An oral French maritime pine bark extract improves hair density in menopausal women: A randomized, placebo-controlled, double blind intervention study.

Background and Aims: Female pattern hair loss affects females of all ages with a trend to increase after menopause. This disorder may have significant psychological impact and lead to anxiety and depression. Objective: In a single center, double blind, randomized, placebo-controlled study, the effects of oral Pycnogenol® intake (3 × 50 mg/day for a total of 6 months) on hair density, scalp microcirculation, and a variety of skin physiological parameters was studied in Han Chinese menopausal women (N = 76) in Shanghai, China. Methods: Measurements were taken at the beginning and after 2 and 6 months, respectively. Hair density was determined by digital photographs and further evaluated by Trichoscan software. Transepidermal water loss was measured by a humidity sensor in a closed chamber on the skin surface. Changes in microcirculation were detected as resting flux on the scalp by reflection photoplethysmography. Results: Pycnogenol® intake significantly increased hair density by 30% and 23% after 2 and 6 months of treatment, respectively, as detected by Trichoscan® evaluation of digital photographs. Interestingly, photoplethysmography revealed that this beneficial effect was associated with a decrease in resting flux of the scalp skin, which might indicate an improvement of microcirculation. None of these effects were observed in the placebo taking group. In addition, a significant transient decrease of transepidermal water loss was observed in scalp skin under Pycnogenol,® but not placebo treatment. Conclusion: Oral intake of Pycnogenol® might have the potential to reduce hair loss in postmenopausal women.

Preventive effects of Pycnogenol® on cardiovascular risk factors (including endothelial function) and microcirculation in subjects recovering from coronavirus disease 2019 (COVID-19).

BACKGROUND: The aim of this open supplement study was to evaluate the effects of Pycnogenol® in comparison with controls on symptoms of post-COVID-19 syndrome and in improving endothelial function, microcirculation, inflammatory markers and oxidative stress over 3 months in symptomatic subjects recovering from COVID-19. METHODS: Sixty subjects recovering from symptomatic COVID-19 were included. One group of 30 followed a standard recovery management while 30 comparable subjects received a supplement of 150 mg Pycnogenol® daily (in 3 doses of 50 mg) in addition to standard management. RESULTS: Two groups of selected subjects were comparable at baseline. The groups progressively improved both with the SM (standard management) and with the SM in combination with the supplement. Patients, supplemented with Pycnogenol® showed significantly better improvement compared to the control group patients. No side effects from the supplementation were observed; tolerability was optimal. The progressive evolution over time was visible in all target measurements. Physiological tests: endothelial function, low in all subjects at inclusion was assessed by flow mediated dilation (FMD) and finger reactive hyperemia in the microcirculation (laser Doppler measurements) after the release of an occluding suprasystolic cuff. It was significantly improved in the Pycnogenol® group after one month and after 3 months (P<0.05 vs. controls). The rate of ankle swelling (RAS) by strain gauge decreased significantly in the supplemented group (P<0.05) in comparison with controls showing an improvement of the capillary filtration rate. At inclusion, the kidney cortical flow velocity indicated a decrease in perfusion (lower systolic and diastolic flow velocity) in all patients. Kidney cortical flow velocity increased significantly with the supplement (P<0.05) in comparison with controls with improvement in systolic velocity and in diastolic component. High sensitivity CRP (hs-CRP) and Il-6 plasma levels decreased progressively over 3 months with a significant more pronounced decrease in the supplement group (P<0.05). The number of patients with normal plasma IL-6 levels at the end of the study was higher (P<0.05) with the supplement. ESR followed the same pattern with a progressive and a more significant decrease in the supplemented subjects (P<0.02). Oxidative stress decreased significantly in the supplemented group (P<0.05) compared with the control group. Systolic blood pressure was significantly lower in the supplemented group (P<0.05) at the end of the study. Finally, the scores of Quality-of-life, mood and fatigue questionnaire and the Karnofsky Scale Performance Index significantly improved in the supplement group (P<0.05) compared to controls after 1 and 3 months. All other blood parameters (including platelets and clotting factors) were within normal values at the end of the study. CONCLUSIONS: In conclusion, Pycnogenol® may offer a significant option for managing some of the signs and symptoms associated with post-COVID-19 syndrome. This pilot evaluation offers some potential rationale for the use of Pycnogenol® in this condition that will have significant importance in the coming years.

