Calcium intake in vegan and vegetarian diets: A systematic review and Meta-analysis.

In recent years, plant-based diets have experienced increasing popularity. However, plant-based diets may not always ensure an adequate supply of micronutrients, in particular calcium. We performed a systematic review and meta-analysis of calcium intake in vegan and vegetarian diets as compared to omnivorous diets. We searched PubMed and Web of Science and identified 2,009 potentially relevant articles. Mean calcium intake values were pooled and standardized mean differences (SMD) and 95% confidence intervals (CI) were computed.We analyzed 74 studies, including 7,356 vegan, 51,940 vegetarian, and 107,581 omnivorous participants. Of these, dietary calcium intake was examined in 23 studies of vegans, 60 studies of vegetarians and 74 studies of omnivores. Vegans showed a substantially lower calcium intake than vegetarians (SMD = -0.57; 95%CI = -0.83 to -0.32; p = <0.0001) and omnivores (SMD = -0.70; 95%CI = -0.95 to -0.59; p < 0.0001), whereas no statistically significant difference in calcium intake was noted between vegetarians and omnivores (SMD = 0.07; 95%CI = -0.04 to 0.19; p = 0.1976). In conclusion, vegans show a lower calcium intake than vegetarians and omnivores. This finding emphasizes the need for vegans to monitor their calcium status.

PUFA-Induced Metabolic Enteritis as a Fuel for Crohn's Disease.

BACKGROUND & AIMS: Crohn's disease (CD) globally emerges with Westernization of lifestyle and nutritional habits. However, a specific dietary constituent that comprehensively evokes gut inflammation in human inflammatory bowel diseases remains elusive. We aimed to delineate how increased intake of polyunsaturated fatty acids (PUFAs) in a Western diet, known to impart risk for developing CD, affects gut inflammation and disease course. We hypothesized that the unfolded protein response and antioxidative activity of glutathione peroxidase 4 (GPX4), which are compromised in human CD epithelium, compensates for metabolic perturbation evoked by dietary PUFAs. METHODS: We phenotyped and mechanistically dissected enteritis evoked by a PUFA-enriched Western diet in 2 mouse models exhibiting endoplasmic reticulum (ER) stress consequent to intestinal epithelial cell (IEC)-specific deletion of X-box binding protein 1 (Xbp1) or Gpx4. We translated the findings to human CD epithelial organoids and correlated PUFA intake, as estimated by a dietary questionnaire or stool metabolomics, with clinical disease course in 2 independent CD cohorts. RESULTS: PUFA excess in a Western diet potently induced ER stress, driving enteritis in Xbp1-/-IEC and Gpx4+/-IEC mice. ω-3 and ω-6 PUFAs activated the epithelial endoplasmic reticulum sensor inositol-requiring enzyme 1α (IRE1α) by toll-like receptor 2 (TLR2) sensing of oxidation-specific epitopes. TLR2-controlled IRE1α activity governed PUFA-induced chemokine production and enteritis. In active human CD, ω-3 and ω-6 PUFAs instigated epithelial chemokine expression, and patients displayed a compatible inflammatory stress signature in the serum. Estimated PUFA intake correlated with clinical and biochemical disease activity in a cohort of 160 CD patients, which was similarly demonstrable in an independent metabolomic stool analysis from 199 CD patients. CONCLUSIONS: We provide evidence for the concept of PUFA-induced metabolic gut inflammation which may worsen the course of human CD. Our findings provide a basis for targeted nutritional therapy.

Intake of micronutrients and fatty acids of vegetarian, vegan, and omnivorous children (1-3 years) in Germany (VeChi Diet Study).

