Effect of high in comparison to low dairy intake intervention on markers of bone and cartilage remodeling and phosphate metabolism in healthy adults with overweight.

BACKGROUND: In the ageing population, issues with bone and joint health are highly prevalent. Both beneficial and potential risks of dairy products on bone and joint health are reported in epidemiological studies. Furthermore, the phosphorus (P) load from dairy could potentially lead to unfavorable changes in P metabolism. OBJECTIVE: To investigate the effect of dairy intake on markers of bone and joint metabolism and P metabolism in an intervention study with high and low dairy intake. METHODS: In a post hoc analysis of a randomized cross-over trial with overweight adults, the effect of a standardized high dairy intake [HDI (5-6 dairy portions per day) versus low dairy intake (LDI, ≤ 1 dairy portion/day)] for 6 weeks on markers of bone and joint health was assessed using enzyme-linked immunosorbent assays and electrochemiluminescence immunoassays. Markers indicative for cartilage breakdown, including urinary CTX-II, serum COMP and 4-hydroxyproline, and markers indicative for bone remodeling, such as serum CTX-I, PTH, 25(OH)D, osteocalcin, P1NP and FGF23, were investigated using linear mixed models. Furthermore, changes in P metabolism, including the main phosphate-regulating hormone FGF23 were explored. RESULTS: This study was completed by 46 adults (57% female, age 59 ± 4 years, BMI 28 ± 2 kg/m2). Following HDI, markers such as urinary CTX-II excretion, COMP, 25(OH)D, PTH and CTX-I were significantly lower after HDI, as compared to LDI. For example, CTX-II excretion was 1688 ng/24 h at HDI, while it was 2050 ng/24 h at LDI (p < 0.001). Concurrently, P intake was higher at HDI than at LDI (2090 vs 1313 mg/day, p < 0.001). While plasma P levels did not differ (1.03 vs 1.04 mmol/L in LDI, p = 0.36), urinary P excretion was higher at HDI than at LDI (31 vs 28 mmol/L, p = 0.04). FGF23 levels tended to be higher at HDI than at LDI (76.3 vs. 72.9 RU/mL, p = 0.07). CONCLUSIONS: HDI, as compared to LDI, reduced markers that are indicative for joint and bone resorption and bone turnover. No changes in P metabolism were observed. CLINICAL TRIAL REGISTRY: This trial was registered at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR4899 as NTR4899.

Protein, Calcium, Vitamin D Intake and 25(OH)D Status in Normal Weight, Overweight, and Obese Older Adults: A Systematic Review and Meta-Analysis.

The aging process is often accompanied by increase in body weight. Older adults with overweight or obesity might have an overconsumption in energy that is accompanied by inadequate intake of protein, vitamin D, and calcium. It is unclear if intake of protein and vitamin D and calcium is sufficient in older adults with overweight/obesity, and whether it differs from older adults with normal weight, since a recent overview of the literature review is lacking. Therefore, we systematically analyzed the current evidence on differences in nutrient intake/status of protein, vitamin D and calcium between older adults with different body mass index (BMI) categories. Randomized controlled trials and prospective cohort studies were identified from PubMed and EMBASE. Studies reporting nutrient intake/status in older adults aged ≥50 years with overweight/obesity and studies comparing between overweight/obesity and normal weight were included. Nutrient intake/status baseline values were reviewed and when possible calculated for one BMI category (single-group meta-analysis), or compared between BMI categories (meta-analysis). Nutrient intake/status was compared with international recommendations. Mean protein (N = 8) and calcium intake (N = 5) was 0.98 gram/kilogram body weight/day (g/kg/d) [95% Confidence Interval (CI) 0.89-1.08] and 965 mg [95% CI: 704-1225] in overweight/obese. Vitamin D intake was insufficient in all BMI categories (N = 5). The pooled mean for vitamin D intake was 6 ug [95% CI 4-9]. For 25(OH)D, the pooled mean was 54 nmol/L [95% CI 45-62], 52 nmol/L [95% CI 46-58], and 48 nmol/l [95% CI 33-62] in normal (N = 7), combined overweight and obese (N = 12), and obese older adults (N = 4), respectively. In conclusion, older adults with overweight and obesity have a borderline sufficient protein and sufficient calcium intake, but insufficient vitamin D intake. The 25(OH)D concentration is deficient for the obese older adults.

