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.

Pharmacokinetics of Sodium and Calcium Salts of (6S)-5-Methyltetrahydrofolic Acid Compared to Folic Acid and Indirect Comparison of the Two Salts.

(6S)-5-Methyltetrahydrofolic acid ((6S)-5-Methyl-THF) salts and folic acid may differ in their abilities to raise plasma (6S)-5-Methyl-THF levels. We compared the area under the curve (AUC), Cmax, and Tmax of plasma (6S)-5-Methyl-THF after intakes of (6S)-5-Methyl-THF-Na salt (Arcofolin®) and folic acid. Moreover, we compared the AUCs after intakes of (6S)-5-Methyl-THF-Na and the calcium salt, (6S)-5-Methyl-THF-Ca, that were tested against folic acid in two independent studies. The study was randomized, double blind, and cross over. Twenty-four adults (12 men and 12 women) received a single oral dose of 436 µg (6S)-5-Methyl-THF-Na and an equimolar dose of folic acid (400 µg) on two kinetic days with two weeks washout period in between. The plasma concentrations of (6S)-5-Methyl-THF were measured at 9 time points between 0 and 8 h. We found that the AUC0-8 h of plasma (6S)-5-Methyl-THF (mean (SD) = 126.0 (33.6) vs. 56.0 (25.3) nmol/L*h) and Cmax (36.8 (10.8) vs. 11.1 (4.1) nmol/L) were higher after administration of (6S)-5-Methyl-THF-Na than after the administration of folic acid (p < 0.001 for both). These differences were present in men and women. Only administration of folic acid resulted in a transient increase in plasma unmetabolized folic acid (2.5 (2.0) nmol/L after 0.5 h and 4.7 (2.9) nmol/L after 1 h). Intake of (6S)-5-Methyl-THF-Na was safe. The ratios of the AUC0-8 h for (6S)-5-Methyl-THF-Na and (6S)-5-Methyl-THF-Ca to the corresponding folic acid reference group and the delta of these AUC0-8 h did not differ between the studies. In conclusion, a single oral dose of (6S)-5-Methyl-THF-Na caused higher AUC0-8 h and Cmax of plasma (6S)-5-Methyl-THF compared to folic acid. The Na- and Ca- salts of (6S)-5-Methyl-THF are not likely to differ in their pharmacokinetics. Further studies may investigate whether supplementation of the compounds for a longer time will lead to differences in circulating or intracellular/tissue folate concentrations.

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.

Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.

Effects of Yeast (1,3)-(1,6)-Beta-Glucan on Severity of Upper Respiratory Tract Infections: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Subjects.

OBJECTIVES: Each year, adults suffer about two to four upper respiratory tract infections (URTIs), mostly in winter. The aim of the study was to evaluate the effects of brewers' yeast (1,3)-(1,6)-beta-glucan on incidence and severity of upper respiratory tract infections (URTIs). METHODS: Generally healthy men and women (n = 299) reporting at least three URTIs during the previous year were randomized to receive either a placebo or 900 mg of yeast beta-glucan daily for 16 weeks during winter. In cases of acute URTI, the severity of URTI symptoms was assessed via the WURSS-21 questionnaire and the Jackson scale, and a clinical confirmation was implemented by the investigator. RESULTS: Overall, 70 subjects under placebo and 71 subjects under yeast beta-glucan experienced at least one clinically confirmed URTI episode. The global severity using WURSS-21 had been quite similar between the study groups (p = 0.5267), whereas during the first days of URTIs the severity was less pronounced in the yeast beta-glucan group. On the episode level, the severity of physical symptoms was significantly lower for all investigated time intervals up to 7 days under yeast beta-glucan (WURSS (Q2-11) (days 1-2: p = 0.0465, days 1-3: p = 0.0323, days 1-4: p = 0.0248, days 1-7: p = 0.0278), also confirmed for the Jackson scale). The reduction of severity was accompanied by a significant increase in the joy subscore of the Perceived Stress Questionnaire (PSQ20) (p = 0.0148). In addition, there was a reduction of systolic (p = 0.0458) and diastolic (p = 0.1439) blood pressure. CONCLUSION: Subjects supplementing with yeast beta-glucan benefit by a reduced severity of physical URTI symptoms during the first week of an episode, even though the incidence and global severity of common colds could not be altered in comparison to placebo. Furthermore, accompanying benefits in terms of blood pressure and mood were identified. Altogether, yeast beta-glucan supports the immune function.

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.

Hormonal Contraceptive Use Is Associated With Higher Total but Unaltered Free 25-Hydroxyvitamin D Serum Concentrations.