Review of Clinical Effects and Presumed Mechanism of Action of the French Oak Wood Extract Robuvit.

Since ancient times, oak wood polyphenols are consumed concomitantly with beverages that are stored and aged in oak wood barrels. Among these polyphenols are roburins, which belong to the class of ellagitannins and only occur in oak. To date, water-extracted standardized French Quercus robur wood extract, commercially known as Robuvit®, has been investigated in 1172 subjects in over 20 published clinical trials. The results of the clinical studies are consistent with reported effects of urolithins regarding increased mitophagy, pointing to enhanced energy capacity. The Robuvit metabolite urolithin A, B, and C levels and the number of urolithin producers were found to be increased after intake of the extract. Mitophagy is a process, which assigns energy inefficient mitochondria to disassembly, followed by reconstruction to new and more efficient replacements. This effect of Robuvit was observed in different study groups. Supplementation of Robuvit is ascribed to aid chronically fatigued or burnt-out individuals to regain higher energy and activity levels. Robuvit has been further shown to improve conditions such as renal insufficiency, liver insufficiency, mild heart failure, posttraumatic stress disorder and fatigue after surgery and facilitate recovery from mild health impairments such as flu or hangover. There are also indications that Robuvit helps improve erectile function and general loss of vigor in elderly men. Ex vivo gene expression experiments using metabolites collected from Robuvit consumers point to increased ribosomal biogenesis in endothelial, neuronal, and keratinocyte cells. Higher ribosome density accelerates the peptide production to meet protein demand, making Robuvit a potential enhancer of physical endurance and performance. A study with recreational athletes, supplemented with Robuvit daily, reported significantly increased performance in triathlon.

Human Metabolites of Hamaforton™ (Hamamelis virginiana L. Extract) Modulates Fibroblast Extracellular Matrix Components in Response to UV-A Irradiation.

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ (Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation.

An Effect of Oak-Wood Extract (Robuvit®) on Energy State of Healthy Adults-A Pilot Study.

The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) - polyphenolic extract obtained from the wood of oak Quercus robur - on the healthy elderly individuals using energy subscale scores of the Activation - Deactivation Adjective Check List. Analysis was focused on the comparison of pre-post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre-treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects.

Influence of oak wood polyphenols on cysteine, homocysteine and glutathione total levels and PON1 activities in human adult volunteers - a pilot study.

Oxidative stress reflects an imbalance between antioxidants and pro-oxidants. Many diseases like atherosclerosis or heart failure are involved in oxidative stress. Increased oxidative stress is one of the potential contributing factors to aging. The aim of this study was to monitor the total thiol levels as markers of oxidative stress in 20 healthy volunteers after polyphenols intake (extract from the French oak wood Quercus robur - Robuvit® (300 mg/day)). Polyphenols are known as biomodulators with antioxidant activities. Homocysteine, cysteine and glutathione total levels were determined by using HPLC with electrochemical detection. The activity of the antioxidant enzyme paraoxonase-1 toward two substrates was determined by spectrophotometry. The level of thiol compounds and paraoxonase-1 activities were controlled after run-in (week 0), intervention (week 4) and washout (week 6) period. After the intervention period the results showed that Robuvit® had no significant influence on glutathione level (p = 0.382) and paraoxonase activities towards both, arylester and lactone substrates. On the other hand, homocysteine and cysteine levels decreased significantly (p = 0.029; p < 0.001, respectively). The negative correlation between paraoxonase lactonase activity and homocysteine level was noticed. This confirms that paraoxonase might play an important role in homocysteine-thiolactone metabolism.

A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol for improving allergic rhinitis symptoms.