Specific Nutritional Biomarker Profiles in Mild Cognitive Impairment and Subjective Cognitive Decline Are Associated With Clinical Progression: The NUDAD Project.

OBJECTIVES: Nutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). DESIGN, SETTING AND PARTICIPANTS: We included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years. METHODS: We measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction (homocysteine-related metabolites), and oxidative stress (minerals and vitamins). Nutritional biomarker associations with clinical progression to MCI/dementia and cognitive decline based on the Mini-Mental State Examination score were evaluated using Cox proportional hazard models and linear mixed models. We used partial least squares Cox models (PLS-Cox) to examine nutritional biomarker profiles associated with clinical progression. RESULTS: In the total group, high high-density lipoprotein (HDL) levels were associated with clinical progression and cognitive decline. In SCD, high folate and low bilirubin levels were associated with cognitive decline. In MCI, low CSF S-adenosylmethionine (SAM) and high theobromine were associated with clinical progression to dementia and high HDL, cholesterol, iron, and 1,25(OH)2 vitamin D were associated with cognitive decline. PLS-Cox showed 1 profile for SCD, characterized by high betaine and folate and low zinc associated with clinical progression. In MCI, a profile with high theobromine and HDL and low triglycerides and a second profile with high plasma SAM and low cholesterol were associated with risk of dementia. CONCLUSION AND IMPLICATIONS: High HDL was most consistently associated with clinical progression. Moreover, different nutritional biomarker profiles for SCD and MCI showed promising associations with clinical progression. Future dietary (intervention) studies could use nutritional biomarker profiles to select patients, taking into account the disease stage.

LDL cholesterol and uridine levels in blood are potential nutritional biomarkers for clinical progression in Alzheimer's disease: The NUDAD project.

INTRODUCTION: We examined associations between nutritional biomarkers and clinical progression in individuals with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD)-type dementia. METHODS: We included 528 individuals (64 ± 8 years, 46% F, follow-up 2.1 ± 0.87 years) with SCD (n = 204), MCI (n = 130), and AD (n = 194). Baseline levels of cholesterol, triglycerides, glucose, homocysteine, folate, vitamin A, B12, E and uridine were measured in blood and S-adenosylmethionine and S-adenosylhomocysteine in cerebrospinal fluid. We determined associations between nutritional biomarkers and clinical progression using Cox proportional hazard models. RESULTS: Twenty-two (11%) patients with SCD, 45 (35%) patients with MCI, and 100 (52%) patients with AD showed clinical progression. In SCD, higher levels of low-density lipoprotein (LDL) cholesterol were associated with progression (hazard ratio [HR] [95% confidence interval (CI)] 1.88 [1.04 to 3.41]). In AD, lower uridine levels were associated with progression (0.79 [0.63 to 0.99]). DISCUSSION: Our findings suggest that LDL cholesterol and uridine play a-stage-dependent-role in the clinical progression of AD.

Vitamin B12 Intake From Animal Foods, Biomarkers, and Health Aspects.

The EAT-Lancet commission recently suggested that transformation to healthy diets by 2050 will require a reduction of at least 50% in consumption of foods such as red meat and sugar, and a doubling in the global consumption of fruits, vegetables, nuts, and legumes. A diet rich in plant-based foods and with fewer animal source foods confers both improved health and environmental benefits. Notably, the risk of vitamin B12 deficiency increases when consuming a diet low in animal products. Humans are dependent on animal foods such as dairy products, meat, fish and eggs. Vitamin B12 deficiency is common worldwide, especially in populations with low consumption of animal foods because of low socioeconomic status, ethical reasons, or because of their lifestyle (i.e., vegans). According to the European Food Safety Authoroty, the recommended adequate intake of vitamin B12 is 4.0 µg/d for adults, and vitamin B12 requirements are higher during pregnancy and lactation. Infants and children from deficient mothers and elderly people are at risk for vitamin B12 deficiency. Diagnosis of vitamin B12 deficiency is hampered by low specificity of available biomarkers, and there is no consensus yet regarding the optimal definition of low vitamin B12 status. In general, a combination of at least two biomarkers is recommended. Therefore, this review presents an overview of vitamin B12 biochemistry and its biomarkers. We further summarize current recommendations of vitamin B12 intake, and evidence on the associations of vitamin B12 intake from different nutrient-dense animal foods with vitamin B12 status markers. Finally, potential consequences of low vitamin B12 status on different health outcomes for pregnant women, infants and elderly are presented.

