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Biomedical subjects

Penny M Kris-Etherton

Publications and source records attributed to Penny M Kris-Etherton.

At least 19 recordsLinked to original sources

An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans.

Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n = 23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 +/- 1.21 nM BCE), relative to the AAD (15.59 +/- 1.21 nM BCE) (p < 0.05). Mean NTx level following the LA diet was 13.80 +/- 1.21 nM BCE. There was no change in levels of BSAP across the three diets. Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFalpha for all three diets. The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation.

Alkaline Phosphatase↗

The changing roles of dietary carbohydrates: from simple to complex.

The dietary recommendations made for carbohydrate intake by many organizations/agencies have changed over time. Early recommendations were based on the need to ensure dietary sufficiency and focused on meeting micronutrient intake requirements. Because carbohydrate-containing foods are a rich source of micronutrients, starches, grains, fruits, and vegetables became the foundation of dietary guidance, including the base of the US Department of Agriculture's Food Guide Pyramid. Dietary sufficiency recommendations were followed by recommendations to reduce cholesterol levels and the risk for cardiovascular disease; reduction in total fat (and hence saturated fat) predominated. Beginning in the 1970s, carbohydrates were recommended as the preferred substitute for fat by the American Heart Association and others to achieve the recommended successive reductions in total fat and low-density lipoprotein cholesterol (LDL-C). Additional research on fats and fatty acids found that monounsaturated fatty acids could serve as an alternative substitution for saturated fats, providing equivalent lowering of LDL-C without concomitant reductions in high-density lipoprotein cholesterol and increases in triglycerides witnessed when carbohydrates replace saturated fat. This research led to a sharper focus in the guidelines in the 1990s toward restricting saturated fat and liberalizing a range of intake of total fat. Higher-fat diets, still low in saturated fatty acids, became alternative strategies to lower-fat diets. As the population has become increasingly overweight and obese, the emergence of the metabolic syndrome and its associated disruptions in glucose and lipid metabolism has led to reconsiderations of the role of carbohydrate-containing foods in the American diet. Consequently, a review of the evidence for and against high-carbohydrate diets is important to put this controversy into perspective. The current dietary recommendations for carbohydrate intake are supported by the evidence.

Dietary Carbohydrates↗

Effects of antioxidant-rich foods on vascular reactivity: review of the clinical evidence.

The foods and nutrients discussed in this paper are components of dietary patterns that have been associated with lower cardiovascular disease risk. The focus of this review is on the effects of antioxidant foods on vascular health and discussion of their potential mechanisms of action. The foods reviewed include fruits and vegetables, red grapes and red wine, tea, cocoa/chocolate, and olive oil. The primary challenge in studying the cardioprotective components of a dietary pattern is in identifying mechanism(s) of action as well as the bioactive nutrients responsible. In selecting papers for this review, we focused on studies of whole foods and beverages that met the following criteria: 1) they are commonly consumed in typical diets, 2) they appear to have direct antioxidant effects, and 3) they have demonstrated effects on endothelial function in several human studies. The evidence presented herein suggests that dietary consumption of fruits and vegetables, red grapes and red wine, tea, chocolate, and olive oil may improve vascular reactivity, in part, by attenuating the adverse effects of oxidation on endothelial function. Additional research is needed to better understand the mechanism(s) by which antioxidant-rich foods and beverages favorably affect endothelial function and the extent to which this reflects direct antioxidant effects.

Antioxidants↗

Tree nuts and the lipid profile: a review of clinical studies.

Tree nuts have a fatty acid profile that favourably affects blood lipids and lipoproteins. They are low in saturated fat and high in unsaturated fatty acids and are rich sources of other nutrients. An extensive database consistently shows total and LDL cholesterol-lowering effects of diets low in saturated fat and cholesterol and high in unsaturated fat provided by a variety of tree nuts. Collectively, a summary of studies conducted to date shows that tree nuts reduce LDL cholesterol by 3-19 % compared with Western and lower-fat diets. Nuts also contain many nutrients and bioactive compounds that appear to contribute to the favourable effects on lipids and lipoproteins--these include plant sterols, dietary fibre and antioxidants. Because of their unique nutrient profile, nuts can be part of a diet that features multiple heart-healthy foods resulting in a cholesterol lowering response that surpasses that of cholesterol-lowering diets typically used to reduce CVD risk.