PURPOSE: There is an ongoing debate whether vegetarian (VG) and especially vegan (VN) diets are nutritionally adequate in early childhood. Hence, the Vegetarian and Vegan Children Study (VeChi Diet Study) aimed to assess the food and nutrient intake of VG and VN infants. METHODS: The study examined the diets of 1-3-year-old VG, VN, and omnivorous (OM) children (n = 430). Dietary intake was assessed via a 3-day weighed dietary record and compared between groups using ANCOVA. Lifestyle data were collected using a questionnaire. Here, the results of micronutrient and fatty acid intakes are presented. RESULTS: Most nutrient intakes (with and without supplements) differed significantly between VN children and the two other groups, with a more favourable overall micronutrient intake in VN, followed by VG children, [e.g., the highest intake of vitamin E (8.3 mg/d vs. VG 7.4 mg/d and OM 5.1 mg/d), vitamin B1 (569 µg/d vs. VG 513 µg/d and OM 481 µg/d), folate (143 µg/d vs. VG 116 µg/d and OM 108 µg/d), magnesium (241 mg/d vs. VG 188 mg/d and OM 164 mg/d), and iron (8.9 mg/d vs. VG 7.3 mg/d and OM 6.0 mg/d)] as well as fat quality [highest intake of polyunsaturated fatty acids (8.7 E% vs. VG 6.9 E% and OM 4.5 E%) and lowest intake of saturated fatty acids (9.1 E% vs. VG 11.9 E% and OM 14.0 E%)]. In contrast, OM children had the highest intake of vitamin B2 (639 µg/d vs. VG 461 µg/d and VN 429 µg/d), calcium (445 mg/d vs. VG 399 mg/d and VN 320 mg/d), iodine (47 µg/d vs. VG 33 µg/d and VN 31 µg/d), and DHA (35.4 mg/d vs. VG 16.6 mg/d and VN 18.4 mg/d). Without supplementation, OM children had the highest average vitamin B12 intake (1.5 µg/d vs. VG 0.6 µg/d and VN 0.2 µg/d), whereas VN children had the highest average vitamin B12 intake with supplementation (73.8 µg/d vs. VG 1.3 µg/d and OM 1.7 µg/d). Without supplementation, none of the groups' median intakes met the harmonised Average Requirement (h-AR) for vitamin D and iodine. Moreover, VG and VN children did not achieve h-ARs for vitamin B2, vitamin B12, and iron-if a low absorption of iron is anticipated; VN children also did not do so for calcium. CONCLUSION: In early childhood, VN and VG diets can provide most micronutrients in desirable amounts and a preferable fat quality compared to an OM diet. Special focus should be paid to (potentially) critical nutrients, particularly vitamin D, iodine, and DHA for all children regardless of diet, as well as vitamin B2, vitamin B12, calcium, and iron for VG and VN children. TRAIL REGISTRATION: This study was registered with the German Clinical Trials Register (DRKS00010982) on (September 2, 2016).

How Does Selenium Intake Differ among Children (1-3 Years) on Vegetarian, Vegan, and Omnivorous Diets? Results of the VeChi Diet Study.

In regions with low selenium soil concentrations, selenium can be considered a critical nutrient for vegetarians and vegans. While the number of vegetarians and vegans is increasing in many countries, a large research gap remains in this field. For example, to date, no study seems to have assessed selenium intake in vegetarian and vegan children. Therefore, the selenium intake of 1- to 3-year-old vegetarian, vegan, and omnivorous children who participated in the cross-sectional VeChi Diet study was determined. Selenium intake was assessed based on 3-day food diaries (not including supplements) and food selenium concentrations provided by the European Food Safety Authority (EFSA). Between-group differences were assessed with analysis of covariance (ANCOVA). The median daily selenium intake was 17 µg, 19 µg, and 22 µg in vegetarian, vegan, and omnivorous children, respectively. However, only the difference between the vegan and omnivorous children was statistically significant. On average, all three groups met the harmonized average requirement (H-AR) for selenium of 17 µg/day. Nevertheless, the hypothesis that vegetarian and vegan children generally consume less selenium than omnivorous children could be confirmed, and 39% of vegetarians, 36% of vegans, and 16% of omnivores fell below the adequate intake for selenium (provided by EFSA) of 15 µg/day.

Fatty acyl availability modulates cardiolipin composition and alters mitochondrial function in HeLa cells.

The molecular assembly of cells depends not only on the balance between anabolism and catabolism but to a large degree on the building blocks available in the environment. For cultured mammalian cells, this is largely determined by the composition of the applied growth medium. Here, we study the impact of lipids in the medium on mitochondrial membrane architecture and function by combining LC-MS/MS lipidomics and functional tests with lipid supplementation experiments in an otherwise serum-free and lipid-free cell culture model. We demonstrate that the composition of mitochondrial cardiolipins strongly depends on the lipid environment in cultured cells and favors the incorporation of essential linoleic acid over other fatty acids. Simultaneously, the mitochondrial respiratory complex I activity was altered, whereas the matrix-localized enzyme citrate synthase was unaffected. This raises the question on a link between membrane composition and respiratory control. In summary, we found a strong dependency of central mitochondrial features on the type of lipids contained in the growth medium. This underlines the importance of considering these factors when using and establishing cell culture models in biomedical research. In summary, we found a strong dependency of central mitochondrial features on the type of lipids contained in the growth medium.

Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease.

The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.

Vitamin B12-fortified toothpaste improves vitamin status in elderly people: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Elderly people are at risk for vitamin B12 deficiency. AIMS: We studied the ability of vitamin B12-enriched toothpaste vs. placebo to increase vitamin B12 status in elderly subjects. METHODS: We conducted a randomized double-blind placebo-controlled intervention in 103 elderly subjects. Serum concentrations of vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), and plasma total homocysteine (tHcy) were measured at baseline and after 3 months. RESULTS: 92 subjects met the inclusion criteria, completed the 3 months study, and were included in the data analysis. After the intervention, concentrations of vitamin B12 were higher [mean (SD) = 368 (123) vs. 295 (123) pmol/L; p = 0.005] and holoTC tended to be higher [112 (48) vs. 91 (68) pmol/L; p = 0.088] in the vitamin B12 group compared with the placebo group. The changes of serum vitamin B12 [54 (74) vs. 3 (60) pmol/L, p < 0.001], holoTC [21 (34) vs. 2 (32) pmol/L, p = 0.007], and tHcy [- 0.9 (2.3) vs. 0.3 (1.9) µmol/L, p = 0.010] were significantly different between the intervention groups. Mean percentage increase of serum vitamin B12 (+ 23% corresponds to + 54 pmol/L) in the vitamin B12 toothpaste group suggests that the intervention had provided an additional daily intake of approximately + 7 µg oral B12. Common diseases and drugs did not predict the change of blood markers in the vitamin group. No side effects were observed. CONCLUSIONS: The toothpaste enriched with 100 µg cyanocobalamin/g has increased vitamin B12 status and can thus be used for preventing vitamin B12 depletion in elderly people. The trial was registered at ClinicalTrials.gov: NCT02679833.