Associations of AD Biomarkers and Cognitive Performance with Nutritional Status: The NUDAD Project.

As malnutrition is common in patients with Alzheimer's disease (AD), we evaluated nutritional status and body composition of patients with AD, mild cognitive impairment (MCI) and controls, and studied associations of AD biomarkers and cognitive performance with nutritional status and body composition. We included 552 participants, of which 198 patients had AD, 135 patients had MCI and 219 controls. We assessed nutritional status (mini nutritional assessment (MNA)) and body composition (body mass index (BMI), fat-free mass (FFM) and waist circumference). Linear regression analyses (adjusted for age, gender and education where appropriate) were applied to test associations of AD biomarkers and cognitive performance on five domains with nutritional parameters (dependent). Patients with MCI and AD had a lower BMI and MNA score than controls. Worse performance in all cognitive domains was associated with lower MNA score, but not with body composition. AD biomarkers were associated with MNA score, BMI and waist circumference, and associations with MNA score remained after adjustment for cognitive performance. Both AD biomarkers and cognitive performance were associated with nutritional status, associations with AD biomarkers remained after adjustment for cognition. Our data suggest that malnutrition is not only related to impaired cognition but also to AD pathology.

Vitamin B12 in Relation to Oxidative Stress: A Systematic Review.

The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B12 (B12) appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers. A systematic query-based search of PubMed was performed to identify eligible publications. The potential antioxidant properties of B12 include: (1) direct scavenging of reactive oxygen species (ROS), particularly superoxide; (2) indirect stimulation of ROS scavenging by preservation of glutathione; (3) modulation of cytokine and growth factor production to offer protection from immune response-induced oxidative stress; (4) reduction of homocysteine-induced oxidative stress; and (5) reduction of oxidative stress caused by advanced glycation end products. Some evidence appears to suggest that lower B12 status is related to increased pro-oxidant and decreased antioxidant status, both overall and for subclinically deficient individuals compared to those with normal B12 status. However, there is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence. Further work is warranted.

Cheese and Healthy Diet: Associations With Incident Cardio-Metabolic Diseases and All-Cause Mortality in the General Population.

Background: Many countries have established Food-Based Dietary Guidelines (FBDG). For some foods, such as cheese, there is no consensus on whether or not to include them in these guidelines. Cheese may, however, be an excellent source of vitamin K2, which is a macronutrient with demonstrated positive results on cardiovascular-related outcomes. Aim: First, we assessed the role of cheese within the recently developed Lifelines Diet Score (LLDS), a score based on the Dutch FBDG 2015 in relation to incident cardio-metabolic diseases and all-cause mortality. Secondly, we assessed the association of cheese intake with desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), a marker for functional vitamin K2 status, in a subset of the population. Methods: From the Lifelines cohort study, 122,653 adult participants were included to test the association between de LLDS and health outcomes. In a subset of 1,059 participants aged 60-75 years, dp-ucMGP levels were measured. Dietary intake was assessed using a 110-item Food Frequency Questionnaire. Logistic regression were applied, adjusted for relevant confounders. Results: Median cheese intake was 23.5 [12.6-40.6] g/day. We found a positive correlation between cheese intake and the LLDS (Spearman's rho = 0.024, p < 0.001). The LLDS in quintiles was associated with T2DM [OR (95% CI) Q5 (healthy diet) vs. Q1 (poor diet) = 0.54 (0.43-0.67)] and all-cause mortality [Q5 vs. Q1 = 0.62 (0.50-0.76)]. Inclusion of cheese did not alter these associations. Additionally, we found no significant association of total cheese intake with plasma dp-ucMGP levels. Conclusion: In this population-based cohort study, the inclusion of cheese in the LLDS did not change the inverse associations with incident cardio-metabolic diseases and all-cause mortality. Furthermore, we found no significant association of total cheese intake with plasma dp-ucMGP. The results suggest that cheese is a neutral food group that fits a healthy diet.

Consumption of dairy products in relation to the presence of clinical knee osteoarthritis: The Maastricht Study.

PURPOSE: Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA). There is lack of information on the role of specific dairy product categories. We explored the association between dairy consumption and the presence of knee osteoarthritis in 3010 individuals aged 40-75 years participating in The Maastricht Study. METHODS: The presence of knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria. Data on dairy consumption were appraised by a 253-item FFQ covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95%CI), while correcting for relevant factors. RESULTS: 427 (14%) participants were classified as having knee OA. Significant inverse associations were observed between the presence of knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and 0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found for other dairy product categories. CONCLUSION: In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with the lower presence of knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA.

