (P < .0006) and a trend to increased energy expenditure compared with sunflower oil (P < .06). None of the 3 treatments exhibited significant effects on fat or carbohydrate oxidation. In conclusion, diets rich in oleic acid derived from olive oil may offer increased oxidation translating into increased energy expenditure postprandially.

Diacylglycerol: efficacy and mechanism of action of an anti-obesity agent.

Obesity is at the forefront of global health issues and directly contributes to many chronic illnesses. Several dietary components show promise in the treatment of obesity, one of which is oil rich in diacylglycerols (DAGs). Present objectives are to examine scientific knowledge concerning DAG to assess evidence supporting the effects on substrate oxidation rates, body weight and fat mass, and blood lipids, and to assess safety, as well as elucidate potential mechanisms of action. DAG can be synthesized by an enzymatic process to produce mainly 1,3-isoform DAG. This 1,3-DAG oil is believed to have the ability to increase beta-oxidation, to enhance body weight loss, to suppress body fat accumulation, and to lower serum triacylglycerol levels postprandially. While certain animal and human studies indicate that consumption of 1,3-DAG has positive physiological effects, others report no effect. The mechanisms of action of DAG are suggested to decrease the resynthesis of chylomicrons as well as shunting them directly to the liver through the portal vein, where they are oxidized. This increased fat oxidation may influence control of food intake by increasing satiety. Further study into the precise mechanism is required to understand its effects. Safety studies show no risks in consuming a diet rich in DAG oil. Overall, consumption of oils with higher amounts of DAG, specifically 1,3-DAG, may be useful in the battle against obesity.