The potential of Pycnogenol for relieving allergic rhinitis (birch pollen) symptoms was explored in a double-blind, placebo-controlled trial. In 2008 19 subjects started treatment 3 weeks prior to the onset of birch pollen season in Ontario, Canada. While there was an improvement of eye and nasal symptoms with Pycnogenol, there was no significance versus placebo. It was postulated that Pycnogenol may require a lag-time between the start of therapy and the onset of action. Therefore 39 subjects were treated 5-8 weeks prior to the 2009 birch allergy season. The evaluation of subjects in 2009 showed much lower scores for eye (-35%) and nasal (-20.5%) symptoms with Pycnogenol compared with placebo. In succession of the allergy season birch specific IgE increased by 31.9% in the placebo group compared with only 19.4% in the Pycnogenol group. Detailed analysis suggested that symptom-relief was better the longer subjects were on Pycnogenol prior to the allergen exposure. The best results were found with subjects who took Pycnogenol 7-8 weeks ahead of the allergy season. With the limited number of 39 patients statistical predications were unattainable. In conclusion, Pycnogenol improved allergic rhinitis symptoms when supplementation was started at least 5 weeks before the onset of the allergy season.

Mirtogenol potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects.

PURPOSE: The dietary supplement Mirtogenol((R)) was previously shown to lower elevated intraocular pressure (IOP). We here present the effects of this supplement on IOP in comparison as well as in combination with latanoprost eye drops. METHODS: Seventy-nine patients with asymptomatic ocular hypertension were randomly assigned to three groups receiving either the supplement, or latanoprost eye drops, or both in combination. Intraocular pressure and retinal blood flow were investigated in monthly intervals over 24 weeks. RESULTS: Mirtogenol alone lowered IOP from baseline 38.1 to 29.0 mmHg after 16 weeks, with little further improvement during the following eight weeks. Latanoprost rapidly lowered IOP from baseline 37.7 to 27.2 mmHg within four weeks, without further effects thereafter. The combination of the supplement and latanoprost lowered IOP from 38.0 to 27.3 mmHg after four weeks, and further decreased IOP to 24.2 mmHg after six weeks. After 24 weeks IOP with the combination treatment (23.0 mmHg) was significantly lower than with latanoprost alone (27.2 mmHg). Mirtogenol and latanoprost individually showed comparable effects for gradually increasing central artery blood flow with treatment duration. Combination treatment showed higher systolic blood flow velocity throughout the trial period. The diastolic blood flow velocity gradually increased with treatment duration in all three groups. From twelve weeks onwards, the diastolic component with combination treatment was higher than with individual treatments. CONCLUSIONS: Mirtogenol lowered elevated IOP in patients almost as effectively as latanoprost, however, it takes much longer (24 vs 4 weeks). The combination of both was more effective for lowering IOP and the combination yielded better retinal blood flow. No serious side effects occurred during the study, apart from standard side effects in patients related to Latanoprost. These promising results warrant further research of Mirtogenol with a larger patient group.

Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects.

PURPOSE: The most important variable risk factor for developing glaucoma is intraocular hypertension. Timely lowering of high intraocular pressure (IOP) significantly lowers the likelihood of developing glaucoma. The aim of this study was to evaluate the effects of the food supplement Mirtogenol (Mirtoselect and Pycnogenol on IOP and ocular blood flow in a product evaluation study. METHODS: Thirty-eight asymptomatic subjects with intraocular hypertension were either given Mirtogenol (20 subjects) or were not treated (18 subjects). The visual acuity, IOP, and ocular blood flow were measured at two, three, and six months. RESULTS: After two months of supplementation with Mirtogenol, the mean IOP decreased from a baseline of 25.2 mmHg to 22.2 mmHg. After three months of treatment with Mirtogenol, the IOP was significantly lowered compared to that of untreated controls (p<0.05) to 22.0 mmHg. No further improvement was found after six months. Nineteen of the twenty patients taking Mirtogenol had a decreased IOP after three months. Only marginal effects on the IOP were found in the 18 control subjects. No side effects were observed. Ocular blood flow (central retinal, ophthalmic, and posterior ciliary arteries) improved both in the systolic and diastolic components as measured by Color Doppler imaging. After three months of treatment, the improvement of ocular blood flow was significant as compared to both baseline and control group (p<0.05). CONCLUSIONS: An improved ocular blood flow may contribute to the prevention of glaucoma. The results of this study indicate that Mirtogenol may represent a safe preventative intervention for lowering the risk for developing symptomatic glaucoma by controlling IOP and improving ocular blood flow.