Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men.

BACKGROUND: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. METHODS: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. RESULTS: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). CONCLUSION: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.

Vitamin D Screening and Supplementation in Community-Dwelling Adults: Common Questions and Answers.

Measurement of vitamin D levels and supplementation with oral vitamin D have become commonplace, although clinical trials have not demonstrated health benefits. The usefulness of serum 25-hydroxyvitamin D levels to assess adequate exposure to vitamin D is hampered by variations in measurement technique and precision. Serum levels less than 12 ng per mL reflect inadequate vitamin D intake for bone health. Levels greater than 20 ng per mL are adequate for 97.5% of the population. Routine vitamin D supplementation does not prolong life, decrease the incidence of cancer or cardiovascular disease, or decrease fracture rates. Screening asymptomatic individuals for vitamin D deficiency and treating those considered to be deficient do not reduce the risk of cancer, type 2 diabetes mellitus, or death in community-dwelling adults, or fractures in persons not at high risk of fractures. Randomized controlled trials of vitamin D supplementation in the treatment of depression, fatigue, osteoarthritis, and chronic pain show no benefit, even in persons with low levels at baseline.

Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement.

DESCRIPTION: New USPSTF recommendation on screening for vitamin D deficiency in adults. METHODS: The USPSTF reviewed the evidence on screening for and treatment of vitamin D deficiency, including the benefits and harms of screening and early treatment. POPULATION: This recommendation applies to community-dwelling, nonpregnant adults aged 18 years or older who are seen in primary care settings and are not known to have signs or symptoms of vitamin D deficiency or conditions for which vitamin D treatment is recommended. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults. (I statement).

Predicted changes in fatty acid intakes, plasma lipids, and cardiovascular disease risk following replacement of trans fatty acid-containing soybean oil with application-appropriate alternatives.

The varied functional requirements satisfied by trans fatty acid (TFA)--containing oils constrains the selection of alternative fats and oils for use as potential replacements in specific food applications. We aimed to model the effects of replacing TFA-containing partially hydrogenated soybean oil (PHSBO) with application-appropriate alternatives on population fatty acid intakes, plasma lipids, and cardiovascular disease (CVD) risk. Using the National Health and Nutrition Examination Survey 24-hour dietary recalls for 1999-2002, we selected 25 food categories, accounting for 86 % of soybean oil (SBO) and 79 % of TFA intake for replacement modeling. Before modeling, those in the middle quintile had a mean PHSBO TFA intake of 1.2 % of energy. PHSBO replacement in applications requiring thermal stability by either low-linolenic acid SBO or mid-oleic, low-linolenic acid SBO decreased TFA intake by 0.3 % of energy and predicted CVD risk by 0.7-0.8 %. PHSBO replacement in applications requiring functional properties with palm-based oils reduced TFA intake by 0.8 % of energy, increased palmitic acid intake by 1.0 % of energy, and reduced predicted CVD risk by 0.4 %, whereas replacement with fully hydrogenated interesterified SBO reduced TFA intake by 0.7 % of energy, increased stearic acid intake by 1.0 % of energy, and decreased predicted CVD risk by 1.2 %. PHSBO replacement in both thermal and functional applications reduced TFA intake by 1.0 % of energy and predicted CVD risk by 1.5 %. Based solely on changes in plasma lipids and lipoproteins, all PHSBO replacement models reduced estimated CVD risk, albeit less than previously reported using simpler replacement models.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study.

BACKGROUND: Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. OBJECTIVE: We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. DESIGN: In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. RESULTS: Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P < 0.01) increased total fecal cholesterol excretion (36 +/- 6% and 74 +/- 10%, respectively) and biliary cholesterol excretion (38 +/- 7% and 77 +/- 12%, respectively) and reduced percentage intestinal cholesterol absorption (-10 +/- 1% and -25 +/- 3%, respectively). Serum LDL cholesterol declined significantly only with the highest phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). CONCLUSIONS: Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Botanicals and the metabolic syndrome.