Context: Intake of hormonal contraceptives (HC) is associated with higher total 25-hydroxyvitamin D [25(OH)D] concentrations, but the effect of HC on free 25(OH)D is unclear. Objective: We investigated whether free 25(OH)D concentrations differ according to use of HC. Design: This is a post hoc analysis of a randomized open trial. Setting: This study was conducted from 13 January to 9 May, 2016, at a clinical research organization in Esslingen, Germany. Participants: We included 201 apparently healthy women of childbearing age. Intervention: Participants were randomly assigned to receive a daily multimicronutrient supplement for 8 weeks; the supplement contained 200 IU (n =100) or 800 IU (n = 101) of vitamin D3. Main Outcome Measures: Primary outcome was the difference in free 25(OH)D between users and nonusers of HC. Results: Overall, 176 participants [median (25th to 75th percentiles) age: 25 (22 to 29) years] with available free 25(OH)D were included in the present analysis. At baseline, total 25(OH)D was significantly higher in users (n = 110) than in nonusers (n = 66) of HC [49.2 (33.4 to 63.4) vs 39.1 (23.8 to 52.5) nmol/L; P < 0.001], whereas there was no difference in free 25(OH)D [7.87 (6.50 to 10.11) vs 7.88 (6.35 to 10.12) pmol/L; P = 0.923]. These results were confirmed after multimicronutrient supplementation and in subgroups according to treatment allocation. Conclusions: Use of HC was associated with, on average, 26% higher total 25(OH)D, whereas free 25(OH)D values did not differ according to use of HC. These findings are relevant for epidemiological studies, but the physiological implications remain to be clarified.

Effects of lemon verbena extract (Recoverben®) supplementation on muscle strength and recovery after exhaustive exercise: a randomized, placebo-controlled trial.

BACKGROUND: Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product. METHODS: The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22-50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise. RESULTS: Participants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength (p = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend (p = 0.0681) and less movement induced pain (p = 0.0788) by trend. Creatine kinase and IL-6 didn't show significant discrimmination between groups. CONCLUSION: Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise. TRIAL REGISTRATION: The trial was registered in the clinical trials registry (clinical trial.gov NCT02923102). Registered 28 September 2016.

Response of Red Blood Cell Folate to Supplementation in Nonpregnant Women is Predictable: A Proposal for Personalized Supplementation.

SCOPE: We modeled red blood cell (RBC)-folate response to supplementation and developed personalized folate supplementation concepts. METHODS AND RESULTS: The changes of RBC-folate were modeled in a time- (4 or 8 weeks) and dose- (400 or 800 µg d-1 folate) dependent manner. Post-supplementation RBC-folate levels were predicted from folate-loading capacities (= measured RBC-folate - [baseline RBC-folate × RBC-survival]). The prediction equations were validated in 119 participants. The median increase of RBC-folate was higher in the 800 µg d-1 than in the 400 µg d-1 group (275 vs 169 nmol L-1 after 4 weeks, and 551 vs 346 nmol L-1 after 8 weeks). Medians (interquartile range) of RBC-folate loading were (4 weeks: 299 (160) vs 409 (237) nmol L-1 ) and (8 weeks: 630 (134) versus 795 (187) nmol L-1 ) in the 400 and 800 µg d-1 group, respectively. The individual measured and predicted RBC-folate values (after 4 weeks/400 µg d-1 = 25 + 1.27 × baseline RBC-folate) and (after 4 weeks/800 µg d-1 = 65 + 1.41 × baseline RBC-folate) did not differ significantly. The measured and predicted concentrations showed high agreement in the validation cohort. CONCLUSIONS: The models can guide nutritional recommendations in women when baseline RBC-folate concentrations are measured and the time to pregnancy between 4 and 8 weeks.

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.

L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation.

PURPOSE: The aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of L-arginine with the vitamins B6, folic acid and B12 (Telcor® Arginin plus) on endothelial dysfunction. METHODS: Subjects aged 40-65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post-pre, visit 3-visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration. RESULTS: The primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators. CONCLUSIONS: This trial confirmed the effective and safe use of dietary management with L-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of L-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation.

Effect of Two Different Multimicronutrient Supplements on Vitamin D Status in Women of Childbearing Age: A Randomized Trial.

The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units (IU) to achieve 25-hydroxyvitamin D (25(OH)D) levels of at least 50 nmol/L, even when endogenous vitamin D synthesis is minimal such as in winter. We aimed to evaluate this recommendation in women of childbearing age. This is a single-center, randomized, open trial conducted from 8 January to 9 May 2016 in Esslingen, Germany. We randomized 201 apparently healthy women to receive for 8 weeks a daily multimicronutrient supplement containing either 200 IU (n = 100) or 800 IU vitamin D3 (n = 101). Primary outcome measure was serum 25(OH)D. 196 participants completed the trial. Increases in 25(OH)D (median with interquartile range) from baseline to study end were 13.2 (5.9 to 20.7) nmol/L in the 200 IU group, and 35.8 (18.2 to 52.8) nmol/L in the 800 IU group (p < 0.001 for the between group difference). At study end, levels of ≥50 nmol/L were present in 70.4% of the 200 IU group and in 99% of the 800 IU group. Participants on hormonal contraceptives had higher baseline levels and a stronger increase in 25(OH)D. In conclusion, daily supplementation of 800 IU vitamin D3 during wintertime in Germany is sufficient to achieve a 25(OH)D level of at least 50 nmol/L in almost all women of childbearing age, whereas 200 IU are insufficient.