Recovery of sperm quality after COVID-19 disease in male adults under the influence of a micronutrient combination: A prospective study.

OBJECTIVE: This study aims to evaluate the safety and efficacy of a standard micronutrient preparation to improve semen parameters and seminal oxidative stress in adult male subjects after Coronavirus Disease 2019 (COVID-19) disease. METHODS: For this prospective pilot study, 30 males aged 20-50 years who had recently recovered from a symptomatic SARS-CoV-2 infection were recruited from June to October 2021 through a public call for participation. Participants of the study group (n = 30) received two semen analyses according to WHO criteria at an interval of 12 weeks, during which they daily received a micronutrient preparation (L-carnitine, L-arginine, coenzyme Q10, vitamin E, zinc, folic acid, glutathione and selenium). Changes in major semen variables and seminal oxidative stress levels before and after therapy were analyzed and compared to a control group (n = 10) adhering to the same inclusion criteria, including subjects who recently recovered from symptomatic COVID-19 disease without micronutrient supplementation within the 12 weeks between the two semen analyses. RESULTS: After 3 months of micronutrient supplementation the rate of normal semen analysis results in the study group increased significantly (p = 0.009) by 66.7%: from 50.0% before to 83.3% after therapy. There was a significant increase in progressive (p = 0.014) and overall motility (p = 0.05) as well as in the vitality (p = 0.0004) of semen cells after 12 weeks of micronutrient intake. In the control group there were no significant changes in any semen parameter or in the rate of normal semen analysis results over the 3-month observation period. In both groups, sperm density, morphology and oxidative stress did not improve significantly. CONCLUSIONS: Our data suggests that supplementation of certain micronutrients may be a safe way to support recovery of impaired semen parameters in male adults recovered from COVID-19 disease.

The effect of micronutrient supplementation on serum anti-Mullerian hormone levels: a retrospective pilot study.

BACKGROUND: The anti-Müllerian-hormone (AMH) is secreted by the granulosa cells of the oocytes and can be used as a marker of the ovarian reserve; helpful to estimate female fertility or the menopause onset. Although various factors may influence AMH levels, the correlation with nutritional factors needs more research. OBJECTIVE: To evaluate the effect of a micronutrient supplementation on female AMH levels. METHODS: This retrospective analysis includes a total of 244 women, who attended the Karl Landsteiner Institute, Korneuburg, Austria from January 2013 to June 2019 due to an unfulfilled desire for a child. All women were treated with an oral micronutrient preparation consisting the dosage of one soft capsule and one tablet per day for 3 months. The soft capsule contains omega-3 fatty acids and the tablet is a standardized combination of coenzyme Q10, vitamin E, folic acid, selenium, catechins from green tea extract, and glycyrrhizin from licorice extract. Serum AMH levels before and after 3 months were compared. In addition, available clinical data such as ovulation frequency, endometrium thickness, and luteal phase duration were analyzed. RESULTS: The mean age of the women was 37.3 ± 1.8 years, the mean body mass index of 24.3 ± 4.6 k/m2. The mean serum AMH levels and endometrial thickness values were significantly higher after micronutrient supplementation as compared to baseline (1.42 ± 0.86 versus 1.86 ± 0.82 ng/mL and 6.10 ± 1.76 versus 7.29 ± 1.65 mm, respectively). In addition, ovulation frequency and luteal phase duration significantly improved in more than 60%. CONCLUSION: Proposed micronutrient supplementation had a positive effect on serum AMH levels, endometrial thickness, ovulation frequency, and luteal phase duration. It could be a simple, risk-free therapeutic option to improve female fertility. More research is warranted to prove this effect.

The impact of a standardized micronutrient supplementation on PCOS-typical parameters: a randomized controlled trial.

PURPOSE: To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS). METHODS: The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the "multinutrient supplementation group" (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the "control group" (two unlabeled soft capsules containing 200 µg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol. RESULTS: In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable. CONCLUSION: A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).

Soy germ extract alleviates menopausal hot flushes: placebo-controlled double-blind trial.