Carya↗

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.

Cardiovascular Diseases↗

Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells.

The effects of linoleic acid (LA), alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA) were compared to that of palmitic acid (PA), on inflammatory responses in human monocytic THP-1 cells. When cells were pre-incubated with fatty acids for 2-h and then stimulated with lipopolysaccharide for 24-h in the presence of fatty acids, secretion of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNFalpha) was significantly decreased after treatment with LA, ALA, and DHA versus PA (P < 0.01 for all); ALA and DHA elicited more favorable effects. These effects were comparable to those for 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) and were dose-dependent. In addition, LA, ALA, and DHA decreased IL-6, IL-1beta, and TNFalpha gene expression (P < 0.05 for all) and nuclear factor (NF)-kappaB DNA-binding activity, whereas peroxisome proliferator-activated receptor-gamma (PPARgamma) DNA-binding activity was increased. The results indicate that the anti-inflammatory effects of polyunsaturated fatty acids may be, in part, due to the inhibition of NF-kappaB activation via activation of PPARgamma.

Anti-Inflammatory Agents↗

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.

Cardiovascular Diseases↗

A quantitative analysis of fish consumption and coronary heart disease mortality.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on coronary heart disease (CHD) mortality and nonfatal myocardial infarction (MI). Other papers quantify stroke risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative review appropriate for the development of a dose-response relationship. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. Relative risk results were averaged, weighted proportionately by precision. CHD risks associated with MeHg exposure were reviewed qualitatively because the available literature was judged inadequate for quantitative analysis. Eight studies were identified (29 exposure groups). Our analysis estimated that consuming small quantities of fish is associated with a 17% reduction in CHD mortality risk, with each additional serving per week associated with a further reduction in this risk of 3.9%. Small quantities of fish consumption were associated with risk reductions in nonfatal MI risk by 27%, but additional fish consumption conferred no incremental benefits.

Adult↗

A quantitative analysis of fish consumption and stroke risk.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of fish consumption on stroke risk. Other papers quantify coronary heart disease mortality risk and the impacts of both prenatal MeHg exposure and maternal intake of n-3 PUFAs on cognitive development. This analysis identified articles in a recent qualitative literature review that are appropriate for the development of a dose-response relationship between fish consumption and stroke risk. Studies had to satisfy quality criteria, quantify fish intake, and report the precision of the relative risk estimates. The analysis combined the relative risk results, weighting each proportionately to its precision. Six studies were identified as appropriate for inclusion in this analysis, including five prospective cohort studies and one case-control study (total of 24 exposure groups). Our analysis indicates that any fish consumption confers substantial relative risk reduction compared to no fish consumption (12% for the linear model), with the possibility that additional consumption confers incremental benefits (central estimate of 2.0% per serving per week).

Adult↗

A quantitative risk-benefit analysis of changes in population fish consumption.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish contain methyl mercury (MeHg), which may harm the developing fetus. U.S. government recommendations for women of childbearing age are to modify consumption of high-MeHg fish, while recommendations encourage fish consumption among the general population because of nutritional benefits. To investigate the aggregate impacts of hypothetical shifts in fish consumption, the Harvard Center for Risk Analysis convened an expert panel (see acknowledgements). Effects investigated include prenatal cognitive development, coronary heart disease mortality, and stroke. Substitution of fish with high MeHg concentrations with fish containing less MeHg among women of childbearing age yields substantial developmental benefits and few negative impacts. However, if women instead decrease fish consumption, countervailing risks substantially reduce net benefits. If other adults (mistakenly and inappropriately) also reduce their fish consumption, the net public health impact is negative. Although high compliance with recommended fish consumption patterns can improve public health, unintended shifts in consumption can lead to public health losses. Risk managers should investigate and carefully consider how populations will respond to interventions, how those responses will influence nutrient intake and contaminant exposure, and how these changes will affect aggregate public health.

