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Background: Hypertension is a key modifiable driver of cardiovascular risk and often clusters with dyslipidemia and insulin resistance within the metabolic syndrome. Olive leaf extract (OLE) and potassium have traditionally been used to support blood pressure (BP) management and cardiometabolic health.

Purpose: To investigate the effect of this OLE - potassium combination on BP and key cardiometabolic markers.

Study design: In this randomized, double-blind, placebo-controlled study, 70 adults with untreated mildly to moderately elevated BP received an OLE - potassium supplement (1000 mg OLE, ≥160 mg oleuropein, 300 mg potassium/day) or placebo for 12 weeks.

Results: While office BP fell significantly over time in both groups, 7-day home-based BP monitoring showed a significant greater response, with morning systolic BP decreasing by 5.4 mmHg, in the verum group. Supplementation also reduced total cholesterol by 11.1 mg/dL, LDL-cholesterol by 6.9 mg/dL, and triglycerides by approximately 22 mg/dL at Week 6, while HDL-cholesterol remained stable. Fasting glucose and HbA1c were unchanged, but fasting insulin and HOMA-Index declined in the verum group, indicating a modest improvement in insulin sensitivity. Additionally, oxidized LDL decreased by ∼23 %, without changes in hs-CRP. Quality-of-life scores remained stable, although global self-ratings favoured the combination. The intervention was well tolerated, with no product-related serious adverse events.

Conclusion: The combination of OLE and potassium is a safe adjunctive strategy for individuals with mildly to moderately elevated BP, with favourable effects on lipid profile, oxidative status, and insulin sensitivity that may help reduce cardiometabolic risk in the context of metabolic syndrome.

Introduction: Plant-derived functional foods are increasingly recognized for their role in managing different health-related risk factors. Despite the known traditional uses of fenugreek seed, its potential and influence on nitric oxide production require further scientific validation.

Aim: To investigate the role of Standardized fenugreek seed extract (Testosurge® and FLG) in enhancing eNOS phosphorylation and nitric oxide production to support endothelial function under in vitro conditions.

Study Design: In vitro experimental study using a Human Umbilical Vein Endothelial Cell (HUVEC) model to evaluate dose-dependent enzymatic signaling and bioactive efficacy.

Study Location: BioTeSys GmbH, Schelzorstrasse 54-56, 73728 Esslingen, Germany, from November 2023 to January 2024.

Methodology: HUVECs were treated with varying concentrations of Standardized fenugreek seed extract. Extracts underwent simulated gastrointestinal digestion prior to treatment of HUVECs. The activity of eNOS was quantified using an indirect immunofluorescence assay specifically targeting phosphorylation at the Serine (S1176) residue. Subsequent enzymatic activation was measured to correlate nitric oxide production with functional output. Significances were calculated using Student’s t-test or One-way ANOVA and Dunnett’s post test.

Results: The extract demonstrated a clear dose-dependent increase in eNOS phosphorylation at S1176. This upregulation may lead to a significant increase in NO production compared to the control groups. The data confirms that the phytochemicals within the extract (flavonoids, alkaloids, and saponins) directly stimulate the eNOS signaling pathway. Testosurge® resulted in a 117% activation at 5 minutes compared to vehicle control.

Conclusion: Standardized fenugreek seed extracts may support endothelial function which leads to improved vascular tone and blood flow. Further in vivo and clinical studies are required to confirm these findings.

Keywords: Fenugreek seed extract, Testosurge®, eNOS activation, NO production, cardiovascular health, blood pressure

Biomarkers of ageing are defined as age‐related changes in body function or composition that could serve as a measure of ‘biological’ age and predict the onset of age‐related diseases and/or residual life expectancy. We conducted the MARK‐AGE Study, a European population study (3300 subjects aged 35–74) to identify a powerful set of biomarkers of ageing. A total of 362 clinical‐chemistry, genetic, cellular or molecular biomarkers were analysed for each subject. Using statistical models as well as machine learning we derived mathematical formulas for females and for males that yield a ‘bioage score’ of an individual, based on sets of 10 biomarkers for females and 10 for males. Collectively, these biomarkers model chronological age of our study population and, thus yield the ‘biological’ age of a certain person. ‘Age difference’ (defined as biological minus chronological age) should then identify biologically older or younger individuals. Using our set of biomarkers, subjects with Down Syndrome and smoking females are biologically older, whereas postmenopausal females taking hormone replacement therapy are biologically younger. Strikingly, our data reveal that age difference of MARK‐AGE subjects, but not chronological age, is linearly correlated with levels of HDL, 25‐hydroxy‐Vitamin D, and CD3+ CD4+/CD45+ ratio in such a way that biologically younger subjects display values that are favourable to good health, whereas other markers such as glucose and HbA1c are correlated with chronological age, but not age difference. This dichotomy of correlations may point to different roles of such markers, that is, drivers of the ageing process versus bystanders of ageing.

Background/Objectives: The milk thistle plant (Silybum marianum) is known for its hepatoprotective properties. However, the poor water solubility of silymarin limits its dissolution in the intestinal tract and restricts its bioavailability following oral administration.

Methods: To improve bioavailability, special formulations, in particular micellar solubilization, are explored. In this study, we examined the transport rate of silymarin in a krill oil-based formulation across a Caco-2 epithelial barrier after upstream digestion simulation in vitro. Furthermore, in a randomized cross-over design study the bioavailability of the krill oil-based formulation was investigated after single dose intake in fasting conditions in healthy participants.

Results: We could demonstrate that the apparent transport coefficient of silybin, measured as lead substance of milk thistle extract, across the epithelium is efficiently boosted by a krill oil formulation, resulting in a 28% increase compared to silymarin powder. Consistent with these findings, a significant enhancement of bioavailability (P < 0.0001) was demonstrated for the krill oil-based formulation in comparison to the milk thistle extract resulting in an 8.59-fold higher AUC_0-8h and a 15.08-fold greater C_max of silybin and faster uptake kinetic after single dose intake.

Discussion and Conclusions: These findings suggest that phospholipid-based delivery systems offer a promising strategy for improving the efficacy of lipophilic bioactives. Furthermore, the combination of krill oil with milk thistle extracts efficiently provides silybin, PUFAs, and choline, which are important nutrients contributing to liver and heart health.

Background: (6S)-5-Methyltetrahydrofolate ((6S)-5-MethylTHF) is the physiological folate form in biological fluids. Salts of (6S)-5-MethylTHF may have advantages compared to folic acid and are increasingly used in foods and supplements. Objective and design: The present study describes the physicochemical properties of the (6S)-5-MethylTHF-2Chol salt as a source of methylfolate with respect to solubility, conductivity, and melting point. The pharmacokinetics of (6S)-5-MethylTHF-2Chol and folic acid were compared in a randomized controlled double-blind cross-over study using a single equimolar oral dose of each of the folate substances. Results: The solubility of the dicholine salt was very high (650 mg/mL in H2O and 40 mg/mL in H2O under acidic conditions). The incremental area under the curve (iAUC0-8h) was significantly higher after the administration of (6S)-5-MethylTHF-2Chol compared to folic acid ([1.64-fold, P < 0.0001] for total folate and 2.56-fold higher for (6S)-5-MethylTHF [P < 0.0001]). Discussion and conclusions: The bioavailability of (6S)-5-MethylTHF-2Chol is higher compared to folic acid. The crystalline structure of (6S)-5-MethylTHF-2Chol and its water solubility are advantageous in terms of stability in nutraceutical products and absorption in the gut. (6S)-5-MethylTHF-2Chol is the source of folate that may enable the development of new applications.

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35-75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.