BACKGROUND/OBJECTIVES: A double-blind, placebo-controlled study was performed to assess the potency of a soy germ preparation for the alleviation of menopausal hot flushes. SUBJECTS/METHODS: Caucasian women with at least seven hot flushes daily were treated with soy germ extract (100 mg isoflavone glycosides) daily or with placebo for 12 weeks, followed by 12 weeks of open treatment with soy. Outcome parameters were the number of hot flushes and the evaluation of the Greene Climacteric Scale. RESULTS: A total of 192 women were included. As the hot flush diaries from one study centre were lost, the assessment of hot flushes was based on 136 participants (soy: 54 women; placebo: 82 women). After 12 weeks, 180 women were available for the analysis of Greene Scale and safety (soy and placebo: each 90 women). Hot flushes were reduced by 43.3% (-3.5 hot flushes) with soy and by 30.8% with placebo (-2.6; p < 0.001). After the open treatment phase with soy, both original groups showed a reduction of 68% of hot flushes. A subgroup analysis showed better effects for soy when symptoms were classified as "severe" at baseline. After 12 weeks of double-blind treatment, there was an improvement from baseline values of 71 and 78% with soy with the items "hot flushes" and "sweating", compared with 24% for both items with placebo. Hormonal safety parameters remained uninfluenced. CONCLUSIONS: Soy germ extract with 100 mg of isoflavone glycosides was shown to modestly, but significantly reduce menopausal hot flushes.

The Impact of a Standardized Oral Multinutrient Supplementation on Embryo Quality in in vitro Fertilization/Intracytoplasmic Sperm Injection: A Prospective Randomized Trial.

The role of micronutrients in fertility has recently gained increased attention. We aimed to test the impact of a standardized, multinutrient supplementation on outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a pilot study. One hundred women undergoing IVF/ICSI were prospectively included and randomized to receive either a multinutrient supplementation named PROfertil® female that included folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids (study group; n = 50), or 400 µg folic acid (control group; n = 50). Outcome parameters were embryo quality on day 3 after oocyte retrieval (good quality vs. poor quality) and the clinical pregnancy rate. In an intention-to-treat analyses, a higher rate of women with at least one good quality embryo (with at least 6 cells and a fragmentation rate <20%) were found for the study (29/50, 58.0%) compared to the control group (18/50, 36.0%; p = 0.045 in chi-square test; relative risk 1.611, 95% CI 1.009-2.597). In conclusion, a multinutrient supplementation that includes folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids seems beneficial in terms of embryo quality.

Comparison of the effect of a combination of eight micronutrients versus a standard mono preparation on sperm parameters.

BACKGROUND: There are reports showing that l-carnitine alone or in combination with other micronutrients improve sperm parameters. However, comparative studies are still lacking. This study was carried out to compare the short term effects of a combination of eight micronutrients including l-carnitine vs. a mono-substance (l-carnitine alone) on sperm parameters. METHODS: This was a prospective, open-labelled, nonrandomized study that included male subjects (20 to 60 years) with at least 1 year of subfertility and at least one pathological semen analysis who received 3 months treatment with a mono-substance (500 mg l-carnitine/twice a day, n = 156) or a combined compound (440 mg l-carnitine + 250 mg l-arginine + 40 mg zinc + 120 mg vitamin E + 80 mg glutathione + 60 µg selenium + 15 mg coenzyme Q10 + 800 µg folic acid/once a day, n = 143) for the same time period. Sperm parameters were analyzed before and after treatment and groups comparisons performed. RESULTS: Baseline characteristics were similar among studied groups (age and body mass indices). Semen parameters (volume, density, overall progressive motility [including slow and fast motility]) and percentage of sperm with normal morphology improved after 3 months in both groups as compared to baseline. However, relative change (expressed as % increase of absolute values) for sperm density and overall progressive motility (including fast motility) was found to be higher for the combined micronutrient treatment group as compared to the mono-treatment using l-carnitine alone. CONCLUSION: Both analyzed groups displayed a positive short term effect on all sperm parameters; however effect on density and motility was significantly better for the combined formulation. There is need for more research in this matter that includes long term outcome data. TRIAL REGISTRATION: Retrospectively registered at ISRCTN (7th October 2016). Study ID: ISRCTN48594239.

Red clover isoflavone metabolite bioavailability is decreased after fructooligosaccharide supplementation.