Vitamin B-12-fortified toothpaste improves vitamin status in vegans: a 12-wk randomized placebo-controlled study.

Background: The oral application of vitamin B-12 may prevent its deficiency if the vitamin is absorbed via the mucosal barrier.Objectives: We studied the effect of the use of a vitamin B-12-fortified toothpaste on vitamin-status markers in vegans and assessed the efficiency of markers in the identification of vitamin-augmentation status.Design: In this 12-wk, double-blinded, randomized, placebo-controlled study, 76 vegans received either a placebo (n = 34) or vitamin B-12 (n = 42) toothpaste. Sixty-six subjects (n = 30 in the placebo arm; n = 36 in the vitamin B-12 arm) completed the intervention. Serum and plasma concentrations of vitamin B-12, holotranscobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) were measured before and after the intervention.Results: Both postintervention concentrations of vitamin B-12 and holotranscobalamin and their changes over 12 wk were higher in the vitamin B-12 group (mean ± SD change: 81 ± 135 pmol/L for vitamin B-12 and 26 ± 34 pmol/L for holotranscobalamin) than in the placebo group (-27 ± 64 and -5 ± 17 pmol/L, respectively) after adjustment for baseline concentrations. Postintervention concentrations of MMA and their changes differed significantly between groups (MMA changes: -0.169 ± 0.340 compared with -0.036 ± 0.544 µmol/L in vitamin B-12 and placebo groups, respectively; P < 0.001). After adjustment for baseline tHcy, postintervention concentrations of tHcy tended to be lower (P = 0.051), and the changes in tHcy (-0.7 ± 4.4 compared with 2.0 ± 5.6 µmol/L, respectively) were greater in the vitamin B-12 group than in the placebo group. Changes in vitamin B-12 markers were more prominent in vegans who reported that they had not taken vitamin B-12 supplements.Conclusion: Vitamin B-12 that is applied to the oral cavity via toothpaste enters the circulation and corrects the vitamin B-12 markers in the blood of vegans who are at higher risk of vitamin B-12 deficiency. This trial was registered at clinicaltrials.gov as NCT02679833.

Self-establishing communities enable cooperative metabolite exchange in a eukaryote.

Metabolite exchange among co-growing cells is frequent by nature, however, is not necessarily occurring at growth-relevant quantities indicative of non-cell-autonomous metabolic function. Complementary auxotrophs of Saccharomyces cerevisiae amino acid and nucleotide metabolism regularly fail to compensate for each other's deficiencies upon co-culturing, a situation which implied the absence of growth-relevant metabolite exchange interactions. Contrastingly, we find that yeast colonies maintain a rich exometabolome and that cells prefer the uptake of extracellular metabolites over self-synthesis, indicators of ongoing metabolite exchange. We conceived a system that circumvents co-culturing and begins with a self-supporting cell that grows autonomously into a heterogeneous community, only able to survive by exchanging histidine, leucine, uracil, and methionine. Compensating for the progressive loss of prototrophy, self-establishing communities successfully obtained an auxotrophic composition in a nutrition-dependent manner, maintaining a wild-type like exometabolome, growth parameters, and cell viability. Yeast, as a eukaryotic model, thus possesses extensive capacity for growth-relevant metabolite exchange and readily cooperates in metabolism within progressively establishing communities.

Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.

PURPOSE: A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells.

St. John's Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer's disease mouse model-role of P-glycoprotein.

The adenosine triphosphate-binding cassette transport protein P-glycoprotein (ABCB1) is involved in the export of beta-amyloid from the brain into the blood, and there is evidence that age-associated deficits in cerebral P-glycoprotein content may be involved in Alzheimer's disease pathogenesis. P-glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John's Wort). To clarify the effect of St. John's Wort on the accumulation of beta-amyloid and P-glycoprotein expression in the brain, St. John's Wort extract (final hyperforin concentration 5%) was fed to 30-day-old male C57BL/6J-APP/PS1(+/-) mice over a period of 60 or 120 days, respectively. Age-matched male C57BL/6J-APP/PS1(+/-) mice receiving a St. John's Wort-free diet served as controls. Mice receiving St. John's Wort extract showed (i) significant reductions of parenchymal beta-amyloid 1-40 and 1-42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P-glycoprotein expression. Thus, the induction of cerebrovascular P-glycoprotein may be a novel therapeutic strategy to protect the brain from beta-amyloid accumulation, and thereby impede the progression of Alzheimer's disease.