Olive Leaf (Blood Pressure)

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.

OBJECTIVES: The aim of this trial was to assess the effects of olive leaf extract (OLE) on blood pressure (BP) control in patients treated for hypertension. METHODS: This is multicenter randomized, double-blind, placebo-controlled trial including 621 participants who were randomly assigned to receive either oral OLE ( n = 307) or placebo ( n = 314). The primary outcome was the change in 24-h SBP and DBP from baseline to week-12. Secondary outcomes included the change in BP load (BPL), BP variability (BPV), metabolic parameters, C-reactive protein (CRP), and body weight. RESULTS: OLE significantly reduced 24-h SBP compared to baseline and placebo group [respectively -6.4 mmHg (95% confidence interval, 95% CI -10 to -2.1) and -1.5 mmHg (95% CI -3.9 to 0.51); P < 0.01]. In OLE group, systolic BPL decreased from 53.9% at baseline to 42.2% at 12-week ( P = 0.03); in placebo group, it did not change significantly ( P = 0.55). Diastolic BPL decreased from 30.7 to 21.2% ( P = 0.03) in OLE group and did not change significantly in placebo group ( P = 0.12). In OLE group, systolic BPV did not change significantly between baseline and week-12 [+2%; P = 0.23] while diastolic BPV significantly decreased [-13.3%; P = 0.04]. In placebo group, BPV did not change significantly at week-12 compared to baseline. OLE was associated with improvement in lipid profile and a significant reduction in blood glucose, triglycerides, CRP, and body weight. No significant adverse events were reported. CONCLUSION: OLE can decrease 24-h BP, BPL, and diastolic BPV with improvement of lipid profile, systemic inflammation, and body weight in hypertensive patients.

PURPOSE: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels. METHODS: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0-8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks. RESULTS: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05). CONCLUSIONS: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels. TRIAL REGISTERED: The trial has been registered at ClinicalTrials.gov (NCT02990637).

The African wild olive (Olea europaea subsp. africana) is traditionally used as a hypotensive agent. Herb-drug interactions may result from the concurrent use of herbal medicines and conventional prescription drugs. This aspect was investigated by determining the effect of the extract on the in vitro intestinal epithelial permeation of selected hypotensive drugs using the Caco-2 cell culture model. The phytochemical profiles of leaf extracts of African wild olive from different localities in South Africa were compared, since efficacy is determined by the chemical composition. Extracts were analysed using ultra-performance liquid chromatography. The oleuropein concentration varied considerably from below the detection limit (4.94 µg/mL) to 59.4 mg/g dry weight. Chemometric models constructed from the aligned chromatographic data indicated only quantitative differences between the profiles. The leaf extract was found to increase the permeability of propranolol in the absorptive direction (Papp = 8.93 × 10-6 cm/s) across Caco-2 cell monolayers, but considerably decreased transport in the secretory direction (Papp = 3.68 × 10-6 cm/s). The permeation of diltiazem was enhanced by the extract in both the absorptive (Papp = 7.33 × 10-6 cm/s) as well as in the secretory direction (Papp = 7.16 × 10-6 cm/s), but a decrease in the efflux ratio was observed. The extract therefore caused a net increase in the transport of both drugs in the absorptive direction due to an inhibition effect on their efflux. This suggests a potential increase in the blood levels of these drugs when taken simultaneously with African wild olive leaf extract, indicating potential adverse effects that must be verified in vivo. Georg Thieme Verlag KG Stuttgart · New York.

CONTEXT: Olive leaf extract (OLE) is rich in phenolic compounds, which are known for their health benefits. Cardiovascular diseases, primarily coronary heart disease and stroke, are leading causes of mortality globally. OBJECTIVE: This systematic review aimed to assess the impact of OLE on cardiometabolic risk factors in adults. The selection of studies was based on intervention and outcomes, using relevant search descriptors. DATA SOURCES: The databases PubMed, EMBASE, and Web of Science were systematically searched for pertinent studies published up to August 2021. DATA EXTRACTION: Only randomized clinical trials, either cross-over or parallel, involving adult individuals aged ≥18 years, were considered. Additionally, trials that had a comparative or placebo group and used pure OLEs for oral treatment were included. DATA ANALYSIS: Twelve randomized clinical trials (RCTs) met the inclusion criteria. These trials had follow-up periods ranging from 2 days to 12 weeks and involved 703 patients aged 18 years-79 years. The outcomes demonstrated a positive correlation between the intervention group and glucose metabolism (4 RCTs), blood pressure (2 RCTs), lipid profile (2 RCTs), and inflammatory markers (2 RCTs). The RoB2 tool and the GRADE system were used to evaluate the risk of bias and the quality of evidence in the studies. CONCLUSIONS: In the meta-analysis, fasting glycemia, as evaluated in studies using a low dose of OLE, showed a significant result favoring the control group. To obtain more consistent results, further clinical studies in humans, using similar methodologies, are required. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020200877. © The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: [email protected].