Dairy products and bone health: how strong is the scientific evidence?

The relevance of dairy produce for the diminishment of osteoporotic risk is still a matter of scientific debate due to the outcome of a few single observational studies. This review will address the most robust point estimate on the role of dairy products, as reported in systematic reviews and meta-analyses on randomised controlled trials in the case of bone mineralisation or prospective studies in the case of fracture risk. Plain dairy products or those fortified with Ca and/or vitamin D improve total body bone mineral content (BMC) by 45-50 g over 1 year when the daily baseline Ca intake is lower than 750 mg in Caucasians and Chinese girls. In Caucasian and Chinese women, Ca from (fortified) dairy products increases bone mineral density (BMD) by 0·7-1·8 % over 2 years dependent on the site of measurement. Despite the results on BMC, there are currently no studies that have investigated the potential of dairy products to reduce fracture risk in children. In adult Caucasian women, daily intake of 200-250 ml of milk is associated with a reduction in fracture risk of 5 % or higher. In conclusion, the role of dairy products for BMC or BMD has been sufficiently established in Chinese and Caucasian girls and women. In Caucasian women, drinking milk also reduces fracture risk. More research on the role of dairy products within the context of bone health-promoting diets is needed in specific ethnicities, other than Chinese and Caucasians, and in men.

Supplemental protein from dairy products increases body weight and vitamin D improves physical performance in older adults: a systematic review and meta-analysis.

The purpose of these systematic review and meta-analysis was to assess the effectiveness of dairy components on nutritional status and physical fitness in older adults, as evidence for efficacy of the supplementation of these components is inconclusive. Scopus and MEDLINE were searched. Main inclusion criteria for articles were as follows: double-blind, randomized, placebo-controlled trials including participants aged ≥55 years who received dairy components or a placebo. Outcome measures were nutrient status (body weight and body mass index) and physical fitness (body composition, muscle strength, and physical performance). Thirty-six trials with 4947participants were included. Most trials investigated protein and vitamin D supplementation and showed no effect on the outcomes. Meta-analysis on the effect of protein on body weight showed a significant increase in mean difference of 1.13 kg (95% confidence interval, 0.59-1.67). This effect increased by selecting trials with study a duration of 6 months in which less nourished and physically fit participants were included. Trials where the participants were (pre-)frail, inactive older adults or when supplementing ≥20 g of protein per day tended to increase lean body mass. Only small significant effects of vitamin D supplementation on Timed Up and Go (mean difference -0.75 seconds; 95% confidence interval -1.44 to -0.07) were determined. This effect increased when vitamin D doses ranged between 400 and 1000 IU. Additional large randomized controlled trials of ≥6 months are needed regarding the effect of dairy components containing an adequate amount of vitamin D (400-1000 IU) and/or protein (≥20 g) on nutritional status and physical fitness in malnourished or frail older adults.

Diet and Exercise: a Match Made in Bone.

PURPOSE OF REVIEW: Multiple dietary components have the potential to positively affect bone mineral density in early life and reduce loss of bone mass with aging. In addition, regular weight-bearing physical activity has a strong positive effect on bone through activation of osteocyte signaling. We will explore possible synergistic effects of dietary components and mechanical stimuli for bone health by identifying dietary components that have the potential to alter the response of osteocytes to mechanical loading. RECENT FINDINGS: Several (sub)cellular aspects of osteocytes determine their signaling towards osteoblasts and osteoclasts in response to mechanical stimuli, such as the osteocyte cytoskeleton, estrogen receptor α, the vitamin D receptor, and the architecture of the lacunocanalicular system. Potential modulators of these features include 1,25-dihydroxy vitamin D3, several forms of vitamin K, and the phytoestrogen genistein. Multiple dietary components potentially affect osteocyte function and therefore may have a synergistic effect on bone health when combined with a regime of physical activity.

Associations of Milk Consumption and Vitamin B2 and Β12 Derived from Milk with Fitness, Anthropometric and Biochemical Indices in Children. The Healthy Growth Study.

