Oil-Based Curcuminoid Phospholipid Formulation Mimicking Natural Digestion Enhances Oral Bioavailability of Curcuminoids in Healthy Subjects.

Curcumin, the fat-soluble active ingredient and major compound of curcuminoids contained in the curcuma root, is known for its physiological low absorption and bioavailability. Various formulations and galenic technologies are currently available on the market. In this study, the product tested was provided as a soft gelatin capsule containing curcuminoids in an oily matrix mixed with phospholipids (oil/phospholipids [PL]-based, no new technologies applied or artificial excipients added). This was intended to improve bioavailability of curcuminoids as well as to mimic the natural digestion process of fat-soluble substances. In particular, the oral bioavailability of curcuminoids in the oil/PL-based formulation was compared with the pure curcuminoids extract alone (reference product), in a randomized, cross-over, single oral dose study design. Twelve healthy subjects were administered 200 mg curcuminoids under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration-time curves of total curcuminoids, as well as the curcumin metabolite tetrahydrocurcumin (THC). Results showed significantly higher AUC0-8h levels after the intake of the oil/PL-based formulation for total curcuminoids (205.60 vs. 112.50 ng/mL*h, P = .0001) as well as for THC (347.30 vs. 118.90 ng/mL*h, P < .0001) in comparison to the pure curcuminoids extract. Cmax was also significantly higher for both parameters analyzed (total curcuminoids: 47.54 vs. 21.16 ng/mL, P = .0001; THC: 96.69 vs. 29.83 ng/mL, P < .0001). In addition, the uptake kinetic of total curcuminoids was significantly fastened with the oil/PL-based curcuminoids formulation compared with the pure curcuminoids extract (P = .0446). These data suggest an improved impact on curcuminoids uptake of the oil/PL-based formulation and confirms its good tolerability.

Comparison of the Hologic Genius Digital Diagnostics System with the ThinPrep Imaging System-A retrospective assessment.

BACKGROUND: Digital cytology (DC) with artificial intelligence (AI) is a new approach. The authors compared DC with liquid-based cytology (LBC) using computer assistance (CAS) in a retrospective, noninterventional study. METHODS: In total, 1994 ThinPrep LBC slides (Hologic), which were previously analyzed in 2020 using an imaging system with CAS in routine cotesting for cytology/human papillomavirus, were reviewed in a blinded mode using the Genius Digital Diagnostics System (Hologic). In 555 cases, a histology result was available. The slides were digitally scanned (volumetric scan) at 14 levels integrated into one. AI algorithms were used to present a gallery of six tiles each (containing objects of interest) in five categories. Six additional tile rows were available, from which the diagnoses were made. All cases with a mismatch between DC and imaging system results were reviewed by an additional cytopathologist. RESULTS: In 86.56% of cases, a complete match between both systems was observed using the same cytology categories. When also considering the histology results, the match was 90.37%. In addition, when a cytology follow-up and/or a retrospective review was applied, the match reached 97.34%. In only 0.65% of cases was a major discrepancy observed (two grades of cytology or a low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion [LSIL/HSIL] shift), and none were identified by DC. Significantly more cases of higher severity (atypical squamous cells cannot exclude high grade [ASC-H], high-grade squamous intraepithelial lesion [HSIL]) were identified with DC, and its negative predictive value was higher. The screening time was significantly shorter with DC. CONCLUSIONS: With the Genius system for DC, the sensitivity for HSIL+/ASC-H and the specificity for LSIL and HSIL were superior to LBC and CAS. Screening time was significantly lower.

Bacterial DNAemia in Older Participants and Nonagenarian Offspring and Association With Redox Biomarkers: Results From MARK-AGE Study.

Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI ≥ 2 compared with those with CCI ≤ 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants.

Association between Maternal Choline, Fetal Brain Development, and Child Neurocognition: Systematic Review and Meta-Analysis of Human Studies.

We studied associations between prenatal and early postnatal choline intake, brain development, and neurocognitive function of children. We conducted a systematic review followed by a meta-analysis and critical appraisal of human studies published from 1997 to 2021. Thirty publications were identified. The meta-analysis included 5 of 7 case-control studies studying neural tube defects (NTDs) in relation to maternal choline intakes/circulating concentrations. Low maternal choline intake/circulating concentrations were associated with a higher OR for NTDs among 1131 mothers of newborns with NTDs and 4439 control mothers (pooled estimate = 1.36; 95% CI: 1.11, 1.67). The 95% prediction intervals were 0.78, 2.36. Findings and critical evaluation of 10 publications with interventional designs showed that higher maternal choline intakes during the second half of pregnancy and early postnatal period (550 mg up to 1 g/d on top of the diet) or a child intake of 513 to 625 mg/d from supplements were safe and likely to demonstrate favorable effects on several domains of child neurocognition, such as memory, attention, and visuospatial learning versus the comparators. Findings from observational studies (n = 13) partly supported the association between maternal choline intake/serum concentrations and child neurocognition, but there was low confidence in the use of plasma choline concentrations as a choline intake marker. In conclusion, low maternal choline intakes were associated with a higher OR for NTDs. The risk could be up to 2.36-fold in some populations. Despite limitations of available trials and observational studies, higher maternal choline intake was likely to be associated with better child neurocognition/neurodevelopment. The results should be used to guide choline intake recommendations in pregnancy and lactation, especially because most young women are not achieving the reference intake of choline. This meta-analysis is registered at PROSPERO as CRD42021233790.