Adolescent↗

Balance of unsaturated fatty acids is important to a cholesterol-lowering diet: comparison of mid-oleic sunflower oil and olive oil on cardiovascular disease risk factors.

OBJECTIVE: To evaluate the effects of a trans fat-free monounsaturated fatty acid-rich vegetable oil (NuSun sunflower oil, National Sunflower Association, Bismark, ND) that is a good source of polyunsaturated fatty acids (PUFA) and low in saturated fatty acids on lipid and lipoprotein levels and oxidative stress. DESIGN: A double-blinded, randomized, three period crossover, controlled feeding study. SUBJECTS/SETTING: Thirty-one men (n=12) and women (n=19) with moderate hypercholesterolemia who were 25 to 64 years of age. INTERVENTION: Experimental diets provided 30% fat (olive oil or NuSun sunflower oil contributed one half of the total fat), 8.3% vs 7.9% saturated fatty acid, 17.2% vs 14.2% monounsaturated fatty acid, and 4.3% vs. 7.7% PUFA (olive oil and NuSun sunflower oil, respectively), and 294 mg cholesterol. The control diet was an average American diet (34% fat, 11.2% saturated fatty acid, 14.9% monounsaturated fatty acid, 7.8% PUFA). Subjects consumed each diet for 4 weeks with a 2-week compliance break before crossing over to another diet. MAIN OUTCOME MEASURES: Lipid and lipoprotein levels were measured, and measures of oxidative stress, including lag time, rate of oxidation, total dienes, and lipid hydroperoxides, were assessed. STATISTICAL ANALYSIS: The mixed model procedure was used to test for main effects of diet, feeding period, and order of diets. Tukey-Kramer adjusted P values were used to determine diet effects. RESULTS: The NuSun sunflower oil diet decreased both total and low-density lipoprotein cholesterol levels compared with the average American diet and the olive oil diet. There was no effect of the olive oil diet compared with the average American diet. Total cholesterol decreased 4.7% and low-density lipoprotein cholesterol decreased 5.8% on the NuSun sunflower oil diet vs the average American diet. There was no effect of the experimental diets on triglyceride levels, rate of oxidation, total dienes, lipid hydroperoxides, or alpha-tocopherol. Lag time was the longest following the olive oil diet and shortest following the NuSun sunflower oil diet. CONCLUSIONS: The higher PUFA content appeared to account for the greater total and low-density lipoprotein cholesterol lowering and reduction in lag time of the NuSun sunflower oil diet. However, the fact that there were no differences in the resulting oxidation products suggests there were no adverse effects on low-density lipoprotein oxidation. Since PUFAs are important for cholesterol lowering, foods that replace saturated fatty acids should include a balance of unsaturated fatty acids.

Adult↗

Provision of foods differing in energy density affects long-term weight loss.

OBJECTIVE: The energy density (kilocalories per gram) of foods influences short-term energy intake. This 1-year clinical trial tested the effect on weight loss of a diet incorporating one or two servings per day of foods equal in energy but differing in energy density. RESEARCH METHODS AND PROCEDURES: Dietitians instructed 200 overweight and obese women and men to follow an exchange-based energy-restricted diet. Additionally, subjects were randomized to consume daily either one or two servings of low energy-dense soup, two servings of high energy-dense snack foods, or no special food (comparison group). RESULTS: All four groups showed significant weight loss at 6 months that was well maintained at 12 months. The magnitude of weight loss, however, differed by group (p=0.006). At 1 year, weight loss in the comparison (8.1+/-1.1 kg) and two-soup (7.2+/-0.9 kg) groups was significantly greater than that in the two-snack group (4.8+/-0.7 kg); weight loss in the one-soup group (6.1+/-1.1 kg) did not differ significantly from other groups. Weight loss was significantly correlated with the decrease in dietary energy density from baseline at 1 and 2 months (p=0.0001) but not at 6 and 12 months. DISCUSSION: On an energy-restricted diet, consuming two servings of low energy-dense soup daily led to 50% greater weight loss than consuming the same amount of energy as high energy-dense snack food. Regularly consuming foods that are low in energy density can be an effective strategy for weight management.