The benefits of dairy consumption seem to extend beyond its significant contribution to ensuring nutrient intake adequacy as indicated by the favourable associations with several health outcomes reported by different studies. The aims of the present study were to examine the associations of milk consumption with fitness, anthropometric and biochemical indices in children and further explore whether the observed associations are attributed to vitamins B2 and B12 derived from milk. A representative subsample of 600 children aged 9-13 years participating in the Healthy Growth Study was examined. Data were collected on children's dietary intake, using 24 h recalls, as well as on fitness, anthropometric and biochemical indices. Regression analyses were performed for investigating the research hypothesis, adjusting for potential confounders and for B-vitamin status indices (i.e., plasma riboflavin, methylmalonic acid and total homocysteine concentrations), dietary calcium intake and plasma zinc concentrations that could possibly act as effect modifiers. Milk consumption was positively associated with the number of stages performed in the endurance run test (ERT) (ß = 0.10; p = 0.017) and negatively with body mass index (BMI) (ß = -0.10; p = 0.014), after adjusting for several potential confounders and effect modifiers. Dietary intakes of vitamin B2 and B12 derived from milk were also positively associated with the number of ERT stages (ß = 0.10; p = 0.015 and ß = 0.10; p = 0.014 respectively). In conclusion, higher intake of milk as well as vitamin B2 and B12 derived from milk were independently associated with higher cardiorespiratory fitness in Greek preadolescents. The key roles of these B-vitamins in substrate oxidation, energy production, haemoglobin synthesis and erythropoiesis could provide a basis for interpreting these associations. However, further research is needed to confirm this potential interpretation.

Conventional foods, followed by dietary supplements and fortified foods, are the key sources of vitamin D, vitamin B6, and selenium intake in Dutch participants of the NU-AGE study.

With aging, energy needs decrease, necessitating a more nutrient-dense diet to meet nutritional needs. To bridge this gap, the use of nutrient-dense foods, fortified foods, and dietary supplements can be important. This observational study aims to describe current micronutrient intakes of Dutch elderly and to identify the contribution of nutrient-dense foods, fortified foods, and dietary supplements to the intake of micronutrients that are often inadequately consumed in Dutch elderly. Data of 245 Dutch volunteers from the NU-AGE study aged 65 to 80 years were used. Dietary intake was assessed by means of 7-day food records, and dietary supplement use was recorded with an additional questionnaire. Information on fortified foods was obtained from the Dutch Food Composition Table 2011. Nutrient density of foods was evaluated using the Nutrient Rich Food 9.3 score. The percentages of participants not meeting their average requirement were high for vitamin D (99%), selenium (41%), and vitamin B6 (54%) based on conventional foods and also when taking into account fortified foods (98%, 41%, and 27%, respectively) and vitamin and mineral supplements (87%, 36%, and 20%, respectively). Conventional foods were the main source of vitamin D, vitamin B6, and selenium intake (42%, 45%, and 82%, respectively), followed by vitamin and mineral supplements (41%, 44%, and 18%) and fortified foods (17%, 11%, and 1%). Foods with the highest nutrient density contributed most to total vitamin B6 intake only. To optimize nutrient intakes of elderly, combinations of natural food sources, fortified foods, and dietary supplements should be considered.

Food group and micronutrient intake adequacy among children, adults and elderly women in Greece.

The aim of the present study was to record the percentage of children, adults and elderly women in Greece meeting food and micronutrient intake recommendations. Additionally, the present study was aiming to identify the main food contributors of micronutrient intakes and assess the degree up to which meeting food intake recommendations also ensures micronutrient intake adequacy. Dietary intake data from three studies conducted in Greece (on 9-13-year-old children; 40-60-year-old adults; and 50-75-year-old women) were used to estimate mean intakes, the percentages of subjects meeting food and nutrient intake recommendations and the contribution of six core food groups to nutrient intake adequacy. The present study showed that more than 50% of children, adults and elderly women were failing to consume the recommended portions of vegetables, dairy and grains. Furthermore, children and adults consuming the recommended portions of individual core food groups had significantly lower percentages of inadequate micronutrient intakes compared to their counterparts not meeting food intake recommendations (p < 0.05). Nevertheless, even among those consuming the recommended portions from a specific core food group, the recommended intake of the corresponding micronutrient (for which this food group is the main contributor) was not always met. Indicatively, 18.2%-44.1% and 4.2%-7.0% of the populations under study were not meeting calcium and vitamin C intake recommendations, although they were consuming the recommended portions of dairy and fruits, respectively. In conclusion, these findings highlight the importance for public health policy makers to take all necessary initiatives to support the population in achieving the recommended intakes from all core food groups, but also emphasize on food variety to ensure adequate intake for all micronutrients.

Flux analysis of the human proximal colon using anaerobic digestion model 1.

The colon can be regarded as an anaerobic digestive compartment within the gastro intestinal tract (GIT). An in silico model simulating the fluxes in the human proximal colon was developed on basis of the anaerobic digestion model 1 (ADM1), which is traditionally used to model waste conversion to biogas. Model calibration was conducted using data from in vitro fermentation of the proximal colon (TIM-2), and, amongst others, supplemented with the bio kinetics of prebiotic galactooligosaccharides (GOS) fermentation. The impact of water and solutes absorption by the host was also included. Hydrolysis constants of carbohydrates and proteins were estimated based on total short chain fatty acids (SCFA) and ammonia production in vitro. Model validation was established using an independent dataset of a different in vitro model: an in vitro three-stage continuous culture system. The in silico model was shown to provide quantitative insight in the microbial community structure in terms of functional groups, and the substrate and product fluxes between these groups as well as the host, as a function of the substrate composition, pH and the solids residence time (SRT). The model confirms the experimental observation that methanogens are washed out at low pH or low SRT-values. The in silico model is proposed as useful tool in the design of experimental setups for in vitro experiments by giving insight in fermentation processes in the proximal human colon.

Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease.

OBJECTIVES: Vitamin K plays a pivotal role in the synthesis of Matrix Gla protein (MGP), a calcification inhibitor in vascular tissue. Vascular calcification has become an important predictor of cardiovascular disease. The aim of the current study was to examine the potential association of circulating desphospho-carboxylated and -uncarboxylated MGP (dp-cMGP and dp-ucMGP), reflecting vitamin K status, with the incidence of cardiovascular events and disease (CVD) in older individuals. STUDY DESIGN: The study was conducted in 577 community-dwelling older men and women of the Longitudinal Aging Study Amsterdam (LASA), aged >55 year, who were free of cardiovascular disease at baseline. Multivariate Cox proportional hazards models were used to analyze the data. MAIN OUTCOME MEASURES: Incidence of CVD. RESULTS: After a mean follow-up of 5.6±1.2 year, we identified 40 incident cases of CVD. After adjustment for classical confounders and vitamin D status, we observed a more than 2-fold significantly higher risk of CVD for the highest tertile of dp-ucMGP with a HR of 2.69 (95% CI, 1.09-6.62) as compared with the lowest tertile. Plasma dp-cMGP was not associated with the risk of CVD. CONCLUSIONS: Vitamin K insufficiency, as assessed by high plasma dp-ucMGP concentrations is associated with an increased risk for cardiovascular disease independent of classical risk factors and vitamin D status. Larger epidemiological studies on dp-ucMGP and CVD incidence are needed followed by clinical trials to test whether vitamin K-rich diets will lead to a decreased risk for cardiovascular events.

Design of the South East Asian Nutrition Survey (SEANUTS): a four-country multistage cluster design study.

Nutrition is a well-known factor in the growth, health and development of children. It is also acknowledged that worldwide many people have dietary imbalances resulting in over- or undernutrition. In 2009, the multinational food company FrieslandCampina initiated the South East Asian Nutrition Survey (SEANUTS), a combination of surveys carried out in Indonesia, Malaysia, Thailand and Vietnam, to get a better insight into these imbalances. The present study describes the general study design and methodology, as well as some problems and pitfalls encountered. In each of these countries, participants in the age range of 0·5-12 years were recruited according to a multistage cluster randomised or stratified random sampling methodology. Field teams took care of recruitment and data collection. For the health status of children, growth and body composition, physical activity, bone density, and development and cognition were measured. For nutrition, food intake and food habits were assessed by questionnaires, whereas in subpopulations blood and urine samples were collected to measure the biochemical status parameters of Fe, vitamins A and D, and DHA. In Thailand, the researchers additionally studied the lipid profile in blood, whereas in Indonesia iodine excretion in urine was analysed. Biochemical data were analysed in certified laboratories. Study protocols and methodology were aligned where practically possible. In December 2011, data collection was finalised. In total, 16,744 children participated in the present study. Information that will be very relevant for formulating nutritional health policies, as well as for designing innovative food and nutrition research and development programmes, has become available.