Metabolic syndrome describes the human condition characterized by the presence of coexisting traditional risk factors for cardiovascular disease, such as hypertension, dyslipidemia, glucose intolerance, and obesity, in addition to nontraditional cardiovascular disease risk factors, such as inflammatory processes and abnormalities of the blood coagulation system. Although the specific etiology for metabolic syndrome is not known, insulin resistance--a clinical state in which a normal or elevated insulin concentration reflects an impaired biological response--is present and is considered a key pathophysiologic abnormality. As such, metabolic syndrome can be considered to be a prediabetic state and contributes greatly to increased morbidity and mortality in humans. Given the public health significance of metabolic syndrome, successful strategies are direly needed to intervene in its development. As such, nutritional supplementation with botanicals that effectively address pathogenic mechanisms, combined with the acceptance and widespread use of botanical supplements by the general public, represents an attractive, novel, and potentially effective approach to the problem. Thus, the overall goal of our botanical research center is to comprehensively evaluate botanicals in addressing the pathophysiologic mechanisms that lead to the development of insulin resistance and metabolic syndrome. Currently, each of the 3 research projects evaluates a specific botanical [Russian tarragon (Artemisia dracunculus L), shilianhua (Sinocrassula indica), and grape (Vitus vinifera) anthocyanins] and assesses the effect on pathogenic mechanisms leading to the development of insulin resistance. With the completion of our research, we anticipate a better understanding of the cellular mechanisms by which insulin resistance develops and the role of botanicals in modulating the progression to metabolic syndrome.

Dietary fatty acids, hemostasis, and cardiovascular disease risk.

The cause of many myocardial infarctions is occlusive thrombosis, or a blood clot that stops blood flow in a coronary artery. Hemostasis involves a complex system of factors, which normally form and degrade blood clots, that work within a delicate balance. Emerging evidence suggests that some hemostatic factors, including factor VII, fibrinogen, and plasminogen activator inhibitor-1, are associated with increased risk for cardiovascular disease (CVD). Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. Dietary supplementation with marine n-3 fatty acids prolongs bleeding time and may decrease risk for thrombosis. Factor VII coagulant activity modestly decreases with reductions in saturated fatty acid (SFA) intake and thereby may contribute to the beneficial effects of low SFA diets. Large triglyceride-rich particles formed during postprandial lipemia can support the assembly and function of coagulation complexes and seem to play a role in the activation of factor VII, and thus may partially explain increased CVD risk associated with increased postprandial triglyceridemia. As our understanding of the role of dietary fatty acids and hemostasis evolves, it is likely that we will be able to make specific dietary recommendations to further decrease CVD risk. At this juncture, however, increasing marine n-3 fatty acids and decreasing certain SFAs are leading strategies to reduce hemostatic CVD risk factors. An array of dietary strategies that target multiple CVD risk factors could have a greater impact on CVD than a single risk factor intervention strategy.

Effect of diets enriched in almonds on insulin action and serum lipids in adults with normal glucose tolerance or type 2 diabetes.

BACKGROUND: Nuts appear to have cardiovascular benefits but their effect in diabetic patients is unclear. OBJECTIVE: The objective was to assess effects of almond-enriched diets on insulin sensitivity and lipids in patients with normoglycemia or type 2 diabetes. DESIGN: Study 1 assessed the effect of almonds on insulin sensitivity in 20 free-living healthy volunteers who received 100 g almonds/d for 4 wk. Study 2 was a randomized crossover study that compared 4 diets in 30 volunteers with type 2 diabetes: 1) high-fat, high-almond (HFA; 37% total fat, 10% from almonds); 2) low-fat, high-almond (LFA; 25% total fat, 10% from almonds); 3) high-fat control (HFC; 37% total fat, 10% from olive or canola oil); and 4) low-fat control (LFC; 25% total fat, 10% from olive or canola oil). After each 4-wk diet, serum lipids and oral glucose tolerance were measured. RESULTS: In study 1, almond consumption did not change insulin sensitivity significantly, although body weight increased and total and LDL cholesterol decreased by 21% and 29%, respectively (P < 0.05). In study 2, total cholesterol was lowest with the HFA diet (4.46 +/- 0.14, 4.52 +/- 0.14, 4.63 +/- 0.14, and 4.63 +/- 0.14 mmol/L with the HFA, HFC, LFA, and LFC diets, respectively; P = 0.0004 for fat level). HDL cholesterol was significantly lower with the almond diets (P = 0.002); however, no significant effect of fat source on LDL:HDL was observed. Glycemia was unaffected. CONCLUSIONS: Almond-enriched diets do not alter insulin sensitivity in healthy adults or glycemia in patients with diabetes. Almonds had beneficial effects on serum lipids in healthy adults and produced changes similar to high monounsaturated fat oils in diabetic patients.