Adult↗

Effects of including soy protein in a blood cholesterol-lowering diet on markers of cardiac risk in men and in postmenopausal women with and without hormone replacement therapy.

BACKGROUND: Increased consumption of soy foods has been associated with reduction in low density lipoprotein cholesterol (LDL-C) in both clinical and observational studies. However, it is not clear whether adding soy to a low-fat diet has additional lipid-lowering benefits, and few previous studies have examined these effects in women using hormone replacement therapy (HRT+). METHODS: We tested whether adding soy protein to a low-fat, high-fiber, Step I diet improved cardiac risk markers in 18 postmenopausal women and 14 men with hypercholesterolemia and examined whether concurrent use of HRT altered diet responsiveness. Diets were matched for macronutrient content, and all food was provided. After 3 weeks on the Step I diet, subjects were randomized to diets (6 weeks) containing 25 g/day protein isolate from soy or cow's milk, with crossover. The soy treatment contained 90 mg/day isoflavones. Lipids, vascular cell adhesion molecule-1 (VCAM-1), p-selectin, and urinary isoflavonoids were measured at the end of each diet. RESULTS: In men and HRT- women only, there were significant reductions in LDL-C (-17.3%), high-density lipoprotein cholesterol (HDL-C) (-15.3%), and triglycerides (-11.5%) during the Step I diet, and soy had no additional effects. At study entry, HRT+ women had lower LDL-C and higher triglycerides than men. Their LDL-C was unchanged, and triglycerides were significantly reduced (-15.1%) by the Step I diets. Isoflavonoid excretion was unrelated to diet response or HRT status. CONCLUSIONS: In men and HRT- women, the diets significantly lowered LDL-C, independent of soy intake. In HRT+ women, the diets improved triglycerides without lowering HDL-C.

Apolipoproteins↗

Long-chain polyunsaturated fatty acids upregulate LDL receptor protein expression in fibroblasts and HepG2 cells.

The objective of this study was to investigate the effect of individual PUFAs on LDL receptor (LDLr) expression in human fibroblasts and HepG2 cells, and to evaluate whether acyl CoA:cholesterol acyltransferase (ACAT) and sterol regulatory element-binding protein 1 (SREBP-1) were involved in the regulation of LDLr expression by fatty acids. When fibroblasts and HepG2 cells were cultured with serum-free defined medium for 48 h, there was a 3- to 5-fold (P < 0.05) increase in LDLr protein and mRNA levels. Incubation of fibroblasts and HepG2 cells in serum-free medium supplemented with 25-hydroxycholesterol (25OH-cholesterol, 5 mg/L) for 24 h decreased LDLr protein and mRNA levels by 50-90% (P < 0.05). Arachidonic acid [AA, 20:4(n-6)], EPA [20:5(n-3)], and DHA [22:6(n-3)] antagonized the depression of LDLr gene expression by 25OH-cholesterol and increased LDLr protein abundance 1- to 3-fold (P < 0.05), but had no significant effects on LDLr mRNA levels. Oleic (18:1), linoleic (18:2), and alpha-linolenic acids [18:3(n-3)] did not significantly affect LDLr expression. ACAT inhibitor (58-035, 1 mg/L) attenuated the regulatory effect of AA on LDLr protein abundance by approximately 40% (P < 0.05), but did not modify the regulatory effects of other unsaturated fatty acids in HepG2 cells. The present results suggest that AA, EPA, and DHA increase LDLr protein levels, and that ACAT plays a role in modulating the effects of AA on LDLr protein levels. Furthermore, the effects of the fatty acids appeared to be independent of any change in SREBP-1 protein.

Arachidonic Acid↗