The betaine and choline content of a whole wheat flour compared to other mill streams

Diets that contain high levels of whole grains have been associated with a reduced risk of several chronic diseases (Marquart et al., 2002). A whole grain, as defined by AACC International, should consist of the bran, germ and endosperm in the same proportions as found in nature (AACC, 1999). Whole grains are an important source of dietary fiber, resistant starch, vitamins, minerals and other bioactive nutrients that can play a role in protecting against chronic disease (Slavin, 2003). One of these nutrients is betaine (also known as trimethyl glycine or glycine betaine), an osmolyte and methyl donor shown to protect internal organs and improve vascular risk factors (Craig, 2004). As an osmolyte, it helps protect a variety of cells from osmotic stress. Betaine also plays an important role in cell biochemistry, donating a methyl group to homocysteine to produce methionine and ultimately S-adenosyl-methionine. Betaine accumulates in many plants under stress from drought, high salinity or low temperature. Cereal plants with betaine accumulation include wheat, barley and rye; those with little or no accumulation include rice, millet and sorghum (Kishitani et al., 1994)

Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective

This Report has a number of inter-related general purposes. One is to explore the extent to which food, nutrition, physical activity, and body composition modify the risk of cancer, and to specify which factors are most important. To the extent that environmental factors such as food, nutrition, and physical activity influence the risk of cancer, it is a preventable disease. The Report specifies recommendations based on solid evidence which, when followed, will be expected to reduce the incidence of cancer

Vision Issues and Space Flight: Evaluation of One-Carbon Metabolism Polymorphisms

Intermediates of the one-carbon metabolic pathway are altered in astronauts who experience vision-related issues during and after space flight. Serum concentrations of homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were higher in astronauts with ophthalmic changes than in those without (Zwart et al., J Nutr, 2012). These differences existed before, during, and after flight. Potential confounding factors did not explain the differences. Genetic polymorphisms could contribute to these differences, and could help explain why crewmembers on the same mission do not all have ophthalmic issues, despite the same environmental factors (e.g., microgravity, exercise, diet). A follow-up study was conducted to evaluate 5 polymorphisms of enzymes in the one-carbon pathway, and to evaluate how these relate to vision and other ophthalmic changes after flight. Preliminary evaluations of the genetic data indicate that all of the crewmembers with the MTRR GG genotype had vision issues to one degree or another. However, not everyone who had vision issues had this genetic polymorphism, so the situation is more complex than the involvement of this single polymorphism. Metabolomic and further data analyses are underway to clarify these findings, but the preliminary assessments are promising

Risk of Visual Impairment and Intracranial Hypertension After Space Flight: Evaluation of the Role of Polymorphism of Enzymes Involved in One-Carbon Metabolism

Data from the Nutritional Status Assessment protocol provided biochemical evidence that the one-carbon metabolic pathway may be altered in individuals experiencing vision-related issues during and after space flight (1, 2). Briefly, serum concentrations of homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were significantly (P<0.001) higher (25-45%) in astronauts with ophthalmic changes than in those without such changes (1). These differences existed before, during, and after flight. Serum folate was lower (P<0.01) during flight in individuals with ophthalmic changes. Preflight serum concentrations of cystathionine and 2-methylcitric acid, and mean in-flight serum folate, were significantly (P<0.05) correlated with postflight changes in refraction (1). A follow-up study was conducted to evaluate a small number of known polymorphisms of enzymes in the one-carbon pathway, and to evaluate how these relate to vision and other medical aspects of the eye. Specifically, we investigated 5 polymorphisms in MTRR, MTHFR, SHMT, and CBS genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances (3). Block regression showed that B-vitamin status at landing and genetics were significant predictors for many of the ophthalmic outcomes studied (3). In conclusion, we document an association between MTRR 66 and SHMT1 1420 polymorphisms and space flightinduced vision changes. These data document that individuals with an altered 1-carbon metabolic pathway may be predisposed to anatomic and/or physiologic changes that render them susceptible to ophthalmic damage during space flight

Effect of Homocysteine-Lowering Nutrients on Blood Lipids: Results from Four Randomised, Placebo-Controlled Studies in Healthy Humans