BACKGROUND: Periodontitis is a prevalent chronic inflammatory disease in older adults, often linked to systemic conditions and metabolic alterations. Standardized plant extracts may provide consistent adjunctive therapeutic benefits. PURPOSE AND STUDY DESIGN: This double-blind, randomized, placebo-controlled clinical trial (OLIVAGING; ClinicalTrials.gov: NCT05482373) evaluated whether a standardized olive leaf extract enriched to 40 % oleuropein, given in addition to non-surgical periodontal therapy, improves clinical outcomes and modulates systemic metabolism. Sixty participants aged ≥50 years were randomized to receive either supplement or placebo for 120 days. Primary and secondary outcomes were probing pocket depth (PPD) and clinical attachment level (CAL). Plasma metabolomics was performed using untargeted UHPLC-QTOF-MS. RESULTS: Forty-three participants completed the study (23 treatment, 20 placebo). Compared with placebo, the treatment group achieved greater reductions in ΔPPD and gains in ΔCAL across multiple tooth categories and surfaces. Metabolomic profiling revealed distinct Δ patterns, with 17 metabolites differing between groups. Several, including tentatively identified valine, cinnamic acid, 10‑hydroxy-2-decenoic acid, and cortisol, correlated with periodontal improvements, suggesting modulation of biological pathways related to inflammation, oxidative stress, and tissue homeostasis consistent with the know pharmacological effects of oleuropein. CONCLUSIONS: Adjunctive use of an oleuropein-enriched leaf extract improved clinical periodontal outcomes and modulated systemic metabolic signatures in older adults. The standardized extract ensured therapeutic consistency, while metabolomics provided mechanistic insights into host inflammatory and metabolic responses. Findings support further evaluation of plant-derived bioactives as safe, multi-target adjunctive strategies for periodontitis management.

BACKGROUND: The polyphenol oleuropein activates mitochondrial calcium import, which increases pyruvate dehydrogenase (PDH) activity. Preclinically, this increase in PDH activity following oleuropein supplementation resulted in improved mitochondrial bioenergetics and fatigue resistance. OBJECTIVES: This study aimed to examine the effects of acute and chronic oleuropein supplementation on muscle energy metabolism, whole-body substrate metabolism, strength, and fatigue resistance in older males. METHODS: In a randomized, double-blind, placebo-controlled trial, 40 healthy older males (60 ± 5y) received either placebo (PLA) or 100 mg oleuropein from 250 mg olive leaf extract (OLE) supplementation daily for 36 d. On day 1 and day 36, muscle and blood samples were collected, and indirect calorimetry was performed before and ≤120 min following supplement intake. Leg strength and fatigue were measured before and after 29 d of supplementation. Results were analyzed using analysis of covariance or robust analysis of covariance. RESULTS: OLE ingestion on day 1 and day 36 increased plasma oleuropein metabolites (P < 0.001). On day 1, no differences were observed in muscle PDH activity, mitochondrial respiration, or whole-body substrate metabolism 120 min after acute OLE ingestion. Ribonucleic acid sequencing revealed upregulation of oxidative phosphorylation gene pathways (false discovery rate < 0.05), whereas PDH-Serine293-phosphorylation was higher after acute OLE compared with PLA ingestion (P = 0.015). Following chronic supplementation, fractional PDH activity was ∼25% greater in OLE compared with PLA (49 ± 14 compared with 38 ± 10%; P = 0.016) with no differences in absolute PDH activity and PDH-Serine293-phosphorylation between groups. Mitochondrial respiration and protein content, whole-body substrate metabolism, leg strength, and fatigue resistance were not different between OLE and PLA. Plasma low-density lipoprotein cholesterol was lower after chronic OLE compared with PLA (P = 0.043), with no differences in other blood metabolic markers. CONCLUSIONS: Chronic OLE supplementation resulted in higher skeletal muscle fractional PDH activity in healthy, older males, wh

Menopause negatively impacts women's health. Objectives: The aim of this study was to investigate whether an olive leaf extract (OLE) improves postmenopausal symptoms, body composition, handgrip strength and blood lipid profile in postmenopausal women. In a randomized, double-blinded parallel study design, 60 healthy postmenopausal women aged 47-70 years received either OLE (250 mg/day) or placebo supplementation for 12 weeks. Postmenopausal symptoms were assessed with the Menopause-Specific Quality of Life Questionnaire (MENQoL), the Hot Flash Interference scale (HFI), and body composition and bone mineral density (BMD) with a DXA scan; the lipid profile was measured in the blood serum. After six and twelve weeks of OLE supplementation, the overall MENQoL score significantly improved (estimated mean difference [95% CI]: -0.2 [-0.4-0.2], p = 0.027) compared to the placebo. A significant improvement (+0.017 [0.003, 0.030], p = 0.019) was recorded in the BMD in the right arm in the OLE group compared to the placebo. The intervention did not affect other body composition outcomes. TG concentrations and the TG/HDL-C ratio were significantly decreased (-0.1 [-0.2, 0.0], p = 0.010; -0.1 [-0.2, -0.0], p = 0.029, respectively) in the OLE group compared to the placebo. Twelve weeks of daily OLE supplementation improved postmenopausal symptoms. Further studies are needed to elucidate the mechanisms underlying the observed effects.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