A Food Supplement with Antioxidative Santa Herba Extract Modulates Energy Metabolism and Contributes to Weight Management.

The plant Santa herba (Eriodictyon californicum) contains high flavonoids, thus potentially exerting beneficial effects in context of obesity, often accompanied by inflammation and metabolic imbalance. The study assessed the impact of Santa herba on oxidative stress, energy metabolism, weight reduction, and eating behavior, combining in vitro models with clinical data. Santa herba binding of the adenosine receptor A2A (ADORA2A) was assessed using a radioligand binding assay. A Caenorhabditis elegans model was used to determine mobility boosting effects, and Santa herba oxygen radical absorbance capacity (ORAC) values were determined in comparison to antioxidative plants. Clinical data, that is, body weight and appetite-related parameters, were obtained from overweight and obese women receiving either Santa herba or placebo for 12 weeks. Results showed that Santa herba extract binds to ADORA2A, stimulates C. elegans motility (+7.5%) and locomotion, and yields high antioxidative capacities (ORAC: 819 trolox equivalent). Clinical data, obtained from 24 overweight and 25 obese women (mean: 47.5 years), demonstrated a reduced body weight (P = .042) and body fat (P = .044), and by trend reduced leptin levels (P = .065) in women with obesity after Santa herba consumption compared to placebo. In conclusion, Santa herba extract has energizing and antioxidative properties and may aid in weight management of people with obesity. ClinicalTrials.gov Identifier: NCT03853603.

Grape Seed Extract Positively Modulates Blood Pressure and Perceived Stress: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Volunteers.

It is well established that maintaining healthy blood pressure is fundamental in order to avoid disorders to the heart and blood vessels. In prevention, and alongside pharmacological therapy, the use of natural substances has been proven to be extremely helpful for pre- and mild hypertensive subjects. Our study was therefore focused on the effects, both in vitro and in humans, of a grape seed extract, Enovita (GSEe), a highly standardized extract in polyphenols of Vitis vinifera L. The in vitro human umbilical vein endothelial cells (HUVEC) model was chosen to explore the extract properties related to vascular inflammation/vasodilation. A significant reduction of both soluble Inter-Cellular Adhesion Molecule-1 (sICAM) and endothelin-1 secretion/release was induced by GSEe in HUVEC cells. A randomized, double-blind, placebo-controlled clinical study in healthy volunteers was further performed to investigate GSEe benefits. In healthy volunteers, both supplementations significantly modulated blood pressure, with a pronounced effect after GSEe tablets (300 mg/day for 16 weeks) in respect to placebo. In the male gender subgroup, no placebo effect was observed as it was for the female group. As an additional outcome, an overall GSEe positive modulation emerged on mood related to stress perception. Thus, GSEe resulted in a benefit of modulating endothelial functionality and blood pressure. It was noteworthy that GSEe relieved the perceived stress, promising new future perspectives on mood comfort.

Plasma Kinetics of Choline and Choline Metabolites After A Single Dose of SuperbaBoostTM Krill Oil or Choline Bitartrate in Healthy Volunteers.

As an essential nutrient, the organic water-soluble compound choline is important for human health. Choline is required for numerous biological processes, including the synthesis of neurotransmitters, and it is an important prerequisite for structural integrity and the functioning of cells. A choline-rich diet provides crucial choline sources, yet additional choline dietary supplements might be needed to fully meet the body's requirements. Dependent on the structure of choline in different sources, absorption and metabolism may differ and strongly impact the bioavailability of circulating choline. This study in healthy volunteers aimed to compare the pharmacokinetics of free choline and of selected choline metabolites between the single dose intake of phosphatidylcholine, present in SuperbaBoostTM krill oil, and choline bitartrate salt. Results demonstrate that albeit free choline levels in plasma were comparable between both choline sources, peak choline concentration was reached significantly later upon intake of SuperbaBoostTM. Moreover, the occurrence of choline metabolites differed between the study products. Levels of the biologically important metabolites betaine and dimethylglycine (DMG) were higher, while levels of trimethylamine N-oxide (TMAO) were substantially lower upon intake of SuperbaBoostTM compared to choline bitartrate.

Artificial intelligence identified peptides modulate inflammation in healthy adults.