BACKGROUND: Red clover is an important source of isoflavones; which has been made commercially available as dietary supplements for the treatment of menopausal symptoms. Bioavailability and metabolism of these red clover isoflavones (RCI) have not been studied in detail. Fructooligosaccharides (FOS) stimulate the growth of intestinal bacteria and play an important role in the formation of certain isoflavone metabolites, such as equol and O-desmethylangolensin. OBJECTIVE: To determine the bioavailability of RCI metabolites and analyse whether FOS supplementation could influence their bioavailability. METHODS: Seventeen healthy adults were enrolled in the study carried out in two periods. In the first, compound bioavailability was determined after consumption of 80 mg of RCI (MF11RCE). In the second, a 6-day supplementation of 2×3000 mg/day of FOS was administered before isoflavone consumption. RESULTS: Biochanin A and formononetin were rapidly absorbed and both reached maximum concentrations at an average of 5-7h. Demethylation was a major reaction in the metabolic pathway. Daidzein serum level peaked after about 12.6h. Supplementation with FOS led to a significant decrease in the bioavailability of daidzein, dihydroformononetin, dihydrogenistein and dihydrodaidzein. An increase in equol production was also observed which did not reach statistical significance (p>0.05). CONCLUSION: This study is the first to provide detailed data on RCI bioavailability in humans and determine no influence of FOS yet a trend toward increased equol production. More research is warranted involving a greater sample size.

The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women.

OBJECTIVE: To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women. METHODS: One hundred and nine postmenopausal women aged 40 or more were assigned to randomly receive either two daily capsules of the active compound (80 mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days. RESULTS: Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline. All indices significantly decreased after red clover phase in Group A, corresponding, respectively to a 73.5%, 72.2% and 75.4% average decrement. These decrements were significantly higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7% respectively). In Group A, after washout and placebo phases all values significantly increased. In Group B, all indices remained similar after placebo and washout phases, however significantly dropping after red clover treatment. These values were also significantly lower than those observed in Group A after placebo phase. No side effects were encountered after treatment with the active compound or placebo. CONCLUSION: Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women.

Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts.

OBJECTIVE: To evaluate the effect of isoflavones derived from red clover extracts (MF11RCE) over anxiety and depressive symptoms among postmenopausal women. METHODS: One hundred and nine postmenopausal women aged 40 or more were randomly assigned to receive two daily capsules of MF11RCE (80mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Anxiety and depressive symptoms were measured at baseline, 90 and 187 days with the Hospital Anxiety and Depression Scale (HADS) and Zung's Self Rating Depression Scale (SDS). RESULTS: After receiving the MF11RCE compound the total HADS (anxiety and depression subscale scores also) and the total SDS scores decreased significantly. This effect was equivalent to a 76.9% reduction in the total HADS score (76% for anxiety and 78.3% for depression) and an 80.6% reduction in the total SDS score. After placebo, total HADS (anxiety and depression subscale also) and total SDS scores also decreased significantly in comparison to baseline but only equivalent to an average 21.7% decline. CONCLUSION: Red clover derived isoflavones (MF11RCE) were effective in reducing depressive and anxiety symptoms among postmenopausal women.

Effects of a red clover extract (MF11RCE) on endometrium and sex hormones in postmenopausal women.

OBJECTIVE: To evaluate the effects of a non-prescription red clover extract (MF11 RCE, Melbrosin International, Vienna, Austria) on selected sex hormones and endometrium in postmenopausal women. PATIENTS AND METHODS: One-hundred and nine postmenopausal women with an age > or =40 years were randomly assigned to one of two groups either two capsules of MF11RCE (80mg isoflavone) per day for a 90 day period, or placebo of equal design. After a 7 day washout period, medication was crossed-over for another 90 days. RESULTS: Combined evaluation demonstrated that supplementation with MF11RCE (verum), in contrast to placebo, significantly increased plasma testosterone levels and decreased endometrial thickness. CONCLUSION: MF11RCE exerts a moderate effect on testosterone levels in postmenopausal women, while estradiol levels remained unchanged. The observed reduction of endometrial thickness provides further support for a safe role for isoflavones in terms of endometrial hyperplasia.