A single-center, randomized, double-blind controlled trial was conducted to assess the efficacy of a food supplement based on a combination of grapefruit, bitter orange, and olive extracts administered for eight weeks (n = 51) versus placebo (n = 45) on reduction of cardiovascular risk in healthy volunteers. Study variables included flow-mediated vasodilation (FMD), blood pressure (BP), lipid profile, thrombotic status, oxidative stress biomarkers, inflammation-related biomarkers, anthropometric variables, quality of life, and physical activity. The per-protocol data set was analyzed. In the active product group, there were statistically significant within-group differences at eight weeks as compared with baseline in FMD, systolic and diastolic BP, total cholesterol, LDL-C, LDL-oxidase, oxidized/reduced glutathione ratio, protein carbonyl, and IL-6. Significant between-group differences in these variables were also found. Significant changes in anthropometric variables and quality of life were not observed in the study groups. Changes in the level of physical activity were not recorded. Treatment with the active product was well tolerated. All these findings, taken together, support a beneficial effect of supplementation with a mixture of grapefruit, bitter orange fruits, and olive leaf extracts on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people.

Upper respiratory illness (URI) has a major impact on both training and competition in an athletic setting. High school athletes are a sub-category who have reported higher illness rates than professional and sub-elite high school athletes of the same sport. Olive leaf extract (OLE) is an over-the-counter supplement that contains polyphenols, notably oleuropein and hydroxytyrosol, that have antiviral, antibacterial, anti-inflammatory and antioxidant properties that may reduce URI rates. Thirty-two high school students who play sport for the elite team at their school were recruited to a randomised controlled trial and allocated to a daily placebo or OLE (extent equivalent to 20 g of olive leaf, containing 100 mg oleuropein) supplementation for nine weeks during their competitive season. Twice weekly measures of wellbeing, training load and respiratory illness (sporting upper respiratory illness (SUPPRESS) questionnaire) were recorded at trainings, meetings or games. There was no significant difference in illness incidence (odds ratio (OR): 1.02 (95% confidence interval (CI) 0.21⁻4.44)), but there was a significant 28% reduction in sick days (OR: 0.72 (95% CI 0.56⁻0.93) p-value = 0.02) when supplemented with OLE. The dietary intakes of the athletes were sub-optimal with regard to immune support. OLE supplementation over a season did not significantly reduce URI incidence, but did decrease duration in high school athletes, potentially aiding return to play.

Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted.

Extracts of olive leaf, green coffee bean and beetroot may deliver cardiovascular benefits. This study sought to evaluate the effects of regularly consuming a combination of these extracts on blood pressure (BP), arterial compliance, blood lipids, blood glucose and insulin sensitivity. A double-blind randomised placebo-controlled crossover trial was conducted in adults with untreated high normal or borderline elevated BP. They were randomised to take an active supplement, comprising 500 mg olive leaf extract, 100 mg green coffee bean extract and 150 mg beet powder, or a matching placebo twice daily for six weeks, followed by the alternate supplement for a further six weeks. Assessments of 24-h ambulatory BP (ABP), clinic BP arterial compliance (pulse-wave analysis), blood lipids, blood glucose and insulin were obtained at baseline and at the end of each treatment phase. Baseline clinic BP in 37 overweight middle-aged men and women who completed the trial averaged 145/84 mmHg. There was no significant effect of treatment on ABP or any other outcome measure. The failure to confirm prior evidence of the antihypertensive benefits of these extracts emphasises the importance of placebo control and the value of ABP monitoring. Further dose-response evaluation of olive leaf, green coffee bean or beetroot extracts is required to confirm or refute the purported benefits.

OBJECTIVE: We determined the effect of dietary supplementation with an olive leaf capsule or liquid extract on oxidative status of young and healthy male and female subjects. METHODS: This was a single-center, randomized, single-blinded, prospective pilot comparison of the effect of dietary supplementation with olive leaf extracts. Healthy young adult male and female subjects (n = 45) were randomized into three groups and received daily doses of control, capsule, or liquid extract of olive leaf. Urinary F(2 alpha)-isoprostane, 8-hydroxy-2'-deoxyguanosine, and Folin-Ciocalteu total reducing power were measured to assess the impact of supplementation. RESULTS: Baseline values (mean +/- standard deviation) of the biomarkers were 0.24 +/- 0.13 microg, 9.16 +/- 2.94 microg, and 424.9 +/- 121.4 mg of gallic acid equivalents per gram of creatinine, respectively, for the control group. Using these markers, supplementation with liquid or capsule did not alter oxidative status compared with the control group. Possible reasons for the lack of an observed correlation are presented. CONCLUSION: Dietary supplementation with olive leaf extract did not alter the oxidative status of healthy young adults.