Dietary bioactive peptides have been, among many functionalities, associated with immune modulation and thereby may improve resolution of inflammation. The goals of this research were to assess (1) whether specific peptides with immune-modulating activity consumed as part of a rice protein hydrolysate could be absorbed into blood and (2) whether they modulate inflammation markers. Artificial intelligence algorithms were applied to target, predict and unlock inflammation-modulating peptides from rice protein. A food application was developed containing four bioactive peptides. Protein docking simulation studies revealed high binding energies of these peptides with inflammation markers. In a small kinetic study 10 healthy subjects consumed the peptides with a single bolus of 20 g protein hydrolysate. Although absorption of the four predicted peptides at plasma concentrations deemed biologically relevant could not be confirmed (quantitative LC-MS/MS), several cytokines responded (ELISA kits). The 24-hour kinetic study revealed a slight suppression of pro-inflammatory TNF-α, IP-10 and NOx, whereas IL-6 increased temporarily (timepoints 2-12 hours). These markers returned to the baseline after 24 hours whereas others were not affected significantly (IL-10, hs-CRP, IL-8, and MCP-1). Consumption of a single dose protein hydrolysate containing immune modulatory peptides induced a mild temporary response most likely through intestinal signaling. Forthcoming studies will examine dietary supplementation in situations of stress.

Effects of an Oil-Free Hydroethanolic Pumpkin Seed Extract on Symptom Frequency and Severity in Men with Benign Prostatic Hyperplasia: A Pilot Study in Humans.

Majority of men are affected by symptomatic benign prostatic hyperplasia (BPH) from a certain age. Botanical extracts are frequently used in the early management of the symptoms. In a single-arm, mono-center pilot study, the effects of a proprietary oil-free hydroethanolic pumpkin seed extract on the symptoms of BPH were investigated. A total of 60 men (62.3 years [95% confidence interval (CI): 60.3-64.3 years]) with a total International Prostate Symptom Score (IPSS) of 14.8 (95% CI: 13.5-16.1) participated between January 2017 and October 2017 in the study by ingesting the oil-free hydroethanolic pumpkin seed extract once daily before going to bed during 3 months. Change in IPSS within treatment period was assessed. Frequency of nocturia was recorded by bladder diary, and postvoid residual urine volume was determined through ultrasound. Between baseline and after 12 weeks of supplementation, a significant symptom reduction of an average 30.1% (95% CI: 23.1-37.1) was seen for the total IPSS. Symptom alleviation had a high impact on quality of life (P < .0001) and was significant after 8 and 12 weeks of intervention (P < .001). Nocturia significantly decreased over time (P < .0001), as confirmed by IPSS questionnaire and bladder diary. Postvoid residual urine volume was significantly reduced at the end of intervention (baseline: 83.67 mL [95% CI: 58.02-109.3]; after 12 weeks: 63.11 mL [95% CI: 45.37-80.85]; P = .0394). These results indicate that the oil-free hydroethanolic pumpkin seed extract seems to be a very well tolerable, appropriate plant extract to support health benefits in a collective suffering from BPH related symptoms without the need of medical treatment.

Dietary and lifestyle predictors of folate insufficiency in non-supplemented German women.

Low folate status is a risk factor for birth defects. We studied concentrations of red blood cell (RBC)- and serum folate in 198 German women in relation to information on dietary folate intake, demographic and lifestyle factors. Median serum- and RBC-folate levels were; (14.7 and 589 nmol/L, respectively. Serum < 7.0 nmol/L or RBC-folate < 405 nmol/L were observed in 3.5% and 18.7% of the women, respectively. Three per cent of the women had both lowered serum and RBC-folate. Whereas RBC-folate > 952 nmol/L (optimal levels around conception) were observed in 9.6%. Serum- and RBC-folate were positively associated; they showed the expected correlations with homocysteine, but only weak correlations with folate intake. Younger age, lower fibre and higher carbohydrate intakes were associated with lower blood folate. Thus, folate intake of approximately 278 µg/d was not sufficient to achieve optimal folate status in young women. In conclusion, in the absence of fortification with folic acid, the majority of the women did not achieve folate status that is optimal for prevention of birth defects.

The effectiveness of daily supplementation with 400 or 800 µg/day folate in reaching protective red blood folate concentrations in non-pregnant women: a randomized trial.