BACKGROUND: Betaine (trimethylglycine) lowers plasma homocysteine, a possible risk factor for cardiovascular disease. However, studies in renal patients and in obese individuals who are on a weight-loss diet suggest that betaine supplementation raises blood cholesterol; data in healthy individuals are lacking. Such an effect on cholesterol would counteract any favourable effect on homocysteine. We therefore investigated the effect of betaine, of its precursor choline in the form of phosphatidylcholine, and of the classical homocysteine-lowering vitamin folic acid on blood lipid concentrations in healthy humans. METHODS AND FINDINGS: We measured blood lipids in four placebo-controlled, randomised intervention studies that examined the effect of betaine (three studies, n = 151), folic acid (two studies, n = 75), and phosphatidylcholine (one study, n = 26) on plasma homocysteine concentrations. We combined blood lipid data from the individual studies and calculated a weighted mean change in blood lipid concentrations relative to placebo. Betaine supplementation (6 g/d) for 6 wk increased blood LDL cholesterol concentrations by 0.36 mmol/l (95% confidence interval: 0.25–0.46), and triacylglycerol concentrations by 0.14 mmol/l (0.04–0.23) relative to placebo. The ratio of total to HDL cholesterol increased by 0.23 (0.14–0.32). Concentrations of HDL cholesterol were not affected. Doses of betaine lower than 6 g/d also raised LDL cholesterol, but these changes were not statistically significant. Further, the effect of betaine on LDL cholesterol was already evident after 2 wk of intervention. Phosphatidylcholine supplementation (providing approximately 2.6 g/d of choline) for 2 wk increased triacylglycerol concentrations by 0.14 mmol/l (0.06–0.21), but did not affect cholesterol concentrations. Folic acid supplementation (0.8 mg/d) had no effect on lipid concentrations. CONCLUSIONS: Betaine supplementation increased blood LDL cholesterol and triacylglycerol concentrations in healthy humans, which agrees with the limited previous data. The adverse effects on blood lipids may undo the potential benefits for cardiovascular health of betaine supplementation through homocysteine lowering. In our study phosphatidylcholine supplementation slightly increased triacylglycerol concentrations in healthy humans. Previous studies of phosphatidylcholine and blood lipids showed no clear effect. Thus the effect of phosphatidylcholine supplementation on blood lipids remains inconclusive, but is probably not large. Folic acid supplementation does not seem to affect blood lipids and therefore remains the preferred treatment for lowering of blood homocysteine concentrations

Repeatability and measurement error in the assessment of choline and betaine dietary intake: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background The repeatability of a risk factor measurement affects the ability to accurately ascertain its association with a specific outcome. Choline is involved in methylation of homocysteine, a putative risk factor for cardiovascular disease, to methionine through a betaine-dependent pathway (one-carbon metabolism). It is unknown whether dietary intake of choline meets the recommended Adequate Intake (AI) proposed for choline (550 mg/day for men and 425 mg/day for women). The Estimated Average Requirement (EAR) remains to be established in population settings. Our objectives were to ascertain the reliability of choline and related nutrients (folate and methionine) intakes assessed with a brief food frequency questionnaire (FFQ) and to estimate dietary intake of choline and betaine in a bi-ethnic population. Methods We estimated the FFQ dietary instrument reliability for the Atherosclerosis Risk in Communities (ARIC) study and the measurement error for choline and related nutrients from a stratified random sample of the ARIC study participants at the second visit, 1990–92 (N = 1,004). In ARIC, a population-based cohort of 15,792 men and women aged 45–64 years (1987–89) recruited at four locales in the U.S., diet was assessed in 15,706 baseline study participants using a version of the Willett 61-item FFQ, expanded to include some ethnic foods. Intraindividual variability for choline, folate and methionine were estimated using mixed models regression. Results Measurement error was substantial for the nutrients considered. The reliability coefficients were 0.50 for choline (0.50 for choline plus betaine), 0.53 for folate, 0.48 for methionine and 0.43 for total energy intake. In the ARIC population, the median and the 75th percentile of dietary choline intake were 284 mg/day and 367 mg/day, respectively. 94% of men and 89% of women had an intake of choline below that proposed as AI. African Americans had a lower dietary intake of choline in both genders. Conclusion The three-year reliability of reported dietary intake was similar for choline and related nutrients, in the range as that published in the literature for other micronutrients. Using a brief FFQ to estimate intake, the majority of individuals in the ARIC cohort had an intake of choline below the values proposed as AI

Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study

<p>Abstract</p> <p>Background</p> <p>Low dietary intake of the essential nutrient choline and its metabolite betaine may increase atherogenesis both through effects on homocysteine methylation pathways as well as through choline's antioxidants properties. Nutrient values for many common foods for choline and betaine have recently become available in the U.S. nutrient composition database. Our objective was to assess the association of dietary intake of choline and betaine with incident coronary heart disease (CHD), adjusting for dietary intake measurement error.</p> <p>Methods</p> <p>We conducted a prospective investigation of the relation between usual intake of choline and betaine with the risk of CHD in 14,430 middle-aged men and women of the biethnic Atherosclerosis Risk in Communities study. A semi-quantitative food frequency questionnaire was used to assess nutrient intake. Proportional hazard regression models were used to calculate the risk of incident CHD. A regression calibration method was used to adjust for measurement error.</p> <p>Results</p> <p>During an average 14 years of follow-up (1987–2002), 1,072 incident CHD events were documented. Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53), controlling for age, sex, education, total energy intake, dietary intakes of folate, methionine and vitamin B₆. No association was found between dietary choline intake and incident CHD when correcting for measurement error.</p> <p>Conclusion</p> <p>Higher intakes of choline and betaine were not protective for incident CHD. Similar investigations in other populations are of interest.</p

Microbiota‐Dependent Metabolite Trimethylamine N‐Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA)

BACKGROUND: Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). METHODS AND RESULTS: Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO. CONCLUSIONS: In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults