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.

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.

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.

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.

Probiotics Lactobacillus reuteri DSM 17938 and Lactobacillus casei CRL 431 modestly increase growth, but not iron and zinc status, among Indonesian children aged 1-6 years.

Probiotics and milk calcium may increase resistance to intestinal infection, but their effect on growth and iron and zinc status of Indonesian children is uncertain. We investigated the hypotheses that cow milk with added probiotics would improve growth and iron and zinc status of Indonesian children, whereas milk calcium alone would improve growth but reduce iron and zinc status. A 6-mo randomized trial was conducted in low-socioeconomic urban communities of Jakarta. Healthy children (n = 494) were randomly assigned to receive low-lactose milk with a low calcium content of ∼50 mg/d (LC; n = 124), a regular calcium content of ∼440 mg/d (RC group; n = 126), regular calcium with 5 × 10(8) CFU/d Lactobacillus casei CRL 431 (casei; n = 120), or regular calcium with 5 × 10(8) CFU/d Lactobacillus reuteri DSM 17938 (reuteri; n = 124). Growth, anemia, and iron and zinc status were assessed before and after the intervention. Compared with the RC group, the reuteri group had significantly greater weight gain [0.22 (95% CI: 0.02, 0.42) kg], weight-for-age Z-score (WAZ) changes [0.09 (95% CI: 0.01, 0.17)], and monthly weight [0.03 (95% CI: 0.002, 0.05) kg/mo] and height [0.03 (95% CI: 0.01, 0.05) cm/mo] velocities. Casei significantly increased monthly weight velocity [0.03 (95% CI: 0.001, 0.05) kg/mo], but not height. However, the changes in underweight, stunting, anemia prevalence, and iron and zinc status were similar between groups. In conclusion, L. reuteri DSM 17938 modestly improved growth by increasing weight gain, WAZ changes, and weight and height velocity, whereas L. casei CRL 431 modestly improved weight velocity. Independent from probiotics supplementation, regular milk calcium did not affect growth or iron and zinc status.

The role of menaquinones (vitamin K2) in human health.

Recent reports have attributed the potential health benefits of vitamin K beyond its function to activate hepatic coagulation factors. Moreover, several studies have suggested that menaquinones, also known as vitamin K2, may be more effective in activating extra-hepatic vitamin K-dependent proteins than phylloquinone, also known as vitamin K1. Nevertheless, present dietary reference values (DRV) for vitamin K are exclusively based on phylloquinone, and its function in coagulation. The present review describes the current knowledge on menaquinones based on the following criteria for setting DRV: optimal dietary intake; nutrient amount required to prevent deficiency, maintain optimal body stores and/or prevent chronic disease; factors influencing requirements such as absorption, metabolism, age and sex. Dietary intake of menaquinones accounts for up to 25% of total vitamin K intake and contributes to the biological functions of vitamin K. However, menaquinones are different from phylloquinone with respect to their chemical structure and pharmacokinetics, which affects bioavailability, metabolism and perhaps impact on health outcomes. There are significant gaps in the current knowledge on menaquinones based on the criteria for setting DRV. Therefore, we conclude that further investigations are needed to establish how differences among the vitamin K forms may influence tissue specificities and their role in human health. However, there is merit for considering both menaquinones and phylloquinone when developing future recommendations for vitamin K intake.

Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial.

Adolescence is a time for rapid growth that represents an opportunity to influence peak bone mass. Prebiotic agents, such as galacto-oligosaccharides (GOS), increase Ca absorption in animal models and postmenopausal women. The objectives of the present study were to investigate the dose-response relationship of GOS supplementation on Ca absorption during growth and to assess changes in colonic microbiota to better understand the mechanism by which GOS is acting. A total of thirty-one healthy adolescent girls aged 10-13 years consumed smoothie drinks twice daily with 0, 2·5 or 5 g GOS for three 3-week periods in a random order. Fractional Ca absorption was determined from urinary Ca excretion over 48 h at the end of each 3-week period using a dual stable isotope method. Faecal microbiota and bifidobacteria were assessed by PCR-denaturing gradient gel electrophoresis and quantitative PCR. Fractional Ca absorption after the 48 h treatment with control, 5 and 10 g GOS/d was 0·393 (SD 0·092), 0·444 (SD 0·086) and 0·419 (SD 0·099), respectively. Significant improvements in Ca absorption were seen with both low and high doses of GOS compared with the control (P,0·02), but itwas not a dose-response relationship. The increase in absorption was greatest in the urine collected after 24 h, which is consistent with lower gut absorption. Faecal bifidobacteria increased (control 10·89 (SD 13·86), 5 g GOS 22·80 (SD 15·74) and 10 g GOS 11·54 (SD 14·20)) with the GOS treatment (P,0·03). The results suggest that daily consumption of 5 g GOS increases Ca absorption, which may be mediated by the gut microbiota, specifically bifidobacteria.

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.

Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II.

The objective of the present study was to examine the effect of dairy products enriched with calcium, vitamin D(3), and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K(2)) on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Postmenopausal women were divided into three intervention groups and a control group (CG). All three intervention groups attended biweekly sessions and received fortified dairy products providing daily 800 mg of calcium and 10 µg of vitamin D(3) (CaD). Furthermore, in two of the three intervention groups the dairy products were also enriched with vitamin K, providing daily 100 µg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). The increase observed for serum 25(OH)D levels in all intervention groups and the increase observed for serum IGF-I levels in the CaDK2 group differed significantly compared to the changes observed in CG (P = 0.010 and P = 0.028, respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P = 0.001 and P = 0.047, respectively). Significant increases in total-body BMD were observed in all intervention groups compared to CG (P < 0.05), while significant increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary calcium intake. In conclusion, the present study revealed more favorable changes in bone metabolism and bone mass indices for the two vitamin K-supplemented groups, mainly reflected in the suppression of serum levels of bone remodeling indices and in the more positive changes in lumbar spine BMD for these two study groups.

A randomised crossover study investigating the effects of galacto-oligosaccharides on the faecal microbiota in men and women over 50 years of age.

Faecal microbial changes associated with ageing include reduced bifidobacteria numbers. These changes coincide with an increased risk of disease development. Prebiotics have been observed to increase bifidobacteria numbers within humans. The present study aimed to determine if prebiotic galacto-oligosaccharides (GOS) could benefit a population of men and women of 50 years and above, through modulation of faecal microbiota, fermentation characteristics and faecal water genotoxicity. A total of thirty-seven volunteers completed this randomised, double-blind, placebo-controlled crossover trial. The treatments - juice containing 4 g GOS and placebo - were consumed twice daily for 3 weeks, preceded by 3-week washout periods. To study the effect of GOS on different large bowel regions, three-stage continuous culture systems were conducted in parallel using faecal inocula from three volunteers. Faecal samples were microbially enumerated by quantitative PCR. In vivo, following GOS intervention, bifidobacteria were significantly more compared to post-placebo (P = 0·02). Accordingly, GOS supplementation had a bifidogenic effect in all in vitro system vessels. Furthermore, in vessel 1 (similar to the proximal colon), GOS fermentation led to more lactobacilli and increased butyrate. No changes in faecal water genotoxicity were observed. To conclude, GOS supplementation significantly increased bifidobacteria numbers in vivo and in vitro. Increased butyrate production and elevated bifidobacteria numbers may constitute beneficial modulation of the gut microbiota in a maturing population.

Fluoride inhibits the response of bone cells to mechanical loading.

The response of bone cells to mechanical loading is mediated by the cytoskeleton. Since the bone anabolic agent fluoride disrupts the cytoskeleton, we investigated whether fluoride affects the response of bone cells to mechanical loading, and whether this is cytoskeleton mediated. The mechano-response of osteoblasts was assessed in vitro by measuring pulsating fluid flow-induced nitric oxide (NO) production. Osteocyte shape was determined in hamster mandibles in vivo as parameter of osteocyte mechanosensitivity. Pulsating fluid flow (0.7 ± 0.3 Pa, 5 Hz) stimulated NO production by 8-fold within 5 min. NaF (10-50 µM) inhibited pulsating fluid flow-stimulated NO production after 10 min, and decreased F-actin content by ~3-fold. Fluid flow-induced NO response was also inhibited after F-actin disruption by cytochalasin B. NaF treatment resulted in more elongated, smaller osteocytes in interdental bone in vivo. Our results suggest that fluoride inhibits the mechano-response of bone cells, which might occur via cytoskeletal changes. Since decreased mechanosensitivity reduces bone mass, the reported anabolic effect of fluoride on bone mass in vivo is likely mediated by other factors than changed bone cell mechanosensitivity.

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.

CE-LIF-MS n profiling of oligosaccharides in human milk and feces of breast-fed babies.

Mixtures of the complex human milk oligosaccharides (HMOs) are difficult to analyze and gastrointestinal bioconversion products of HMOs may complicate analysis even more. Their analysis, therefore, requires the combination of a sensitive and high-resolution separation technique with a mass identification tool. This study introduces for the first time the hyphenation of CE with an electrospray mass spectrometer, capable to perform multiple MS analysis (ESI-MS(n)) for the separation and characterization of HMOs in breast milk and feces of breast-fed babies. LIF was used for on- and off-line detections. From the overall 47 peaks detected in off-line CE-LIF electropherograms, 21 peaks could be unambiguously and 11 peaks could be tentatively assigned. The detailed structural characterization of a novel lacto-N-neo-tetraose isomer and a novel lacto-N-fucopentaose isomer was established in baby feces and pointed to gastrointestinal hydrolysis of higher-Mw HMOs. CE-LIF-ESI-MS(n) presents, therefore, a useful tool which contributes to an advanced understanding on the fate of individual HMOs during their gastrointestinal passage.

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 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.

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.

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.

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.