PURPOSE: Folate required to achieve desirable red blood cell (RBC) folate concentrations within 4-8 weeks pre-pregnancy is not known. We studied the effect of supplementation with 400 or 800 µg/day folate in achieving RBC-folate ≥906 nmol/L. METHODS: Non-pregnant women were randomized to receive multinutrient supplements containing 400 µg/day (n = 100) or 800 µg/day (n = 101) folate [folic acid and (6S)-5-CH3-H4folate-Ca (1:1)]. The changes of folate biomarkers were studied after 4 and 8 weeks in the 198 women who returned at least for visit 2. RESULTS: At baseline, 12 of the 198 participants (6.1%) had RBC-folate <340 nmol/L, but 88% had levels <906 nmol/L. The RBC-folate concentrations increased significantly in the 800 µg/day (mean ± SD = 652 ± 295 at baseline; 928 ± 330 at 4 weeks; and 1218 ± 435 nmol/L at 8 weeks) compared with the 400 µg/day [632 ± 285 at baseline (p = 0.578); 805 ± 363 at 4 weeks (p < 0.001); 1021 ± 414 nmol/L at 8 weeks (p < 0.001)]. The changes of RBC-folate were greater in the 800 µg/day than in the 400 µg/day at any time (changes after 8 weeks: 566 ± 260 vs. 389 ± 229 nmol/L; p < 0.001). Significantly more women in the 800 µg group achieved desirable RBC-folate concentrations at 4 weeks (45.5 vs. 31.3%; p = 0.041) or 8 weeks (83.8 vs. 54.5%; p < 0.001) compared with the 400 µg group. RBC-folate levels below the population median (590 nmol/L) were associated with a reduced response to supplements. CONCLUSIONS: 88% of the women had insufficient RBC-folate to prevent birth defects, while 6.1% had deficiency. Women with low RBC-folate were unlikely to achieve desirable levels within 4-8 weeks, unless they receive 800 µg/day. The current supplementation recommendations are not sufficient in countries not applying fortification. TRIALS REGISTER: The trial was registered at The German Clinical Trials Register: DRKS-ID: DRKS00009770.

Zinc-Induced Metallothionein in Centenarian Offspring From a Large European Population: The MARK-AGE Project.

Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn) homeostasis and protect against oxidative damage. Studies in transgenic mice have shown that MT favorably influence longevity, although their role in human aging is not completely understood. Within the European multicenter study MARK-AGE, we analyzed MT induction after Zn treatment in peripheral blood mononuclear cells (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects (35-75 years) including the general population (RASIG), centenarian offspring (GO), and their spouses (SGO). We found that the lymphocyte capability to induce MT in response to Zn is not affected by aging. However, GO participants showed lower Zn-induced MT and increased basal expression of MT1A, MT1X, and ZnT-1 genes than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine, and malondialdehyde) in the whole population, but not in GO subjects. In conclusion, our results support the hypothesis that the response to Zn is attenuated in PBMCs of centenarian offspring compared to the general population as a consequence of a tighter control of Zn homeostasis which is likely to provide them constant protection against stress stimuli over the whole lifespan.

In Vitro Activation of eNOS by Mangifera indica (Careless™) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation.

Mangifera indica fruit preparation (Careless™) activates the evolutionary conserved metabolic sensors sirtuin 1 and adenosine monophosphate-activated protein kinase, which have been identified as playing a key role in microcirculation and endothelial function. Here, an acute effect of a single dose of 100 mg or 300 mg Careless™ on microcirculation was investigated in a randomized, double-blind, crossover pilot study in ten healthy women to determine the effective dosage. Microcirculation and endothelial function were assessed by the Oxygen-to-see system and pulse amplitude tonometry (EndoPAT™), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300 mg (35% over pre-value, p = 0.209) Careless™. The EndoPAT™ reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless™. Furthermore, activation of endothelial nitric oxide synthase, as an important regulator for endothelial function, was tested in vitro in primary human umbilical vein endothelial cells. Careless™, after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 µg/mL), 42% (1500 µg/mL), and 60% (3000 µg/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless™ on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation.

Macular pigment and fixation after macular translocation surgery.

BACKGROUND: After full macular translocation (MT) surgery with 360 degrees retinotomy, the fovea is rarely identifiable. Our aim was to verify the position of the fovea, to determine how patients fixate after MT and to examine distribution and optical density of macular pigment (MP). METHODS: 9 patients after MT were investigated. The Utrecht Macular Pigment Reflectometer was used to quantify the MP optical density. A scanning laser ophthalmoscope (SLO) was used to identify the fovea as the centre of MP distribution and determine the retinal locus of fixation. RESULTS: In all patients, the fovea was identified as the centre of MP distribution. The retinal areas used for fixation were displayed by SLO fixation analysis. Comparing their spatial relationship with the fovea, five patients fixated centrally and four eccentrically up to 7.5 degrees . In those patients, microperimetry showed that the atrophy caused by choroidal neovascularisation (CNV) extraction prevented central fixation. CONCLUSION: The combination of MP distribution and fixation analysis allows fixation behaviour to be quantified, even if the fovea morphologically cannot be localised. Our results suggest that the scotoma caused by spreading chorioretinal atrophy is the main cause for reduced visual acuity after MT, and so the MT rotation angle is crucially important.